BIOINTEGRATION OF BONE GRAFTING MATERIALS AND...

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1 BIOINTEGRATION OF BONE GRAFTING MATERIALS AND OSSEOINTEGRATED IMPLANTS IN ORAL AND MAXILLOFACIAL SURGERY Semmelweis University PhD School Thesis Dr. Umberto Garagiola Dental and Stomatologic Clinic Department Oral Surgery University of Milan – Italy Clinical Medical Sciences Dental Research Head of the School Head of the programme Prof. Dr. Zsolt Tulassy Prof. Dr. Árpád Fazekas Supervisor Prof. Dr. György Szabó Semmelweis University Department of Oral and Maxillofacial Surgery, Budapest Head Dr. József Barabás Budapest 2006

Transcript of BIOINTEGRATION OF BONE GRAFTING MATERIALS AND...

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BIOINTEGRATION OF BONE GRAFTING MATERIALS AND

OSSEOINTEGRATED IMPLANTS IN ORAL AND MAXILLOFACIAL

SURGERY

Semmelweis University PhD School Thesis

Dr. Umberto Garagiola

Dental and Stomatologic Clinic

Department Oral Surgery

University of Milan – Italy

Clinical Medical Sciences Dental Research

Head of the School Head of the programme

Prof. Dr. Zsolt Tulassy Prof. Dr. Árpád Fazekas

Supervisor

Prof. Dr. György Szabó

Semmelweis University

Department of Oral and Maxillofacial Surgery, Budapest

Head Dr. József Barabás

Budapest 2006

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CONTENTS

List of abbreviation pag. 3

1. Introduction pag. 4

2. Aim pag. 10

3. Osseointegration in implant dentistry pag. 11

3.1 Sinus Elevation pag. 15

3.2 Ectodermal Dysplasia pag. 18

4. Bone grafts and substitutes: materials pag. 21

4.1 Autogenous and allogeneic bone pag. 21

4.2 Synthetic bone substrates materials: alloplastic grafts pag. 27

4.3 Xenogeneic bone material pag. 29

5. Bone grafts and substitutes: mechanism pag. 33

5.1 Bone conduction pag. 33

5.2 Bone induction (protein-BMP) pag. 34

5.3 Guided tissue regeneration pag. 35

6. Material and methods pag. 38

6.1 Material and methods: Sinus elevation pag. 38

6.2 Material and methods: Ectoderma Dysplasia pag. 41

7. Results pag. 44

7.1 Results: Sinus elevation pag. 44

7.2 Results: Ectodermal Dysplasia pag. 51

8. Discussion pag. 53

8.1 Discussion: Sinus elevation pag. 53

8.2 Discussion: Ectodermal Dysplasia pag. 57

9. Conclusions pag. 60

10. Summary pag. 61

11. Bibliography pag. 63

12. List of Author’s publications pag. 83

12.1 List publications connected with the topic pag. 83

12.2 List publications non connected with the topic pag. 86

13. List of Author’s abstracts pag. 89

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13.1 List of abstracts connected with the topic pag. 89

13.2 List of abstracts non connected with the topic pag. 109

14. Acknowledgements pag. 125

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LIST OF ABBREVIATIONS

Guided Bone Regeneration GBR

Scanning Electron Microscopic SEM

Transmission Electron Microscopic TEM

Titanium Plasma-Sprayed TPS

Hydroxyapatite HA

Bovine Spongiform Encephalopathy BSE

Particulate Marrow Bone Cancellous PMBC

Tricalcium Phosphate TCP

Recombinant Human Bone Morphogenetic Protein rh-BMP

Deoxyribonucleic Acid DNA

Hard Tissue Replacement HTR

Polyhydroxyethyl Methacrylate PHEMA

Computerized Tomography CT

Ectodermal Dysplasia ED

Expanded Polytetrafluoroethylene e-PTFE

Probing Depth PD

Modified Plaque Index mPLI

Modified Sulcus Bleeding Index mSBI

Tricalcium Phosphate Granule CG

Osteogenic Mesenchyme OM

Bone Graft BG

Anorganic Bovine Bone ABB

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1. - INTRODUCTION

The reconstruction of large skeletal deficiencies presents a challenging problem

to the oral and maxillofacial surgeon and surgical community. Such defects in the facial

skeleton can be the result of trauma, infection, congenital defects, cranio-facial

syndromes, severe periodontitis, or tumor resection. In the reconstructive process there

is often a need to create new bone.

A solely prosthetic approach to management of alveolar bone loss frequently

leads to esthetic and/or functional compromises. Today, specific surgical techniques

extend implant options and optimize their final results:

- extraction and immediate implant placement

- tuberosity and pterygomaxillary implants

- partial intrasinus and nasal fossa implants

- sinus grafting

- onlay bone grafts

- dental nerve repositioning

- guided bone regeneration (GBR)

- osteotomies and bone grafts

- tissue engineering procedures

- alveolar distraction osteogenesis

A main hindrance for successful bone healing and for creation of new bone is

the rapid formation of the soft connective tissue. Ingrowth of soft tissue may disturb or

totally prevent osteogenesis in a defect or a wound area. The mechanisms behind the

influence of soft connective tissue on osteogenesis are not yet fully understood.

Experiments in vitro have demonstrated that fibroblasts produce one or more soluble

factors that are inhibitory to bone cell differentiation and osteogenesis.1 Another

possible explanation suggested by Schmitz et al2 is that a bony non-union development

may be due to the failure of the cells that are present to calcify the matrix, perhaps

caused by the lack of appropriate bone derived growth and differentiation factors in

large bony defects. Another frequently occurring clinical situation that causes

significant problems for reconstruction is the atrophic edentulous jaw, since the

introduction of reliable oral implant techniques, partially or totally edentulous patients

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can be successfully treated with jawbone-anchored prostheses. However, a prerequisite

for the use of oral implants is a sufficient amount of bone to fully cover the implant and

to allow the implant to support a fixed prosthetic restoration. Even a minor lack of bone,

either horizontal or vertical, may cause a significant problem. A narrow or buccally

concave alveolar ridge may result in exposed threads at the alveolar crest or at bone

fenestrations. Anatomic restrictions, such as the nasal cavity, maxillary sinuses, and

inferior alveolar nerve, in combination with insufficient amounts of bone may dictate a

less advantageous placement of the implants, compromising the final restorative result.

Numerous methods have been used in an attempt to solve this problem. One of the most

common methods involves the harvesting and implantation of fresh autogenous bone

grafts.3 (Figures 1., 2., 3., 4.)

Fig. 1. A narrow alveolar ridge Fig. 2. Bilateral harvest from mental symphisis

Fig. 3. Autogenous grafts fixed by mini screws Fig. 4. After reconstruction of bone defect,

and covered by anorganic bovine bone optimal for implant insertion

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However, this is an expensive procedure that requires hospitalization as well as

the potential risk for donor site morbidity. Even though similar methods have been used

in more advanced situations of oral reconstructive therapy, only limited scientific data

exist regarding the long-term outcome of such treatment. Other methods use bone

powder implants or various commercially available allografts. Most of these materials

act as passive scaffolds, and it is questionable whether such techniques have any real

inductive effects on osteogenesis at the cellular level.

In recent years, much research has been focused on the osteogenic potential of

demineralised bone powder implants. The stimulatory effects appear to be due to local

morphogenic factors inherent in the implanted bone matrix. In general the technique has

shown good experimental results,4 but more research is necessary before it can be

applied routinely in patients.

Thus, whereas many different methods to improve bone healing and regenerative

capacity have been tested, with varying degrees of success, few have reached the stage

of routine clinical application. While the future holds promise for new ideas in this area,

it is tempered by the realization that the restoration of a deficient skeleton by natural

bone remains the ultimate goal.5

Autogenous graft or allogeneic graft? For many years, the reconstruction of bone

defects has been achieved using a variety of bone substitute materials. The question of

the “best” graft material has been addressed intensively by researchers, and as a result, a

large number of experimental and clinical publications have appeared on this topic.6-19

In 1996, a Consensus Conference on sinus grafting made an attempt to summarize and

evaluate the research findings.20

One of the most important conclusions of the conference was that retrospective analyses

did not reveal any bone substitute material that was equivalent to autogenous spongiosa.

Accordingly, “…many participants believed that autografts were the most

efficacious…” and “the doubts raised revealed the need for controlled prospective

multicenter clinical trials”.

In essence, the question lies in how to avoid morbidity at bone graft donor sites.21,22 It is

increasingly clear that, in addition to basic animal experiments, there is a need for

clinical investigations that apply the gold standard principle to compare autogenous

bone and various bone substitute materials. (Figures 5., 6., 7.)

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Fig. 5. Bone window of lateral sinus wall Fig. 6. Elevated sinus membrane and bone

with inserted implants

Fig. 7. Sinus filled by bone graft

An important publication in this respect is that of Groeneveld and coworkers.23

They compared 4 materials: osteogenic protein 1 (on a collagen carrier), human freeze-

dried demineralized bone matrix, autogenous bone, and nongrafted alveolar crest. In a

total of 12 patients (3 for each of the materials), histologic and histomorphometric

methods were used to detect new bone formation during sinus floor elevation and

implantation. All grafted sinuses exhibited an increased proportion of osteoid, as

compared with nongrafted sinuses. It was concluded that in human sinus floor elevation,

osteogenic protein has a potential bone-inductive capacity; however, the results with

this material were inconsistent.

Yildirim and associated24 used a combination of Anorganic Bovine Bone (ABB) and

venous blood as a graft material. Six months after sinus floor augmentation, they found

14.7% new bone, 29.7% ABB, and 55.6% soft tissue in the tissue samples (soft

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tissue=blood vessels and connective tissue composed of various proportions of

fibroblasts and collagenous fibres). It is interesting to compare these results with the

data reported in 1991 by Schenk,25 who found that the bone content of the human iliac

crest was 20% to 25%, depending on age. Naturally, one of the problems to be

considered in this regard is the extent to which Anorganic Bovine Bone (ABB) is

resorbed.

In the literature, the resorption of bovine bone substitute materials has been the subject

of controversy. Schlegel and Donath26,27 were able to identify the presence of ABB

granules even after a resting time of up to 7 years. It was demonstrated histologically by

Skoglund and colleagues 28 that ABB particles could be found in the maxilla 44 months

after implantation. Some publications based on animal experiments have furnished

histologic evidence of the resorption of ABB.24,29-31

An example of control is provided by the paper by Tadjoedin and coworkers.32 Bilateral

sinus grafting was performed on 10 patients; 1:1 mixture of autogenous bone particles

and bioactive glass particles was used on the experimental side, and autogenous bone

alone was used on the control side. At 6 months, bone tissue on the experimental side

had increased to 32%, differing only slightly from the control side, which contained

38% bone by volume. At 16 months, the total bone volume on the experimental side

was similar to that on the control side. After 16 months, the quality and density of bone

in the augmented sinus floor were similar, regardless of whether or not bone particles or

a mixture of bone particles and bioactive glass particles had been applied.

In addition to histology and histomorphometry,33-38 modern imaging procedures39-47 are

being applied more frequently for sinus graft examination. At the Sinus Consensus

Conference,20 panoramic radiographs appeared logical for the comparison of a large

number of patients. Long-term results of sinus grafting may be monitored by a number

of known computer tomographic methods, but these have seen limited use. Kent,40 for

example, examined bone levels from the new sinus floor to the alveolar crest and the

apex of the implant. Alveolar bone height was considered satisfactory if the new bone

exceeded the apex of the implant by at least 2 mm even after 5 to 10 years.

These data and the Consensus Conference20 have raised the question (among others) of

how the immediate and long-term success of planned sinus grafting can be monitored,

not only histologically, as with delayed implant placement, but also more accurately.

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The significance of pure-phase β-tricalcium phosphate as a bone substitute material has

increased in recent years. It has been used in maxillofacial preprosthetic surgery,

implant dentistry, traumatology, orthopedics, and hand surgery.48-55 The treatment

modes in maxillofacial surgery have included the filling of large cysts, sinus grafting,

augmentation, and the filling of periodontal lesions. It has been demonstrated that β-

tricalcium phosphate is fully resorbed in 12 to 18 months and is replaced by bone that is

similar both functionally and anatomically to the original bone. In view of these

favourable properties, some Authors sought to determine whether this bone substitute

alone is an appropriate sinus graft material and whether it is suitable for the filling of

large bone cysts.55 Accordingly, prospective controlled studies were planned in selected

patients.

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2. – AIM

The purpose of this work is to show the role of the implant osseointegration

associated to bone regeneration and to the reconstruction of large skeletal defects used

in oral and maxillofacial surgery, for restoring function and esthetics in edentulous

patients. The resorbed ridge may compromise loading and function of the implants

because of off-axis loading, compromising the predictability of implant therapy.

Ridge augmentation and sinus elevation procedures are now being employed to regain

lost alveolar structures. These surgical procedures include the use of autogenous,

allogeneic and xenogeneic bone grafts, synthetic bone substitutes, and non-resorbable or

resorbable barrier membranes as described in the guided bone regeneration (GBR)

principle. So they have expanded the treatment modality for patients whose ridges are

not ideal for implant placement.

The preferred bone graft material during a bone reconstructive procedure, as in ridge

augmentation and sinus elevation, is autogenous bone, as it carries proteines such as

bone-enhancing substrates, minerals and vital bone cells, but this often needs

hospitalization, other surgical operations and it has a potential risk for donor site

morbidity.

Two different studies have been performed.

1. The objective of the former was to determine whether during sinus elevation the

donor site morbidity could be avoided by using pure-phase β-tricalcium phosphate.

2. The objective of the latter was to verify if it is possible to achieve an optimal bone

reconstruction through osseointegrated implants, bone grafts and guided bone

regeneration also in patients affected by severe orofacial syndromes as Ectodermal

Dysplasia.

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3. – OSSEOINTEGRATION IN IMPLANT DENTISTRY

Based on fundamental experimental studies performed by the research teams of P.-I.

Brånemark from the University of Göteborg, Sweden, and A. Schroeder from the

University of Berne, Switzerland, the use of dental implants has become a scientifically

accepted treatment concept in dentistry to replace lost or missing teeth in fully and

partially endentulous patients. This breakthrough in implant dentistry was initiated by

the discovery that dental implants made of commercially pure titanium can be anchored

in the jawbone with direct bone contact. In a landmark paper published in 1969,

Brånemark et al56 described this phenomenon for submerged titanium implants from a

clinical point of view and with decalcified histologic sections (the implants had to be

removed before sectioning).

Seven years later, Schroeder et al57 provided the first true histologic evidence of direct

bone-to-implant contact for nonsubmerged titanium implants using nondecalcified

histologic sections with the titanium implant still present in the specimens. Later, these

authors created the terms osseointegration and functional ankylosis58 to describe this

phenomenon. In the past 10 years, the terms osseointegration and osseointegrated

implants have been widely used in the literature.

An osseointegrated implant is characterized in light microscopic analysis by a direct

apposition of bone to the titanium surface without evidence of a separating connective

tissue layer between the bone and the implant. Hereby, the bone has all characteristics

of living bone, such as osteocytes or blood vessels, close to the implant surface. (Figure

8.)

Fig. 8. Osseointegrated implant

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Osseointegration has also been documented in scanning electron microscopic (SEM)

studies58 as well as in a transmission electron microscopic (TEM) study.59

To achieve an osseointegrated titanium implant with high predictability, the implant

must be inserted with a low-trauma surgical technique, avoiding overheating of the bone

during preparation of a precise recipient site; must be placed with initial stability; and

should not be functionally loaded during the healing period of 3 to 6 months. When

these clinical guidelines are followed, successful osseointegration will occur predictably

for nonsubmerged titanium implants (one-stage procedure) as well as for submerged

titanium implants (two-stage procedure), as has been demonstrated in comparative

experimental studies.60

The best-documented two-stage implant system is the Brånemark System, whereas the

most prominent one-stage system using nonsubmerged titanium implants with a

titanium plasma-sprayed (TPS) surface is the ITI System. The basic characteristics,

indications, and clinical procedures of both implant systems have been described in

detail in textbooks written by Brånemark et al.61

In addition to demands from patients for high reliability and optimal esthetics, it is

desirable to shorten the treatment period for economic and social reasons. One way of

reducing the treatment period is to use 1-stage surgery and non-submerged implants.62,63

Another way of reducing the treatment period is to shorten the time between implant

insertion and the placement of a prosthetic suprastructure on the implants.

During the healing period, in cases of complete or partial edentulism, the patient usually

wears some sort of removable prosthesis. Normally, the patient has to refrain from

wearing the removable prosthesis during the first 2 weeks after implant placement and

thereafter must wear it during the entire healing period of about 3 to 6 months. In recent

studies, the problems of unfavourable loading caused by removable prostheses after 1-

stage surgery have been discussed.64-66

The idea has arisen that the prostheses cause the implants exposed through the mucosa

to undergo micromotion, leading to crater-shaped marginal bone defects. One possible

way to minimize micromotion is to enhance the stability of the implants by splinting the

implants with a provisional, screw-retained, implant supported prosthesis in a fixed

position immediately after surgery.67 A prerequisite for such an immediate technique is

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1-stage surgery with non-submerged implants. Few studies have been published on the

effects of immediate loading of implants. In the mandible, success rates similar to those

with healing times of 3 to 6 months before loading have been reported. 68 Studies on

immediate loading of maxillary implants are scarce, but the results reported indicate that

this method is also viable.67,69-71 The scientific documentation, however, is poor.72-73

Bergkvist et al64 indicated that immediate splinting of the implants with a fixed

provisional prosthesis might protect non-submerged implants from unfavourable and

uncontrolled loading and improve the healing conditions. Immediately loaded ITI SLA

solid-screw dental implants supporting fixed prostheses in the edentulous maxilla can be

a viable treatment alternative when restoring the edentulous maxilla.

The long-term documentation of osseointegrated implants was first reported by Adell et

al74 in a retrospective clinical study treating fully edentulous patients with Brånemark

implants. The authors reported estimated implant survival rates of 86% in the mandible

and 78% in the maxilla at 15 years.74 Data published from prospective studies on fully

edentulous patients by Zarb et al75 have confirmed these results. Similar results of

retrospective studies have also been reported for nonsubmerged ITI implants placed in

fully edentulous patients by Babbush et al,76 Bruggenkate et al,77 and Krekeler et al.78

In the mid-1980s, clinical investigators started to focus more on the treatment of

partially edentulous patients in order to expand indications for osseointegrated implants.

Although related 10 year data are still lacking for any implant system, encouraging

results with ITI implants were found in a prospective study on partially edentulous

patients at the University of Berne. Applying strict criteria for success, the examination

up to 5 years demonstrated success rates above 95%. Mean success rates above 90%

have also been reported for Brånemark implants in a prospective study by Zarb and

Schmitt.79,80 5-year results with success rates above 90% applying life table analysis,

have also been presented for the IMZ system (Interpore International, Irvine, CA) for

fully and partially edentulous patients.

Encouraging treatment results of patients with standard indications have, in the past 5 to

10 years, led to increasing interest in the use of dental implants in “borderline”

indications, such as recipient sites with insufficient bone volume, recipient sites close to

specific anatomic structures (mandibular nerve, maxillary sinus, etc), extraction sockets,

and esthetically demanding sites.

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One of the most important prerequisites to achieve the above mentioned success

rates with any kind of osseointegrated implants is the presence of a sufficient amount of

healthy jawbone at the recipient site. This does not only include an adequate bone

height, but also a sufficient crest width. Clinical studies have clearly demonstrated that

the success rate of Brånemark implants is compromised in areas of poor bone quality or

on those with good quality but inadequate bone height. Screw-type implants with a

larger, 5-mm diameter have been recommended for that special situations.81 An

alternative solution for this problem is the use of titanium implants with a rough

titanium surface in the bone-anchoring section, such as the TPS surface. Experimental

studies have indicated that the anchorage of titanium implants with a TPS surface is

significantly improved when compared with polished or fine-structured surfaces. Thus,

titanium implants with a TPS surface, have also been successfully utilized in recipient

sites with poor bone quality or reduced vertical bone height. In addition, titanium

implants with a hydroxyapatite (HA) coating have been recommended for these

indications, because the HA coating accelerates bone apposition to the implant surface

in the early healing period and significantly improves the anchorage in bone.82

However, several publications have reported that the HA coating is biologically

unstable over time and shows signs of resorption in histologic studies. This observation

might be a contributing factor for the increased rate of complications 3 to 5 years after

implant placement, such as severe bone defects around failing or failed HA implants.

New surgical techniques have recently been developed to allow the placement of dental

implants in areas with extremely reduced vertical bone height. One of these techniques

is the simultaneous use of dental implants with autogenous bone grafts from the iliac

crest in severely atrophied mandibles or maxillae.83-85 In the posterior maxilla, the

vertical bone height at potential implant recipient sites is often limited by the extension

of the maxillary sinus, and the placement of endosseous implants with a standard

technique is not possible. Sinus lift procedures have been recommended to allow the

placement of implants even in sites with less than 5mm of bone height.9 In the posterior

mandible, the vertical bone height is limited by the mandibular canal with the

neurovascular bundle. To overcome this anatomic limitation, nerve lateralization has

been proposed. However, this technique is questionable for routine use in dental offices

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and appears to be associated with an increased risk for postoperative morbidity, such as

dysfunction of the inferior alveolar nerve.85,86

A further problem is the lack of a sufficient crest width. Clinical studies have clearly

shown that the long-term prognosis of osseointegrated implants is compromised when

the buccal bone wall is missing at the time of implant placement. Various surgical

techniques have been developed to increase the width of the crest. One of the methods

uses a split technique of the narrow alveolar crest and subsequent filling of the created

gap between the two cortical bone walls with either autogenous/homologous bone grafts

or hydroxyapatite.85,87 The latest surgical technique to improve the volume of jawbone

at implant recipient sites involves the principle of guided bone regeneration (GBR).

This principle, utilizing barrier membranes, was first evaluated in the late 1950s and

early 1960s by the research teams of Bassett et al88,89 and Boyne et al90 for the healing of

cortical defects in long bones and osseous facial reconstruction. These authors utilized

microporous cellulose acetate laboratory (Millipore) filters to establish a suitable

environment for osteogenesis by excluding connective tissue cells from bone defects. In

the early 1980s, this principle was tested in a number of systematic experimental studies

for the regeneration of lost periodontal tissues. In implant dentistry, such membranes

have been clinically tested in various indications.91-95

3.1 - SINUS ELEVATION

Sinus elevation (sinus lifting, sinus grafting) has become one of the most

commonly performed routine surgical procedures in preprosthetic surgery. The essence

is that the alveolar process of the atrophic maxilla is made thicker towards the maxillary

sinus, and made suitable to receive the implant.

The surgical procedure is a standard aseptic procedure, carried out under local or

general anaesthesia. The sinus augmentation procedure was described by Boyne and

James: For grafting of the maxillary sinus floor with autogenous marrow and bone, a

supracrestal incision is made from the canine or first premolar area and extended

posteriorly to the ipsilateral maxillary tuberosity region. Vertical releasing incisions

may be made in the canine and tuberosity region. A mucoperiosteal flap is raised to

expose the lateral wall of the sinus. A rectangular osteotomy is outlined with a round

burr, ensuring that the inferior osteotomy is outlined with a burr, ensuring that the

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inferior osteotomy is about 5 mm above the sinus floor. The osteotomy is completed

with hand instrumentation. The superior osteotomy is left intact to allow infracture of

the lateral sinus wall. The sinus membrane is carefully elevated within the sinus cavity

so that it is completely free inferiorly, anteriorly, posteriorly and medially.

Simultaneously, the lateral sinus wall is fractured inwardly. A portion of the antral

space is filled with the graft material or autogenous cancellous bone.

The bone graft or/and bone-substituting material is placed in this cavity. A

number of donor sites come into consideration, like the mental region, the maxillary

tuber, etc. The enossal implantation may be performed at the same time; for undisturbed

healing, at least 5 mm thickness of the sinus floor is necessary in order to ensure

appropriate primary stability for the implants. (Figure 9.)

The mucoperiosteal flap is repositioned and sutured.

9a

9b

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9c

9d

9e Fig. 9. a-e Outline of sinus grafting: A bone window is formed in the facial wall of the maxillary sinus; this is broken in, but maintaining the integrity of the sinus mucosa the maxillary sinus is filled. If there is primary stability, implant is inserted

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3.2 – ECTODERMAL DYSPLASIA

Ectodermal dysplasias (EDs) are a large, heterogeneous group of inherited

disorders that involve primary defects in the development of two or more tissues

derived from ectoderm. (Figure10.)

a b

Fig. 10. (a) X-linked hypohidrotic Ectodermal Dysplasia: localization within the region Xq11-

q21.1.

(b) Tissues derived from Ectoderm.

These tissues include the hair, teeth, nails, skin, secretory glands (sweat, eccrine,

tear, and salivary glands), and mucous glands in the throat, larynx, respiratory system,

and intestinal tract.

The typical dysmorphic facial features include frontal bossing, malar hypoplasia, a

flattened nasal bridge or saddle nose, prominent supraorbital ridges, wrinkled,

hyperpigmented periorbital skin, thick, everted lips, and prominent low-set ears (Figure

11.).

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Fig. 11. Typical facial features of Ectodermal Dysplasia (ED).

The dental findings range from complete anodontia to hypodontia of the primary

or permanent teeth, widely spaced, peg-shaped, or conical teeth, delayed eruption, and

defective enamel of the permanent teeth. (Figures 12., 13.)

Figs. 12-13 Intraoral and radiographic aspects: hypodontia and dental anomalies.

When teeth are missing, the jawbone alveolar processes do not develop properly,

so the skeletal vertical dimension is reduced, resulting in protuberance of the lips. This

leads to a typical old-age appearance of the face. The palatal arch is frequently high and

a cleft lip and palate may be present.96,97 Congenital absence of the teeth is more

frequent in the lower jaw and affects the growth of the jawbones, leading to a lack of

alveolar bone in both height and width. (Figures 14., 15., 16.)

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Figs. 14. 15. 16. Decreased edentulous alveolar bone ridge and reduced occlusal vertical dimension

by clinical and radiographic points of view.

The salivary secretion rates are reduced and the salivary glands may be absent. This

causes dryness of the mouth and an increased risk of caries. Mouth dryness can make it

difficult to soften and swallow food, and may reduce the senses of smell and taste.98,99

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4. – BONE GRAFTS AND SUBSTITUTES: MATERIALS

The types of grafts available for the maxilla and mandible are the autogenous,

allogeneic, alloplastic, and xenogeneic.

Autogenous grafts are taken from the same person.100-102

Allogeneic grafts are composed of tissues taken from another individual of the same

species.

Alloplastic materials are synthetic substances used as substitutes for bone in grafting,

and Xenogeneic grafts are composed of tissue taken from another species (from an

animal source, usually bovine).

Characterization and analysis of any bone graft substitute prior to its use in human bone

sites involves consideration of several material properties of the graft:

1. Chemical and physiologic composition.

2. Morphologic structure.

3. Physical properties.

4. Absence of xenogeneic, allogeneic, and/or other foreign protein in the material.

Based on these properties, ideal bone substitutes should demonstrate:

1. Excellent biocompatibility, to be fully accepted by the living organism.

2. High osteoconductivity, to promote conduction of new bone formation from the

walls of the host bone defect.

3. A large inner surface area, to become fully revascularized by the host bone site.

4. High porosity, to be completely incorporated in new bone.

5. Moderately slow resorption, to remain in place, promoting long-term bone

remodelling.

6. An adequate modulus of elasticity, to guarantee a natural stress/strain

environment.

4.1 - AUTOGENOUS AND ALLOGENEIC BONE

Autogenous bone grafts (from the patient’s own body) and allogeneic (or

homologous) bankered bone (from another individual of the same species) are

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frequently and successfully employed to promote regeneration of parts of the skeleton.

The use of these types of grafts is limited, however, by the cost of a donor site operation

for autogenous bone or by fear of the risk of infection (with human immunodeficiency

virus, hepatitis) with use of allogeneic materials.85,86,101

Autogenous grafts are usually harvested from one of the following donor sites:

1. Iliac crest (anterior superior crest or posterior superior crest)

2. Rib

3. Calvaria

4. Anterior tibia

5. Intraoral sites

6. Free flaps (fibula with microvascular anastomosis)

The principal harvesting sources of bone grafting materials are selected primarily to

provide the maximal amount of particulate marrow and cancellous bone (PMCB) to

deliver the highest potential number of pluripotential or osteogenic precursor cells in the

graft material mass. These cells are used in effecting the restoration of the deficient

bone area. Although some pluripotential cells exist in the host bone wall, depending on

the type of defect involved, delivery of a graft of high osteogenetic material with a great

number of these preosteoblastic cells and pluripotential cells102,103,104 tends to increase

the potential for success and enhance the quality of the final restorative result.

Therefore, most of the donor sites used for autogenous bone grafting provide a basis for

obtaining an optimally high amount of PMCB.

The iliac crest graft is considered to be the gold standard of graft materials

because of the high population of pluripotential cells in the particulate cancellous bone

and marrow portion of the graft. These cells are available for introduction to become

osteoblasts and to form new bone. These pluripotential cells are located primarily in the

vascular marrow spaces of the cancellous bone (PMCB).85,105

The principal complications of taking bone from the posterior iliac crest are adynamic

ileus and hernia. However, in reviewing more than 170 cases involving posterior iliac

crest harvesting performed over 18 years, some Authors have not observed a single case

of ileus or bowel hernia1.

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Harvesting of the anterior iliac crest has been reported to be associated with paresthesia

of the lateral femoral cutaneous nerve1. In an experience with more than 300 anterior

iliac crest donor sites, only one patient has experienced paresthesia of the lateral femoral

cutaneous nerve. This complication occurs primarily when the incision is made too far

inferiorly on the lateral aspect of the thigh or too far anteriorly, involving an incision

immediately below the anterior iliac spine, creating an opportunity for interdiction of

the lateral femoral cutaneous nerve. Thus, the harvesting of bone from the iliac crest is,

in our experience, met with very little postoperative morbidity.

Patients are usually ambulated on the first postoperative day and released from the

hospital on the second postoperative day (sometimes even on the first day after surgery)

and are allowed to use a cane or a walker during ambulation for the first 5 days at home.

Except for not being able to climb several sets of stairs, to drive an automobile, or to

elevate the leg forcefully during the first postoperative week, patients experience very

little restriction in their range of motion or ambulation. The patient is allowed to

ambulate at will and to move slowly during the first few days postoperatively. The

principal minor complication that we have observed after this iliac crest procedure has

been formation of hematomas. When a hematoma occurs following an anterior iliac

crest procedure in which the medial table is allowed to remain intact, simple

reapplication of a pressure dressing with or without aspiration of the hematoma or

seroma suffices to treat the swelling.

If the medial table approach has been used in an anterior iliac crest harvesting procedure

and a postoperative hematoma occurs, it is very difficult to reach the involved area for

aspiration and also difficult to apply a pressure dressing in the correct direction to

effectively control the hemorrhage. Although the medial table technique is used by

many surgeons, we believe that the lateral table approach results in fewer postoperative

hematomas.

If the anterior superior iliac spine is inadvertently taken in the surgical procedure,

several complications can ensue. One of these is interference in the function of the

sartorius muscle. This affects the patient’s walking and, particularly, the patient’s ability

to lift and abduct the leg (in the manner of crossing the knees when sitting). There is

also an increased incidence of postoperative hernia when the anterior superior iliac

spine is taken. Additionally, the patient tends to experience considerable discomfort

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during ambulation with a full-gaited walk, experiencing a delay in final rehabilitation

for a matter of 3 to 4 weeks. Therefore, we believe that the safest bone-harvesting

procedure is one in which the anterior iliac crest is harvested through the lateral

approach, leaving the medial table, the iliac crest itself, and the anterior superior iliac

spine all intact. (Figure 17.)

a b Figs. 17. a-b Iliac crest donor site

Cranial or calvarial bone grafts are usually obtained by taking the outer table of

the calvarium with the underlying cancellous bone and marrow. The cortical bone of the

calvarial graft may be used in one piece or morselized and mixed with the cancellous

bone particles. (Figure 18. a)

One problem associated with calvarial grafts is that they are composed primarily of

cortical bone matrix. This property makes such a graft excellent for recontouring facial

bone areas. Such a graft, however, does not have the same results when applied to the

alveolar bone of the mandible and maxilla, particularly when the case involves the

reconstruction of the mandible and maxilla for root-form implants. The amount of

PMCB obtainable from cranial grafts is limited compared to the amount found in the

iliac crest. Calvarial bone grafts, when subjected to the stress of occlusal forces through

conventional prostheses or root-form, implant-bone prostheses, tend to resorb and tend

not to maintain the form and contour of the reconstructed bone area.

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The anterior tibial surface can be used also as a source for cancellous bone and

marrow. A moderate amount of PMCB may be obtained from the tibia and the

procedure usually results in very little morbidity. Thus, as an alternative site for

autogenous bone when approximately 30 to 40 cm3 of PMCB is needed, the anterior

tibial surface can be used preferentially after the posterior and anterior iliac crest have

been considered. (Figure 18. b) All donor sites already discussed produce PMCB graft

material that can be used in reconstructing the maxilla and mandible and for the

insertion of root-form implants. If small amounts of cancellous and marrow bone are

needed, an intraoral source may be used.

a b Figs. 18. a-b Calvaria and anterior tibia harvests

A fibular bone transfer, when used as a free graft with microvascular

anastomosis, tends to produce a very successful soft-tissue graft transfer. However, the

osseous portion of the composite graft is composed, for the most part, of thick cortical

bone and as a result does not usually offer a high quantity of viable cells for facilitating

osseointegration with titanium root-form implant surfaces. Root-form implants placed

in such grafts require a longer period of time for integration than do similar implants

placed in PMCB grafted areas. Once implants are well integrated, however, the result

can be prosthetically satisfactory.

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The intraoral sites most frequently used are the mentum, which contains mostly

cortical bone; the area behind the mandibular third molar; mandibular tori, which also

contain largely cortical bone and the maxillary tuberosity. The intraoral site mostly

prefered is the retromolar area of the mandible. This site can be entered by simply using

a small, round bur to perforate the cortical bone of the anterior surface of the ascending

ramus posterior to the third molar. The small cortical bone plate is elevated to expose

the underlying cancellous bone, which is then curretted in a horizontal direction

posteriorly into the ramus. The currette is always kept in a plane parallel to the occlusal

surface of the mandibular teeth to prevent injury to the mandibular canal and the inferior

alveolar nerve. These is little chance of postoperative morbidity if care is taken

measuring from the anterior border of the ramus to the mandibular canal. The procedure

can be used bilaterally if additional graft material is needed.1,85,86

The symphysis region is an intraoral donor site of choice. The advantages of this site

versus an extraoral site are:105-111

- surgery time is shorter

- easy access

- more rapid healing

- absence of visible scars

- the postsurgical effects are well tolerated

- surgery may be performed under local anesthesia

The disadvantages of this donor of this donor site are:

- a limited quantity of bone to harvest

- risk of loss of sensitivity on the mandibular incisors

Following local and regional anesthesia (Spix’s spine), a linear incison is performed on

the mucosa between the respective distal aspects of the two canines. Reflection of a full-

thickness flap gives access to the symphysis bone. Osteotomy is performed using a bone

bur. The upper limit must be located 5 mm under the teeth apices. The depth of the bone

graft depends on the width of the symphysis and on the bony defect to be treated. The

use of osteotomes allows mobilization and harvesting of the graft. The graft is then

adapted to the recipient site. The donor site may be filled using a bone substitute or

bone hemostatic wax. The flap is repositioned and sutured using a resorbable suturing

material. (Figure 19. )

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a b Figs. 19. a-b Intraoral donor sites

4.2 - SYNTHETIC BONE SUBSTRATES MATERIALS: ALLOPLASTIC

GRAFTS

The use of modern bone substitutes allows regeneration to occur without scar

formation and interstitial reconstruction, in contrast with the spontaneous healing

process. The implanted materials must satisfy a number of conditions. They should not

damage the host organism, they should not contain any infective agent, and thus they

cannot transmit any type of infection. If possible, they should be fully resorbed and

should progressively be replaced by newly-formed bone tissue, these processes

proceeding synchronously. The principle of remodelling should hold, and the bone

formed should be similar to the original bone. The process of ossification should not be

slowed down, but if possible be influenced in a positive manner, by osteoconductive

means. These materials should or give rise to the formation of bone at sites where there

was originally no bone, outside the periosteum.6,53 In this work a 99% pure phase ß-

Tricalcium phosphate (beta-TCP) has been used for the regeneration of bone defects.

ß-Tricalcium phosphate exists in α and ß phases. These are identical chemically, but

under physiological conditions they behave differently. α -Tricalcium phosphate is

resorbed only very slowly, and can be detected in the new bone even years after its

implantation, whereas the ß form is fully resorbed after a few months, being replaced by

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new bone. A certain proportion of the ß phase enters the tissues, so that phosphate ions

are present in the implanted area. The ß-TCP – ceramic phases are very stable

chemically, they are integrated into the bone without causing any reaction, on operated

site heals with scar formation and connective tissue formation. ß-TCP is fully resorbed

and replaced by new bone within a few months. It has osteoconductive effects. It is

manufactured in various grain sizes. Neither the bone-substitute material itself nor any

of its breakdown products is toxic or contains any virus, prion or other protein. It has

coherent porous structure, into which the new bone tissue (osteon) may grow. It breaks

down synchronously with the bone regeneration, and the resulting bone tissue exhibits a

structure similar to the original. It is transformed quantitatively into functioning bone.

TCP gives an X-ray shadow, whereby its fate can readily be followed.39

Collagen fibres and blood vessels invade the interconnecting micro-pores of the TCP

granules (micro-pores) and the intergranular cavities (macrospores).

The collagen fibres serve as a guide-rail for capillaries and newly formed bone and

stimulate the taking of the bone on the implant surface prior to the beginning of its

resorption.

Despite its high porosity, TCP possesses optimal stability and high abrasion resistance.

Its purity of phase provides a stable structure and homogenous solubility under

physiologic conditions. The primary-grain size of 10-63µm does not provoke

phagocytosis by macrophages.112-114 (Figures 20., 21.)

• As a purely synthetic material TCP is free from any risk of material-induced

infection.

• There is no immunologic defence reaction.

• The rounded surface of the TCP granules prohibits mechanical irritation of the

surrounding tissue and reduces inflammatory reaction.

• The physiologic pH-value in aqueous solution results in excellent

biocompatibility.

• The high mechanical stability of TCP prevents the premature degradation of the

material into micro particles and thus avoids undesirable macrophage activity.

• TCP is integrated into the natural bone without connective tissue encapsulation

or tissue degeneration.

• ß-Tricalcium phosphate is a highly osteoconductiv material.

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Fig. 20. β-tricalcium phosphate (25x) Fig. 21. Alloplastic graft: β-tricalcium

phosphate

4.3 - XENOGENEIC BONE MATERIAL

When the organic material is removed from xenogeneic bone, a special mild

treatment must be used to preserve the original composition and structure of the

inorganic substance.

The technical process used in producing the xenograft from a bovine bone source makes

possible the removal of all organic components of the bone product, leaving a pure,

nonorganic bone matrix in unchanged inorganic form avoiding the risk of BSE or other

virus transmission too.

Anorganic Bovine Bone (ABB) is a finely crystalline, carbonated apatite practically

identical to natural human bone mineral.1,115,116 The chemical extraction process makes

possible the desirable properties of this material. The implantation of ABB in surgical

sites leads to ample formation of well-vascularised new bone, which integrates with the

ABB particles to restore proper structure and function in the defect site.

The resulting high bone-to-matrix ratio gives the surgeon an excellent basis for

operations involving use of titanium root-form implants or orthopedic devices in

reconstructive or orthognathic surgery.

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The chemical composition of a graft material influences the rate and extent to which it

is incorporated into the host tissue and the subsequent physical characteristics of the

graft site.

Even more important is the crystalline structure of biomaterials. ABB bone consists of

very tiny crystals similar to those of human bone. The small crystals are represented in

x-ray diffraction analysis by broad spectrum. (Figure 22.)

Fig. 22. Deproteinized bovine bone cristal (50x)

Absence of any protein in the bone substrate materials is important to be certain that no

allergic or immunologic reaction occurs after implantation of the xenograft material in

human patients. The complete removal of all organic materials is confirmed for each

batch of ABB material produced.

Investigations have shown ABB to have a natural morphologic structure; a chemical

composition identical to that of bone; a large inner surface and porosity comparable to

that of bone; a crystalline structure identical to that of bone tissue; and a composition

that is purely anorganic.

The biologic character of the xenograft has been examined in a number of animal and

clinical experiments. The ABB spongiosa offers greater space for the regeneration of

new bone tissue and seems to be one of the best materials of choice for the regenerative

process in the maxilla and the mandible. The enlargement of histologic views showed,

for both ABB spongiosa and ABB cortical bone, internal pores that are filled by new

bone. Porous areas with diameters of approximately 80 μm and more were invaded by

new bone.

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To distinguish between the blood vessels from ABB and those newly formed bone,

Schenk used a different staining method.25 The number of blood vessels penetrating a

ABB cortical particle was impressive and demonstrated the revascularizing and

remodelling of the anorganic material through the invasion of blood vessels and new

bone. Spector implanted ABB in 30 rabbits and evaluated the results after 10, 20, and

40 days.1 As a control, synthetic calcium phosphate was used. These results were

evaluated by histomorphometric methods.

The structure of the material varies significantly from the surrounding bone spongious

structure. In contrast, 1 week after implantation of ABB, osteoblasts are lining up and

starting the mineralization process to form new matrix.

A line of osteoid tends to form, embedding the osteoblastic cells in the mineral matrix.

The osteoid covers the ABB surfaces and represents the first immature bone.

This bone formation continues and will lead to the union of bone matrix and ABB

particles across the defect to the walls of the host defect. Six weeks after implantation,

the newly formed bone is interconnecting the ABB particles. The bridging by new bone

is leading to the stabilization of the host bone in the defect area. The particles are

difficult to recognize and distinguish from the surrounding bone tissue because of the

intense proliferation of new osseous repair matrix.

Indications of the resorption process can be identified by osteoclasts on the Anorganic

Bovine Bone surface next to areas of bone formation. Bone is a living tissue that usually

is transformed by approximately 2% to 3% per year by a constant remodeling process.

In surgical defects, however, the bone may remodel faster from the woven bone, and the

transforming process to lamellar bone may occur completely within several months,

depending on various factors involving graft site, vascularity, and functional forces.

Resorption lacunae were also reported in human histologic specimens examined by

Shenk.25 The cylinder shows reconstruction of the cortical crest with underlying

spongiosa structures. ABB is integrated in the newly formed lamellar bone. The lacunae

in the ABB particles are filled with new bone next to osteoclasts, indicating an ongoing

remodeling process.

These data indicate that the resorbing remodeling process may go on for years. This has

also been confirmed in various investigations of humans material. The initial integration

of ABB into lamellar structures can be seen in the specimens. Later the resorbing

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process follows, involving the surrounding bone in a delayed remodeling process. The

resorption, remodeling and new bone formation process is prolonged by the presence of

residual ABB particles, thus assuring a constant bone matrix density, an increase in

bone density, and an increase of the thickness and quantity of osseous trabeculae and

bone cortex. Boyne has shown that the slow resorption and remodeling of porous bone

mineral imparts a high degree of permanency to the restored mandibular edentulous

area. The physical and chemical properties of porous bone mineral (ABB) are host

compatible, offering excellent conductive surfaces for the promotion of bone repair.

(Figure 23.)

Fig. 23. Xenogeneic graft: Anorganic Bovine Bone.

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5. – BONE GRAFTS AND SUBSTITUTES: MECHANISM

The use of bone grafts involves three mechanisms: conduction, induction, and

guided tissue regeneration, which formerly was termed osteophylic response. All are

involved in bone regeneration.1,85,117

5. 1 – BONE CONDUCTION

Conduction involves the use of inert bone substitute materials or nonviable

autogenous and allogeneic banked bone grafts, which offer little or no inductive

stimulation to the pluripotential cells of the host defect but do serve as scaffolding over

which the bone-forming cells of the host may grow. Particulate conductive materials

can be placed, for example, between the root-form implant and the tooth extraction

socket wall so that the bone repair can more rapidly proceed from the socket wall to the

implanted surface, stimulating bone formation and integration of the root-form implant.

Thus, conduction is used mostly in those defects in which there are three bony walls and

in surgical sites in which a good supply of osteoblastic cells is provided by the bony

walls.

Conductive materials alone should not be used on single bony surface, such as the crest

of the alveolar ridge, in an effort to encourage bone to grow outwardly from that bone

interface. In this situation, the supply of osteoblasts available is not able to produce the

osteogenesis necessary to regenerate bone on the surface of the edentulous alveolar

ridge; therefore, a highly inductive bone graft material that supplies the pluripotential

cells necessary to regenerate the area should be used. Thus, for example, an iliac-crest

bone graft with cancellous bone and high inductive capacities should be used to

regenerate the ridge height of large edentulous areas. Therefore it is felt that inductive

autograft material, in conjunction with conductive material, should be considered a

necessary part of such grafting procedures.118

If bone grafts are used in children for cleft palate repair, the growth of the child and the

large numbers of pluripotential cells available in the growing child’s bony surfaces are

conductive to “induction” of the bone graft material, and to a favourable result. Thus,

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the bony recipient site itself can be “inductive”. Clinicians are conditioned to think that

it is necessary to add something to the bone graft (eg, exogenous growth factor

materials) to produce the inductive effects. However, the recipient site itself may serve

as an inductor of the bone reparative cells.101

Conductive materials are used in three major areas of clinical concern:

1. In two- or three-walled bony defects with ample supply of pluripotential cells

2. As a carrier for bone inductors, eg, as a substrate for rhBMP-2 that releases the

inductor over an appropriate period of time

3. To increase bone density and to produce slow remodeling in the area. This

remodeling ensures both the prolonged presence of bone mineral and a thickened

trabecular pattern for a protective response to the occlusal and functional changes that

may occur in the lifetime of the root-form implant.

5.2. – BONE INDUCTION (PROTEIN-BMP)

One of the bone growth factor materials that can bring about induction of bone

in areas in which bone regeneration would not normally occur (the crest of the ridge of

the maxilla) is rhBMP-2. This material can be obtained in a highly refined form by

genetic engineering using recombinant DNA.119 This growth factor, when used in a

surgically appropriate manner, is able to stimulate the pluripotential or precursor cells of

the existing host wall and even the pluripotential cells in the cancellous portion of any

bone graft that may be placed along with the inductor material. In addition, rhBMP-2

may be simply placed on a carrier without any concomitant use of autogenous

cancellous bone at the time.

Regeneration of large critical sized discontinuity defects by use of rhBMP-2 in a simple

collagen sponge has been demostrated. Such restored hemimandibulectomy defects in

Macaca fascicular is have been shown to support root-form implants in full function for

6 to 8 months. Bone morphogenetic protein-induced bone in the antral floor of patients

also has supported implants for prostheses. In the past, demineralized freeze-dried bone

has been used by some surgeons on the premise that it is an “inductive material”.10,15

However, there is very little inductive capacity in demineralized freeze-dried bone,

because there is very little BMP in the product. Therefore, the effect of demineralized

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bone powder is primarily one of conduction and not induction. This material should not

be used in an effort to build bone superiorly on the crest of the ridge of the maxilla or

the mandible, unless it is used in conjunction with the autogenous bone grafts of the

type previously described or as a carrier for true BMP in the concentrated, recombinant-

DNA-produced biologic form (rhBMP).

The growth factor rhBMP-2 is both a mitogen and a morphogen, and its functions are

both to recruit progenitor cells and to morphologically change cells to the osteoblastic

line of cellular maturation to produce bone. Such an effect may be needed for a short or

long period, depending on the defect being regenerated. Carrier materials for rhBMP

can be designed for a short-term, a medium-term, or a long-term effect, depending on

the desired time of release of the rhBMP in the regenerating area.

Examples of materials that will carry rhBMP and be degraded over a short period (2 to

4 weeks) are collagen sponge and various degradable alloplastic materials (eg,

polylactic acid and plyglycolic acid). Carriers that will release rhBMP over a slightly

longer period are more slowly degradable. This class of materials would include such

substances as calcium carbonate and tricalcium phosphate. Carriers that will release

rhBMP over a long period are those that are slowly remodeled and resorbed, such as

porous bone mineral (ABB).

Examples of carriers that are relatively inert and degraded very slightly, or not at all,

HTR (hard tissue replacement), which is a polyhydroxyethyl methacrylate (PHEMA)

product in the form of beads, and certain types of porous hydroxyapatite.

Thus, a significant part of the clinical effect of the use of rhBMP may be determined by

the degradability and other characteristics of the carrier itself. It is believed that the best

type of carrier for rhBMP surrounding a root-form titanium implant may be a material

that is slowly degradable, providing prolonged bone induction and availability for

remodeling to obtain a higher density of cancellous bone resistant to future bone

resorptive processes.18,85

5.3 - GUIDED TISSUE REGENERATION

The term guided tissue regeneration is now used to describe the phenomenon in

which alloplastic membrane surface exclude various types of cells from a surgical

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defect site.1,120 This phenomenon, formerly called osteophylic response, was used

extensively, beginning in 1965, in connection with bone grafting of large trauma-

induced, and postoncologic defects. The effect of the membrane depends on its pore

size. If the pores are large, many of the cells (including fibroblasts) that the surgeon

usually wishes to exclude will migrate through, allowing soft tissue, instead of new

osseous matrix, to form in the bony defect. Normally a membrane with pores on the

order of 0.5 µm is used; one with pores of 100.0 µm or more would allow a great many

unwanted cells to enter the regenerating defect area.

Whether a membrane-type barrier should be used in bone grafting for regeneration of

the maxilla, for example, depends on the type of prosthetic restoration to be used. If the

area is to be restored with a removable prosthesis requiring a deep vestibule for

retention, a membrane should not be used because membranes tend to prevent a new

periosteum from forming underneath the titanium next to the generating bone. Without

the new periosteum, it is not possible to reposition the oral mucosa by suturing the

mucosal flap at a superior level to recostruct the vestibule after the removal of the

titanium mesh.121,122

If a membrane is not used with the titanium mesh, a new periosteal surface forms

beneath the metal and overlying the regenerating bone. This newly formed periosteum

will be thick and nonfriable and will retain the sutures used to attach the mucosa to

produce an excellent vestibular height when the metal mesh is removed after 3 to 5

months. This vestibule-producing technique is really a secondary epithelialization

procedure.

If the surgeon and the prosthodontist are restoring the area with root-form implants and

a fixed prosthesis, a deep vestibule is of lesser importance. If root-form implants are

being used, a membrane may be placed inside the titanium mesh and the mucosa merely

closed over to the crest of the ridge following the removal of the mesh. The optimal

effect of the membrane is to exclude the ingrowth of fibrous tissue, thereby increasing

bone formation. However, if the use of the membrane would prevent the surgical

development of a desirable vestibule, then the membrane should not be used.

Membranes should not be used when there are insufficient bony walls to provide the

critical mass of precursor cells necessary to form bone. If the surgical defect has only

one bony wall with very few cells available for osseous regeneration, the effect of the

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membrane would be to exclude the pluripotential precursor cells from the periosteal

flap, thus excluding the necessary additional pool of cells that would be available if the

membrane were not used. Therefore, the filter or membrane should not be used when

there is only one bony wall with a poor blood supply that offers a diminished number of

cells to regenerate the defect.118

If, however, the defect has a minimum of three bony walls with excellent vascularity

and a good reservoir of pluripotential cells from the host bone available to be induced to

form osteoblasts and bone, the membrane may be used. The cells from the periosteum

can be excluded, because they will not be necessary for appropriate regeneration of the

defect. An excellent example of a complete, functional, and anatomically correct

reconstruction of a large defect is the using the membrane system. 123-126

When, cells from the mucoperiostel flap are excluded, a large amount of fibrous tissue

will be prevented from entering the bone-regenerating area; this effect will contribute to

an excellent result when used in an appropriate surgical bone site. For enhancement of

bone density in the final reconstructive product, a 50-50 mixture of PMBC with

Anorganic Bovine Bone and Tricalcium phosphate have been found to be most

effective.127 (Figure 24.)

Fig. 24. (a) Implants inserted in a narrow alveolar ridge with exposed threads and (b) non-resorbable Titanium reinforced membrane

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6. – MATERIALS AND METHODS

6.1 - MATERIALS AND METHODS: SINUS ELEVATION

Twenty edentulous patients were scheduled for bilateral sinus floor grafting at the

following 4 centres:

1. Semmelweis University, Department of Oral and Maxillofacial Surgery,

Budapest, Hungary

2. Dental and Stomatologic Clinic, Department of Oral Surgery and Oral

Implantology, University of Milan Italy

3. Department of Oral and Maxillofacial Surgery, Manchester Royal Infirmary,

Manchester, United Kingdom

4. Periodontology, Oral Implantology, Dento-Alveolar Surgery Clinic, Brugge,

Belgium

At each centre, identical protocols were followed for patient selection,

preoperative examinations, surgical procedure, implantation, biopsy specimen removal,

postoperative treatment, and patient follow-up. In 10 cases, the operation was combined

with onlay bone grafting.

All of the patients had conventional denture retention problems because of severe

anterior and posterior maxillary alveolar ridge atrophy. All had a residual sinus floor

less than 5 mm high (using the Cawood and Howell classification);128,129 bone loss was

3 to 4 in 3 of the 20 patients, 5 in 7 patients, and 5 to 6 Howell class in the other 10

patients). In 10 patients, the maxilla was atrophied to such an extent that sinus grafting

alone was insufficient; in these case, a large section of the residual alveolar arch had

thinned to a knife edge in the horizontal and sagittal directions. The patient population

consisted of 9 men and 11 women who ranged in age from 38 to 67 years (mean 52

years). After routine oral and physical examinations, the patients were selected and bone

reconstruction procedures were planned. In 10 patients, the reconstruction included only

bilateral sinus floor grafting; in the other 10 patients, bilateral sinus grafting was

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performed, with onlay bone grafting in the anterior and part of the posterior maxilla,

followed by implant placement 6 months later.

All of the patients were healthy, with no disease that might influence the treatment

outcome. The patients were fully informed about the procedures, including the surgery,

bone-substitute material, and implants. They were asked for their cooperation during

treatment and research; all gave their written informed consent. The ethics committees

of the various institutions approved the research protocol.

Routine panoramic radiographs were obtained in all cases pre- and postoperatively, 6

months after the first surgery (prior to implant placement), and immediately after

implant placement. Additional panoramic radiographs were taken at 6-month intervals

after implant placement. Moreover, in the 10 patients in which onlay bone grafting was

performed, 2D and 3D examinations were performed pre- and postoperatively and 6

months after implant placement, using a General Electric Pro- Speed Plus (General

Electric Medical Systems, Milwaukee, WI). The lateral exposures were taken in the

same plane and direction as the preoperative ones.

In all 20 patients, surgery was performed under general anesthesia. Before or at the time

of sinus grafting, 5 to 6 cm3 of spongious bone were harvested from the left iliac crest

by a second team of surgeons. In the cases that included onlay grafting, the spongiosa

was removed together with a piece of cortical bone about 3 cm wide and 4 to 6 cm long.

The bilateral sinus grafting procedure followed Tatum’s classical description.130 A door

was created with a round hollow bur in the lateral maxillary sinus wall. After

mobilization, the door was reflected inward. On one site, the sinus-elevation space was

filled only with 1.5 to 2 g of β-TCP (particle size 1,000 μm); on the other side, it was

filled with 3 to 4 cm3 of autogenous bone. The TCP side was the experimental side; the

autogenous bone side was the control side. The choice of sides was randomized using

the coin-toss method. In 12 of the 20 patients, the experimental side was on the right; in

8, it was on the left.

In 10 of the 20 patients, it was necessary to widen the alveolar crest, which had become

extremely thin in places. This was performed at the same time as the bilateral sinus

grafting. The harvested cortical bone was attached to the buccal side of the

compromised maxilla using microscrews.

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Next, the uneven bone edges were smoothed with spongiosa, the buccal and labial

periosteum was extended in the customary way, and the wound was closed in a tension-

free manner. No membrane was used to cover the bone. The sutures were removed 7 to

10 days later. The following postoperative regime was applied to avoid infection:

ciprofloxacin 500 mg 2 times daily for 5 days and ibuprofen 400 mg 3 times daily to

reduce pain and swelling. The patients were instructed not to wear removable prostheses

for 30 days and not to blow their noses for 7 days.

After 6 months of healing, the patients received implants. Eighty cylindric bone biopsy

specimens were taken from the grafted posterior maxilla (2 from the experimental side

and 2 from the control side in every patient) using a trephine bur with an inner diameter

of 2 mm and an outer diameter of 3 mm. After biopsy specimen removal, osteotomy

sites were prepared for implant placement. In 4 patients, 16 Protetim implants were

placed at the sinus elevation sites. In the other 16 patients, 64 Ankylos implants were

used. In addition to the 80 implants placed at the sites of the β-TCP or autogenous bone

grafts, many more implants were required for the complete rehabilitation of the

edentulous maxillae of the 20 patients, but the remaining implants were not directly

related to this study.

The bone biopsy samples contained both the grafted area and the previously existing

area of sinus floor, but the residual native crestal bone was not included in the histologic

and histomorphometric examinations. Cortical bone in samples from patients with onlay

grafts was not included either. Biopsy samples from all 4 centres were fixed in 4%

formaldehyde and then submitted for histologic examination to the oral pathology unit

of the Department of Oral and Maxillofacial Surgery of Semmelweis University. The

bone samples were processed and stained as reported earlier.6Briefly, they were fixed in

4% formaldehyde in phosphate buffer, dehydrated in an ascending series of graded

alcohols, and embedded in methylmethacrylate resin at 4°C. Five-μm-thick histologic

sections were cut in the longitudinal plane with a diamond knife and stained with

toluidine blue and hematoxylin-eosin. Goldner’s trichrome method was used for light

microscopy.

The β-TCP particles were achromatic. If they had broken out of the section, their places

were recognizable because of their characteristic shape and size, or because of the

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granule remnants at the interface between the β-TCP granules and the surrounding

tissue.

Morphometric studies were performed according to the principles of Parfitt and

colleagues.131 Sections of each sample were taken for histomorphometry from 4 levels

at 150-μm intervals. The samples were measured semiautomatically using an Olympus

microscope (Olympus, Tokyo, Japan) connected to a computer using Analysis software

(Soft Imaging System, Münster, Germany). The total surface area of each sample, the

surface area that consisted of bone, and the area that consisted of graft material were

measured in mm2, and bone and graft material were analyzed as a percentage of the

total. Bone from the original sinus floor was not involved in the bone area

measurement.

The Student t test was used to determine statistical significance. Values of P<.05 were

considered significant.

6.2 – MATERIAL AND METHODS: ECTODERMAL DYSPLASIA

In Ectodermal Dysplasia study, 186 titanium implants associated with guided

bone regeneration (GBR) were placed in 33 patients. All the patients were nonsmokers.

The ED patient group consisted of 13 patients, nine men and four women, aged 16–45

years, all with reduced vertical dimension or skeletal deep-bite. Sixty-six implants were

placed in this group, 15 in the upper jaw and 51 in the lower jaw, and GBR was used for

local bony dehiscence and fenestration defects. Ten bioabsorbable membranes and 21

non-resorbable membranes were used. The non-ED patient control group comprised 20

patients, 11 men and nine women, aged 16–68 years, selected with the same dentofacial

features as the ED patients: hypodontia or missing teeth with reduced occlusal and

skeletal vertical dimension (15 skeletal deep-bite and five normovertibite, no open-bite),

decreased alveolar bone, with a typical old-age appearance and poor aesthetics of the

face. Both groups had a severe lack of the alveolar ridge in both height and width,

corresponding to edentulous sites. All the mandibular alveolar ridges had a knife-edge

contour, which usually makes ideal implant placement difficult without GBR and bone

grafts.

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In the non-ED group, 36 fixtures were placed in the maxilla and 84 in the mandible.

Ninety-three of the recipient sites were associated with localized bone defects or

insufficient alveolar ridge width resulting in exposed fixture threads at installation.

Twenty-two bioabsorbable membranes and 34 non-resorbable expanded

polytetrafluoroethylene (e-PTFE) membranes were adapted to cover the exposed threads

at buccal fenestration and dehiscence defects. To produce bone regeneration, GBR was

applied in combination with autogenous bone and Anorganic Bovine Bone.

( Figure 25.)

a b

c d Fig. 25. Guided bone regeneration by non-resorbable membrane and Anorganic

Bovine Bone mixed to autogenous bone. (a-b-c-d)

Two-stage surgery was used, with a 6- to 8-month healing period before functional

loading.

Together with radiographic evaluations, the following clinical parameters were

assessed around the fixtures: probing depth (PD) (mm) (mesial, distal, buccal, and

palatal); peri-implantitis; mucosal recession; modified plaque index (mPLI) and

modified sulcus bleeding index (mSBI); clinical mobility; and Periotest value before

final prosthetic rehabilitation and after 3 years, when implant bridge removal was

possible.132 (Figure 26.)

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Fig. 26. Second stage surgery after 6 month healing

period.

After delivering the prosthetic-implant reconstructions, the patients were involved in a

maintenance care program, in accordance with individual needs. (Figure 27.)

Fig. 27. Temporary and final implantological- prosthetic rehabilitation

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7. – RESULTS

7. 1 – RESULTS: SINUS ELEVATION

After sinus elevation, no postoperative complications occurred in any of the

patients. Normal wound healing was observed after both the first and second operations

(graft harvesting/sinus elevation and implant placement). Minor nose bleeds occurred in

3 patients.

One patient had permanent sensory loss in the distribution of the lateral femoral

cutaneous nerve, and 2 patients had prolonged wound drainage (2 to 3 weeks). No other

postoperative complications were observed in conjunction with the donor sites.

Panoramic Radiograph. Three panoramic radiographs were compared for every

patient: 1 taken shortly after graft implantation surgery, 1 taken at 6 months

postoperatively (at implantation), and 1 taken 12 months postoperatively (ie, at

suprastructure fabrication). These radiographs clearly showed the positions of both

types of graft material and the height of the new sinus floor.

The autogenous bone was initially less visible than the β-TCP, but new bone formation

was clearly observed for both materials. The consecutive images also revealed changes

in the graft materials and their incorporation. β-TCP was markedly more radiopaque

than autogenous bone.

After 6 months, the β-TCP had changed slightly in the radiographs: the contour of the

bone around the graft became more defined. After 12 months, the graft was similar to

bone because of absorption of the β-TCP and the simultaneous formation of new bone.

Computerized Tomography. A comparison of the panoramic radiographs and CT

images in 10 patients revealed the advantages of supplementing the panoramic

radiographs with 2D CT images. In planning the surgery, the thickness and width of the

alveolar bone and the process of new bone formation could be better assessed in this

way. The 3D CT reconstruction best revealed the postoperative sinus graft height and

new sinus floor, as well as the ossification process. (Figures 28., 29.)

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Fig. 28.a Preoperative 3-dimensional (3D) computerized tomogram (CT)

demonstrating that a large part of the alveolar crest has atrophied

Fig. 28.b Preoperative 2-dimensional (2D) CT. Using the classification of Cawood and Howell

the bone loss grade was 6 (the height of the residual sinus floor was less than 2 mm)

Fig. 28.c Postoperative 3D CT. The bilateral sinus grafts are clearly visible

(β-TCP in the right maxilla and autogenous bone in the left maxilla)

Fig. 28.d 3D CT reconstruction. The onlay bone grafting is clearly

visible

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Fig. 28.e Panoramic radiograph 6 months after the sinus grafting. Ankylos implants

were placed

Fig. 28.f One year after sinus grafting, after prosthetic rehabilitation. The β-TCP

graft (right) appeared similar to bone

a b Fig. 29.a and 29.b Preoperative (a) 2D and (b) 3D CT scans. The right side of the residual alveolar

crest has thinned to a knife edge in the horizontal and sagittal directions. The 2D CT clearly reveals the situation of the residual sinus floor.

c Fig. 29.c After sinus grafting and onlay bone graft. The heads of the microscrews are

visible in the right and middle parts of the maxilla

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d

Fig. 29.d Three- dimensional CT 6 months after onlay bone grafting; bone

integration is clearly visible

e

Fig. 29.e Twelve months after the first surgery, prosthetic rehabilitation

of the Protetim implants was completed. With absorption of the β-TCP

and the simultaneous formation of new bone, the grafted areas have become

similar to bone

In the biopsies from the experimental side, the β-TCP graft was identified as

achromatic rounded or scalloped granules, depending on the phase of resorption. They

were partially embedded in newly formed bone, which was predominantly lamellar

bone. (Figure 30a.)

Bone formation was preceded by the abundant proliferation of a cell-rich osteogenic

mesenchyme and a new capillary network in the pores of the resorbing granules. (Figure

30b.)

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Fig. 30.a Fig. 30.b

β-TCP graft and new bone formation. Osteogenic mesenchyme growing on the surface

CG = β-TCP granule; and in pores of a β-TCP granule.

B = new bone CG = β- TCP granule;

S = soft tissue (toluidine blue; original magnification x2) B = bone OM = osteogenic mesenchyme (toluidine blue; original

magnification x25)

Newly formed bone replaced the resorting β-TCP particles continuously. Bone

deposition characteristically occurred along the surface and in the pores of the

disintegrated graft material. There was no foreign body-type giant cell reaction in the

grafted samples. In 1 sample, there was a focal lack of bone formation and an intense

inflammatory reaction, suggesting a local infection.

The majority of the biopsy samples from the control side contained mature lamellar

bone. (Figure 31a.)

The bone trabeculae contained osteocytes in their lacunae. Signs of dynamic bone

formation with osteoblast activity or lacunar osteoclastic resorption were rare. The

remnants of the autogenous bone grafts could be seen in several foci as homogeneous

tissue fragments that stained like living bone. (Figure 31b.)

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Fig. 31.a Fig. 31.b

Autogenous bone graft and newly formed Bone graft focus and newly formed

lamellar bone. lamellar bone. B = bone B = bone

BG = bone graft BG = bone graft

S = soft tissue (Goldner’s trichrome; original magnification x2) S = soft tissue (Goldner’s trichrome;

original magnification x25)

In these samples, there was intimate contact between the graft particles and new bone.

Several samples were typified by torpid bone formation, a predominantly fibrous bone

marrow, and a diffuse, thin network of bone trabeculae.

The mean percentage of bone area for the 20 patients was 36.47% ± 6.9% on the

experimental side and 38.34% ± 7.4% on the control side; the difference was not

significant (P = .25).

In a majority of the patients (n = 13), the intensity of new bone formation was similar

on both sides. When the volume occupied by the graft remnants was considered, these

data suggest that the bone density was sufficient on both sides. (Table 1.)

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Tab.I.

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Nevertheless, the new bone was markedly less dense on the experimental side in 4 of

the 20 cases compared to the control side (H2, B2, B4, l1). In 1 of these patients, the

lethargic bone formation process could be explained by a local inflammatory reaction.

In the other 3 cases, the percentage of the graft area was quite high (H2 25.9%, B4

25.6%, l1 21.1%), ie, the graft material took up too much space in the bone samples.

The bone-forming capacity on the control side was more sluggish than on the

experimental side in 3 cases (H5, H7, B3). In these cases, no inflammatory reaction or

delayed graft resorption hampered bone regeneration. In 2 cases (H1 and B1), the

ossification process was uniformly weak on both sides; the respective percentages of

newly formed bone were 25.6% and 27.5% on the experimental side and 24.0% and

28.1% on the control side. In these 2 cases, the new bone trabeculae were uniformly

thin, with no focal inflammatory lesion.

The rate of graft resorption was generally lower on the experimental side than on the

control side. The mean graft area percentages were 13.95% ± 5.38% and 8.47% ±

3.17%, respectively, and the difference was highly significant (P< .001).

The mean areas of the biopsy samples taken from the 2 sides were quite similar: 9.18 ±

2.42 mm 2 on the experimental side and 8.98 ± 1.76 on the control side.

In the 6-month period between implantation and loading of the implants, 2 of the 80

implants were lost (both Ankylos); 1 on the experimental side and 1 on the control side.

Both were replaced, but delivery of the definitive restoration was delayed by 3 to 6

months.

7.2 – RESULTS: ECTODERMAL DYSPLASIA

In the Ectodermal Dysplasia study group, the patients were evaluated at the

second-stage surgery, after prosthetic reconstruction, and after 1-, 2-, and 3-year follow-

ups. Almost all of the patients had a good level of oral hygiene, which was reflected by

the low mPLI and mSBI scores. Peri-implant mucosal complications, in which the

implant threads were not covered, were observed in patients with less-optimal oral

hygiene.

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In the ED patient group, of the 66 fixtures inserted, 60 were associated with clinically

healthy peri-implant soft tissues, low bleeding scores, and minimal probing depths,

without signs of inflammation, suppuration, mucosal irritation, or increased mobility.

Radiographic evaluation demonstrated that these 60 fixtures were osseointegrated

because of the absence of peri-implant radiolucency. Only three membrane-treated

implants showed mucosal recession and intraoral exposure of the first buccal fixture

thread. Six implants were lost: two in the upper jaw and four in the lower jaw; four

during the healing period and two following functional loading. In this clinical study,

the ED patients had a 91% successful osseointegration rate of the installed fixtures. In

the non-ED control group, 115 osseointegrated implants showed no signs of pathology,

despite the intraoral exposure of threads in six cases. Only five fixtures showed

increased mobility and clinical instability at the second-stage surgery (three in the

maxilla and two in the mandible); these five fixtures failed.

The exposure of six membranes before complete healing led to observation of the

threads of the fixtures, indicating a loss of buccal bone. In another six fixtures, the first

thread was exposed, but without inflammation, mucosal irritation, or mobility. In the

non-ED control group, the 95.8% osseointegration rate was confirmed by the

radiographic evaluation and Periotest values.132

The two groups were compared statistically using the chi-square test. The

regenerated bone at peri-implant bony defects in the experimental group using GBR and

bone grafts responded in a similar way to the control group (Table II.). The

osseointegration rate and failure frequency of the two groups did not differ significantly

(χ2=1.86, p=0.1731; χ2 with the Yates continuity correction=1.08, p=0.2996)

Table II. Osseointegration Rate of ED patients vs non-ED patients. χ2 with Yates continuity correction = 1,08 P= 0,2996

Patient Group Implants Inserted Implants

Osseointegrated Implants Lost Success Rate (%)

ED patients (n=13) 66 60 6 91% Non-ED patients (n=20) 120 115 5 95,8%

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8. - DISCUSSION

8.1 – DISCUSSION: SINUS ELEVATION

One of the most important conclusions of a Consensus Conference on sinus

grafting held several years ago133 was that, “retrospective analyses did not reveal any

bone substitute material that was equivalent to autogenous spongiosa...Accordingly,

many participants believed that autografts were the most efficacious....(but) the doubts

raised revealed the need for controlled prospective multicenter clinical trials”.

Therefore, since some authors had achieved good results with various bone-substitute

materials (especially ß-tricalcium phosphate [ß-TCP]), a prospective multicenter study

was initiated to shed more light on this question.

In a preliminary study6 involving bilateral sinus elevation in 4 patients in 2001 ß-TCP

was used on one side and autogenous bone on the other. Sixteen bone biopsy specimens

were taken at the time of implant placement. The aim of work was to compare 2

different graft materials, β-tricalcium phosphate and autogenous bone, when used in the

same patient. Evaluations were performed by means of 2- and 3-dimensional (2D and

3D) computerized tomography (CT) and histologic and histomorphometric

examinations. The duration of the study was 6 months, which is the usual waiting

period after sinus grafting. It was concluded that the implantation of ß-TCP was

followed by the formation of new bone of similar quality and quantity to that observed

after grafting with autogenous bone. The histologic and histomorphometric results

indicated that when new bone formation was slow, it was slow on both the ß-TCP side

and the autogenous bone side, and when it was rapid, it was rapid on both sides.

Individual patient factors strongly influenced the results.

In essence, the present study is a continuation of that previous work, but on a broader

basis. A prospective, multicenter study of 20 patients was organized to confirm the

findings of the initial study of 4 patients and to examine whether ß-TCP alone is a

suitable graft material for sinus elevation.

A number of articles have examined the significance of pure-phase ß-TCP53,112,114 and

other alloplastic materials7,9,15,26,117,-134-143 as bone substitute materials. However, very

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few studies have involved bilateral sinus elevation with 2 different materials in the same

patient.

Tadjoedin and associates32 applied autogenous bone mixed with bioactive glass on the

experimental side and autogenous bone alone on the control side. They noted that

“bioactive glass particles in the size range 300 to 355 µm clearly show a bone-

augmenting capacity, and the cotransplantation of autogenous bone may not be

necessary for sinus floor augmentation”. This was somewhat contradicted by 2

publications by Yildirim and colleagues,144,145 who used a xenogenic bone-substitute

material, ABB first in combination with venous blood and later with autogenous

intraoral bone. The combination of osteoconductive ABB and osteoinductive

autogenous bone proved better for sinus floor augmentation than did venous blood and

ABB. In animal experiments, Mc Allister and coworkers115 demonstrated radiographic

evidence that bone density and height stability were maintained for 1.5 years after sinus

grafting with ABB. Valentini116 retrospectively evaluated the rates of survival of 2

different types of implants in sinuses grafted with inorganic bovine bone alone or with

inorganic bovine bone mixed with a demineralized freeze dried bone allograft. They

concluded that inorganic bovine bone used alone appeared to be a suitable material for

sinus floor augmentation. A meta-analysis by Wallace and Froum146 showed that there

was no difference in regard to implant survival between grafting with 100% autogenous

bone or grafting with composites that included autogenous bone as a component. In a

pilot study, Schmelzeisen and associates147 used tissue-engineered bone for sinus floor

augmentation. Their results suggested that periosteum-derived osteoblasts on a suitable

matrix form lamellar bone within 4 months, which allows reliable implantation.

Despite this encouraging research, in everyday practice most surgeons believe that no

matter what bone-substitute material is used, the results are always better if autogenous

bone is added. Since the autogenous bone must be taken from somewhere, a second

operation is necessary, which puts the patient at risk of donor site morbidity. This study

examined whether donor site morbidity can be avoided by using synthetic bone

substitute.

The primary aim of this work was to compare the implanted graft material using

clinical, radiologic, and histologic studies. Two of the 80 implants (2.5%) were lost, 1

from each side, suggesting the equivalence of the 2 materials. The comparison of the

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bone-forming activity of β-TCP and autogenous bone confirmed earlier findings. New

bone production was similar on both sides; the difference between the 2 sides was not

significant. These results support the view that β-TCP can be a satisfactory graft

material, even without the addition of autogenous bone.

Radiologic examinations indicated that the grafted area changed in contour during the

period of study (from sinus floor augmentation to definitive prosthetic rehabilitation).

The vertical height of the grafts was not analyzed in the present study. Several factors

can influence new bone formation, in addition to the nature of the graft. In 2 cases (H1

and B1), the rate of new bone formation was low on both sides. This might be the result

of general factors, such as old age, hormonal dysfunction, or distrurbances in calcium

metabolism.

Local factors can explain 1-sided lethargic bone formation. Disturbances in the blood

supply or inflammation at the site of surgery can also delay bone regeneration. In the

present study, unilateral lower rates of bone formation were seen on the experimental

and control sides in different patients, which supports the important role of local factors.

The size of the biopsy sample can also influence the quantitative comparison of the

effects of the graft materials. The greater the area of the bone sample, the more

representative the quantitative measurement. In the present study, the areas of the bone

samples derived from the 2 sides did not differ significantly.

In the introduction, the question was posed whether, under certain conditions, a bone-

substitute material can be equivalent to the patient’s own spongiosa. These results

suggest a positive answer to this question.

In sinus elevation surgery, β-Tricalcium phosphate can be as effective as autogenous

bone. Naturally, this does not necessarily hold true for other operations. For instance,

inlay grafting should still be performed with autogenous bone.

This study investigated 20 patients. Strict patient selection was necessary, mainly for

ethical reasons. In the 10 onlay grafting cases, which required autogenous bone, use of

the control material could be justified. However, in those cases with no onlay grafting,

the question was not so clear-cut. The number of cases had to be restricted to the

minimum number necessary to drawn reliable conclusion. The examination of the 80

biopsy samples taken from the 20 patients led to unambigous findings. The conclusion

drawn appears to be supported by the clinical and radiologic data.

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Initially, more working groups had been planned. However, 2 groups were forced to

withdraw from participation in the investigation because patients did not agree to the

excision of autogenous bone. This further demonstrates the importance of having a

suitable bone-substitute material. Onlay grafting was necessary in 10 of the 20 patients.

In these cases, the alveolar crest of the maxilla was so thin at many sites bilaterally that

stability of the implants could not have been ensured by sinus elevation alone. The

vertical augmentation had to be supplemented with horizontal augmentation. A porous

bone substitute is not very suitable for this purpose; on the other hand, cortical bone

taken from the hip is integrated into the outer surface of the maxilla within a few

months.

Onlay bone grafting clearly has no effect on the healing process following sinus

elevation, as one of the processes occurs on the outer surface of the maxilla, while the

other proceeds internally.

Regarding the question of spongiosa as the gold standard, while it is true that the quality

of new bone obtained using any of the bone substitutes may be compared with this as a

standard, this standard does have disadvantages. The most important of these are donor

site morbidity, the relatively high number of complications, the need for general

anesthesia, and the high costs of hospitalization.148 Niedhart and associated148 have given a clear picture of the cost: removal of the bone

requires an average of 30 minutes, a second surgical team, and an anesthesiologist.

These costs far exceed the price of the bone substitute. With careful surgical techniques,

the rate of complications may be reduced; nevertheless, it generally ranges from 20 % to

30%. When all these factors are taken into consideration, it appears important to avoid

the excision of autogenous bone whenever possible.

Mention must be made of the membrane question. On the basis of more than 40

publications, Wallace and Froum146 performed a comparative meta-analysis of the use

of barrier membranes over the lateral window. They found that implant survival rates

were higher when a membrane was applied. A long-term clinical, histologic,

histomorphometric, and radiographic study of the sinus elevation procedure led Tarnow

and coworkers149 to the following conclusions:

• Application of a barrier membrane tends to increase vital bone formation.

• Application of a barrier membrane has a positive effect on implant survival.

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• Membrane application should be considered for all sinus elevation procedures.

As these findings were accepted, no membrane was used in the present study. In 10 of

the 20 patients, an onlay graft was applied on the lateral wall of the sinuses. This

autogenous bone served as a barrier to soft tissue invasion. In the interest of

comparison, in the other 10 cases no membrane was applied over the lateral window.

The tissue-engineering procedures mentioned in the introduction, which also aim to

minimize donor site morbidity, may be the procedures of choice in the future.

Obviously, if the application of tissue engineered bone becomes as routine as the use of

skin or mucosa, the debate over graft materials will become less relevant. This may take

considerable time, and at present, materials are needed that avoid the excision of

autogenous bone.

In addition, with regard to the publications by Skoglund and associates, 150, 151 Tadjoedin

and associates,32 and Yildirim and colleagues,144 which consider natural bone mineral,

bioactive glass, and so on, the present work did not set out to compare and contrast

individual graft materials. If “remodeling” is considered, pure-phase β-TCP used alone

appears to be a suitable material for sinus floor augmentation.

8.2. – DISCUSSION: ECTODERMAL DYSPLASIA

The dental treatment of patients with ED is important, since it involves ensuring

a normal diet, optimal dentofacial aesthetics and function, good speech, and appropriate

psychological and emotional development. Since this may be complicated, it requires an

interdisciplinary approach involving various branches of dentistry and medicine.

Prosthetic dental rehabilitation usually consists of different combinations of complete or

partial removable dentures, overdentures, and fixed partial dentures. The use of dental

implants has become an important, well accepted treatment for replacing missing teeth

in adults. Guckes et al. reported that the clinical integration rates of fixtures in the

mandibles of ED patients approached that of non-ED patients.152 Some years ago, the

implant position was often determined by the alveolar ridge anatomy, which sometimes

presented aesthetic problems and resulted in mucosal inflammation because of this

unfavourable position.153-155 Today, prosthetically guided implants are usually used to

improve the hard and soft tissue aesthetics. Many authors have obtained successful

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clinical outcomes with guided bone regeneration (GBR) using the barrier membrane

technique, in combination with autogenous or heterologous bone during implant

insertion.120,121,123,124 The use of a space-maintaining biomaterial, such as autogenous

bone or Anorganic Bovine Bone, has increased the volume and stability of regenerated

bone. The length of time required for maturation of newly regenerated bone before

functional loading depends on the morphology and dimensions of the lesion,

vascularization, surrounding bone quality, and optimal oral hygiene. In larger defects,

the use of a non-resorbable membrane together with a bone graft and an extended

healing period is indicated.122,125,126,156

Ectodermal dysplasia is diagnosed from the patient’s appearance and symptoms.

An early diagnosis of Ectodermal Dysplasia in infancy or childhood is very important to

avoid severe complications and to improve the quality of life. The morbidity and

mortality depend on the absence or presence of eccrine and mucous glands. Recurrent

high fever (hyperpyrexia) may lead to brain damage, neurological complications, and a

mortality rate of up to 30% in infancy. Beyond early childhood, the life expectancy is

normal or slightly reduced. Both the oral and maxillofacial surgeon and the pediatric

dentist can help to detect these syndromes using clinical observations and radiographic

imaging. Jaw radiography is indicated for infants with a fever of unknown origin and

possible hypohidrotic ED. The teeth buds may be absent. If unusual dental

abnormalities and hypodontia are present at an early age, panoramic radiographs,

intraoral dental radiographs, teleradiographs, and radiographs of the hands and feet may

detect specific deformities.

Other general medical examinations used to reach the diagnosis include sweat

pore counts, the perspiration test, and a skin biopsy to demonstrate the absence or

hypoplasia of the sweat glands, hair follicles, and sebaceous glands; genetic studies to

localize genes or mutations in ED families; and the prenatal diagnosis of hypohidrotic

ED using fetal skin biopsies. A detailed anamnesis with a family history of Ectodermal

Dysplasia in other family members may lead to an early diagnosis. Arriving at the

diagnosis requires a multidisciplinary approach, since the treatment will involve many

specialists, including pediatricians, dermatologists, dentists, and oral maxillofacial

surgeons.157 Children with ED often have serious dental disease requiring necessary and

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timely rehabilitative therapy beginning at the first phase of the manifestation of this

pathology.158-162

The precocious dental treatment is finalized to improve both functional and

aesthetic aspects, which include nutrition, phonetics, and emotional and psychological

factors. The disease involves growing children in whom the restoration of masticatory

function leads to remarkable benefits in their subsequent growth and development. The

absence of numerous dental elements inevitably involves an alteration of the articulation

of words, and numerous sounds are altered. The absence or reduction of dental elements

accents the sensation of difference felt by patients with Ectodermal Dysplasia with

respect to their peers. The goal of the dentist and oral surgeon is to recreate a harmonic

smile that gives a natural, pleasant appearance to the face.

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9. - CONCLUSIONS

About sinus elevation, it was concluded that the grafting of β –TCP was

followed by the formation of new bone of similar quality and quantity to that observed

after grafting with autogenous bone. Comparisons with other studies reveal that β-

Tricalcium Phosphate is a satisfactory graft material, even without autogenous bone.

Since a second operation is not necessary, donor site morbidity can be avoided by using

β –TCP.

Notwithstanding the anatomic restrictions, titanium screw implants may be

inserted successfully in Ectodermal Dysplasia patients in association with GBR and

bone grafts to provide a very stable dentition, and improved chewing ability, speech,

and psychological and emotional well-being.

The novelty and originality of this research:

1. For the first time a multicenter study on a broader basis was organized to

examine whether β- TCP alone is a suitable graft material for sinus elevation.

2. Concomitantly on the same patient, two sinus elevations by two different bone

grafting materials were performed: β- TCP alone as the experimental side and

autogenous bone alone as control side.

3. Donor site morbidity was avoided by grafting β- TCP alone.

4. For the first time a study to assess the possibility to insert osseointegrated

implants associated to bone grafts and guided bone regeneration also in

Ectodermal Dysplasia patients was performed.

5. For the first time in a study about ED patients, implants also in the upper jaw

were included.

6. The improved appearance and self-confidence, with a better function helped ED

patients to become accepted by their friends and families and resulted in a better

quality of life.

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10. - SUMMARY

Two different studies have been performed. The objective of the former was to

determine whether donor site morbidity could be avoided by using pure-phase β-

tricalcium phosphate (β-TCP). Bilateral sinus grafting was performed on 20 selected

patients; β-TCP was used on the experimental side, and autogenous bone was used on

the control side. In each patient, one side was randomly designated the experimental

side. In 10 of the 20 patients, the maxilla reconstruction included sinus grafting and

onlay bone grafting. Implants were placed 6 months after the procedure. Eighty bone

biopsy specimens were taken at the time of implant placement. Histologically and

histomorphometrically, there was no significant difference (P=.25) between the

experimental and control grafts in terms of the quantity and rate of ossification.

Comparisons with other studies reveal that β-TCP is a satisfactory graft material, even

without autogenous bone. The objective of the latter was to verify if it is possible to use

osseointegrated implants in Ectodermal Dysplasia Syndrome (EDS) patients. Dental and

surgical-implantological treatment for EDS patients may be very complicated. Guided

Bone Regeneration (GBR) membrane technique associated to bone grafting was used to

facilitate placement of osseointegrated implants in a guided prosthetically position. Two

groups with the same bony anatomical features were assessed. The first consisted of 13

Ectodermal Dysplasia patients, where 66 implants together bone grafts and membranes

were inserted. In the second control group 120 implants with GBR were placed in 20

patients. The implants were controlled at second stage surgery, and at a follow-up of a 1

year, 2 and 3 years functional loading period. The results showed no statistically

significant difference in the osseointegration rate between the two groups. Despite

anatomical defects associated with decreased occlusal vertical dimension and the

diminished edentulous alveolar ridges, both in height and in width, osseointegrated

implants together GBR and bone grafts may be successfully used in EDS.

Garagiola U, Maiorana C, Ghiglione V, Marzo G, Santoro F, Szabò G. 2006:

Osseointegration and guided bone regeneration in Ectodermal Dysplasia patients.

J Craniofacial Surg 17(6) (in press)

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Szabò G, Huys L, Coulthard P, Maiorana C, Garagiola U, Barabás J, Németh Z,

Hrabák K, Suba Z. 2005: A prospective multicenter randomized clinical trial of

autogenous bone versus ß-tricalcium phosphate graft alone for bilateral sinus elevation:

histologic and histomorphometric evaluation.

Int J Oral Maxillofac Impl 20(3):371-381.

Suba Z, Hrabák K, Huys L, Coulthard P, Maiorana C, Garagiola U, Szabó G. 2004 : A

ß-trikalcium-foszfát graft csontregeneráló hatásának hisztológiai és hisztomorfometriai

vizsgálata (multicentrikus tanulmány).

Orv Hetil 145:1431-1437. Hungarian

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11. - BIBLIOGRAPHY

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Notes Figures 9.: Taken from Szabó G. Oral and maxillofac surgery. Semmelweis Publishing House. Budapest, 2001.

Figures 10.: Taken from National Foundation for Ectodermal Dysplasias. A dental guide to the Ectodermal Dysplasia. NFED 1999.

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12. – LIST OF AUTHOR’S PUBLICATIONS

12.1 – LIST OF PUBLICATIONS CONNECTED WITH THE TOPIC

1. Garagiola U, Maiorana C, Ghiglione V, Marzo G, Santoro F, Szabò G.

Osseointegration and guide bone regeneration in Ectodermal Dysplasia patients.

J Craniofac Surg 2006;17(6) (in press) IF: 1.017

2. Mortellaro C, Rimondini L, Farronato G, Garagiola U, Vercellino V, Berrone

M. Temporomandibular disorders due to improper surgical treatment of

mandibular fracture: Clinical Report.

J Craniofac Surg 2006:17(2):373-382. IF: 1.017

3. Mortellaro C, Garagiola U, Greco Lucchina A, Grivetto F, Milone G,

Pappalardo S, Palmieri A, Scorsone D, Sammartino G. The use of silicon

elastomer in maxillofacial rehabilitation as a substitute for or in conjunction with

resins.

J Craniofac Surg 2006:17(1):152-162. IF: 1.017

4. Szabò G, Barabás J, Hrabák K, Suba Zs, U. Garagiola, B. Kádár Autologer

knochen versus ß-tricalcium phosphat allein eine radiologische und

histologische evaluation.

Z Oral Implantologie 2005(4): 2-8.

5. Szabò G, Huys L, Coulthard P, Maiorana C, Garagiola U, Barabás J, Németh Z,

Hrabák K, Suba Z. A prospective multicenter randomized clinical trial of

autogenous bone versus ß-tricalcium phosphate graft alone for bilateral sinus

elevation: histologic and histomorphometric evaluation.

Int J Oral Maxillofac Impl 2005:20(3):371-381. IF: 1.772

6. Mortellaro C, Garagiola U, Carbone V, Cerutti F, Marci V, Foglio Bonda PL.

Unusual oral manifestations and evolution in glycogen storage disease type 1b.

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J Craniofac Surg 2005:16(1):45-53. IF: 1.017

7. Suba Z, Hrabák K, Huys L, Coulthard P, Maiorana C, Garagiola U, Szabó G.A

ß-trikalcium-foszfát graft csontregeneráló hatásának hisztológiai és

hisztomorfometriai vizsgálata (multicentrikus tanulmány).

Orv Hetil 2004:145:1431-1437. Hungarian

8. Garagiola U, Gioventù S, Ghiglione V. Silver-Russell Syndrome.

Doctor Os 2003:Sep;14(7):721 – 726. Italian

9. Garagiola U. Orthognathic surgery, osseointegration and adult orthodontics:

multidisciplinary synergy to correct dentofacial deformities.

J Japan Ass Adult Orthod 2003:10(1):17-26. Japanese

10. Garagiola U. Interdisciplinary synergy to ensure best long-term outcomes:

osseointegration- orthodontics.

Pravissimo Journal 2002:Mar;4:16-19. English

11. Garagiola U, Nishiyama K, Eisenmann E. Aesthetics and function in the

production of posterior crowns on single implants: the Ankylos Balance system.

Quintessenza Odontotecnica 2002:Mar;19(3):208-219. Italian

12. Garagiola U, Santoro E, Ghiglione V. Oral and cranio-facial manifestations in

Axenfeld-Rieger Syndrome.

Mondo Ortodont 2001:Sep-Oct;26(5):369-383. Italian

13. Ghiglione V, Garagiola U, Cangiano A, Redemagni M. Uprighting of

mesioinclined molars using the NiTi-SE steel spring.

Mondo Ortodont 1999:May-Jun;24(3)165-176. Italian

14. Ghiglione V, Garagiola U, Folegatti P. Combined orthognathodontic–

implantologic treatment in patients affected with Ectodermal Dysplasia.

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Implant Oral 1998:Oct;1(4 ):23-30. Italian

15. Ghiglione V, Garagiola U, Maspero C. Orthodontic-osseointegration: an

interdisciplinary approach in a dental agenisis case.

Mondo Ortodont 1997:Nov-Dec;22(6 ):553-558. Italian 16. Santoro F, Ghiglione V, Garagiola U, Maiorana C. An orthodontic-surgical

approach for the diagnosis and treatment of class III open-bite.

Electromyographic and Kinesiographic evaluation. Description of two clinical

cases.

Ortognatodonzia Italiana 1996:5(6):811-823. Italian

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12.2 – LIST OF PUBLICATIONS NON CONNECTED WITH THE TOPIC

1. Farronato G, Garagiola U, Farronato D, Bolzoni L, Parazzoli E. Temporary lip

paresthesia during orthodontic molar distalization: a case report.

Am J Orthod Dentofacial Orthop 2006 (in press) IF: 0.916

2. Farronato G, Garagiola U, Ghiglione U, Farronato D, Gioventù S, Selicorni A.

Moebius syndrome: a case report.

Quintessence Int 2006 (in press) IF: 0.540

3. Mortellaro C, Garagiola U, Torchio R, Gulotta G, Foglio Bonda PL, Farronato

G. Upper airway obstruction and orofacial deformity: an evaluation using the

whole body plethysmography technique.

Ear Nose & Throat Journal 2006 (in press)

4. Garagiola U, Vedani L, Ghiglione V. The Nd-YAG laser in orthognathodontics:

clinical considerations and biocompatibility. Part 1.

ORTEC 2001:2:7-18. Italian

5. Ghiglione V, Garagiola U. Electrokinesiographic evaluations of the skeletal

open-bite surgical treatment.

Medimond 2005:169-173. Italian

6. Garagiola U, Vedani L, Ghiglione V. The Nd-YAG laser in orthognathodontics:

clinical considerations and biocompatibility. Part 2.

ORTEC 2001:3:7-14 Italian

7. Garagiola U, Santoro E. Parodontal prevention in orthodontic treatment of child

and adolescent patient.

Professione Odontoiatria 2001: Jan;1:9-13. Italian

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8. Garagiola U, Costanza C, Cocuzza L, Ghiglione V. Orthodontics-prosthesis

interdisciplinary techniques in the use of the Maryland Bridge.

Doctor OS 2000:Apr;11(4):357-362. Italian

9. Garagiola U, Ghiglione V. Parodontal prevention in adult orthognathodontic

patients.

Professione Odontoiatra – Suppl Doctor OS 2000:5:7-10. Italian

10. Ghiglione V, Garagiola U, Addamiano G, Addamiano F. Selective molar

intrusion by means of a double cantilever system.

Doctor OS 2000:May;11(5): 509-517. Italian

11. Ghiglione V, Garagiola U, Addamiano F, Cangiano A. Role of the stabilometric

board in orthognathodontics.

Attual Dental 1999:Sep;6(7):6-25. Italian

12. Ghiglione V, Maspero C, Garagiola U, Cocuzza L. The correlation between the

skeletal vertical dimension and the neuro-muscular system. A clinical case.

Attual Dental 1999:Feb;6(2): 14-26. Italian

13. Garagiola U, Zucchi P, Ghiglione V. Frankel’s functional regulator.

Attual Dental 1998: Sep; 5(7): 6-22. Italian

14. Ghiglione V, Garagiola U, Persia M. The role of the activator in interceptive

treatment of class II skeletal malocclusions.

Doctor OS 1998: Feb;9(2):19-26. Italian

15. Ghiglione V, Garagiola U. Handbook of Periodontics.

Ariesdue; Como; 1998:1-9. Italian

16. Ghiglione V, Garagiola U. Handbook of Oral Hygiene.

Ariesdue; Como; 1997:1-12. Italian

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17. Ghiglione V, Goggi P, Garagiola U. Combined therapy by rapid palatal

expander - Delaire mask in early correction of skeletal class III.

Mondo Ortod 1997:May – Jun; 23(3):235-242. Italian

18. Ghiglione V, Garagiola U, Mori P. Role of Electromyographic investigation in

orthognathodontic diagnosis and treatment.

Doctor OS 1995: Jun – Jul;6(6):54-63. Italian

19. Ghiglione V, Garagiola U, Frisoni A. Role of the Ginevra type monoblock in

interceptive therapy: discussion of a clinical case.

Mondo Ortod 1995: Apr;20(2):373-378. Italian

20. Maiorana C, Garagiola U, Santoro F. Neuromuscular system and the Rolfing

method in craniomandibular disorders.

Mondo Ortod 1992: July - Aug;17(4):369-375. Italian

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13. - LIST OF AUTHOR’S ABSTRACTS

13. 1 - LIST OF ABSTRACTS CONNECTED WITH THE TOPIC

1. Garagiola U., Toia M., Arnaboldi O., Santoro G.

Osseointegration and bone regeneration in patients affected by Ectodermal

Dysplasia.

15th Annual Meeting of the European Association for Osseointegration; Zurich,

Switzerland, 2006.

2. Garagiola U., Maiorana C., Santoro F., Szabò G.

Osseointegration and bone reconstruction in patients affected by Ectodermal

Dysplasia.

XVIII Congress of the European Association for Cranio-Maxillofacial Surgery;

Barcelona, Spain, 2006.

3. Garagiola U. Nishiyama K., Szabò G. Timing and effects of orthodontic loading on mini-implants for skeletal

anchorage .

106th Congress of the American Association of Orthodontists; Las Vegas, USA,

2006.

4. Garagiola U., Ghiglione V.

Dentofacial deformities in adult patient: Multidisciplinary surgical-orthodontic

treatment.

7° Congresso Nazionale di Medicina Estetica; Milan, Italy, 2005.

5. Garagiola U., Szabò G., Santoro F.

Occlusal overload as primary risk factor of prosthetic implant failures.

14th Annual Scientific Meeting of the European Association for

Osseointegration; Munich, Germany, 2005.

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Clin Oral Implants Res 2005:16(4):402. IF: 1.897

6. Garagiola U., Nishiyama K., Szabò G.

Skeletal anchorage for tooth movements: mini implants vs osseointegrated

implants.

6th International Orthodontics Congress; Paris, France, 2005.

World Journal of Orthodontics 2005:6(Suppl):117.

7. Garagiola U., Szabò G., Santoro E.

Osseointegrated implants use in craniomandibular disorder patients: implant

overload prevention.

17th International Conference on Oral & Maxillofacial Surgery; Vienna, Austria,

2005.

Int J Oral Maxillofac Surg 2005: Aug;34(1):19. IF: 1.123

8. Garagiola U., Ghiglione V., Farronato G.

Potential risk of periodontal breakdown during surgical-orthodontic therapy.

81st European Orthodontic Society Congress; Amsterdam, The Netherlands,

2005.

9. Garagiola U., Santoro F., Ghiglione V., Farronato G.

Potential periodontal consequences during orthodontic tooth movement in

orthognathic surgery.

105th Congress of the American Association of Orthodontists; San Francisco,

USA, 2005.

10. Ghiglione V., Garagiola U., Santoro F.

Class III malocclusion and vertical dimension: interceptive orthodontics or

orthognatic surgery?

XIX Congresso Nazionale SIDO; Rimini, Italy, 2005.

11. Garagiola U., Szabò G., Santoro F., Spadari F.

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Early detection and multidisciplinary management of Gorlin-Goltz syndrome:

the dentists’role.

10th International Congress on Oral Cancer, Island of Crete, Greece, 2005.

Oral Oncology 2005:Apr;1(1):140. (Suppl) IF: 2.266

12. Garagiola U., Szabò G., Santoro F.

Potential risk factors of implant use in temporomandibular disorders patients.

83rd General Session & Exhibition of the IADR/AADR/CADR; Baltimore, USA,

2005.

J Dent Res 2004:84:Special Issue A. (Cd-Rom) IF: 3.192

13. Garagiola U., Laskin DM., Santoro F.

Potential risk factors for implant failure in temporomandibular disorders

patients.

4th World Congress of Osseointegration; Venice, Italy, 2004.

Italian J Osseointegration 2004: May-Aug;4(2):64.

14. Garagiola U., Ghiglione V.

Videocephalometric prediction of facial aesthetic changes in orthognathic

surgery and psyche.

6th Congresso Nazionale di Medicina Estetica; Milan, Italy, 2004.

15. Garagiola U., Santoro F., Szabo’ G.

Stability and relapse after surgical-orthodontic correction of skeletal open-bite

deformities.

XVII Congress of the European Association for Cranio-Maxillofacial Surgery;

Tours, France, 2004.

J Cranio Maxillofac Surg 2004: Sep;32(1):148. IF: 0.991

16. Garagiola U., Santoro E., Bodin C., Laskin DM.

Potential success and risk factors for implant use in temporomandibular

disorders patients.

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XVIIth Congress of the European Association for Cranio-Maxillofacial Surgery;

Tours, France, 2004.

Journal Cranio Maxillofac Surg 2004: Sep;32(1):311. IF: 0.991

17. Foglio Bonda P.L., Garagiola U., Rocchetti V.

In vitro corrosion resistance of titanium in fluorinated environment.

13th European Association for Osseintegration ; Paris, France, 2004.

Clin Oral Implants Res 2004: Aug;15(4):43. IF: 2.139

18. Garagiola U., Santoro F., Szabo’ G.

Gorlin-Goltz Syndrome: early detection and multidisciplinary management.

7th Congress of the European Academy of Paediatric Dentistry; Barcelona,

Spain, 2004.

European J Paediatric Dentristry 2004:Sep;5:59.

19. Garagiola U., Ghiglione V., Farronato G.

Orthognathic surgery and temporomandibular joint disorders: functional and

neuromuscular evaluation.

80th European Orthodontic Society Congress; Aarhus, Denmark, 2004.

20. Garagiola U., Santoro F.

Predictability and stability of orofacial deformities correct by orthognathic

surgery

5th International Danubius Conference on Oral and Maxillofacial Surgery; 8th

Congress of the Hungarian Association of Oral and Maxillofacial Surgeons;

Budapest, Hungary, 2004.

21. Garagiola U., Gioventù S., Ghiglione V., Farronato G.

Odontostomatological aspects of Silver-Russell Syndrome.

11th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, La

Prevenzione e La Sicurezza per il Professionista e l’Utenza in Odontoiatria;

Rome, Italy, 2004.

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22. Garagiola U., Foglio Bonda P.L., Dall’Oca S., Migliario M., Rocchetti V.

Antihemorrhage preventive treatment in dental patients suffering from

coagulopathy.

11th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, La

Prevenzione e La Sicurezza per il Professionista e l’Utenza in Odontoiatria;

Rome, Italy, 2004.

23. Garagiola U., Gioventù S., Ghiglione V., Farronato G.

Early and delayed loads in orthodontic skeletal anchorage through the use of

mini-implants.

11th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, La

Prevenzione e La Sicurezza per il Professionista e l’Utenza in Odontoiatria;

Rome, Italy, 2004.

24. Garagiola U., Mortellaro C., Migliario M., Scorsone D., Pappalardo S.

Indications and contraindications of the surgical treatment of impacted teeth in

adults.

11th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, La

Prevenzione e La Sicurezza per il Professionista e l’Utenza in Odontoiatria;

Rome, Italy, 2004.

25. Garagiola U., Mortellaro C., Carbone V., Bello L., Pappalardo S.

Craniomandibular disorders after surgical treatment of mandibular fracture

consolidated in wrong position.

11th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, La

Prevenzione e La Sicurezza per il Professionista e l’Utenza in Odontoiatria;

Rome, Italy, 2004.

26. Garagiola U., Ghiglione V.

Treatment of serious dento-facial aesthetic problems: multidisciplinary synergy.

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XIV International Odontostomatologic Congress; Monte Carlo, Principality of

Monaco, 2003.

27. Garagiola U., Ghiglione V.

Implantology and orthodontics in the synergic interdisciplinary correction of

dento-facial aesthetics.

5th Congresso Nazionale di Medicina Estetica; Milan, Italy, 2003.

28. Garagiola U., Nishiyama K., Santoro F.

Orthodontic skeletal anchorage in complex cases: mini-implants vs

osteointegrated fixtures.

91 FDI Annual World Dental Congress; Sydney, Australia, 2003.

29. Garagiola U., Spadari F., Foglio Bonda P.L.

Early detection and management of Gorlin-Goltz Syndrome : the dentists’ role.

91 FDI Annual World Dental Congress; Sydney, Australia, 2003.

30. U. Garagiola

Implant prosthodontics timing, loading and management in Ectodermal

Dysplasia patients.

6 ème Symposium Sociètè Internationale de Prothèse Adjointe Fonctionelle

(SIPAF) - Annual Meeting 2003 American Academy of Implant Prosthodontics

(AAIP); France, 2003.

31. Garagiola U., Ghiglione V., Nishiyama K.

Timing, loading and placement of mini-implants and implants as orthodontic

anchorage.

79th Congress of the European Orthodontic Society; Prague, 2003.

Eur J Orthod 2003: Aug;25(4):430-431. IF: 0.656

32. Garagiola U., Ghiglione V., Farronato G.

Effects of bimaxillary surgery on the mid and lower facial soft tissues.

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79th Congress of the European Orthodontic Society; Prague, 2003.

33. Garagiola U., Farronato G., Re E.

Early detection and management of Gorlin-Goltz Syndrome – The orthodontist’s

role.

79th Congress of the European Orthodontic Society; Prague, 2003.

34. Garagiola U., Re E., Farronato G.

Ectodermal Dysplasia: Multidisciplinary Synergy.

79th Congress of the European Orthodontic Society; Prague, 2003.

35. Garagiola U., Ghiglione V., Cressoni P., Re E., Spadari F.

Odontostomatological manifestations of Gorlin-Goltz syndrome.

10th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Tecnologie

Avanzate in Odontoiatria; Rome, Italy, 2003.

36. Garagiola U., Fusco M., Farronato G., Maiorana C.

Orthodontic skeletal anchorage by the means of osseointegrated implants and

mini-implants.

10th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Tecnologie

Avanzate in Odontoiatria; Rome, Italy, 2003.

37. Garagiola U., Spadari F., Re E., Fusco M., Farronato G.

Relapse and stability of skeletal open-bite corrected by means of bimaxillary

surgery.

10th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Tecnologie

Avanzate in Odontoiatria; Rome, Italy, 2003.

38. Garagiola U., Ghiglione V., Re E., Maiorana C.

Peri-implant bone resorption following the supracrestal positioning of the

implant collar.

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10th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Tecnologie

Avanzate in Odontoiatria; Rome, Italy, 2003.

39. Nishiyama K., Garagiola U.

Harmonic aesthetics and function in implantology: clinical evaluations in

posterior partially edentolous patients.

XIV International Odontostomatologic Congress; Monte Carlo, Principality of

Monaco, 2002.

40. Garagiola U., Ghiglione V., Nishiyama K.

Osseointegration-orthodontics: interdisciplinary treatment in patients with

Ectodermal Dysplasia.

6° European Academy of Paediatric Dentistry; Dublino, Ireland, 2002.

J Eur Academy of Paediatric Dentistry; 2002: Sep;3:142.

41. U. Garagiola

Implantology, Orthodontics, Orthognathic Surgery: An interdisciplinary

approach to managing complex treatment plans.

5th International Implant Dentistry Meeting; Cologne, Germany, 2002.

42. Garagiola U., Ghiglione V., Farronato G.

Skeletal orthodontic anchorage: mini-implants compared to osseointegrated

implants.

XVII Convegno Nazionale SIDO; Florence, Italy, 2002.

43. Garagiola U., Ghiglione V., Farronato G.

Stability and relapse in dysgnathia corrected by means of orthognathic surgery.

XVII Convegno Nazionale SIDO; Florence, Italy, 2002.

44. Garagiola U., Ghiglione V.

Genioplasty in combination with orthognathic surgery for the correction of

orofacial deformities.

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4th Congresso Nazionale di Medicina Estetica; Medicina di Prevenzione ed

Orientamenti Terapeutici; Milan, Italy, 2002.

45. Farronato G., Bellintani C., Garagiola U.

Facial asymmetry: diagnostic protocol and therapeutic indications.

4th Congresso Nazionale di Medicina Estetica; Medicina di Prevenzione ed

Orientamenti Terapeutici; Milan, Italy, 2002.

46. Garagiola U., Ghiglione V., Nishiyama K.

Skeletal anchorage for tooth movements: mini-implants vs. osseointegrated

implants.

11th European Association for Osseointegration; Brussels, Belgium, 2002.

Clin Oral Implants Res 2002: Aug;13(4) :36. IF: 1.503

47. U. Garagiola

Orthognathic surgery, osseointegration and adult orthodontics: multidisciplinary

synergy to correct dentofacial deformities.

1st International Congress of Japan Association of Adult Orthodontics; Tokyo,

Japan, 2002.

Japan Ass Adult Orthod 2002:102-103.

48. Garagiola U., Ghiglione V., Santoro E.

Stability and relapse of dentofacial disharmonies after orthognathic surgery.

78th Congress of the European Orthodontic Society; Sorrento, Italy, 2002.

49. Garagiola U., Ghiglione V., Nishiyama K.

Orthodontic skeletal anchorage: mini-implants versus osseointegrated implants.

78th Congress of the European Orthodontic Society; Sorrento, Italy, 2002.

50. Garagiola U., Re E., Motta B., Ghiglione V.

Facial tissue profile and aesthetic appearance after bimaxillary surgery.

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Convegno Internazionale sull’Estetica Orale e Facciale: Armonia tra forma e

funzione: la costante ricerca dell’estetica in odontoiatria, Milan, Italy, 2002.

51. Garagiola U., Fusco M., Re E., Ghiglione V.

Multidisciplinary synergy in the correction of deformities and dento-facial

beauty problems.

9th Congresso Nazionale del Collegio dei Docenti; L’Odontoiatria del Terzo

Millennio; Rome, Italy, 2002.

52. Garagiola U., Santoro E., Cressoni P., Ghiglione V.

Videocephalometric prediction of the effects of orthognathic surgery on the soft

tissues of the face.

9th Congresso Nazionale del Collegio dei Docenti; L’Odontoiatria del Terzo

Millennio; Rome, Italy, 2002.

53. Garagiola U., Ghiglione V., Nishiyama K.

Peri-implant bone levels after supracrestal implant collar placement in

submerged implants.

17th Annual Meeting of the Academy of Osseointegration; Dallas, USA, 2002.

54. Nishiyama K., Garagiola U.

Clinical evaluation of the use of mini-implants as skeletal orthodontic

anchorage.

XIII International Odontostomatologic Congress; Monte-Carlo, Principality of

Monaco, 2001.

55. Garagiola U., Santoro E., Paini L., Ghiglione V.

Effects of bimaxillary orthognathic surgery on facial soft tissue profile.

XIII International Odontostomatologic Congress; Monte-Carlo, Principality of

Monaco, 2001.

56. Garagiola U.

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Interdisciplinary synergy osseointegration-orthodontics to ensure the best long-

term outcomes. 4th International Implant Dentistry Meeting; Hanover, Germany,

2001.

57. Garagiola U., Cressoni P., Gualano M.G., Ghiglione V.

Genioplasty in association with orthognathic surgery in serious facial

deformities.

XVI Congresso Nazionale SIDO; Genoa, Italy, 2001.

58. Garagiola U., Ghiglione V., Bellintani C.

Multidisciplinary synergy in the treatment of serious dento-facial deformities.

3rd Congresso Nazionale di Medicina Estetica; Milan, Italy, 2001.

59. Garagiola U., Santoro E., Nishiyama K.

Orofacial deformities requiring genioplasty associated with orthognathic surgery

in both jaws.

89th FDI Annual World Dental Congress, Kuala Lumpur, Malaysia, 2001.

Int Dental J 2001:Oct51(5):368. IF: 0.713

60. Garagiola U., Ghiglione V., Nishiyama K.

Supracrestal implant collar placement vs short fixtures in submerged implants.

10th European Association for Osseointegration, Congress; Milan, Italy, 2001

Clin Oral Implants Res 2001:Aug;12( 4):402. IF: 1.205

61. Garagiola U., Santoro E., Ghiglione V.

Bimaxillary orthognathic surgery with concomitant genioplasty to correct

orofacial deformities.

77th Congress of the European Orthodontic Society; Ghent, Belgium, 2001.

Eur J Orthod 2001:Aug;23(4):450. IF: 0.591

62. Garagiola U., Ghiglione V., Szabò G.

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Relationship between postsurgical stability and orofacial muscle activity of

skeletal open-bite deformities.

15th International Conference on Oral and Maxillofacial Surgery; Durban, South

Africa, 2001

Int J Oral Maxillofacial Surg 2001:Jun ;30:87. (suppl) IF: 0.972

63. Garagiola U., Santoro E., Cressoni P., Ghiglione V.

Genioplasty associated with orthognathic surgery in serious orofacial deformity.

8th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Il Futuro

dell’Odontoiatria Ricerca Materiali Tecnologie; Rome, Italy, 2001.

64. Ghiglione V., Garagiola U., Bellintani C.

Aesthetic objectives of orthognathic surgery in the treatment of facial

deformities.

2nd Congresso Nazionale di Medicina Estetica; Milan, Italy, 2000.

65. Garagiola U., Santoro E., Ghiglione V.

Videocephalometric prediction of aesthetic changes in facial tissues in

bimaxillary orthognathic surgery.

XVI Convegno Nazionale SIDO, Florence, Italy, 2000.

66. Garagiola U.

Osseointegration & Orthodontics to achieve optimal aesthetics and function.

XX ICOI World Congress - 30th Anniversary of DGZI., Berlin, Germany,

October 2000.

67. Garagiola U., Ghiglione V., Nishiyama K.

Early diagnosis and multidisciplinary management of the Axenfeld-Rieger

Syndrome.

5th Congress of the European Academy of Paediatric Dentistry; Bergen,

Norway, 2000.

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68. Garagiola U., Ghiglione V., Maspero C., Fukai M.

Orofacial muscle adaptation after surgical correction of severe anterior open

bite.

76th Congress of the European Orthodontic Society; Crete, Greece, 2000.

Eur J Orthod 2000:Oct;22(4) :444-45. IF: 0.593

69. Garagiola U., Ghiglione V., Maspero C., Nishiyama K.

The orthodontist’s role in the early diagnosis and management of Axenfeld-

Reiger syndrome.

76th Congress of the European Orthodontic Society; Crete, Greece, 2000.

Eur J Orthod 2000:22(5) :579. IF: 0.593

70. Ghiglione V., Garagiola U., Maspero C., Marchetti C.

Multidisciplinary synergism in the early detection and management of Axenfeld-

Rieger Syndrome.

100th Congress of the American Association of Orthodontists; Chicago, USA,

2000.

71. Garagiola U., Ghiglione V., Maspero C.

Orofacial muscle activity patterns after the surgical correction of skeletal open-

bite.

100th Congress of the American Association of Orthodontists; Chicago, USA,

2000.

72. Garagiola U., Ghiglione V., Maspero C.

Use of osseointegrated implants in orthodontic treatment of adult patients.

100th Congress of the American Association of Orthodontists, Chicago, USA,

2000.

73. Garagiola U., Ghiglione V., Cressoni P., Motta B.

The facial profile of the soft tissues after bimaxillary orthognathic surgery.

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7th Congresso Nazionale del Collegio dei Docenti di Odontoiatria;

L’Odontoiatria nel Mondo Anno 2000; Rome, Italy, 2000.

74. Ghiglione V., Garagiola U., Bellintani C.

Dento-facial aesthetic motivation in adult orthognathodontics.

7th Congresso Nazionale del Collegio dei Docenti di Odontoiatria;

L’Odontoiatria nel Mondo Anno 2000; Rome, Italy, 2000.

75. Garagiola U., Ghiglione V., Nishiyama K.

Osseointegrated fixtures placement in patients with Ectodermal Dysplasia.

15th Annual Meeting of the Academy of Osseointegration; New Orleans, USA,

2000.

Int J Oral Maxillofacial Implants 2000:15(3):457. IF: 1.316

76. Garagiola U., Bellintani C.

Effects of bimaxillary orthognathic surgery on the profile of the soft tissues of

the face.

1st Congresso Nazionale di Medicina Estetica; Milan, Italy, 1999.

77. Garagiola U., Ghiglione V., Costanza C., Vedani L.

Ectodermal Dysplasia: the role of the orthodontist in its multidisciplinary

treatment.

XV Congresso SIDO; Rome, Italy, 1999.

78. Garagiola U., Ghiglione V., Maspero C., Bellintani C.

Forecast of the effects of bimaxillary orthognathic surgery on the profile of the

soft tissues of the face.

XV Congresso SIDO; Rome, Italy, 1999.

79. Ghiglione V., Garagiola U., Fukai M.

Oral and craniofacial manifestations in patients with Axenfeld-Rieger syndrome.

87th FDI Annual World Dental Congress; Mexico City, Mexico, 1999.

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Int Dental J 1999:Oct;49(5):281. IF: 0.713

80. Garagiola U., Ghiglione V.

Relationship between bimaxillary orthognathic surgery and the effects on the

soft tissues in predicting facial changes.

3rd International Danubius Conference on Oral and Maxillofacial Surgery;

Hévìz, Hungary, 1999.

81. Garagiola .U, Ghiglione V., Nishiyama K.

Facial soft tissue profile and aesthetic appearance after bimaxillary surgery.

75th Congress of the European Orthodontic Society; Strasburg, France 1999.

82. Garagiola U., Ghiglione V., Maspero C.

Implant, periodontal, and prosthodontic considerations of NiTi-SE steel

uprighting springs.

75th Congress of the European Orthodontic Society; Strasburg, France, 1999.

Eur J Orthod 1999:Oct;21(5):589. IF: 0.607

83. Garagiola U., Ghiglione V., Nishiyama K.

Soft and hard tissue analysis in treatment planning of patients requiring

orthognathic surgery.

99th Congress of the American Association of Orthodontists, San Diego, USA,

1999.

84. Garagiola, U. Ghiglione V., Hofele C.

Effects of bimaxillary orthognathic surgery on the soft tissues.

14th International Conference on Oral and Maxillofacial Surgery; Washington

DC, USA, 1999.

Int J Oral & Maxillofacial Surg 1999: 28(1):87. (Suppl) IF: 0.948

85. K. Nishiyama, U. Garagiola

An evaluation of treatment system for better implant aesthetics.

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ISAOIA; Hong Kong, China, 1999.

Asia-Pacific Dental News 1999.

86. Garagiola U., Maspero C., Bonifacio C., Ghiglione V.

Odontostomatological aspects of Axenfeld-Rieger Syndrome.

6th Congresso Nazionale del Collegio dei Docenti di Odontoiatria; Odontoiatria

Europea Verso il 2000; Roma, Italy, 1999.

87. Garagiola U., Ghiglione V., Nishiyama K.

Use of titanium screw implants for Ectodermal Dysplasia patients.

8th European Association for Osseointegration Congress; Copenhagen,

Denmark, 1999.

Clin Oral Impl Res 1999:10(2):183. IF: 1.816

88. Fukai M., Nishiyama K., Garagiola U.

Sinus lift: Three-dimensional diagnosis by Sim/plant.

X International Odontostomatologic Congress; Monte-Carlo, Principality of

Monaco, 1998.

89. Ghiglione V., Garagiola U., Maspero C.

Orthodontic preparation to implantological-prosthetic rehabilitation.

X International Odontostomatologic Congress; Monte-Carlo, Principality of

Monaco 1998.

90. Garagiola U., Ghiglione V., Re E.

Clinical aspects, inheritance patterns, management of x-linked hypohidrotic

Ectodermal Dysplasia.

86th FDI Annual World Dental Congress; Barcelona, Spain, 1998.

Int Dental J 1998: Oct;48(5):424. IF: 0.713

91. Garagiola U., Ghiglione V., Rebagliati M.

Facial soft and hard tissue changes after bimaxillary orthognathic surgery.

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86th FDI Annual World Dental Congress; Barcelona, Spain, 1998.

Int Dental J 1998: Oct;48(5):424. IF: 0.713

92. Garagiola U., Ghiglione V., Maspero C.

Skeletal open-bite and the neuromuscular system: surgical vs non-surgical

correction.

74th Congress of the European Orthodontic Society; Mainz, Germany, 1998.

93. Garagiola U., Ghiglione V., Maspero C.

Skeletal open-bite: surgical vs. non surgical treatment.

98th Congress of the American Association of Orthodontists, Dallas, USA, 1998.

94. Garagiola U., Ghiglione V., Maspero C.

Ectodermal Dysplasia: a multidisciplinary approach.

4th Congress of the European Academy of Paediatric Dentistry; Porto Cervo,

Italy, 1998.

Italian J Paediatric dentistry 1998:1:64.

95. Ghiglione V., Maspero C., Garagiola U.

Clinical and therapeutic approach to patients with orthognathodontic surgical

problems combined with cranio-cervical-mandibular dysfunction.

5° Congresso Nazionale del Collegio dei Docenti di Odontoiatria(vol. II);

Odontoiatria Italiana verso il 2000; Rome, Italy, 1998.

96. Garagiola U., Ghiglione V., Marchetti C.

A multidisciplinary approach in patients affected by Ectodermal Dysplasia.

5° Congresso Nazionale del Collegio dei Docenti di Odontoiatria (vol. II);

Odontoiatria Italiana verso il 2000; Rome, Italy, 22nd – 25th April 1998.

97. Garagiola U., Santoro F., Maiorana C., Szabò G., Vìzkelety T.

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Special problems before and after the orthognathic surgery on an acrobat patient.

2nd International Danube Symposium of Cranio-Maxillo-Facial Surgery;

Bratislava, Slovenia, 1997.

98. Ghiglione V., Garagiola U., Ciancio P.

Interdisciplinary treatment orthodontics-implantology in the Ectodermal

Dysplasia patients.

IX International Odontostomatologic Congress; Monte Carlo, Principality of

Monaco, 1997.

99. Garagiola U., Ghiglione V., Ciancio P.

Treatment of the vertical dimension in the deep-bite and open-bite cases by

surgical-orthognathic approach.

IX International Odontostomatologic Congress; Monte Carlo, Principality of

Monaco, 1997.

100. Ghiglione V., Garagiola U., Maspero C.

Therapeutic approach in the correction of the vertical dimension in skeletal class

III deep-bite and open-bite.

XIV Congresso SIDO;Venice, Italy, 1997.

101. Garagiola U., Ghiglione V., Nishiyama K.

Neuromuscular evaluation of the surgical-orthodontic diagnosis and treatment of

skeletal open-bite.

13th International Conference on Oral and Maxillofacial Surgery; Kyoto, Japan,

1997.

Int J Oral Maxillofacial Surg 1997:1(26):142. IF: 0.749

102. Garagiola U., Ghiglione V.

Aesthetic and functional improvements in the surgical-orthodontic therapy of

skeletal open bite.

73rd Congress of the European Orthodontic Society; Valencia, Spain, 1997.

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103. Ghiglione V., Garagiola U., Maspero C.

Electromyographic benefits the skeletal Class III Deep-Bite malocclusions after

orthognathic surgery.

97th Congress of the American Association of Orthodontists, Philadelphia, USA,

1997.

104. Garagiola U., Ghiglione V., Ciancio P.

An orthognathodontic-surgical approach in the treatment of the vertical

dimension in skeletal class III Open-Bite.

4th Congresso Nazionale del Collegio dei Docenti di Odontoiatria (vol. II); From

prevention to rehabilitation; Rome, Italy, 1997.

105. Ghiglione V., Garagiola U., Maspero C., Maiorana C.

Aesthetic and functional benefits in orthognatic surgery.

VIII International Odontostomatologic Congress; Monte Carlo, Principality of

Monaco, 1996.

106. Ghiglione V., Garagiola U., Ciancio P.

An orthodontics-implantology interdisciplinary approach with regards to

functional aesthetics.

VIII International Odontostomatologic Congress; Monte Carlo, Principality of

Monaco, 1996.

107. Garagiola U., Ghiglione V.

An interdisciplinary treatment to perfect long term results in implantology: Case

report.

Academy of Osseointegration and the European Association for

Osseointegration; Amsterdam, The Netherlands, 1996.

108. Ghiglione V., Garagiola U., Maiorana C.

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Importance of electromyography and kinesyography in orthognathodontic-

surgical diagnosis and treatment of the skeletal Class III.

3rd Congresso Nazionale del Collegio dei Docenti di Odontoiatria(vol. II); from

Research at the Clinic; Rome, Italy, 1996.

109. Ghiglione V., Garagiola U., Maiorana C.

An orthodontic-implantology interdisciplinary approach.

3rd Congresso Nazionale del Collegio dei Docenti di Odontoiatria(vol. II); from

Research at the Clinic; Rome, Italy, 1996.

110. Santoro F., Ghiglione V., Garagiola U.

An interdisciplinary approach in implantology: Case Report.

83rd FDI Annual World Dental Congress, Hong Kong, 1995.

Int Dental J 1995:45(5):300. IF: 0.713

111. Santoro F., Maiorana C., Garagiola U.

Use of titanium mesh in the therapy of jawbone atrophies.

12th International Conference on Oral and Maxillofacial Surgery; Budapest,

Hungary, 1995.

112. Santoro F., Maiorana C., Garagiola U.

Jaw resorption on and surgical rehabilitation: a necessity for the future.

2th International Conference on Oral and Maxillofacial Surgery; Budapest,

Hungary, 1995.

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13.2 - LIST OF ABSTRACTS NON CONNECTED WITH THE TOPIC

1. Garagiola U.

Elastodonzia: indicazioni ed obiettivi in età precoce.

XIX Congresso Nazionale SIDO; Reggia di Caserta, Italia, 2006.

2. Garagiola U., Ghiglione V., Santoro F.

Orofacial deformities and craniomandibular disorders: combined surgical-

orthodontic approach.

6th International Orthodontics Congress; Paris, France, 2005.

3. Ghiglione V., Garagiola U.

Forensic medicine in Clinical Dentistry

XVI International Odontostomatologic Congress; Monte Carlo, Principality of

Monaco, 2005.

4. Ghiglione V., Garagiola U.

Dentofacial deformities in evolutive patient: Orthopedic-functional treatment.

7° Congresso Nazionale di Medicina Estetica; Milano, Italia, 2005.

5. Garagiola U., Ghiglione V., Santoro F.

Maxillary molar distalization by Pendex appliance.

81st European Orthodontic Society Congress; Amsterdam, The Netherlands,

2005.

6. Garagiola U., Santoro F., Ghiglione V.

Bilateral maxillary molar distalization by Pendex appliance.

105th Congress of the American Association of Orthodontists; San Francisco,

USA, 2005.

7. Ghiglione V., Garagiola U., Santoro F.

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Multidisciplinary Gnathologic treatment of Craniomandibular Disorders

XIX Congresso Nazionale SIDO; Rimini, Italia, 2005.

8. Costantinides F., Migliario M., Garagiola U., Gerloni A., Bodin C.

Studio TAC dell’angolo di overjet immediato.

12° Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Roma, Italia,

2005.

9. Ghiglione V., Garagiola U.

Forensic medicine and odontostomatology: clinical cases.

XVI International Odontostomatologic Congress; Monte Carlo, Principality of

Monaco, 2004.

10. Garagiola U., Ghiglione V.

Mesially tipped molar uprighting in adult: the NiTi-Se steel spring.

XVIII Congresso Nazionale SIDO; Florence, Italy, 2004.

11. Ghiglione V., Garagiola U.

Potential success and risk factors of periodontal tissues in adult othodontics.

XVIII Congresso Nazionale SIDO; Florence, Italy, 2004.

12. Ghiglione V., Garagiola U.

Orthognathodontic aesthetics: psychological motivation and quality of life.

6th Congresso Nazionale di Medicina Estetica; Milan, Italy, 2004.

13. Garagiola U., Ghiglione V., Farronato G.

Appropriate timing of early orthodontic treatment in Class III malocclusion

subjects.

80th European Orthodontic Society Congress; Aarhus, Denmark, 2004.

14. Garagiola U., Ghiglione V., Re E.

Dental and craniofacial anomalies in Silver-Russell Syndrome.

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7th Congress of the European Academy of Paediatric Dentistry; Barcelona,

Spain, 2004.

J Paediatric Dentristry 2004:Sep;5:61.

15. Garagiola U., Mortellaro C., Bello L., Dall’Oca S., Palmeri A.

Benefits and limitations in the use of Wilson’s 3D lingual arch.

11th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Rome, Italy,

2004.

16. Garagiola U., Rocchetti V., Matassa A., Dall’Oca S., Migliario M.

The importance of plaque control in the preparation of the surgical parodontal

patient.

11th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Rome, Italy,

2004.

17. Garagiola U., Rocchetti V., Carcieri P., Dall’Oca S., Migliario M.

Protocol for the maintenance of oral hygiene in the hospitalized patient.

11th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Rome, Italy,

2004.

18. Garagiola U., Loguidice M., Dall’Oca S., Migliario M., Rocchetti V.

Protocol for the maintenance of oral hygiene in the patients suffering from

coagulopathy.

11th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Rome, Italy,

2004.

19. Ghiglione V., Garagiola U.

The role of neuromuscular gnathology in the quality of life of dysfunctional

patients.

5th Congresso Nazionale di Medicina Estetica; Milan, Italy, 2003.

20. Garagiola U., Ghiglione V., Farronato G.

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Orthodontic aesthetics: motivation and life quality in adult patients.

XVII Convegno Nazionale SIDO; Rimini, Italy, 2003.

21. Garagiola U., Foglio Bonda P.L., Pregarz M., Bodin C.

Temporo-mandibular joint kinetics and chewing cycles in healthy children. A 6

year follow-up.

91th FDI Annual World Dental Congress; Sydney, Australia, 2003.

22. Garagiola U., Bodin C., Pregarz M., Foglio Bonda P.L.

Clinical and radiological study of the temporomandibular osteonecrosis in 50

patients.

91th FDI Annual World Dental Congress; Sydney, Australia, 2003.

23. Garagiola U., Ghiglione V., Spadari F., Maiorana C.

Nd: YAG laser and biocompatibility in orthodontics.

2nd Congress of the European Society for Oral Laser Applications ESOLA – 2nd

Congresso della Società Italiana di Laser in Odontoiatria SILO; Florence, Italy,

2003.

Quintessenz. Verlags 2003:9.

24. Garagiola U., Ghiglione V.

Interdisciplinary parodontology-orthognathodontics synergy: the relationship

between dental movement and parodontal health.

XIV International Odontostomatologic Congress; Monte Carlo, Principality of

Monaco, 2002.

25. Ghiglione V., Garagiola U.

Neuromuscular evaluation of craniomandibular disorders in orthodontics:

diagnosis and therapy.

XIV International Odontostomatologic Congress; Monte Carlo, Principality of

Monaco, 2002.

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26. Ghiglione V., Garagiola U.

Aesthetic and neuromuscular evaluation in the three-dimensional diagnostic and

therapeutic protocol of deformities.

4th Congresso Nazionale di Medicina Estetica; Milan, Italy, 2002.

27. Garagiola U., Ghiglione V., Nishiyama K.

Stability and relapse of orofacial deformities after orthognathic surgery.

102nd Congress of the American Association of Orthodontists, Philadelphia,

USA, 2002.

28. Ghiglione V., Maspero C., Garagiola U.

Comparison between two different activators in skeletal class II therapy.

102nd Congress of the American Association of Orthodontists, Philadelphia,

USA, 2002.

29. Maspero C., Biffi S., Garagiola U., Ghiglione V.

Therapeutic effects of Air Rotor Stripping: a clinical case.

9th Congresso Nazionale del Collegio dei Docenti; Rome, Italy, 2002.

30. Maspero C., Santoro E., Garagiola U., Ghiglione V.

Facial mask in combination with a bonded expander: a clinical case.

9th Congresso Nazionale del Collegio dei Docenti; Rome, Italy, 2002.

31. Ghiglione V., Garagiola U., Maspero C., Bellintani C.

Early treatment and prevention of skeletal deformities.

9th Congresso Nazionale del Collegio dei Docenti; Rome, Italy, 2002.

32. Garagiola U., Alicino C., Maspero C., Ghiglione V.

The Pendex in the treatment of Class II without the need for collaboration.

9th Congresso Nazionale del Collegio dei Docenti; Rome, Italy, 2002.

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33. Bellintani C., Gazzola F., Cressoni P., Farronato G., Garagiola U.

Juvenile idiopathic arthritis, stomatognathic interest: a clinical-diagnostic

protocol.

9th Congresso Nazionale del Collegio dei Docenti; Rome, Italy, 2002.

34. Ghiglione V., Maspero C., Garagiola U., Paini L.

Aesthetic reasons for orthodontic treatment in children and adolescents.

XIII International Odontostomatologic Congress; Monte-Carlo, Principality of

Monaco, 2001.

35. Garagiola U., Gualano M.G., Re E., Ghiglione V.

Parodontal limits, risks and benefits connected with orthodontic movement of

the teeth.

XVI Congresso Nazionale SIDO; Genoa, Italy, 2001.

36. Maspero C., Santoro E., Garagiola U., Ghiglione V.

Diagnosis and treatment in a case of a cyst caused by mandibular eruption.

XVI Congresso Nazionale SIDO; Genoa, Italy, 2001.

37. Ghiglione V., Garagiola U., Cressoni P., Bellintani C.

Aesthetic orthognathodontics: static and dynamic analyses of the soft and hard

tissues of the face.

3rd Congresso Nazionale di Medicina Estetica; Milan, Italy, 2001.

38. Bellintani C., Ghiglione V., Gazzola F., Garagiola U.

Functional orthodontics and correction of facial beauty problems.

3rd Congresso Nazionale di Medicina Estetica; Milan, Italy, 2001.

39. Garagiola U., Ghiglione V., Nishiyama K.

Periodontal benefits, limitations and risks during orthodontic therapy.

89th FDI Annual World Dental Congress, Kuala Lumpur, Malaysia, 2001.

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Int Dental J 2001: Oct; 51 (5):368. IF: 0.713

40. Garagiola U., Ghiglione V., Nishiyama K.

Relationship between orthodontic tooth movement and periodontal problems.

77th Congress of the European Orthodontic Society; Ghent, Belgium, 2001.

41. Maspero C., Garagiola U., Ghiglione V.

Diagnosis and therapy of eruption cysts. A case report.

77th Congress of the European Orthodontic Society; Ghent, Belgium, 2001.

42. Ghiglione V., Garagiola U., Nishiyama K.

Nd:YAG laser welding for orthodontic appliances: biocompatibility and

corrosion.

77th Congress of the European Orthodontic Society; Ghent, Belgium, 2001.

43. Ghiglione V., Maspero C., Garagiola U.

Effects of the protraction facemask on vertical dimension – a cephalometric

study.

77th Congress of the European Orthodontic Society; Ghent, Belgium, 2001.

Eur J Orthod 2001:23(5).608. IF: 0.519

44. Garagiola U., Santoro E., Bellucci G., Ghiglione V.

The periodontal tissue in the adult orthognathodontic patient.

8th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Rome, Italy,

2001.

45. Garagiola U., Santoro E., Cressoni P., Ghiglione V.

Uprighting of mesioinclined molars using the NiTi-SE steel spring.

8th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Rome, Italy,

2001.

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46. Ghiglione V., Garagiola U., Maspero C., Vedani L.

Biocompatibility and electrochemical corrosion of orthodontic materials: the

Nd:YAG laser.

8th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Rome, Italy,

2001.

47. Ghiglione V., Bardare M., Bellintani C., Garagiola U.

Chronic juvenile arthritis: stomatological point of view.

8th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Rome, Italy,

2001.

48. Bellintani C., Ghiglione V., Garagiola U., Cressoni P.

Orthodontic treatment of dysgnathia.

XXXVII Congresso Nazionale della Società di Reumatologia; Milan, Italy,

2000.

49. Bellintani C., Ghiglione V., Garagiola U., Cressoni P.

Progenism and facial aesthetics: interceptive orthodontics.

2nd Congresso Nazionale di Medicina Estetica; Milan, Italy, 2000.

50. Garagiola U., Ghiglione V., Bellintani C.

Dento-facial aesthetics as a reason for adolescent orthodontic treatment.

2nd Congresso Nazionale di Medicina Estetica; Milan, Italy, 2000.

51. Garagiola U., Ghiglione V., Maspero C.

Periodontal considerations in adult orthodontic treatment.

XII International Odontostomatologic Congress; Monte-Carlo, Principality of

Monaco, 2000.

52. Ghiglione V., Maspero C., Garagiola U.

The periodontal tissue in mixed dentition.

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XII International Odontostomatologic Congress; Monte-Carlo, Principality of

Monaco, 2000.

53. Ghiglione V., Bellintani C., Garagiola U.

Prevention and treatment of juvenile rheumatoid arthritis.

5th Congress of the European Academy of Paediatric Dentistry; Bergen,

Norway, 2000.

Eur J Paediatric Dentistry 2000:32.

54. Garagiola U., Maspero C., Ghiglione V.

Orofacial developmental disturbancies and vertical dimension: interceptive

approach.

5th Congress of the European Academy of Paediatric Dentistry; Bergen, Norway,

2000.

55. Garagiola U., Maspero C., Ghiglione V.

The Pendulum appliance in class II therapy.

5th Congress of the European Academy of Paediatric Dentistry; Bergen, Norway,

2000.

56. Garagiola U., Ghiglione V., Ruspa A.

Contributing factors to relapse after surgical correction of skeletal open-bite.

88th FDI Annual World Dental Congress, Paris, France, 2000.

Int Dental J 2000:50(6):334. IF: 0.419

57. Garagiola U., Maspero C., Ghiglione V.

Skeletal Class II therapy – Effects of Bionator and Teuscher appliances.

76th Congress of the European Orthodontic Society, Crete; Greece, 2000.

58. Maspero C., Garagiola U., Ghiglione V.

Protraction facemask reponse with banded and bonded appliances.

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76th Congress of the European Orthodontic Society; Crete, Greece, 2000.

59. Maspero C., Ghiglione V., Garagiola U.

Comparison between the protraction facemask response with banded and bonded

appliances.

100th Congress of the American Association of Orthodontists; Chicago, USA,

2000.

60. Bellintani C., Ghiglione V., Garagiola U., Cressoni P.

Chronic infantile rheumatism: stomatognathic interest.

7th Congresso Nazionale del Collegio dei Docenti di Odontoiatria; Rome, Italy,

2000.

61. Ghiglione V., Garagiola U., Bellintani C.

Dento-facial aesthetic harmony in adult orthognathodontics.

1st Congresso Nazionale di Medicina Estetica; Milan, Italy, 1999.

62. Ghiglione V., Maspero C., Garagiola U., Cressoni P.

Distalization of the upper molars in class IIs by the use of the Pendulum.

XV Congresso SIDO; Rome, Italy, 1999.

63. Bellintani C., Ghiglione V., Garagiola U., Maspero C., Farronato G.

A.T.M: Articular damage in juvenile rheumatoid arthritis: prevention and cure.

X Congresso S.I.O.H.; Rome, Italy, 1999.

64. Garagiola U., Ghiglione V., Maspero C.

Aesthetical considerations in adult orthodontic treatment.

XI International Odontostomatologic Congress; Monte-Carlo, Principality of

Monaco, 1999.

65. Garagiola U., Ghiglione V., Nishiyama K.

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Implantology and periodontal considerations of using NiTi-SE steel uprighting

springs.

87th FDI Annual World Dental Congress; Mexico City, Mexico, 1999.

Int Dental J 1999:Oct;49(5):282. IF: 0.713

66. Ghiglione V., Garagiola U., Maspero C.

Interceptive orthodontic treatment of serious skeletal discrepancies.

XI International Odontostomatologic Congress; Monte-Carlo, Principality of

Monaco, 1999.

67. Ghiglione V., Maspero C., Garagiola U.

The pendulum appliance in class II therapy.

75th Congress of the European Orthodontic Society; Strasburg, France, 1999.

Eur J Orthod 1999:Aug;21(4):440. IF: 0.607

68. Garagiola U., Ghiglione V., Fukai M.

Craniomandibular disorders: treatment planning using the electromyograph and

kinesyograph.

75th Congress of the European Orthodontic Society, Strasburg, France 1999.

Eur J Orthod 1999:Oct ;21(5):586. IF: 0.607

69. Ghiglione V., Maspero C., Garagiola U.

Ultrasound bone measurement in orthodontic patients with congenitally missing

teeth.

75th Congress of the European Orthodontic Society; Strasburg, France, 1999.

Eur J Orthod 1999:Oct;21(5):588. IF: 0.607

70. Maspero C., Garagiola U., Ghiglione V.

Ultrasound bone measurement in orthodontic patients with osteopenic

pathologies.

75th Congress of the European Orthodontic Society; Strasburg, France, 1999.

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Eur J Orthod 1999:Oct;21(5):604. IF: 0.607

71. Ghiglione V., Garagiola U., Maspero C.

NiTi-SE Steel uprighting springs vs other molar uprighting devices.

99th Congress of the American Association of Orthodontists, San Diego, USA,

1999.

72. Ghiglione V., Garagiola U., Bellintani C.

Interceptive orthodontics through the use of Frankel’s function regulator.

6th Congresso Nazionale del Collegio dei Docenti di Odontoiatria; Roma, Italy,

1999.

73. Ghiglione V., Maspero C., Garagiola U.

The role of stabilometry in orthognathodontic diagnosis and therapy.

6th Congresso Nazionale del Collegio dei Docenti di Odontoiatria; Roma, 1999.

74. Maspero C., Ghiglione V., Garagiola U.

The ultrasound densitometer for the diagnostic monitoring of bone tissue in

orthognathodontics.

XV Convegno Nazionale S.I.D.O., Florence, Italy, 1998.

75. Ghiglione V., Garagiola U., Marchetti C.

The contribution of electromyography and kinesiography to the diagnosis of

temporomandibular disorders.

86th FDI Annual World Dental Congress; Barcelona, Spain, 1998.

Int Dental J 1998: Oct;48(5):425. . IF: 0.713

76. Ghiglione V., Maspero C., Garagiola U.

Three-dimensional approach to orthodontic patients with temporomandibular

disorders.

74th Congress of the European Orthodontic Society; Mainz, Germany. 1998.

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77. Maspero C., Ghiglione V., Garagiola U.

Activation of mandibular growth with the Teuscher appliance. Cephalometric

study of the structural variations in patients with class II malocclusions.

XIV Congresso SIDO, Venice, Italy, 1997.

78. Ghiglione V., Garagiola U., Nishiyama K.

Dentofacial orthopaedic treatment with Teuscher appliance of significant

skeletal discrepancies in children.

FDI Annual World Dental Congress, Seoul, 1997.

Int Dental J 1997: Aug;47:(4):234.

79. Ghiglione V., Maspero C., Garagiola U.

Therapeutic approaches for dental-skeletal and muscular benefits in Class III

patients with skeletal deep bites.

73rd Congress of the European Orthodontic Society; Valencia, Spain, 1997.

80. Garagiola U., Ghiglione V.

An interdisciplinary treatment to perfect long-term results in orthodontics.

97th Congress of the American Association of Orthodontists, Philadelphia, USA,

1997.

81. Ghiglione V., Garagiola U., Maspero C.

Restoration of the skeletal vertical dimension: therapeutic protocol in Deep-Bite

cases.

4th Congresso Nazionale del Collegio dei Docenti di Odontoiatria, Rome, Italy,

1997.

82. Maspero C., Ghiglione V., Garagiola U.

Orthopaedic treatment with Ginevra type monoblock. Cephalometric study of

structural variations in patients with class II malocclusions.

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4th Congresso Nazionale del Collegio dei Docenti di Odontoiatria Rome, Italy,

1997.

83. Ghiglione V., Garagiola U., Ciancio P.

A multisciplinary treatment to perfect long term results in orthodontics.

84th FDI Annual World Dental Congress; Orlando, USA, 1996.

Int Dental J 1996:Oct;46(5):459. IF: 0.713

84. Ghiglione V., Garagiola U., Ciancio P.

Neuromuscular Aids to treatment planning of open-bite skeletal Class III

malocclusion.

84th FDI Annual World Dental Congress; Orlando, USA, 1996.

Int Dental J 1996:Oct;46(5):459. . IF: 0.713

85. Ghiglione V., Garagiola U., Ciancio P.

The Bionator in the control of the anterior and posterior vertical dimension in

interceptive orthodontics: presentation of a clinical case.

XIV Congresso Nazionale SIDO; Venice, Italy, 1996.

86. Ghiglione V., Maspero C., Garagiola U.

Control of the anterior-posterior vertical dimension with mixed treatment

(monoblock, Ginevra type). Long term follow-up. Presentation of a clinical case.

XIV Congresso Nazionale SIDO; Venice, Italy, 1996.

87. Ghiglione V., Garagiola U., Maspero C.

Importance of the electromyography for the diagnosis and treatment planning in

interceptive orthodontics.

3rd Congress of the European Academy of Paediatric Dentistry; Bruges,

Belgium, 1996.

Eur J Paediatric Dentistry 1996:71.

88. Ghiglione V., Garagiola U., Ciancio P.

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Functional orthopaedics with Teuscher appliance in early treatment of skeletal

Class II malocclusion.

3rd Congress of the European Academy of Paediatric Dentistry; Bruges,

Belgium, 1996.

Eur J Paediatric Dentistry 1996:72.

89. Ghiglione V., Garagiola U., Ciancio P.

The importance of an interdisciplinary approach for the optimization of long

term results in orthodontics.

XIII Convegno Nazionale SIDO; Genoa, Italy, 1995.

90. Ghiglione V., Garagiola U., Restelli L.

Role of interceptive therapy in the long term stability of orthodontic results.

XIII Convegno Nazionale SIDO; Genoa, Italy, 1995.

91. Ghiglione V., Garagiola U., Mori P.

Role of the neuromuscolar system in orthodontic diagnosis and treatment.

2th Congresso Nazionale del Collegio dei Docenti di Odontoiatria; IX Congress

SIOI; Rome, Italy, 1995.

92. Garagiola U., Ghiglione V., Nishiyama K.

Different approaches in the treatment of skeletal deep-bite and open-bite

malocclusions.

85 FDI Annual World Dental Congress, Seoul, 1997.

Int Dental J 1997:Aug;47(4):234. . IF: 0.713

93. Ghiglione V., Garagiola U., Maspero C.

Electromyographic benefits in early treatment of posterior Cross Bite.

XIII Convegno Nazionale SIDO; Florence, Italy, 1994.

94. Ghiglione V., Maspero C., Maiorana C., Garagiola U.

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Importance of bionator II for the atypic deglutition and muscular activity

2nd Congress of the European Academy of Paediatric Dentistry; Athens, Greece,

1994.

Eur J Paediatric Dentistry 1994:31.

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14. - ACKNOWLEDGMENTS

I would like to thank Professor Gyorgy Szabò and Professor Franco Santoro my heads,

teachers and mentors both of the profession and of the life, that allowed to constitute the

international twinship between Semmelweis and Milan University and perform PhD

studies.

I would also like to acknowledge Professor Jozsef Barabás that helped me to complete

my PhD Programme and Professor Zsuzsanna Suba for the valuable histological

material.

Furthermore, I wish to thank Professor Carlo Maiorana and Professor Attila Fodor for

their precious guidance and great friendship, that inspirated the University twinship and

afterward my PhD studies.

Thanks to my fabulous staff whose hard work and dedication given to me the

cooperation and time needed to write my PhD Thesis.

My sincerest appreciation to Dani for her invaluable help, support and patience for my

professional career.