bios graft

Histomorphometric analysis ofextraction sockets augmented withBio-Oss Collagen after a 6-weekhealing period: A prospective study

Susanne HebererBassem Al-ChawafDetlef HildebrandJohn J. NelsonKatja Nelson

Authors’ affiliations:Susanne Heberer, Bassem Al-Chawaf, KatjaNelson, Clinic for Oral and Maxillofacial Surgery,Clinical Navigation and Robotics, Charite-CampusVirchow Clinic, Berlin, GermanyJohn J. Nelson, Department of Pathology,University of South Alabama, Mobile, AL, USA.Detlef Hildebrand, Private Practice, Berlin,Germany

Correspondence to:Katja NelsonClinic for Oral and Maxillofacial SurgeryCharite-Campus Virchow ClinicAugustenburger Platz 1, 13353 Berlin, GermanyTel.: þ 49 30 4 50 55 50 22Fax: þ 49 30 4 50 55 59 01e-mail: [email protected]

Key words: analysis, biomaterials, clinical research, morphometric, socket preservation,

tissue physiology, wound healing

For a predictable esthetic outcome of

implant-retained restoration after tooth

removal, the biology of the healing of ex-

traction sockets needs to be considered

(Quirynen et al. 2007). Based on a number

of studies including human and animal

experiments, it is known that there are a

series of events involved in the process

of healing, such as: (1) formation and

maturation of blood clot, (2) infiltration of

immature mesenchymal cells, and (3) es-

tablishment of a provisional matrix from

which bone formation results (Amler 1969;

Cardaropoli et al. 2003; Araujo & Lindhe

2005). The various stages of the process of

healing in mandibular extraction sockets of

canines show an initial phase with a boost

of bone formation within the first 30 days

and a subsequent resorption of this newly

formed bone to about 15% of the initial

amount and gradual replacement by the

bone marrow (Cardaropoli et al. 2003).

After the removal of teeth, ridge alterations

in width and height occur based on resorp-

tive processes of the newly formed bone

within the socket and also of the original

bone in canine models (Cardaropoli et al.

2003; Araujo & Lindhe 2005) and humans

(Atwood 1963; Winkler 2002; Schropp

et al. 2003b). The increased reduction

in width can be approximately 50% of

the original dimension after 12 months

(Schropp et al. 2003a, 2003b) based on a

pronounced resorption of the buccal

wall (Araujo & Lindhe 2005). Immediate

implant placement, originally thought to

prevent this resorption, shows no evident

decrease of the resorption rate or pattern in

clinical studies or animal experiments

(Schropp et al. 2003a, 2003b; Botticelli

et al. 2004; Covani et al. 2004; Araujo &

Lindhe 2005). Several studies have pro-

posed the use of heterologous graft material

such as hydroxyapatite, b-Tri-calcium

phosphate, polylactide sponge, and depro-

teinized bovine bone mineral as a ridge-

preservation technique during bone healing

(Carmagnola et al. 2003; Serino et al. 2003;

Luczyszyn et al. 2005; Rothamel et al.

2007). Bovine bone mineral displays osteo-

conducive properties forming an effective

bone/graft matrix when used in defect

regeneration, sinus floor elevation, and

repair of periodontal defects for the place-

ment of implants (Nemcovsky et al. 2002;

Norton et al. 2003; Esposito et al. 2006).

The efficiency of a heterologous bone sub-

stitute placed in extraction sockets has

been evaluated in experimental and clinical

studies regarding bone formation and the

substitute’s influence on the resorption

pattern (Artzi et al. 2000; Carmagnola

et al. 2003; Fugazzotto 2003, 2005; Serino

et al. 2003) and in defect sites with Bio-Oss

Collagen (Cardaropoli et al. 2005). The

healing period in all the previous studies

Date:Accepted 3 May 2008

To cite this article:Heberer S, Al-Chawaf B, Hildebrand D, Nelson JJ,Nelson K. Histomorphometric analysis of extractionsockets augmented with Bio-Oss Collagen after a6-week healing period: A prospective study. Clin. OralImpl. Res. 19, 2008; 1219–1225doi: 10.1111/j.1600-0501.2008.01617.x

c� 2008 The Authors. Journal compilation c� 2008 Blackwell Munksgaard 1219

mentioned encompassed three or more

months before histomorphometric evalua-

tion was performed that revealed sufficient

bone formation rates of up to 80%.

Limited information is available on

the rate of bone formation in extraction

sockets of humans filled with Bio-Oss

spongiosa granules (a bovine bone substi-

tute) with the addition of 10% highly

purified porcine collagen (Bio-Oss Col-

lagens

) after shortened healing periods of

less than 3 months. The aim of the present

study was to assess the amount of new

bone formation in the human extraction

socket after 6 weeks as well as the amount

and mode of incorporation of Bio-Oss par-

ticles at this time point.

Material and methods

The study protocol was approved by the

Ethics Committee of the Charite Univer-

sity Medicine in Berlin, Germany.

Patients and surgical procedure

Sixteen patients (10 females and 6 males)

with a mean age 50.5 years (ranging from

28 to 69 years) participated in this prospec-

tive study. The patients were referred for

the removal of teeth for endodontic rea-

sons. Teeth with evident periapical radi-

olucency and/or periapical abscess were

excluded from this study. Patients with a

severe periodontitis or active periodontal

lesions as well as severely resorbed sockets

with a remaining height o5 mm were not

included. All patients were healthy, not

having any systemic disease or taking reg-

ular medications. A subsequent implant

procedure was planned for all of the extrac-

tion sites. The extraction procedure was

performed under local anesthesia without

the elevation of a mucoperiosteal flap;

therefore, no primary wound closure was

performed. Meticulous care was taken to

avoid surgical trauma of the surrounding

tissue by using a periotome and the appro-

priate dental forceps. For consideration in

the study, all extraction sockets had to

be intact (4-wall), with no alveolar wall

loss. A thorough curettage of all soft tissue

debris in the alveolus was performed to

ensure the removal of all granulation tissue

and to stimulate bleeding from the osseous

base. Thereafter, Bio-Oss Collagens

(Geis-

tlich Pharma AG, Wohlhusen, Switzer-

land) was applied, not exceeding the

height of the alveolar crest, into the extrac-

tion site without pressure and care was

taken to ensure that the collagen was

saturated with blood. The Bio-Oss Col-

lagens

was cut to the appropriate dimen-

sion of the alveolar socket to enable

uncondensed placement with a dental for-

ceps (Aesculap AG & Co KG, Tuttlingen,

Germany). The patients were clinically

evaluated at days 1, 7, and 30 post-

operatively for the assessment of complica-

tions such as inflammation, mucosal

erythema, wound dehiscences, or loss of

graft material.

At the time of implant placement, 6

weeks post-operatively, a mucoperiosteal

flap was raised, the site of extraction was

clearly identified, and a core biopsy was

taken from the center of the extraction site

with a minimum depth of 8 mm. For this,

a trephine bur (+ 2 mm) (Straumann AG,

Basel, Switzerland) was used for the retrie-

val of the bone biopsy for histologic evalua-

tion, followed by dental implant placement

according to the manufacturer’s surgical

protocol. For implant placement, Camlog

RootLine implants (Camlog Biotechnolo-

gies, Wimsheim, Germany) or Straumann

ITI (Straumann AG, Basel, Switzerland)

implants were utilized. The mucoperios-

teal flaps were closed with interrupted

sutures (5-0 Monocryl, Ethicon, Hamburg,

Germany).

Histological evaluation

Before histological preparation, the tissue

samples were marked with blue ink

(Marker II/Superfrost, Precision Dynamics

Corp., San Fernando, CA, USA) at the

coronal side to identify the coronal and

apical region. Bone biopsy specimens

(length 8–10 mm) obtained from the

grafted areas were fixed in 4% formalin

for 2 days and then decalcified in 17%

nitric acid for 12 h (Callis 2002). After

routine tissue processing in a Pathcenter

(Thermo Shandon, Frankfurt a.M.,

Germany), tissues were embedded in par-

affin and 5mm thick serial sections were

prepared and stained with Hematoxylin–

Eosin and Masson’s trichrome. The two

most central sections were obtained from

each specimen. The sections were line-

scanned using ScanScope T3 (Aperio Tech-

nologies Inc., Vista, USA) with a resolution

of 0.25mm/Pixel and a � 40 objective. For

the qualitative analysis of the remodeling

process, the stained preparations were

examined under a light microscope (Axio-

Phot I) at a magnification of up to � 40.

Two regions of interest (ROI) were deter-

mined within each specimen, located

within the same proximity within the

specimens, in the apical and the coronal

portion. Each ROI was subdivided into four

regions in which the amount of new bone

and Bio-Oss particles as well as fibrous

tissue or bone marrow was calculated by

a single experienced observer who was

blinded to the clinical data using the digital

imaging system AXIO VISION 4.6 (Zeiss,

Jena, Germany). The intra-observer relia-

bility of the histomorphometric measure-

ments was based on recording the blindly

assessed data of each slide at three different

time points. A stage micrometer 25þ50/

10 mm (Zeiss, Gottingen, Germany) was

placed diagonally across the image for

calibration before histologic evaluation.

The relative volumes of provisional matrix

(connective tissue including mesenchymal

cells embedded in a fibrous matrix), viable

bone, and bone marrow (fibroadipose tis-

sue) were calculated in every section at

� 40 magnification. Viable bone (new

bone) was defined as, the presence of

mineralized tissue matrix containing osteo-

cytes within lacunae. Descriptive histolo-

gic appearance of the total specimens was

assessed.

Statistics

The intraclass correlation coefficient (ICC)

was used to determine the intra-observer

reliability (SPSS 13.0, SPSS Inc., Chicago,

IL, USA). The histological and histomor-

phometrical data were descriptively ana-

lyzed. Comparative statistical analysis

between the apical and coronal region of

the specimens was performed using the

Wilcoxon signed-rank test with the soft-

ware version SPSS 13.0 (SPSS Inc.).

Results

For all patients (n¼ 16) with 18 extraction

sites, the time of implant placement was

6 weeks after the grafting procedure. All

extraction sites, except one, healed un-

eventfully and showed no signs of inflam-

mation. In one patient, one surgical site

infection after the extraction and grafting

Heberer et al . Bio-Oss Collagen augmented extraction sockets at 6 weeks

1220 | Clin. Oral Impl. Res. 19, 2008 / 1219–1225 c� 2008 The Authors. Journal compilation c� 2008 Blackwell Munksgaard

procedure occurred and a re-entry was

performed to remove all material from the

socket. This site was excluded from further

analysis. The distribution of the sites

within the jaw is given in Table 1. Of the

17 sites, 12 were located in the molar

region of the maxilla and two in the molar

region of the mandible. Two sites were

located in the premolar region and one in

the anterior of the maxilla. The clinical

appearance of the augmented area showed

soft tissue closure after 40 days in all cases.

Seventeen implants were placed in 16

patients, respectively, in 17 sites.

After elevation of the mucoperiosteal

flap before implant placement, all extrac-

tion sites were clearly differentiable from

the original alveolar crest, allowing the

retrieval of samples from the center of the

extraction socket. A total of 17 surgical

sites were quantitatively analyzed in 16

patients. The ICC determined for the in-

tra-observer reliability trial of the histo-

morphometric technique used for this

study was 0.889, with a 95% CI of

0.721–0.974, indicating an excellent relia-

bility of the measurements. All specimens

were free of inflammatory cells, except

one; this specimen showed a focal lympho-

cytic inflammatory infiltrate in the coronal

region with bone formation adjacent to the

area. The mean overall new bone forma-

tion was 28% (range 9–57%) while the

amount of Bio-Oss remnants was 11%

(range 3–31%). Connective tissues consist-

ing of collagen and fibroblasts were present

in the grafted sites, comprising 54% (range

31–77%) of tissue. Table 1 summarizes the

histologic and morphometric evaluation.

The specimens collected from the molar

region (n¼ 12) showed a mean of 30% of

newly formed bone (range 11–57%), 15%

(range 3–31%) of Bio-Oss particles, and

56% (range 33–77%) of connective tissue.

The Bio-Oss Collagen-grafted areas in the

molar region (n¼ 2) of the mandibula dis-

played 19% and 33% of newly formed

bone and 23% and 13% of Bio-Oss rem-

nants in the biopsies obtained from these

regions, respectively. In three specimens of

the maxilla, the connective tissue com-

prised fibroadipose tissue (Fig. 1); in these

biopsies the amount of bone consisting of

lamellar and woven bone (Fig. 2) showed

an average of 47%, varying between 42%

and 49%, whereas the remaining Bio-Oss

particles were estimated at 6%, 18%, and

24%. Four specimens predominantly

showed provisional matrix ranging from

67% to 77%, accompanied by small

amounts of newly formed bone ranging

from 9 to 19% and Bio-Oss particles from

3 to 14% (Figs 3–5). The remaining biop-

sies (n¼ 10) displayed an average of 32%

(14–56%) of new bone formation and 19%

(7–30%) of Bio-Oss remnants as well as

50% (31–64%) of connective tissue (Fig.

6). There was a variation of the amount of

tissues in the apical compared with the

coronal portion of the biopsies. The apical

portion (Fig. 7) of the specimens consisted

of a mean of 40% of new bone formation

within a range of 19–63%. Up to 10% of

remnant Bio-Oss particles were found in

this region, ranging from 3% to 32%, and

the connective tissue consisted of 50% of

the specimen with a range of 19%–78%.

The coronal region (Fig. 8) had a mean of

20% new bone formation (1–53%) and

20% of remaining Bio-Oss particles (1–

55%), with 60% of provisional matrix

(30–91%) visible. The rate of newly formed

bone was significantly different between

the apical and the coronal region

(P¼ 0.002). The amount of connective tis-

sue and Bio-Oss remnants did not show a

significant difference between the apical

and the coronal region within the speci-

mens (P¼ 0.4 and 0.1).

Early phase matrix with red blood cells

and neutrophil granulocytes embedded in a

network of fibrin were not visible in any of

the specimens; rather, a maturing provi-

sional matrix, if it was not yet bone, with

oriented collagen fibers and a developing

vasculature was present.

Discussion

The present histomorphometric investiga-

tion of Bio-Oss Collagen-filled extraction

sockets demonstrates marked de novo bone

formation after a healing period of 6 weeks.

The findings are consistent with early hu-

Table 1. Mean percentage of the tissues found in the histologic specimen with regard tolocalization

Gender Localizationwithin jaw (FDI)

Localizationwithin specimen

Newbone (%)

Bio-Ossparticles (%)

Fibroustissue (%)

M 26 Coronal 37 17 46Apical 53 3 44

F 16 Coronal 27 34 38Apical 38 27 35

F 26 Coronal 26 3 70Apical 28 8 63

27 Coronal 15 3 82Apical 23 4 73


F 37 Coronal 24 11 56Apical 45 14 53




F 46 Coronal 41 10 57Apical 26 16 58

F 16 Coronal 16 17 66Apical 36 12 68

M 16 Coronal 33 36 30Apical 52 11 37


F 15 Coronal 25 25 50Apical 42 10 58



F 16 Coronal 29 28 43Apical 50 32 18


c� 2008 The Authors. Journal compilation c� 2008 Blackwell Munksgaard 1221 | Clin. Oral Impl. Res. 19, 2008 / 1219–1225

man studies showing equivalent time points

for the formation of bone in unfilled extrac-

tion sockets, although these studies did not

document the rate of bone formation as

they did not perform any histomorpho-

metric analysis (Boyne 1966; Amler 1969).

One experimental animal study of ex-

traction sockets in the mandible is avail-

able to give comparable data (Cardaropoli

et al. 2003). Studies in canine models have

shown a bone formation rate of up to 80%

after 30 days, which is equivalent to a

40-day healing period in humans as the

physiologic bone turn-over in dogs is 1.5 �that of humans (Cardaropoli et al. 2003;

Pearce et al. 2007). The average bone for-

mation rate found in the specimens ob-

tained within the current investigation is

lower than that found in the extraction

sockets in the mandible of dogs in the

previous studies mentioned. In 20% of

the defects evaluated, over 40% of mature

lamellar bone with the bone marrow was

seen, suggesting an advanced stage of

remodeling, whereas only two sockets

showed a bone formation rate o10% sur-

rounded by a mature provisional matrix

with the onset of bone formation. In the

study performed on dogs, two defect sites

were evaluated for each time point (1, 3, 7,

14, 30, 60, 90, 120, and 180 days) and the

specimens retrieved at 30 days showed a

high rate of bone formation; thus, these

might represent the extraction sites with a

high bone formation rate. The considerable

variation in bone formation within the

sockets evaluated cannot be elucidated

within this study and might be due to a

difference in individual factors influencing

bone physiology. Nicotine, known to be an

inhibitor of osteogenesis, can be excluded

as none of the patients smoked (Rosen

et al. 1996; Glowacki et al. 2008; Ziran

et al. 2007).

The biopsies obtained within this study

demonstrate a partial area of the healing

socket, allowing the assessment of the

healing process of the apical and coronal

region. Whether bone formation was also

initialized from the sides of the socket

cannot be determined from the data of

this study. The marginal entrance has

been described to show a hard tissue bridge

in studies with primary wound closure

(Cardaropoli et al. 2005). The specimens

analyzed showed low bone formation in

the most coronal region, in concordance

to the results found in other studies in

which surgical soft tissue closure was

not performed (Boyne 1966; Amler 1969;

Cardaropoli et al. 2003). This might be

attributed to the fact that the periosteum

could not contribute to the formation of

the provisional matrix. In this study, the

extraction sockets filled with the Bio-Oss

Collagen were left to heal openly and

wound closure was achieved by gradual

lateral epithelial overgrowth. Epithelial in-

vagination or proliferation into the extrac-

tion socket was described in unfilled

extraction sockets in humans with an in-

complete wound closure after 21 days and a

not yet complete fusion of the touching

adjacent epithelium after 32 days (Amler

1969). Experimental animal studies sug-

gest that the degree of invagination with

Bio-Oss Collagen-filled mandibular defects

seems to be decreased in comparison

with unfilled defects, suggesting a

placeholder or a scaffolding function for

the epithelialization by the heterologous

material (Cardaropoli et al. 2005). In this

study, after 40 days, wound closure was

seen in all patients with varying degrees of

thickness of the overlying mucosa. A quan-

tification of the thickness and the degree of

invagination of the epithelium cannot be

concluded from this study, as it was not

evaluated.

Therefore, the bone formation could

only be initiated from the apical or lateral

regions of the extraction socket. As evi-

denced in the study by Amler (1969), the

bone formation is seen first in the apical

region of the socket. The provisional ma-

trix was predominant in the coronal region

and Bio-Oss remnants embedded in it,

without signs of acute inflammation.

Bone formation in the human socket has

been described to take place as early as

9–10 days (Boyne 1966; Amler 1969) after

the extraction, with at least two-thirds of

the socket filled with trabeculae after 38

Fig. 1. Hematoxylin and Eosin Staining of a speci-

men with 440% of new bone formation and mature

bone marrow without hematopoetic elements (mag-

nification � 2).

Fig. 2. Bio-Oss particle (arrows) surrounded by mature lamellar bone and woven bone (Hematoxylin and

Eosin � 40).



days. The study by Amler (1969) does not

describe the surgical procedure or the loca-

tion of the extraction sites analyzed, but it

can be concluded that no primary tissue

closure was performed in their study as the

fusion of the epithelium is discussed with

regard to the observation period.

The successful formation of bone in

extraction sockets in rodents has been

correlated to the existence of cells from

the periodontal ligament (PDL), whereas

studies in canines and rodents have not

shown any correlation (Lin et al. 1994;

Cardaropoli et al. 2005). In this study, all

PDL was removed from the extraction

sockets as they were instrumented thor-

oughly after root removal, minimizing the

importance of the PDL for the formation of

bone in human extraction sockets.

Human extraction sockets filled with

bovine bone mineral investigated after a

healing period of 3 months show only

slightly higher rates of bone compared

with this study with a 6-week healing

period (Artzi et al. 2000). Existing animal

studies suggest that there might be a boost

of bone formation within the first few

weeks after extraction and that after a

prolonged period of missing mechanical

load there is onset of resorption. The pro-

cess of osseointegration is known to en-

hance bone density by stimulation of the

remodeling process, which has been de-

scribed as the regional acceleratory phe-

nomenon (RAP) (Frost 1994). Therefore,

it is necessary to acquire data of human

extraction sockets over various time points

to determine the optimal time point for the

placement of implants.

The degree of compression with which

the Bio-Oss Collagen was applied may be

crucial for the amount of Bio-Oss particles

within a defined space and therefore for the

rate of osteogenesis. There was no primary

wound closure after the uncompressed ap-

plication of the Bio-Oss Collagen, allowing

a possible displacement of the Bio-Oss

particles from the extraction socket and

accounting for the low amount of Bio-Oss

remnants found in this study. A higher

amount of Bio-Oss remnants were found

in defects filled with Bio-Oss Collagen in a

canine study with primary wound closure

(Cardaropoli et al. 2005) as well as in hu-

man extraction sockets filled with bovine

bone mineral (Artzi et al. 2000) after 3 and

9 months of healing, respectively.

The bone formation rate in the extraction

socket found after only 6 weeks is high

when compared with augmentation proce-

dures with bovine bone mineral in the sinus.

This might be due to the fact that there is a

more favourable blood supply as the sur-

rounding walls are in close proximity, re-

sulting in a smaller distance to the center

(Artzi et al. 2000; Yildirim et al. 2000).

This descriptive study provides data

showing that the bone formation in human

extraction sockets filled with Bio-Oss Col-

lagens

displays a variation in their histolo-

gic appearance after a healing period of 6

weeks. This study demonstrates sockets

presenting bone formation rates similar to

those found after a 3-month healing period

as well as sites predominantly presenting

mature provisional matrix, which is

known to precede the formation of bone,

whereas no sites were found to show gran-

Fig. 3. Biopsy predominantly displaying provisional

matrix. Bio-Oss remnants are visible in the coronal

region (a) and islands of beginning bone formation

located throughout the central and apical portion (b)

(Toluidine blue stain, � 2).

Fig. 4. Area (a) of Figure 3 in higher magnification ( � 20). Mature, oriented collagen fibers visible with

fibroblasts and beginning bone formation.

Fig. 5. Area (b) of Figure 3 (magnification � 20, Toluidine blue-stain) showing newly woven bone with

osteoblasts and ongoing bone formation embedded in oriented collagen fibers.



ulation tissue with inflammatory cell in-

filtrates. This study does not allow a con-

clusion regarding the osteoconductivity of

Bio-Osss

, but it allows the assumption that

it does not hinder early bone formation.

Bone formation in extraction sockets with

no primary wound closure is initiated from

the apical region as this shows a signifi-

cantly higher rate of new bone formation

compared with the coronal region. Future

studies should focus on different time

points with sockets not augmented with a

heterologous material.

Acknowledgement: All materials

used in this study were purchased

by the Charite University Hospital,

and it is therefore free of any

commercial interest. We would like

to thank Mrs Kruse-Boitschenko

for her technical assistance and

Dipl. Math. G. Siebert for her help

with statistics.

Fig. 6. This histologic picture resembles the appear-

ance of the majority of the specimens obtained from

extraction sockets after a 6-week healing period. It

shows bone formation in the apical region (b) and

mature provisional matrix surrounding Bio-Oss par-

ticles in the coronal region (a) with a minor focus of

lymphocytes at the surface of the specimen (Hema-

toxylin and Eosin, � 2).

Fig. 7. Area (a) of Figure 6 at � 20 magnification. Bone formation around the Bio-Oss remnants next to an

islands of chronic inflammatory cells (lymphocytes) and provisional matrix with a slit-like blood vessel in the

upper left corner.

Fig. 8. Area (b) of Figure 6. Woven bone surrounding and streaking the barely visible Bio-Oss particle (arrows),

with provisional matrix in between (magnification � 40, Hematoxylin and Eosin stain).



References

Amler, M.H. (1969) The time sequence of tissue

regeneration in human extraction wounds. Oral

Surgery Oral Medicine Oral Pathology 27: 309–

318.

Araujo, M.G. & Lindhe, J. (2005) Dimensional ridge

alterations following tooth extraction. An experi-

mental study in the dog. Journal of Clinical

Periodontology 32: 212–218.

Artzi, Z., Tal, H. & Dayan, D. (2000) Porous bovine

bone mineral in healing of human extraction

sockets. Part 1: histomorphometric evaluations

at 9 months. Journal of Periodontology 71: 1015–

1023.

Atwood, D.A. (1963) Postextraction changes in the

adult mandible as illustrated by microradiographs

of midsagittal sections and serial cephalometric

roentgenograms. The Journal of Prosthetic Den-

tistry 13: 810–824.

Botticelli, D., Berglundh, T. & Lindhe, J. (2004)

Hard-tissue alterations following immediate im-

plant placement in extraction sites. Journal of

Clinical Periodontology 31: 820–828.

Boyne, P.J. (1966) Osseous repair of the postextrac-

tion alveolus in man. Oral Surgery Oral Medicine

Oral Pathology 21: 805–813.

Callis, G.M. (2002) Bone. In: Bancroft, J.D. &

Stevens, A., eds. Theory and Practice of Histolo-

gical Techniques. 5th edition, 269–301. New

York: Churchill Livingstone.

Cardaropoli, G., Araujo, M., Hayacibara, R., Suke-

kava, F. & Lindhe, J. (2005) Healing of extraction

sockets and surgically produced – augmented and

non-augmented – defects in the alveolar ridge. An

experimental study in the dog. Journal of Clinical

Periodontology 32: 435–440.

Cardaropoli, G., Araujo, M. & Lindhe, J. (2003)

Dynamics of bone tissue formation in tooth ex-

traction sites. An experimental study in dogs.

Journal of Clinical Periodontology 30: 809–818.

Carmagnola, D., Adriaens, P. & Berglundh, T.

(2003) Healing of human extraction sockets filled

with Bio-Oss. Clinical Oral Implants Research

14: 137–143.

Covani, U., Bortolaia, C., Barone, A. & Sbordone, L.

(2004) Bucco-lingual crestal bone changes after

immediate and delayed implant placement. Jour-

nal of Periodontology 75: 1605–1612.

Esposito, M., Grusovin, M.G., Coulthard, P. &

Worthington, H.V. (2006) The efficacy of various

bone augmentation procedures for dental implants:

a Cochrane systematic review of randomized con-

trolled clinical trials. International Journal of Oral

& Maxillofacial Implants 21: 696–710.

Frost, H.M. (1994) Wolff’s Law and bone’s struc-

tural adaptations to mechanical usage: an over-

view for clinician. The Angle Orthodontist 64:

175–188.

Fugazzotto, P.A. (2003) GBR using bovine bone

matrix and resorbable and nonresorbable mem-

branes. Part 2: clinical results. International Jour-

nal of Periodontics and Restorative Dentistry 23:

599–605.

Fugazzotto, P.A. (2005) Treatment options follow-

ing single-rooted tooth removal: a literature

review and proposed hierarchy of treatment selec-

tion. Journal of Periodontology 76: 821–831.

Glowacki, J., Schulten, A.J., Perrott, D. & Kaban,

L.B. (2008) Nicotine impairs distraction osteogen-

esis in the rat mandible. International Journal of

Oral and Maxillofacial Surgery 37: 156–161.

Lin, W.L., McCulloch, C.A. & Cho, M.I. (1994)

Differentiation of periodontal ligament fibroblasts

into osteoblasts during socket healing after tooth

extraction in the rat. Anatomical Records 240:

492–506.

Luczyszyn, S.M., Papalexiou, V., Novaes, A.B. Jr.,

Grisi, M.F., Souza, S.L. & Taba, M. Jr (2005)

Acellular dermal matrix and hydroxyapatite in

prevention of ridge deformities after tooth extrac-

tion. Implant Dentistry 14: 176–184.

Nemcovsky, C.E., Artzi, Z., Moses, O. & Gelern-

ter, I. (2002) Healing of marginal defects at im-

plants placed in fresh extraction sockets or after

4–6 weeks of healing. A comparative study. Clin-

ical Oral Implants Research 13: 410–419.

Norton, M.R., Odell, E.W., Thompson, I.D. &

Cook, R.J. (2003) Efficacy of bovine bone mineral

for alveolar augmentation: a human histologic

study. Clinical Oral Implants Research 14:

775–783.

Pearce, A.I., Richards, R.G., Milz, S., Schneider, E.

& Pearce, S.G. (2007) Animal models for implant

biomaterial research in bone: a review. European

Cell Materials 13: 1–10.

Quirynen, M., Van Assche, N., Botticelli, D. &

Berglundh, T. (2007) How does the timing of

implant placement to extraction affect outcome?

International Journal of Oral & Maxillofacial

Implants 22: 203–223.

Rosen, P.S., Marks, M.H. & Reynolds, M.A. (1996)

Influence of smoking on long-term clinical results

of intrabony defects treated with regenerative ther-

apy. Journal of Periodontology 11: 1159–1163.

Rothamel, D., Schwarz, F., Herten, M., Chiriac,

G., Pakravan, N., Sager, M. & Becker, J. (2007)

[Dimensional ridge alterations following tooth

extraction. An experimental study in the

dog]. Mund- Kiefer- und Gesichtschirurgie 11:

89–97.

Schropp, L., Kostopoulos, L. & Wenzel, A. (2003a)

Bone healing following immediate versus delayed

placement of titanium implants into extraction

sockets: a prospective clinical study. The Interna-

tional Journal of Oral & Maxillofacial Implants

18: 189–199.

Schropp, L., Wenzel, A., Kostopoulos, L. & Karring,

T. (2003b) Bone healing and soft tissue contour

changes following single-tooth extraction: a

clinical and radiographic 12-month prospective

study. International Journal of Periodontics and

Restorative Dentistry 23: 313–323.

Serino, G., Biancu, S., Iezzi, G. & Piattelli, A.

(2003) Ridge preservation following tooth extrac-

tion using a polylactide and polyglycolide sponge

as space filler: a clinical and histological study in

humans. Clinical Oral Implants Research 14:

651–658.

Winkler, S. (2002) Implant site development and

alveolar bone resorption patterns. Journal of Oral

Implantology 28: 226–229.

Yildirim, M., Spiekermann, H., Biesterfeld, S. &

Edelhoff, D. (2000) Maxillary sinus augmentation

using xenogenic bone substitute material Bio-Oss

in combination with venous blood. A histologic

and histomorphometric study in humans. Clin-

ical Oral Implants Research 11: 217–229.

Ziran, B.H., Hendi, P., Smith, W.R., Westerheide,

K. & Agudelo, J.F. (2007) Osseous healing with a

composite of allograft and demineralized bone

matrix: adverse effects of smoking. The Amer-

ican Journal of Orthopaedics 36: 207–209.



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