Clinical evaluation of a new collagen matrix (Mucograft® prototype) to enhance the width of...

Clinical evaluation of a newcollagen matrix (Mucografts

prototype) to enhance the width ofkeratinized tissue in patients withfixed prosthetic restorations: arandomizedprospectiveclinical trial

Sanz M, Lorenzo R, Aranda JJ, Martin C, Orsini M. Clinical evaluation of a newcollagen matrix (Mucografts prototype) to enhance the width of keratinized tissue inpatients with fixed prosthetic restorations: a randomized prospective clinical trial. JClin Periodontol 2009; 36: 868–876. doi: 10.1111/j.1600-051X.2009.01460.x.

AbstractAim: The aim of this study was to test a new collagen matrix (CM) aimed to increasekeratinized gingiva/mucosa when compared with the free connective tissue graft(CTG).

Material and Methods: This randomized longitudinal parallel controlled clinicaltrial studied 20 patients with at least one location with minimal keratinized tissue(41 mm).

Main Outcome Measure: The 6-month width of keratinized tissue. As secondaryoutcomes, the aesthetic outlook, the maintenance of periodontal health and the patientmorbidity were assessed pre-operatively at 1, 3 and 6 months.

Results: At 6 months, the CTG attained a mean width of keratinized tissue of 2.6(0.9) mm, while the CM was 2.5 (0.9) mm, these differences being insignificant. Inboth groups, there was a marked contraction (60% and 67%, respectively) although theperiodontal parameters were not affected. The CM group had a significantly lowerpatient morbidity (pain and medication intake) as well as reduced surgery time.

Conclusions: These results prove that this new CM was as effective and predictableas the CTG for attaining a band of keratinized tissue, but its use was associated with asignificantly lower patient morbidity.

Key words: aesthetics; collagen; connectivetissue graft; keratinized tissue

Accepted for publication 22 June 2009

The keratinized gingiva (KG) is a spe-cialized mucosa covered with keratin orparakeratin that includes the free and the

attached gingiva and extends from thegingival margin to the mucogingivaljunction. The width of the KG aroundteeth may vary between 1 and 9 mmdepending on the subject’s age and thejaw and tooth location and position. Fordecades, there was a controversy regard-ing the need for an ‘‘adequate’’ width ofKG in order to preserve periodontalhealth, although a general clinical

impression still remains that the pre-sence of a certain width of keratinizedtissue is important in maintaining perio-dontal health and preventing soft tissuerecession. Some classic studies sug-gested a minimum of 2 mm of KG tomaintain gingival health (Lang & Loe1972), corresponding to 1 mm of at-tached gingiva. However, several clin-ical and experimental investigations

Mariano Sanz, Ramon Lorenzo,Juan J. Aranda, Conchita Martin andMarco Orsini

Section of Periodontology, Faculty of

Odontology, University Complutense of

Madrid, Madrid, Spain

Conflict of interest and source offunding statement

The authors declare that there are no con-flict of interests in this study.This study was partially supported by aresearch grant from Geistlich Pharma.

J Clin Periodontol 2009; 36: 868–876 doi: 10.1111/j.1600-051X.2009.01460.x

868 r 2009 John Wiley & Sons A/S

have shown that the absence of attachedkeratinized tissue is compatible with themaintenance of periodontal health (Dorf-man et al. 1980, Wennstrom et al. 1981,Wennstrom 1983, Wennstrom & Lindhe1983, Kennedy et al. 1985). In a similarway, it has not been demonstrated thatthe presence of keratinized mucosa is aprognostic factor for the survival ofdental implants (Adell et al. 1986).

In spite of this controversy, there areclinical situations, however, where amucogingival surgical procedure maybe considered, because a thin gingivamight be less resistant in the presenceof inflammation or toothbrushing traumaand could lead to gingival recession.Several clinical studies have shown thatthis event may occur more likely insituations when the absence of kerati-nized tissue is combined with orthodontictreatment (Karring et al. 1971, Rate-itschak et al. 1979, Ericsson & Lindhe1984); when vestibular depth is needed inpatients with removable partial dentures,and in patients with fixed prostheticrestorations, when margins are placedsubgingivally (De Trey & Bernimoulin1980, Hangorsky & Bissada 1980). Asimilar clinical behaviour has beenreported in relation to the mucosa arounddental implants. Experimental studies inmonkeys have demonstrated that the lackof keratinized mucosa around implantsincreases plaque accumulation and theensuing long-term effect of undisturbedplaque-derived inflammation causedbone loss around the implants in theseanimals (Warrer et al. 1995). Clinicalstudies in humans have shown similarresults with regard to the significantlyhigher amounts of plaque and inflamma-tion at implant sites without keratinizedtissue, when compared with sites withadequate amounts, although its possibleimpact on the survival of the implantswas not demonstrated (Chung et al.2006). Recently, Zigdon & Machtei(2008), in a retrospective clinical study,have shown that both the peri-implantwidth and thickness of the mucosa had asignificant negative correlation with therecession of the mucosa.

Many surgical techniques have beenutilized to augment gingival tissuedimensions, the free gingival graft (Sul-livan & Atkins 1969) being the mostfrequently used. Longitudinal studieshave shown that procedures using pedi-cle and free gingival grafts are predict-able and effective for providing newlycreated keratinized tissue up to 4 years(Dorfman et al. 1982). Histologically,

heterotopic gingival and alveolar muco-sal transplants in animal models havedemonstrated that transplanted tissuesalways retained their original structureand specificity even after 1 year post-operatively (Karring et al. 1971). Whenusing epithelialized grafts, healing,however, often results in compromisedaesthetics (‘‘patch-like area’’). Alterna-tively, free connective grafts have beenproposed (Edel 1998) with similar clin-ical predictability, but with better resultsin terms of aesthetics and colour match-ing (Roccuzzo et al. 2002, Orsini et al.2004). Both techniques are, however,associated with significant patient mor-bidity due to the need to create a woundat the palatal donor site.

In order to avoid this patient morbid-ity, acellular dermal allografts havebeen used as a substitute for the palataldonor tissue, demonstrating the feasibil-ity of using allograft materials (Park2006, Yan et al. 2006, Imberman2007). However, because this allograftmaterial is derived from human cada-vers, it is associated with ethical con-cerns and the possible risk of diseasetransmission. An alternative option,both avoiding the need for palatal donortissue and allograft material, is the useof collagen membranes of porcine ori-gin, which are already standard in oralwound-healing procedures in associa-tion with bone augmentation (Hammerleet al. 2002, Wallace & Froum 2003).Recently, a new collagen matrix (CM)of similar porcine origin (Mucografts

Prototype) has been produced by Geis-tlich Pharma AG (Wolhusen, Switzer-land). Even though its qualitativeproperties and safety have been evalu-ated according to the procedures estab-lished in ISO 14971 and ISO 10993-1,no clinical trial data are as yet availablefor this CM graft material. The objectiveof this clinical trial is, therefore, to testthe efficiency of this new CM(Mucografts Prototype) to build up aclinically sufficient width of newlyformed KG and secondarily to assessthe aesthetic outcomes and post-opera-tory morbidity, when compared with thestandard treatment, the free connectivetissue graft (CTG).

Material and Methods

Patients

Twenty patients were selected fromthose attending the Periodontal Post-graduate Clinic at the Faculty of Odon-

tology in the University Complutense ofMadrid, if they fulfilled the followingcriteria:

Inclusion criteria

� Older than 18 years and perio-dontally and systemically healthy.

� Presenting at least one location withminimal or no keratinized tissue(41 mm). The selected tooth/implant must be part of a fixedpartial restoration.

� The patient should demonstrategood plaque control (FMPSo20%)and should be able to comply withall procedures related to the study.

Patients were excluded if they wereheavy smokers (410 cigarettes perday), had any systemic disease thatwould negatively influence wound heal-ing or known allergy to collagen.

The point of enrolment, followingrecruitment, was the time the subjectsigned the informed consent form. Thishappened after a full periodontal exam-ination with registration of probingpocket depths (PPD), bleeding scores(FMBS) and plaque scores (FMPS),after checking whether the patient meetsthe inclusion criteria, and most impor-tantly, after the patient has receivedthorough information from the investi-gator and has signed the ethics commit-tee-approved informed consent form.

Experimental design

This study was designed as a longitudi-nal parallel-designed controlled clinicaltrial comparing the CM (Mucografts

Prototype) with the free CTG. The studyprotocol was approved by the EthicsCommittee of San Carlos Clinical Hos-pital in Madrid and by the SpanishMinistry of Health who authorized thisclinical trial.

Four weeks before enrolment, allpatients received periodontal treatmentconsisting of oral hygiene instructions, aprofessional prophylaxis and, if needed,scaling and root planning. A new tooth-brush was given to each patient topractice oral hygiene according to thegiven instructions. Four weeks after thisinitial treatment, all subjects underwenta full periodontal examination withrecording of PPD and registration ofFMBS and FMPS that enabled patientsto be included in the study. For properstandardization between baseline andfollow-up data, the probes were labelled

A collagen matrix to enhance keratinized tissue around restorations 869

r 2009 John Wiley & Sons A/S

and the same probe was always used inthe same patient for all measurementsand the same examiner different fromthe surgeon took all the measurements(R. L.).

Surgical procedure

At the time of the surgery, the appro-priate local anaesthesia was adminis-tered and recorded and the surgicalprocedure was performed as follows:

After patient selection, the controland test groups underwent a mucogingi-val surgical procedure in order toenlarge the area of keratinized tissue.All surgeries were performed by the

same two calibrated surgeons (M. O.and J. J. A.). Immediately before thesurgery, the following clinical para-meters were recorded (Figs 1a and 2a):

� The width of the KG/mucosa mea-sured from the free gingival marginto the mucogingival junction, usinga North Carolina University probe.

� Periodontal indexes of the adjacentteeth [gingiva index (GI), plaqueindex (PI), PPD, and clinical attach-ment levels (CAL)].

� Clinical photographs of the surgeryarea to register baseline colour char-acteristics.

The surgical technique used consistedof the following steps:

Using a #15 blade, an intra-sulcularincision was made and a mucosal par-tial-thickness flap was raised. The reci-pient site was prepared by sharpdissection in order to create a periostealbed free of any muscle attachment. Theresulting flap was excised or sutured atthe base of the newly created vestibulewith 5-0 non-resorbable T-mattressbraided nylon sutures (Figs 1b and 2b).

At this point, the treatment groupswere assigned by means of sealed envel-opes containing a code derived from arandomized list, to receive

� free CTG – control group (Fig. 2c).� CM – test group (Fig. 1c).

In the control group, once the size ofthe graft was pre-determined using a tinfoil stent prepared over the recipientsite, a free CTG was harvested fromthe palate, following the classical pro-cedure by Langer & Langer (1985). TheCTG thickness varied depending on thepatient’s palate availability, but rangedbetween 1 and 3 mm. The CTG obtainedwas then sutured in the recipient bedwith 5-0 non-resorbable braided nyloninterrupted single sutures (Fig. 2d).

In the experimental group, thetrimmed CM was measured with a probeand was then sutured in the recipient bedwith 5-0 non-resorbable braided nyloninterrupted single sutures (Fig. 1d).

The surgery time was recorded inboth groups to the closest minute fromthe start of the first incision to theaccomplishment of the last suture.

Patients were then instructed to rinsetwice daily with a chlorhexidine mouthrinse (0.12%) for 2 weeks. Anti-inflam-matory therapy (Ibuprofen 400 mg) wasprescribed and patients were giveninstructions to take this drug in case ofpain or swelling. The patients wereprompted to record the dosage used ina customized form retrieved at the fol-low-up visits. Sutures were removedafter 10 days and clinical photographswere taken to document the healingprocess (Figs 1e and 2e). All patientswere asked to fill out a first pain ques-tionnaire.

At 1, 3 and 6 months after the sur-gery, follow-up visits took place withexamination of the gingiva or mucosalcondition. Clinical photographs weretaken and the following parameterswere measured and recorded: widths of

Fig. 1. (a) Pre-surgical image from an experimental site. Note the minimal amount ofkeratinized tissue around an implant supported restoration. (b) Split-thickness flap elevated toprepare the surgical bed for the Mucografts in the experimental sites. (c) Experimental softtissue substitute, a three-dimensional collagen tissue matrix (Mucografts Prototype). (d)Experimental collagen matrix sutured on the prepared surgical bed. (e) Healing of thecollagen matrix at 10 days post-surgery. (f) Presence of a band of keratinized gingival/mucosa (3 mm) at 6 months in the experimental site treated with the collagen matrix.

870 Sanz et al.


KG, PPD, CAL, GI and PI (Figs 1f and2f).

During each of these visits, thepatient filled out a pain questionnaireand returned the anti-inflammatory med-ication forms.

Experimental product information

The CM is a class III medical deviceaccording to the Medical Device Direc-tive 93/42 (EEC definitions: 1.1. long-term implant; 1.2. implantable; 8:resorbable and 17: animal origin). Ithas not achieved CE labelling yet, as itis a new device with distinctive features.

The structure of the CM consists oftwo functional layers: a cell occlusivelayer consisting of collagen fibres in acompact arrangement and a porouslayer. Its general architecture is similarto the clinically available collagenmembrane for bone regeneration, Bio-Gides (Geistlich Pharma, Wolhusen,

Switzerland); however, the CM porouslayer is thicker in order to achieve morekeratinized tissue by inducing a space-creating effect and by favouring bloodclot formation (Fig. 1c).

Outcome measurements

An adequate width of the KG wasselected as the primary endpoint of thestudy. The clinical evaluation of thisoutcome was performed by measuringthe distance from the free gingival(mucosal) margin to the mucogingivaljunction, using a North Carolina Uni-versity probe, pre-operatively and 1, 3and 6 months after the treatment (Figs 1fand 2f).

As secondary endpoints, we selectedthe aesthetic outcome, the maintenanceof periodontal (peri-implant) health inthe affected teeth (implant) and thepatient morbidity after the surgical pro-cedure.

For the assessment of the periodontaland marginal health status, the follow-ing parameters were measured:

� graft size: size of the CTG or the cutCM in mm, measured using a perio-dontal probe.

� GI according to Loe and Silness.� PI, according to Silness and Loe.� PPD, measured using a periodontal

probe in millimetres.� CAL, measured using a periodontal

probe in millimetres.

The periodontal indexes were mea-sured before the surgery (baseline) andat the follow-up visits, 1, 3 and 6 monthsafter the surgery.

The aesthetic outcome was assessedfrom standardized photos taken of theaugmented sites during each visit, byjudging the colour blending of thegrafted site with the adjacent tissuesthrough a qualitative questionnaire car-ried out by an independent examiner forthe aesthetic evaluation.

The patient morbidity was assessedthrough a questionnaire filled out by thepatient at each visit for pain assessmentusing a visual analogue scale (0–10).The investigator, using a specified form,recorded the presence of complications,additional treatments and medication inconnection to the surgical treatment.

Data analysis

For the power analysis the values for thecontrol (CTG) were taken from the testgroup of (Orsini et al. 2004), and in thetest group it was assumed that a similaramount of increase in the width ofkeratinized tissue as well as graft shrink-age would be achieved. We thusassumed that 1 mm was the maximum,clinically non-relevant difference bet-ween both procedures. For non-inferior-ity of the CM with respect to the CTG, asample size n 5 19, was then estimatedand taking into account a drop-out rateof 5%, a total of 20 patients weretreated.

The study was monitored by an exter-nal agency in accordance with ISO14155-1 and the source data obtainedwere verified for correctness and com-pleteness before statistical analysis.

Descriptive statistics were generatedfor both the primary and the secondaryoutcome measurements as means, stan-dard deviations and 95% confidenceintervals. The normality of the distribu-tion of these parameters was tested and

Fig. 2. (a) Pre-surgical image from a control site. Note the minimal amount of keratinizedtissue around an implant supported restoration. (b) Split-thickness flap elevated to prepare thesurgical bed for the connective tissue auto-graft in the control sites. (c) Dimension of theconnective tissue graft retrieved from the patient’s palate. (d) Connective tissue graft suturedon the prepared surgical bed. (e) Healing of the connective tissue graft at 10 days post-surgery. (f) Presence of a band of keratinized gingival/mucosa (2 mm) at 6 months in thecontrol site treated with the connective tissue graft.



except for the variable recession, therest proved not to be normally distrib-uted and hence, non-parametric statisti-cal tests were used for all comparisons.The intra-group comparisons across thedifferent evaluation times were testedwith the Friedman test, and if provento be statistically significant, Dunn’sMultiple Comparison Test was used toidentify the statistical significancefor the different intervals. The two-way analysis of variance for repeatedmeasurements tested the inter-groupcomparisons across the different evalua-tion times. Mann–Whitney’s non-para-metric test was used for comparing thedifferent variables between the controland the test groups at baseline and at 6months. For all these comparisons weused a level of significance of 0.05.

Results

The study population consisted of 20patients, 10 in the Control Group (CTG)and 10 in the Experimental Group (CM),recruited between September (2007) andFebruary (2008). All patients fulfilledthe protocol and attended all the follow-up visits. No patient in any of the groupsdeveloped any significant complication.In the control group (CTG), threepatients showed partial necrosis of theirCTGs at 10 days post-surgery; however,in no case was there a total loss of thegraft. The rest of the patients in thisgroup and all the patients in the experi-mental group (CM) healed uneventfully.

At baseline, both groups were wellbalanced with regard to the patientcharacteristics, location of selected sitesand the clinical parameters assessed,demonstrating lack of significant gingi-val inflammation and the presence ofshallow sulci (Table 1).

The changes in the primary outcomeof this study (increase in keratinizedtissue) are shown in Table 2. This tabledepicts the results for all the studypatients. The mean width of keratinizedtissue at baseline in the control and thetest group was 0.2 (0.42) and 0.4(0.51) mm, respectively. After the surgi-cal procedure, there was a statisticallysignificant increase in both groups at 30days, being 3.1 (0.8) and 2.8 (1.0) mm,respectively, but the differences bet-ween groups were not statistically sig-nificant. Between day 30 (1 month) andday 180 (6 months), there was a con-traction in the grafted area, althoughdifferences in the width of keratinized

tissue were not statistically significant inany of the groups. At 6 months, GroupCTG attained a mean width of kerati-nized tissue of 2.6 (0.9) mm, while thecorresponding figure in Group CM was2.5 (0.9) mm, this difference not beingstatistically significant (Fig. 3). Theamount of graft contraction in bothgroups is shown in Table 3. There wasa marked contraction in both groupsbetween surgery and the 1-month eva-luation (60% in group CTG and 67% ingroup CM). Between 30 and 180 days,this contraction continued in bothgroups although in a small percentage(17% and 8%, respectively) (Figs 1f and2f).

The surgical procedure in both groupsdid not alter significantly the periodontal

parameters in the affected teeth

(implants). In Group CTG, the GI chan-ged from 0.1 (0.3) at baseline to 0.3(0.4) at 6 months. The correspondingfigure in Group CM was 0.3 (0.6) and0.2 (0.4), respectively. There were nostatistically significant differencesbetween the groups in any of the eva-luation intervals. As can be seen in Fig.

Table 1. Patient description and clinical outcome measurements at baseline

Baseline (mm)

group (CTG) group (CM) p

PatientsAge (mean–range) 59.2 (39–62) 64.3 (57–79) NSGender (female/male) 8/2 7/3 NS

SitesTooth/implant 4/6 2/8 NSAnterior/posterior 3/7 3/7 NS

Clinical outcome measurementsKeratinized tissue 0.20 (0.42) 0.40 (0.52) 0.36 (NS)Gingival index 0.1 (0.31) 0.30 (0.67) 0.54 (NS)Probing pocket depth 2.0 (0.47) 2.12 (0.83) 0.68 (NS)Recession 0.9 (0.87) 0.80 (1.45) 0.59 (NS)

NS, not significant; CTG, connective tissue graft; CM, collagen matrix.

Table 2. Primary outcome: increase in keratinized tissue

Patient # Keratinized Tissue

group CTG group CM

0 day 30 days 90 days 180 days 0 day 30 days 90 days 180 days

1 1 3 3 3 1 2 2 22 0 3 3 2 1 3 3 33 0 4 4 4 1 5 4 34 0 3 3 3 0 4 4 45 0 2 2 2 0 3 3 36 0 5 4 4 0 2 2 27 0 3 3 3 0 2 2 28 0 3 2 2 1 3 3 29 0 2 2 1 0 2 2 210 1 3 2 2 0 2 2 2Mean 0.20 3.10 3.10 2.60 0.4 2.8 2.6 2.5SD 0.42 0.87 0.87 0.96 0.52 1.03 0.7 0.795% CI 0.03–0.77 2.06–3.53 2.10–3.10 1.99–3.00 0.03–0.77 2.06–3.53 2.10–3.10 1.99–3.00

Differences between 0 and 30 days, 90 and 180 days were statistically significant in both groups.

Differences between 30 and 90 days, between 30 and 180 days and between 90 and 180 days were

not statistically significant in any of the groups.

Differences between Group A and Group B were not statistically significant, both accross the study

(two-way ANOVA analysis) or at any of the evaluation visits (Mann–Whitney analysis).

CTG, connective tissue graft; CM, collagen matrix.

Table 3. Mean graft contraction

Day0–30

Day30–90

Day90–180

CTG (%) 59.7 8.6 8.3CM (%) 67.2 2 5.8

CTG, connective tissue graft; CM, collagen

matrix.

872 Sanz et al.


4, between the surgical procedure andthe one-month evaluation, there was anincrease in gingival inflammation, simi-lar in both groups, probably due to thepost-surgical healing process. Similarly,the PPD in the affected teeth remainedstable during the study in both groups.Figure 5 depicts these changes, withoutevidencing significant differences bet-ween the groups in any of the evaluation

periods. The changes in the position ofthe gingival (mucosal) margin (reces-sion) are shown in Fig. 6. Althoughgroup CTG demonstrated a higherrecession post-operatively, when com-pared with group CM, these differenceswere not statistically significant at 6months.

The evaluation of the clinical photo-graphs provided similar results in aes-thetics and colour blending with theadjacent tissues in both groups. Theblind evaluators were not able to distin-guish between both procedures in termsof colour or aesthetic outlook.

In spite of the similar results obtainedin both groups for the clinical para-meters, statistically significant differ-ences were detected between GroupsCTG and CM for the outcome variablesmeasuring the post-operative morbidity.The amount of pain referred by thepatient was measured through a visualanalogue scale, filled by each patient atthe post-operative visits at 10 and 30days. Figure 7 depicts these changes. At

10 days patients in Group CTG had amean pain score of 4.01 (8.5), while inthe CM group the corresponding scorewas 2.30 (2.39), these differences beingstatistically significant (p 5 0.0002). At30 days, no patient in the CM group hadany pain, while in the CTG group therewere still patients suffering from pain,with a mean pain score of 1.30 (3.19).The amount of pain was also measuredindirectly by the amount of pain and anti-inflammatory medication (Ibuprofens)needed during the post-operative periodby the patients. These data are depicted inFig. 8. In the CTG group, the measuredtotal dose at 10 days was 5140 (5336) mg,while the corresponding figure for groupCM was 720 (860) mg, these differencesbeing statistically significant (p 5 0.0013).

The total surgery time spent in bothsurgical procedures was also differentwhen both groups were compared. TheCTG surgeries lasted a mean of 47.20(10) min., while the CM surgeries lasteda mean of 30.80 (7) min. (Fig. 9). Thesedifferences were statistically significant(p 5 0.0006).

Fig. 3. Changes over time in the amount ofkeratinized tissue. Comparison between thecollagen matrix (CM) and the connectivetissue graft (CTG).

Fig. 4. Changes over time in the gingivalindex. Comparison between the collagenmatrix (CM) and the connective tissue graft(CTG).

Fig. 5. Changes over time in the periodontalprobing depths. Comparison between thecollagen matrix (CM) and the connectivetissue graft (CTG).

Fig. 6. Changes over time with regards togingival recession. Comparison between thecollagen matrix (CM) and the connectivetissue graft (CTG).

Fig. 7. Changes over time in patient’s pain.Comparison between the collagen matrix(CM) and the connective tissue graft (CTG).

Fig. 8. Comparison between the collagenmatrix (CM) and the connective tissue graft(CTG) with regards to the amount of painand anti-inflammatory medication taken(Ibuprofens).

Fig. 9. Comparison between the collagenmatrix (CM) and the connective tissue graft(CTG) with regards to the time needed to dothe surgical procedure.



Discussion

Although the controversy regarding theneed for an ‘‘adequate’’ width of KGaround teeth in order to preserve perio-dontal health still exists, there areclinical situations where the presenceof a certain width of keratinized tissuemay be important in maintaining perio-dontal health and preventing soft tissuerecession, such as in areas around fixedprosthetic restorations, when marginsare placed subgingivally. In fact, Orsiniet al. (2004) showed in a 1-yearlongitudinal clinical study that the pre-sence of a wide band of keratinizedtissue favoured proper plaque controland reduced gingival inflammation inteeth abutments of fixed restorations.Augmentation of gingival keratinizedtissue has been carried out traditionallyusing the free gingival graft. Rateitschaket al. (1979) evaluated this surgicaltechnique in a 4-year longitudinalstudy. The transplanted grafts demon-strated an average shrinkage of 25%,while the gingival margin remainedstable during the observation period. Inorder to avoid the patient morbidityproblems associated with the donor sitewhen using this graft technique, Edel(1998) demonstrated that the use of freeCTGs could be a feasible alternativeprocedure, avoiding an open wound inthe palate and attaining better colourmatching with adjacent tissues. Usingthis surgical procedure, Orsini et al.(2004) reported a mean shrinkage ofthe graft of 40% at 1 year, attaining awide band of KG (around 5 mm) andexcellent colour blending with the sur-rounding gingiva.

There is also scarcity of informationconcerning the importance of the kera-tinized mucosa around dental implantsand its effect on the peri-implant tissuehealth. An experimental study usingimplants in monkeys with minimal orno keratinized mucosa and plaque accu-mulation demonstrated significantlymore recession and bone loss in theseimplants when compared with implantssurrounded by keratinized mucosa(Warrer et al. 1995). These findingshave been confirmed in humans (Block& Kent 1990, Bragger et al. 1997,Chung et al. 2006), demonstrating thatthe lack of keratinized mucosa aroundimplants correlated with plaque accu-mulation and soft tissue inflammation.Moreover, recent studies have shown apositive correlation between lack orminimal amounts of keratinized mucosa

and mucosa recession (Artzi et al.2006, Chung et al. 2006, Zigdon &Machtei 2008), although a direct rela-tionship with bone loss around implantshas not been demonstrated (Adell et al.1986).

The results from this investigationdemonstrate a statistically significantamount of keratinized tissue achievedwith both surgical procedures, the CTGand the CM, with mean widths of 2.60and 2.50 mm, respectively. Althoughthese results are more modest comparedwith those reported by Orsini et al.(2004) using the CTG, these differencesmay be due to the location, since in thisstudy, most of the treated sites wereposterior tooth/implant sites with shal-low vestibules and high muscle attach-ments, which makes the establishmentof a wide band of keratinized tissuedifficult. In this study, most of the graftcontraction occurred within the firstmonth of healing, both with the CTGand the CM (60% and 67%, respec-tively). In fact, the differences between1 month and 1 year were small in bothgroups (CTG 17% versus CM 8%).These findings are also in agreementwith Orsini et al. (2004), who reported37% contraction at 4 weeks and then43% at 1 year. In spite of this significantincrease in KT with both grafting mate-rials, a small although visible recessionwas not prevented, evidencingthe clinical margins of the restorationsand implant abutments in the affectedsites.

Although the clinical outcomes ob-tained with both surgical procedures inboth studies were similar, there weresignificant differences in terms ofpatient morbidity, evaluated by the sub-jective patients pain perception and bythe amount of pain and inflammatorymedication needed. Most of this mor-bidity was associated with the need for asecond surgical procedure in the palateto obtain the donor tissue in the CTGtechnique. In fact, other investigatorshave used other soft tissue substitutesin order to achieve a significant amountof KG or mucosa without the need forprocuring a graft from the palate. One ofthese substitutes has been the use of anacellular dermal matrix (ADM) allo-graft. This allograft was originallyintended for covering burn wounds. Itis a structurally integrated basementmembrane complex and extracellularmatrix in which collagen bundles andelastic fibers are the main components.This allogenic graft will eventually

degrade by the production of newconnective tissue and will become com-pletely replaced by host tissues (Wei etal. 2002). Several clinical studies haveevaluated this allograft for its capabilityto increase the width of keratinizedtissue around dental implants (Weiet al. 2000, Park 2006, Yan et al.2006, Imberman 2007). Park (2006), ina prospective case series evaluatingADM to increase the width of kerati-nized mucosa around implants, obtainedsatisfactory results, with a meanincrease of 2.2 mm at 6 months,although the contraction of the graftedarea between 3 and 6 months was sig-nificant (58%). Wei et al. (2000)compared the clinical efficacy of ADMwith CTG in achieving increasedattached keratinized tissue aroundimplants. Although there was a statisti-cally significant increase in both groups,this gain in keratinized mucosawas significantly higher in the CTGwhen compared with ADM (5.5 versus2.5 mm) and also the contraction asso-ciated with this allograft was substantial(71%). Moreover, the use of allograftsderived from human cadavers maybe associated with ethical concerns andthe risk of disease transmission. To date,besides ADM, there are no othersoft tissue substitutes available for thisclinical indication and therefore, thisstudy is the first clinical trial reportingthe efficacy of a three-dimensionalCM to increase the band of keratinizedtissue. Its intended mechanism of actionis by acting as a three-dimensionalcaffold that allows the in-growth andre-population of fibroblasts, blood ves-sels and epithelium from surroundingtissues, eventually being transformedinto keratinized tissue. In this clinicalinvestigation, this matrix has demon-strated a good healing pattern and clin-ical behaviour, attaining similar clinicaloutcomes in terms of increase of kerati-nized tissue, maintenance of the margin-al tissue health and colour blendingwhen compared with the standardCTG. Moreover, it has shown excellenthandling properties with a significantreduction in surgery time and patientmorbidity.

In conclusion, the results of this studyprove that this new three-dimensionalCM, when used as a soft tissue substi-tute aiming to increase the width of KGor mucosa, was as effective and pre-dictable as the CTG, but its use wasassociated with a significantly lowerpatient morbidity.

874 Sanz et al.


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Supporting Information

Additional Supporting Information maybe found in the online version of thisarticle:

Table S1. Supporting information inaccordance with the CONSORT State-ment 2001 checklist used in reportingrandomized trials.

Please note: Wiley-Blackwell is notresponsible for the content or function-ality of any supporting materials sup-plied by the authors. Any queries (otherthan missing material) should be direc-ted to the corresponding author for thearticle.

Address:

Mariano Sanz

Facultad de Odontologıa

Universidad Complutense de Madrid

Plaza Ramon y Cajal

28040 Madrid

Spain

E-mail: [email protected]



mailto:[email protected]

Clinical Relevance

Scientific rationale for the study:Although the importance of thepresence of keratinized tissue isdiscussed controversially in the lit-erature, most clinicians would seek astable soft tissue around fixedrestorations, free of inflammation.There are clinical situations, there-fore, where there is an indication to

increase the amount of keratinizedtissue. The objective of this clinicaltrial is to test the efficiency of a newCM to build up a clinically sufficientwidth of newly formed KG whencompared with one of the standardtreatments: the placement of a freeCTG.Principal findings: This study hasshown that a similar amount of KG/

mucosa was achieved with the newCM. This outcome, however, wasachieved with less post-operativemorbidity and using less surgicaltime.Practical implications: This new CMmay be a useful soft tissue substitutein those clinical situations requiringan adequate amount of keratinizedtissue.

876 Sanz et al.


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