Collagen Matrix for Periodontal Plastic Surgery Procedures

Volume 39, Number 4, 2019

e129

Submitted March 9, 2018; accepted August 18, 2018. ©2019 by Quintessence Publishing Co Inc.

1 State Key Laboratory of Oral Diseases; National Clinical Research Center for Oral Diseases; Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

2 Department of Evidence Based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China. *These authors contributed equally to this work. Correspondence to: Dr Lei Zhao, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, NO.14 Ren min South Road 3rd Section, Chengdu, Sichuan 610041, China. Fax: +86 28 85582167. Email: [email protected]

Collagen Matrix for Periodontal Plastic Surgery Procedures: A Meta-analysis Update

This review aims to evaluate the effectiveness of a collagen matrix (CM) utilized in periodontal plastic surgeries around natural teeth and implants. This review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Review Manager 5.3 software was used for data analysis. Subgroup analyses were conducted by defect categories and follow-up periods. The GRADE system was applied to classify the quality of evidences. Out of 3,652 articles in the literature, 14 studies were included, totaling 1,260 defects in 565 participants. The meta-analysis showed that CM is superior to coronally advanced flaps (CAF) regarding gains in mean root coverage (MRC) and width of keratinized tissue (KTW). Insufficient evidence demonstrated that CM had higher complete root coverage (CRC). Connective tissue graft (CTG) presented better results in CRC, MRC, and KTW. Greater KTW was also found favoring CTG in implants. In subgroup analysis, moderate evidence showed that, compared to CTGs, CMs present similar results in CRC, MRC, and KTW when treating single gingival recessions. CTGs showed greater efficiency in KTW of multiple gingival recessions and long-term observations. CM presents suitable capabilities as an alternative to soft tissue graft, while CTG still shows better results in most clinical parameters. Int J Periodontics Restorative Dent 2019;39:e129–e155. doi: 10.11607/prd.3814

Treatment of gingival recession and insufficient keratinized tissue (KT) is a common requirement to improve periodontal health and solve es-thetic concerns.1 Today, coronally advanced flap (CAF) with connec-tive tissue graft (CTG) is considered the gold standard to treat Miller Class I and II gingival recessions.2 For KT < 2 mm,3 free gingival grafts (FGGs) may be the best option for augmentation of KT.4–6 However, the need for a second surgical site increases postoperative discom-fort, bleeding, and swelling from the donor site.6,7 In addition, the patient’s esthetic evaluation of the surgical site is unpredictable.6 It is quite challenging to use the mul-tiple adjacent gingival recession (MAGR) method due to the limita-tions of the donor site or implant size.7,8 To overcome these disadvan-tages, alternative materials, such as acellular dermal matrix (ADM), have gradually become an alterna-tive for periodontal plastic surger-ies.2,6,9–12 Some studies report that alternative materials can result in complete root coverage (CRC) similar to that of CTG.13–18 However, CTG with CAF is still associated with increased esthetic satisfaction compared to other techniques.19 In addition, the application of ADM is still subject to ethical restrictions in Europe, China, and other countries and regions.

Chunmei Xu, DDS1*QianTing Wang, DDS1*Jin Chen, PhD2

Yafei Wu, DDS, PhD1

Lei Zhao, DDS, PhD1

© 2019 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER.

mailto:[email protected]

The International Journal of Periodontics & Restorative Dentistry

e130

Recently, some trials describe the effectiveness of a novel bilay-ered porcine collagen matrix (CM) in periodontal plastic surgeries. This CM is composed of type I and type III collagens. The compact layer with a low-porosity surface is less cell-permeable. The porous layer consists of diffusely packed collagen fibers, which can support blood clot stabilization and the in-growth of soft tissue cells.20 Studies demonstrate20–23 that the spongy layer facing the tooth facilitates good tissue integration with sur-rounding connective tissue, and the compact layer with less cell in-filtration functions as a barrier for soft tissue regeneration.

Some advantages that CM presents include a lack of ethical issues, no donor-site discomfort, less postoperative morbidity, and no limitation of the implant size.24,25 One meta-analysis demonstrated that, compared with other tech-niques, CM obtains enhanced augmentation in KT.17 A previously published systematic review report-ed numerous valuable conclusions about clinical and patient-centered outcomes, but no data about MAGRs and long-term results were reported due to the limited number of included studies.26

This systematic review and meta-analysis aims to reevaluate the efficiency of CM in periodon-tal plastic surgeries involving teeth and implants and to provide more detailed information for CM’s clini-cal application.

Materials and Methods

The systematic review was prepared according to the guidelines of the Preferred Reporting Items for Sys-tematic Reviews and Meta-Analyses (PRISMA) statement.27 The criteria used in this review for trial selection were based on the PICO (patient, intervention, comparison, outcome) method.28

Types of Studies

Only randomized controlled trails (RCTs) using the same porcine CM to treat gingival recessions or in-sufficient KT were considered for inclusion. Considering the hetero-geneity between results of different studies at various time points, only RCTs followed up to 6 months, 12 months, or both time points were involved. Non-RCTs, animal studies, or trials lacking information like data of primary outcomes, allocation methods, or other information for assessing risk of bias were excluded.

Types of Participants

Systemically and periodontally healthy patients (≥ 18 years old) with demand for periodontal plas-tic surgeries to treat gingival reces-sion or insufficient KT were enrolled. Patients with contraindications for periodontal surgery or clinical signs of active periodontal disease were excluded.

Types of Intervention and Comparison

The CM utilized in the surgery was considered as experimental inter-vention. Use of autografts like CTG and FGG, which were thought to be the gold standards for root coverage and KT augmentation, respectively, were comparator interventions. The most-used technique, CAF, was also set as comparator intervention. Studies included were grouped into four categories according to the techniques used in surgeries: CM vs CTG; CM vs CAF alone; CM vs FGG; CM vs CTG in dental implants.

Types of Outcome Measures

Primary outcomes: percentage of CRC and mean root coverage (MRC); gain in width of KT (KTW).

Secondary outcomes: recession reduction (RD); changes in recession width (RW), gingival tissue thickness (GT), probing pocket depth (PPD), and clinical attachment level (CAL); participants’ esthetic satisfaction; postoperative discomfort and mor-bidity; operating time.

Search Strategy

The following electronic databases were searched for ongoing and unpublished trials up to November 10, 2017: MEDLINE, EMBASE, The Cochrane Central Register of Con-trolled Trials (CENTRAL), and the System for Information on Grey Lit-erature in Europe (http://www.open-grey.eu). The searching terms were



e131

in English, but no language restric-tion was applied. The search was performed independently and in duplicate by two reviewers (C.M.X. and Q.T.W.). The following keywords were used as search terms in the electronic databases: ([“Collagen matrix”(All fields)] OR [“collagen”(All fields)] OR [“matrix”(All fields)] OR [“xenogeneic collagen matrix”(All fields)] OR [“porcine collagen matrix”(All fields)] OR [“xenograft”(All fields)]) AND ([“gin-gival recession”(All fields) OR [“Mar-ginal tissue recession”(All fields) OR [“Root coverage”(All fields) OR [“Keratinized gingiva”(All fields) OR [“Mucogingival therapy”(All fields) OR [“Mucogingival surgery”(All fields) OR [“Periodontal surgery”(All fields) OR [“Periodontal plastic surgery”(All fields)]). The bibliog-raphies of all eligible papers were scrutinized for additional studies. A hand-search of the last 10 years of relevant available dental journals (Journal of Clinical Periodontology, Journal of Periodontology, Journal of Periodontal Research, Clinical Oral Implants Research, and Inter-national Journal of Pharmaceutical Research and Development) was carried out to identify potential pa-pers to include.

Selection of Studies

The same two independent re-viewers who performed the search also screened each article’s title, abstract, and keywords in dupli-cate. Then the full texts of studies that met the inclusion criteria were obtained and assessed by the two

reviewers separately. The final de-cision about the eligibility of all studies was made by mutual agree-ments or in consultation with a third author (Z.L.). The reasons for exclud-ing studies were noted.

Data Extraction

The following information of in-cluded trials was extracted in-dependently by the same two independent reviewers applying a specifically designed data-col-lection form in duplicate: authors’ names, study location, year of pub-lication, numbers of participants and recession sites, source of study funding, study design, method of randomization, duration of study, al-location concealment and blinding, length of observation period, type of defects, patients’ characteristics, comparison of interventions, and outcomes. Any disagreements were resolved by reaching a consensus or contacting corresponding authors of the included studies.

Quality Assessment

The two independent reviewers ap-plied (in duplicate) the Cochrane Collaboration’s Risk of Bias tool to assess the risk of bias of included RCTs.29 After quality assessment of six domains of the tool, relative parts of studies were grouped into three categories15: low risk of bias if all the criteria were met; moderate risk of bias if three or more criteria were partially met; high risk of bias if less than three criteria were met.

Final outcomes provided by this review were evaluated by the GRADE (Grading of Recommenda-tions, Assessment, Development, and Evaluation) system to classify the quality of the evidence.

Data Analysis

Data were analyzed using a statisti-cal software program (Review Man-ager, version 5.3). For dichotomous outcomes, the effect of the interven-tion was estimated by risk ratio (RR) and 95% confidence intervals (CIs). For continuous outcomes, mean dif-ferences (MDs) and standard devia-tions (SDs) were used to summarize the effect. The missing SD of an MD in an intervention group was computed from the CI, and the SD change of an MD change was calcu-lated from a correlation coefficient calculated from a study reported in considerable detail according to the principles and techniques described in the Cochrane Handbook.

Inconsistencies in quantifying heterogeneity across studies were expressed as an I2 statistic tested by Cochran’s Q test. An I2 value > 50% indicated significant heterogene-ity, in which case a random-effects model and sensitivity analysis were applied. A fixed-effects model was used when I2 < 50%. Statistical sig-nificance was set at P < .05. The generic inverse variance option in the statistical software program was used to combine both split-mouth and parallel group trials. Subgroup analyses were conducted to explore related factors causing heteroge-neity. With fewer than 10 studies



e132

in each group, publication bias was not formally assessed due to the limited power.

Results

Results of the Search

The search strategy identified 3,652 references (Fig 1), of which 27 ar-ticles were considered eligible by scanning titles and keywords. Only 14 studies met the inclusion criteria after full-text evaluation and were selected in the review.25,30–42 The exclusion reasons for the 13 studies are noted in Fig 1. The hand-search did not provide any further studies. Out of the 14 RCTs, 11 applied CM in the treatment for natural teeth, of

which a following long-term–results subgroup analysis was also con-ducted. The other 3 RCTs were all performed around dental implants.

Quality Assessment and Basic Characteristics of Included Studies

Results (Table 1) showed that all RCTs were evaluated as having a moderate risk of bias. Among the RCTs, two trials were performed in the United States, three in Italy, two in Spain, one in Hungary, one in Poland, two in Brazil, and three were multiple-center RCTs, of which one was performed in Germany, Italy, Sweden, and Spain; one in Germany and Italy; and one provided no de-

tails of study location. Nine trials were partially or totally supported by Geistlich Pharma, two were self-funded, one was supported by Re-search Funding Agency from São Paulo State, one was supported by the Piracicaba Dental School, and one did not report the source of monetary support. There were five RCTs in the CM vs CTG group, with three studies treating MAGRs; four studies in the CM vs CAF alone group, with only one study treat-ing MAGRs; one study in the CM vs FGG group; three studies in the CM vs CTG in dental implants group. Details of included studies are shown in Tables 2 and 3.

Meta-analysis

CM vs CTG in Natural TeethFive trials under moderate risk of bias were included.30–34 The meta-analysis showed (Appendix 1) that the CM group had significantly greater reductions in PPD (P = .0001, I2 = 9%, 95%CI: –0.16 to –0.05), surgery time (P < .00001, I2= 0%, 95%CI: –17.87 to –14.40), and post-operative discomfort (P < .00001, I2 = 34%, 95%CI: –6.77 to –3.38). Patient-centered esthetic satisfac-tion also favored the CM group (P = .14, I2 = 89%, 95%CI: –15.01 to 2.20), though no significant differ-ence was detected.

There was a significantly high-er percentage of CRC (P = .0004, I2 = 58%, 95%CI: 1.17 to 1.72) and MRC (P = .03, I2 = 82%, 95%CI: 0.66 to 16.31) in the CTG group, and greater changes were also found in RD (P = .005, I2 = 58%, 95%CI: 0.08

Articles identified from search of electronic database (n = 3,652)

Studies excluded after scanning titles and abstracts (n = 3,625)

Studies excluded with reasons for exclusion (n = 13)

• Insufficient data for meta-analysis (n = 4)

• Histologic study (n = 1)

• No detailed information of resorbable membrane used (n = 1)

• XCM differs from soft tissue substitute (n = 4)

• XCM is not the variable used for comparison (n = 1)

• Defects at surgical sites that may affect final outcomes (n = 2)

Citations identified for full-text assessment (n = 27)

Studies included for meta-analysis (n = 14)

Trials applying XCM around natural teeth

(n = 11)

Trials applying XCM around

implants (n = 3)

Fig 1 Flow diagram for the search process and result. XCM = xenogeneic collagen matrix.



e133

to 0.45), KTW (P < .00001, I2 = 47%, 95%CI: 0.30 to 0.56), GT (P < .00001, I2 = 0%, 95%CI: 0.21 to 0.38), and CAL (P < .0001, I2 = 48%, 95%CI: 0.15 to 0.45). Obvious heterogeneity was detected in CRC, MRC, RD, and RW (P = .23, I2 = 94%, 95%CI: –0.37 to 1.57), with RW values not signifi-cantly higher than the CM group.

CM vs CAF Alone in Natural TeethFive trials at moderate risk of bias were included.35–39 The meta-anal-ysis (Appendix 2) showed that the CM group resulted in significant-ly better improvements in MRC (P = .006, I2 = 65%, 95%CI: –13.86 to –2.26), KTW (P = .006, I2 = 0%, 95%CI: –0.50 to –0.09), CAL (P = .01, I2 = 0%, 95%CI: –0.56 to –0.07), and GT (P = .02, I2 = 93%, 95%CI: –0.74 to –0.06). Though CM shows a potential advantage in achieving CRC (P = .05, I2 = 0%, 95%CI: 0.64 to 1.00), this parameter presents no significant difference between the two groups after sensitivity analysis or subgroups analysis. In addition, patients’ esthetic satisfaction, which was not significantly different be-tween two groups (P = .38, I2 = 0%, 95%CI: –0.82 to 0.31), slightly fa-vored the CM group. No difference was found in terms of PPD (P = .73, I2 = 74%, 95%CI: –0.15 to 0.21) and RD (P = .61, I2 = 76%, 95%CI: –0.55 to 0.32). Obvious heterogeneity was detected in MRC, GT, RD, and PPD, which indicated essential heteroge-neity analysis. Only one study35 pro-vided information for surgery time and postoperative discomfort, both of which favored CAF and were not suitable for meta-analysis.

CM vs FGG in Natural TeethOnly one trial at moderate risk of bias was included, which was not enough for a suitable meta-analy-sis.40 However, this study also pro-vided a lot of useful information for this review. This trial found that FGG was associated with higher KT gain compared with CM, while patients in the CM group reported greater esthetic satisfaction. No significant differences were detected in PPD, RD, and CAL.

CM vs CTG in Dental ImplantsIn this group, three trials at moder-ate risk of bias were included.25,41,42 Limited data demonstrated that the final result favored CM in KTW (Ap-pendix 3) (P = .92, I2 = 19%, 95%CI: –0.29 to 0.27), though the difference between the two groups was not statistically significant. All studies in this analysis reported similar es-thetic satisfaction for both groups, while the CM group presented bet-ter improvement in postoperative discomfort and operating time. One trial41 showed that using CTG could achieve greater GT gains.

Table 1 Quality Assessment of Included RCTs

Study, publication year RSG ALC BOA ICD SLR OSB

Risk of bias

Sanz et al,25 2009 Y UN Y Y Y UN Moderate

Tonetti et al,30 2018 Y Y Y Y Y UN Moderate

Cieslik-Wegemund et al,31 2016

Y Y Y Y Y UN Moderate

Aroca et al,32 2013 Y UN Y Y Y UN Moderate

Cardaropoli et al,33 2012

Y UN Y Y Y UN Moderate

McGuire and Scheyer,34 2010

Y UN Y UN Y UN Moderate

Jepsen et al,35 2013 Y Y Y Y UN UN Moderate

Cardaropoli et al,36 2014


Stefanini et al,37 2016 Y Y Y Y UN UN Moderate

Sangiorgio et al,38 2017

Y Y Y Y Y UN Moderate

Moreira et al,39 2016 Y Y Y Y Y UN Moderate

McGuire and Scheyer,40 2014


Cairo et al,41 2017 Y Y Y N Y UN Moderate

Lorenzo et al,42 2012 Y Y Y Y Y UN ModerateRCT = randomized controlled trial; RSG = random sequence generation; ALC = allocation concealment; BOA = blinding of outcome assessment; ICD = incomplete outcome data; SLR = selective reporting; OSB = other source of bias; UN = unclear; Y = yes; N = no.



e134

Table 2 Characteristics of Included Studies (in Natural Teeth)

McGuire and Scheyer,34,a CM vs

CTG

Cardaropoli et al,33

CM vs CTGAroca et al,32 CM vs CTG

McGuire and Scheyer,34,a CM vs CTG

Cieslik- Wegemund

et al,31 CM vs CTG

Tonetti et al,30 CM vs CTG

Year of publication

2010 2012 2013 2010 2016 2018

Study location United States Italy Hungary United States Poland 14 centers (not specified)

Study design Split-mouth Parallel group Parallel group Split-mouth Parallel group Parallel groupParticipants/ recession sites

25/50 18/22 22/156 25/50 28/106 187/485

Methods of assessment

Periodontal probe, VASb

Periodontal probec

Periodontal probe,c VASb


Periodontal probe,d VASb


Type of defects

Dehiscence-type recession defects ≥ 3 mm deep × ≥ 3 mm wide

Miller Class I or II recession

Miller Class I and II multiple adjacent gingival recession

Dehiscence-type recession defects ≥ 3 mm deep × ≥ 3 mm wide

Miller Class I and II multiple adjacent gingival recession

At least two adja-cent recessions of the gingival margin (one of which is at least ≥ 3 mm)

Complete root coverage (%)

NR CM: 72 CTG: 81

CM: 42 CTG: 85

CM: 70.6 CTG: 94.1

CM: 70 CTG: 83

CM: 48 CTG: 70

Mean root coverage (%)

CM: 88.5 ± 21.2 CTG: 99.3 ± 3.5

CM: 94.32 ± 11.68 CTG: 96.97 ± 6.74

CM: 71 ± 21 CTG: 90 ± 18

CM: 89.5 ± 19.2 CTG: 97.5 ± 10.4

CM: 91 ± 13 CTG: 95 ± 11

NR

Recession depth (mm)

CM: –2.78 ± 0.678 CTG: –3.17 ± 0.388

CM: –2.86 ± 0.39 CTG: –2.95 ± 0.69

CM: –1.3 ± 0.624e CTG: –1.6 ± 0.479e

CM: –2.61 ± 0.727 CTG: –3.10 ± 0.460

CM: –2.6 ± 0.744e CTG: –2.5 ± 0.84e

CM: –1.7 ± 1.1 CTG: –2.1 ± 1.0

Recession width (mm)

CM: –3.22 ± 1.647 CTG: –4.22 ± 0.969

NR CM: –2.4 ± 1.021e CTG: –3.3 ± 0.915e

CM: –2.72 ± 1.769 CTG: –4.04 ± 1.114

CM: –2.9 ± 0.822e CTG: –2.6 ± 0.822e

NR

Width of KT (mm)

CM: 1.11 ± 0.824 CTG: 1.09 ± 1.599

CM: 1.23 ± 0.61 CTG: 1.27 ± 0.65

CM: 0.3 ± 0.674e CTG: 0.7 ± 0.615e

CM: 1.34 ± 1.018 CTG: 1.26 ± 1.526

CM: 0.8 ± 1.366e CTG: 1.0 ± 1.311e

CM: –0.1 ± 1.1 CTG: 0.5 ± 1.2

Gingival thick-ness (mm)

NR CM: 1.00 ± 0.32 CTG: 1.23 ± 0.47

CM: 0.2 ± 0.247e CTG: 0.5 ± 0.334e

NR NR NR

Probing pocket depth (mm)

CM: 0.50 ± 0.824 CTG: 0.24 ± 0.751

CM: 0.27 ± 0.41 CTG: 0.23 ± 0.26

CM: –0.1 ± 0.2e CTG: 0 ± 0.2e

CM: 0.34 ± 0.800 CTG: 0.32 ± 0.630

NR CM: 0.1 ± 0.7 CTG: 0.3 ± 0.8

Clinical attachment level (mm)

CM: –2.26 ± 1.211 CTG: –2.85 ± 0.630

CM: –2.41 ± 0.83 CTG: –2.95 ± 0.82

CM: –1.3 ± 0.691e CTG: –1.7 ± 0.525e

CM: –2.28 ± 1.042 CTG: –2.70 ± 0.678

CM: –2.6 ± 0.754e CTG: –2.6 ± 0.765e

NR

Esthetic satisfaction

Not statistically significant (data not available)

NR CM: 92.9 ± 8.4 CTG: 90.6 ± 7.9

NR CM: 98.8 ± 1.9 CTG: 87.7 ± 18.0

NR

Postoperative discomfort and morbidity

Not statistically significant (data not available)

NR CM: 7.3 ± 3.4 CTG: 12.8 ± 7.5

NR Test group reported significantly greater pain than control group

CM: 9.2 ± 14.1 CTG: 11.6 ± 17.6

Operating time (min)

NR NR CM: 42.5 ± 4.8 CTG: 58.6 ± 6.6

NR NR CM: 53.2 ± 17.7 CTG: 69.7 ± 24.3

Follow-up period (mo)

12 12 12 6 6 6

Source of study funding

Supported in part by an educational grant from Geistlich Pharma

Geistlich Pharma supplied the col-lagen membranes used in this research.

Funded through a grant from Geistlich

Supported in part by an educational grant from Geistlich Pharma

NR Supported in part by an unrestricted grant from Geistlich Pharma

Method of randomization

Computer-generated randomization






Blinding Masked examiner Masked examiner Masked examiner Masked examiner Masked examiner Masked examiner and questionnaire

aThe long-term observation studies with long-term outcomes of part of patients.bVisual analogue scale was used to evaluate patient-centered outcomes.c#15 UNC Novatech Color-Coded Probe, Hu-Friedy.dCP15 periodontal probe, Carl Martin.e The missing standard deviation of a mean difference was calculated from a correlation coefficient calculated from a study reported in considerable detail according to the principles and techniques described in the Cochrane Handbook.

CM = collagen matrix; CTG = connective tissue graft; VAS = visual analog scale; NR = not reported; KT = keratinized tissue.



e135

Table 2 Characteristics of Included Studies (in Natural Teeth), continued

Jepsen et al,35 CM vs CAF alone

Cardaropoli et al,36 CM vs CAF alone

Stefanini et al,a CM vs CAF alone

Moreira et al,39 CM vs CAF alone

Sangiorgio et al,38 CM vs CAF alone

McGuire and Scheyer,40

CM vs FGG

Year of publication

2013 2014 2016 2016 2017 2014

Study location Germany, Italy, Sweden, and Spain

Italy Germany, Italy Brazil Brazil United States

Study design Split-mouth Split-mouth Split-mouth Parallel group Parallel group Split-mouthParticipants/ recession sites

45/90 32/113 45/90 40/40 34/34 30/60



Periodontal probec




Periodontal probec

Type of defects

Miller Class I and II recession

Miller Class I and II multiple adjacent recession


Miller Class I or II recession


Keratinized tissue < 2 mm

Complete root coverage (%)

CM: 36 CAF: 31

CM: 72 CAF: 58

CM: 42 CAF: 38

CM: 40 CAF: 35

CM: 53 CAF: 24

NR

Mean root coverage (%)

CM: 75.29 ± 26.68 CAF: 72.66 ± 26.19

CM: 93.25 ± 10.01 CAF: 81.49 ± 23.45

CM: 76.28 ± 28.07 CAF: 75.05 ± 26.24

CM: 77 ± 0.21 CAF: 72 ± 0.14

CM: 87.20 ± 15.01 CAF: 68.04 ± 24.11

NR


CM: –2.59 ± 1.11 CAF: –2.32 ± 0.99

CM: –2.28 ± 0.874e CAF: –1.85 ± 1.104e

CM: –2.48 ± 1.47 CAF: –2.26 ± 1.17

CM: –2.41 ± 0.73 CAF: –2.25 ± 0.50

CM: –2.71 ± 0.51 CAF: –2.16 ± 0.75

CM: –0.13 ± 0.52 FGG: –0.22 ± 0.49

Recession width (mm)

CM: –1.91 ± 1.73 CAF: –1.84 ± 1.48

NR CM: –2.07 ± 1.85 CAF: –2.09 ± 1.55

NR NR NR

Width of KT (mm)

CM: 0.93 ± 1.15 CAF: 0.57 ± 0.98

CM: 1.07 ± 0.74e CAF: 0.7 ± 0.85e

CM: 1.06 ± 1.07 CAF: 0.64 ± 1.05

CM: 0.20 ± 0.695e CAF: 0.15 ± 0.775e

CM: 0.35 ± 1.04 CAF: 0.30 ± 1.4

CM: 2.04 ± 0.653e FGG: 3.65 ± 0.537e

Gingival thick-ness (mm)

CM: 0.59 ± 0.44 CAF: 0.34 ± 0.55

CM: 0.97 ± 0.403e CAF: 0.13 ± 0.332e

CM: 0.52 ± 0.46 CAF: 0.27 ± 0.43

CM: 0.40 ± 0.19 CAF: 0.14 ± 0.29

CM: 0.36 ± 0.47 CAF: 0.13 ± 0.32

NR


CM: –0.11 ± 0.446e CAF: –0.29 ± 0.441e

CM: 0.06 ± 0.314e CAF: –0.03 ± 0.316e

CM: –0.07 ± 0.431 CAF: –0.3 ± 0.411

CM: –0.05 ± 0.247e CAF: 0.10 ± 0.272e

CM: –0.18 ± 0.50 CAF: –0.03 ± 0.74

CM: 0.08 ± 0.49 FGG: 0.05 ± 0.55

Clinical attachment level (mm)

CM: –2.7 ± 1.354e CAF: –2.61 ± 1.243e

CM: –2.23 ± 0.944e CAF: –1.88 ± 1.107e

CM: –2.7 ± 1.341 CAF: –2.71 ± 1.217

CM: –2.46 ± 0.858 CAF: –2.15 ± 0.773e e

CM: –2.87 ± 0.75 CAF: –2.18 ± 1.11

CM: 0.05 ± 0.70 FGG: –0.12 ± 0.61


NR NR CM: 8.58 ± 1.86 CAF: 8.38 ± 2.46

CM: 94.0 ± 10.46 CAF: 93.5 ± 7.45

CM: 8.65 ± 1.58 CAF: 8.29 ± 1.36

(preference) CM: 70 (n = 21) FGG: 30 (n = 9)


CM: 0.68 ± 1.21 CAF: 0.59 ± 0.91

NR NR NR NR NR


CM: 39 ± 14 CAF: 31 ± 14

NR NR NR NR CM: 11.13 ± 3.66 FGG: 10.73 ± 3.85

Follow-up period (mo)

6 12 12 6 6 6


Supported by a research grant from Geistlich Pharma

Self-funded Self-funded Supported by the Piracicaba Dental School, State Uni-versity of Campinas

Supported by Research Fund-ing Agency from São Paulo State (FAPESP)

Supported partly by an educational grant provided by Geistlich Pharma


Computer- generated randomization






Blinding Masked examiner Masked examiner Masked examiner Masked examiner Masked examiner and patient

Masked examiner

aThe long-term observation studies with long-term outcomes of part of patients.bVisual analogue scale was used to evaluate patient-centered outcomes.c#15 UNC Novatech Color-Coded Probe, Hu-Friedy.dCP15 periodontal probe, Carl Martin.e The missing standard deviation of a mean difference was calculated from a correlation coefficient calculated from a study reported in considerable detail according to the principles and techniques described in the Cochrane Handbook.

CM = collagen matrix; CTG = connective tissue graft; VAS = visual analog scale; NR = not reported; KT = keratinized tissue.



e136

Sensitivity Analysis

When I2 values were over 50%, sen-sitivity analyses were performed by excluding particular studies one by one, and the results showed that the heterogeneity of some clinical out-comes were both related to types

of defects and follow-up periods. Random-effect model was applied among clinical outcomes with high heterogeneity.

In the CM vs CTG comparison group (Appendix 4), obvious het-erogeneity was found regarding CRC, MRC, RD, and RW. Sensitivity

analysis was applied to these clini-cal parameters, after which a great reduction of these parameters was detected. Significantly greater out-comes in terms of CRC (P < .00001, I2 = 0%, 95%CI: 1.22 to 1.62), MRC (P = .02, I2 = 0%, 95%CI: 0.83 to 8.03), RD (P < .00001, I2 = 0%, 95%CI: 0.23 to 0.46), and RW (P < .00001, I2 = 0%, 95%CI: 0.67 to 1.24) were found in the CTG group com-pared with the CM group.

As for the CM vs CAF compari-son group (Appendix 5), sensitiv-ity analysis was performed among MRC, RD, GT, and PPD. Eventually, MRC (P < .0001, I2 = 0%, 95%CI: –19.24 to –7.22), RD (P = .02, I2 = 0%, 95%CI: –0.56 to –0.05), and GT (P < .00001, I2 = 0%, 95%CI: –0.36 to –0.14) turned out to be in favor of the CM group at low heterogene-ity. The CAF group showed greater change in PPD (P = .01, I2 = 40%, 95%CI: 0.03 to 0.21) than the CM group after sensitivity analysis.

Subgroup Analysis

Subgroup analyses were performed by two related factors: follow-up periods and defect categories. Con-sidering the characteristics of the included studies and the target of the review, for each clinical param-eter, only the subgroup with at least two available studies included was eligible for meta-analysis. Eventu-ally, four subgroups were presented in the comparison group CM vs CTG in natural teeth, which were: MAGRs, single gingival recession (SGR), and the 6- and 12-month stages. In comparison, in the group

Table 3 Characteristics of Included Studies (in Dental Implants)

Cairo et al,41 CM vs CTG

Sanz et al,25 CM vs CTG

Lorenzo et al,42 CM vs CTG

Year of publication

2017 2009 2012

Study location Italy Spain SpainStudy design Parallel group Parallel group Parallel groupParticipants/ recession sites

60/60 20/20 24/24


Periodontal probe,a VASb

North Carolina University probe, VASb

North Carolina University probe, VASb

Type of defects Single sites Minimal keratinized tissue ≤ 1 mm

Minimal keratinized tissue ≤ 1 mm


NR NR CTG: 0.5 ± 1.0 CM: 0.4 ± 1.51

Width of KT (mm) CTG: 0.9 ± 0.8 CM: 1.1 ± 0.8

CTG: 2.4 ± 0.655c CM: 2.1 ± 0.395c

CTG: 2.33 ± 1.162c CM: 2.3 ± 0.290c

Gingival thickness (mm)

CTG: 1.2 ± 0.3 CM: 0.9 ± 0.2

NR NR


NR NR CTG: 0.0 ± 1.13 CM: –0.4 ± 1.07

Width of keratinized mucosa (%)

NR NR NR


CTG: 91 ± 9 CM: 95 ± 5

Not significant Not significant


Less pain favoring CM (P < .0001)

CTG: 4.01 ± 8.5 CM: 2.30 ± 2.39

NR


Less chair time favor-ing CM (P < .0001)

CTG: 47.20 ± 10 CM: 30.80 ± 7

CTG: 46.25 CM: 32.50

Length of observa-tion period (mo)

6 6 6


Partially supported by a research grant from Geistlich Pharma.

Partially supported by a research grant from Geistlich Pharma.

Supported by a research grant from Geistlich Pharma.



Code derived from a randomized list


Blinding Masked examiner Masked examiner Masked examinera#15 UNC Novatech Color-Coded Probe, Hu-Friedy.bVisual analogue scale was used to evaluate patient-centered outcomes.cThe missing standard deviation of a mean difference was calculated from a correlation coefficient calculated from a study reported in considerable detail according to the principles and techniques described in the Cochrane Handbook.CM = collagen matrix; CTG = connective tissue graft; VAS = visual analog scale; NR = not reported; KT = keratinized tissue.



e137

of CM vs CAF alone in natural teeth, there was only one eligible study in the MAGRs group, and thus the MAGRs subgroup was not avail-able for this comparison. Due to the limited number of studies and insufficient data, and in an effort to maintain the quality of the analy-sis, no subgroup analysis was per-formed with information provided by only one study in other groups or clinical parameters.

As the results show in Appendi-ces 6 to 9, the CTG group showed greater efficiency in achieving CRC in the MAGRs and 6-month–observa-tion subgroups, while no difference was found between the CM and CTG groups in the SGR and 12-month–observation subgroups. As for MRC, only the 6-month subgroup results showed significance with low het-erogeneity, while no difference was found between the CTG group and CM group in the MAGR, SGR, and 12-month subgroups. In terms of RD, the CTG group pre sents greater advantages in the subgroups SGR and 12 months, but limited evidence was observed to determine the significant difference in the MAGR and 6-month subgroups. Two sub-groups (MAGR and 6 months) of RW showed no statistically significant different outcomes compared to the results of the overall analysis of the group. CM could present similar outcomes in KTW gain in the SGR subgroup at low heterogeneity, but CTG had a significantly higher gain in KTW in the MAGR and 12-month–observation subgroups. The PPD in the SGR subgroup showed different outcomes compared with the overall group analysis, which indicated that

CM may not have a better outcome when treating SGR. Regarding CAL, the CTG group showed obvious ad-vantages over the CM group when treating SGR and achieved better 12-month results, which were not found in the MAGR and 6-month subgroups.

The results of subgroup analy-sis for comparison CM vs CAF alone were presented in Appendices 10 through 12. No difference was de-tected between CM and CAF alone in all subgroups at low heterogene-ity in terms of CRC and MRC. Sig-nificantly better improvements were found in both RD and GT of the SGR and 6-month subgroups. Although the results of RD and GT in the 12-month–observation subgroup showed no statistical significance, the high heterogeneity may indicate potential demand for more studies to detect the difference. Meanwhile, PPD and KTW in the 12-month sub-group presented better outcomes in CM group, showing greater efficacy in achieving stable long-term results. No significant difference was found in CAL of the 12-month subgroup.

Quality Classification of Evidence of the Review

The GRADE system was applied to evaluate the quality of evidence in the three comparison groups (CM vs CTG; CM vs CAF alone in natural teeth; CM vs CTG for den-tal implants). Outcomes at low het-erogeneity of overall meta-analysis or after sensitivity analysis were as-sessed by GRADE using a different process. The GRADE system has

four levels for rating the quality of evidence: high, moderate, low, and very low, which is identified based on the study design (RCT) and specific criteria to lower or raise the quality of studies included in that group.43

As the results showed in Tables 4 and 5, all outcomes were identi-fied at a moderate level of quality in the CM vs CTG and CM vs CAF alone comparisons. Additionally, the only outcomes of the group CM vs CTG for dental implants were also identified at moderate level of quality (Table 6).

Discussion

CM was first applied in periodon-tal plastic surgeries for augmenta-tion of KTW in 2009,25 and a series of studies and systemic reviews were subsequently conducted to evaluate the effectiveness of CM in treating gingival recession and in-sufficient KT.

According to a network meta-analysis published in 2013 that in-cluded two studies of SGR,17 CM plus CAF was less effective than ADM with CAF in terms of RD and CAL but more effective than enamel matrix derivative (EMD) with CAF. This network meta-analysis sug-gests that CM is possibly the best option for KT gain. In contrast, CM ranks as the last to obtain an advis-able rate of CRC compared with ADM or EMD. Although this net-work meta-analysis provides wider information about the clinical effi-cacy of CM compared with several other periodontal plastic proce-dures, it involves only two studies



e138

of CM. Another review published in 2014 mentions the comparison of CM vs CAF alone for SGR,44 but only one study is included in this net-work meta-analysis. A newly pub-lished systemic review included two studies in the comparison of CM vs CTG for SGR in natural teeth at 6- or 12-month follow-ups.45 This latest review45 reports similar outcomes in the CM group compared with the CTG group in terms of CRC, RD,

and KTW. No significant difference was observed between CM and CAF in the parameters CRC and RD, while CM had a statistically greater gain of KTW than CAF. Meta-anal-ysis has not been performed in this review, thus no detailed information of comparisons among different techniques is provided.

A recent review of six papers firstly reports a systemic evaluation and meta-analysis of CM, which

demonstrates comprehensive eval-uation of the application of CM in both clinical and patient-centered parameters.26 The results of that re-view indicate that CTG presents sig-nificantly higher efficacy compared with CM in improving CRC, RD, GT, and CAL. CM exhibits greater changes compared with CAF alone in terms of MRC, RD, KTW, and GT. In terms of other clinical parameters, like PPD, RW, or patient-centered

Table 4 Quality of Evidence from the Comparison of CM and CTG in Natural Teeth

Quality assessment No. of patients Effect

Quality ImportanceNo. of studies Design

Risk of bias1 Inconsistency Indirectness Imprecision

Other considerations CM CTG

Relative (95% CI) Absolute

Complete root coverage (follow-up mean 6 months) 3 Randomized trials Serious No serious inconsistency2 No serious indirectness No serious imprecision None 195/279

(69.9%)137/278 (49.3%)37.4%

RR 1.40 (1.22–1.62)

20 more per 100 (from 11 more to 31 more)15 more per 100 (from 8 more to 23 more)

Moderate Critical

Recession reduction (follow-up mean 9 months; better indicated by lower values) 4 Randomized trials Serious No serious inconsistency2 No serious indirectness No serious imprecision None 356 357 – MD 0.35 higher

(0.23 to 0.46 higher)Moderate Important

Changes of recession width (follow-up mean 9 months; better indicated by lower values) 2 Randomized trials Serious No serious inconsistency2 No serious indirectness No serious imprecision None 103 103 – MD 0.95 higher

(0.67 lower to 1.24 higher)Moderate Important

Width of keratinized tissue (follow-up median 12 months; better indicated by higher values) 5 Randomized trials Serious No serious inconsistency No serious indirectness No serious imprecision None 404 415 – MD 0.43 higher

(0.30 to 0.56 higher)Moderate Critical

Changes of probing pocket depth (follow-up mean 9 months; better indicated by lower values) 4 Randomized trials Serious No serious inconsistency No serious indirectness No serious imprecision None 356 357 – MD 0.11 lower

(0.16 to 0.05 lower)Moderate Critical

Changes in clinical attachment level (follow-up median 12 months; better indicated by lower values) 4 Randomized trials Serious No serious inconsistency2 No serious indirectness No serious imprecision None 173 161 – MD 0.30 higher


Changes in gingival tissue thickness (follow-up mean 12 months; better indicated by higher values) 2 Randomized trials Serious No serious inconsistency No serious indirectness No serious imprecision None 89 89 – MD 0.3 higher


Esthetic satisfaction (follow-up mean 9 months; better indicated by higher values) 2 Randomized trials Serious No serious inconsistency2 No serious indirectness No serious imprecision None 125 137 – MD 6.4 lower


Postoperative discomfort and morbidity (follow-up mean 9 months; better indicated by lower values) 2 Randomized trials Serious No serious inconsistency No serious indirectness No serious imprecision None 169 172 – MD 5.08 lower

(6.77 to 3.38 lower)Moderate Important

Operating time (follow-up mean 9 months; better indicated by lower values) 2 Randomized trials Serious No serious inconsistency No serious indirectness No serious imprecision None 169 172 – MD 16.13 lower


CM = collagen matrix; CTG = connective tissue graft; CI = confidence interval; RR = risk ratio; MD = mean difference.1All studies showed unclear risk of bias in the evaluation of quality.2High heterogeneity.



e139

outcomes like postoperative dis-comfort and esthetic satisfaction, the published review provides fi-nite evidence as a result of a limited number of included studies.

Compared with the previously mentioned study, the present sys-temic analysis involves more stud-ies and provides more detailed information for the comparison of CM with other techniques. In this re-view, according to the overall analy-

sis and sensitivity analysis and with two more studies included in the comparison of CM vs CAF alone in natural teeth, CM exhibits signifi-cantly greater gains in MRC and KT. Though CM also shows greater im-provement in CRC, this parameter presents no significant difference between two groups after sensitiv-ity and subgroup analysis. Signifi-cant differences were also detected in CAL and GT (favoring the CM and

CAF group). A significantly higher reduction of PPD was observed in CAF group in this review. In terms of patients’ esthetic satisfaction, which is not mentioned in the published review, no significant difference was detected between the two groups.

When compared with CTG, two more papers were included in the comparison, with CM exhibit-ing significantly greater efficiency in improving PPD as well as reducing postoperative discomfort and sur-gery time, which were not mentioned in the published review. The non–statistically significant differences noted in MRC and KTW in the pub-lished review26 are found significantly favoring CTG in the present review. An additional measure parameter is patients’ esthetic satisfaction, which presented no significant difference between the groups. Yet, CTG main-tains its advantage in achieving bet-ter CRC, RD, RW, GT, and CAL in this review, as reported above.

Moreover, an analysis of the effectiveness of CM used around dental implants to improve KT has not been previously mentioned, and this review demonstrates that CM can result in advisable outcomes in KT similar to those of CTG. The analysis potentially indicates with moderate-level evidence that CM can also reach suitable results in the treatment of peri-implant–induced insufficient KT.

The present review includes more studies with different follow-up periods and types of defects than previously published meta-analyses on the same subject. To evaluate overall the clinical efficien-cy of CM, a detailed subgroup and

Table 4 Quality of Evidence from the Comparison of CM and CTG in Natural Teeth



Risk of bias1 Inconsistency Indirectness Imprecision



Complete root coverage (follow-up mean 6 months) 3 Randomized trials Serious No serious inconsistency2 No serious indirectness No serious imprecision None 195/279

(69.9%)137/278 (49.3%)37.4%

RR 1.40 (1.22–1.62)

20 more per 100 (from 11 more to 31 more)15 more per 100 (from 8 more to 23 more)

Moderate Critical

Recession reduction (follow-up mean 9 months; better indicated by lower values) 4 Randomized trials Serious No serious inconsistency2 No serious indirectness No serious imprecision None 356 357 – MD 0.35 higher


Changes of recession width (follow-up mean 9 months; better indicated by lower values) 2 Randomized trials Serious No serious inconsistency2 No serious indirectness No serious imprecision None 103 103 – MD 0.95 higher


Width of keratinized tissue (follow-up median 12 months; better indicated by higher values) 5 Randomized trials Serious No serious inconsistency No serious indirectness No serious imprecision None 404 415 – MD 0.43 higher

(0.30 to 0.56 higher)Moderate Critical

Changes of probing pocket depth (follow-up mean 9 months; better indicated by lower values) 4 Randomized trials Serious No serious inconsistency No serious indirectness No serious imprecision None 356 357 – MD 0.11 lower


Changes in clinical attachment level (follow-up median 12 months; better indicated by lower values) 4 Randomized trials Serious No serious inconsistency2 No serious indirectness No serious imprecision None 173 161 – MD 0.30 higher


Changes in gingival tissue thickness (follow-up mean 12 months; better indicated by higher values) 2 Randomized trials Serious No serious inconsistency No serious indirectness No serious imprecision None 89 89 – MD 0.3 higher


Esthetic satisfaction (follow-up mean 9 months; better indicated by higher values) 2 Randomized trials Serious No serious inconsistency2 No serious indirectness No serious imprecision None 125 137 – MD 6.4 lower


Postoperative discomfort and morbidity (follow-up mean 9 months; better indicated by lower values) 2 Randomized trials Serious No serious inconsistency No serious indirectness No serious imprecision None 169 172 – MD 5.08 lower


Operating time (follow-up mean 9 months; better indicated by lower values) 2 Randomized trials Serious No serious inconsistency No serious indirectness No serious imprecision None 169 172 – MD 16.13 lower


CM = collagen matrix; CTG = connective tissue graft; CI = confidence interval; RR = risk ratio; MD = mean difference.1All studies showed unclear risk of bias in the evaluation of quality.2High heterogeneity.



e140

sensitivity analysis was performed to obtain more information. By grouping studies into subgroups of various defects and follow-up peri-ods, the heterogeneity among stud-ies was reduced for most clinical parameters.

In the comparison of CM vs CAF, outcomes initially had insig-

nificant differences in subgroups SGR and CRC at 6 and 12 months. The insignificant results with no ob-served heterogeneity may be due to the limited number of papers included, which were not enough to draw a meaningful conclusion. Secondly, the MRC for SGR and the 6-month and 12-month stages in

this comparison also show no sig-nificant difference between CM and CAF. Additionally, the heterogene-ity in the three subgroups is so high that the truly estimated effects can’t be revealed completely. Lastly, CM shows greater effects in improving KTW at the 12-month stage with no heterogeneity observed, which may

Table 5 Quality of Evidence from Comparison of CM and CAF Alone in Natural Teeth



Risk of bias Inconsistency Indirectness Imprecision

Other considerations CM CAF


Complete root coverage (follow-up mean 9 months) 4 Randomized trials Serious1 No serious inconsistency No serious indirectness No serious imprecision None 60/137

(43.8%)78/140 (55.7%)40%

RR 0.80 (0.64 to 1.0)

11 fewer per 100 (from 20 fewer to 0 more)8 fewer per 100 (from 14 fewer to 0 more)

Moderate Critical

Recession reduction (follow-up mean 8 months; better indicated by lower values) 3 Randomized trials Serious1 No serious inconsistency2 No serious indirectness No serious imprecision None 182 182 – MD 0.31 lower


Width of keratinized tissue (follow-up median 6 months; better indicated by higher values) 4 Randomized trials Serious1 No serious inconsistency No serious indirectness No serious imprecision None 137 140 – MD 0.29 lower


Changes in gingival tissue thickness (follow-up mean 8 months; better indicated by higher values) 3 Randomized trials Serious1 No serious inconsistency2 No serious indirectness No serious imprecision None 82 82 – MD 0.25 lower


Changes in probing pocket depth (follow-up mean 10 months; better indicated by lower values) 3 Randomized trials Serious1 No serious inconsistency2 No serious indirectness No serious imprecision None 120 117 – MD 0.12 higher


Changes in clinical attachment level (follow-up mean 9 months; better indicated by lower values) 4 Randomized trials Serious No serious inconsistency No serious indirectness No serious imprecision None 140 137 – MD 0.31 lower


Esthetic satisfaction (follow-up mean 9 months; better indicated by higher values) 2 Randomized trials Serious1 No serious inconsistency No serious indirectness No serious imprecision None 62 62 – MD 0.25 lower


CM = collagen matrix; CAF = coronally advanced flap; CI = confidence interval; RR = risk ratio; MD = mean difference. 1All studies showed unclear risk of bias in the evaluation of quality. 2High heterogeneity.

Table 6 Quality of Evidence from the Comparison of CM and CTG in Dental Implants






Width of keratinized tissue (follow-up mean 6 months; better indicated by higher values)3 Randomized trials Serious1 No serious inconsistency No serious indirectness No serious imprecision None 50 52 – MD 0.01 lower

(0.29 lower to 0.27 higher)Moderate Critical

CM = collagen matrix; CTG = connective tissue graft; CI = confidence interval; MD = mean difference.1All studies showed unclear risk of bias in the evaluation of quality.



e141

suggest that CM has better long-term stability in KTW compared with CAF alone. The difference in KTW at the 6-month stage shows no significant difference.

As for the comparison of CM vs CTG, CM had an effect similar to CTG in the SGR and 12-month sub-groups in CRC, while the MGR and

6-month subgroups still slightly fa-vor CTG. In terms of MRC, only the 6-month follow-up subgroup was found to be significantly greater in the CTG group, and the other three subgroups showed insignificant differences between CM and CTG groups in MRC. For KTW, the CM group showed comparable results

in the SGR and 6-month subgroups, while the CTG group had a great-er gain in KTW in the MGR and 12-month subgroups.

In the subgroup analysis, though different outcomes were provided than the overall estimated effects presented before, the unevenly presented heterogeneity limited the quality of evidence. Since the subgroups were classified by single factors (types of defects or various follow-up periods), studies of differ-ent defects could be included in the same follow-up–period subgroup, which may explain the high hetero-geneity detected. All these results suggest that the subgroups for two comparisons cannot avoid all poten-tial factors that may affect the analy-sis outcomes. Therefore, to increase the reliability of the results, it is nec-essary to conduct more clinical trials with larger numbers of patients and longer observation periods for dif-ferent defects.

Remarkably, the patient-centered esthetic-satisfaction analy-sis in the comparison of CM vs CTG in natural teeth was performed based on information provided by two MAGR studies. One study34 reported familiar patient-centered esthetic satisfaction in SGR with no significant difference, and in the present study, the esthetic satisfac-tion in the comparison of CM vs CAF in natural teeth also presented no significant difference in SGR be-tween the two groups (though the CM group was favored slightly). Therefore, CM can possibly provide advisable esthetic satisfaction com-pared with CTG and CAF alone, es-pecially for MAGRs in root-coverage

Table 5 Quality of Evidence from Comparison of CM and CAF Alone in Natural Teeth




Other considerations CM CAF


Complete root coverage (follow-up mean 9 months) 4 Randomized trials Serious1 No serious inconsistency No serious indirectness No serious imprecision None 60/137

(43.8%)78/140 (55.7%)40%

RR 0.80 (0.64 to 1.0)

11 fewer per 100 (from 20 fewer to 0 more)8 fewer per 100 (from 14 fewer to 0 more)

Moderate Critical

Recession reduction (follow-up mean 8 months; better indicated by lower values) 3 Randomized trials Serious1 No serious inconsistency2 No serious indirectness No serious imprecision None 182 182 – MD 0.31 lower


Width of keratinized tissue (follow-up median 6 months; better indicated by higher values) 4 Randomized trials Serious1 No serious inconsistency No serious indirectness No serious imprecision None 137 140 – MD 0.29 lower


Changes in gingival tissue thickness (follow-up mean 8 months; better indicated by higher values) 3 Randomized trials Serious1 No serious inconsistency2 No serious indirectness No serious imprecision None 82 82 – MD 0.25 lower


Changes in probing pocket depth (follow-up mean 10 months; better indicated by lower values) 3 Randomized trials Serious1 No serious inconsistency2 No serious indirectness No serious imprecision None 120 117 – MD 0.12 higher


Changes in clinical attachment level (follow-up mean 9 months; better indicated by lower values) 4 Randomized trials Serious No serious inconsistency No serious indirectness No serious imprecision None 140 137 – MD 0.31 lower


Esthetic satisfaction (follow-up mean 9 months; better indicated by higher values) 2 Randomized trials Serious1 No serious inconsistency No serious indirectness No serious imprecision None 62 62 – MD 0.25 lower


CM = collagen matrix; CAF = coronally advanced flap; CI = confidence interval; RR = risk ratio; MD = mean difference. 1All studies showed unclear risk of bias in the evaluation of quality. 2High heterogeneity.

Table 6 Quality of Evidence from the Comparison of CM and CTG in Dental Implants






Width of keratinized tissue (follow-up mean 6 months; better indicated by higher values)3 Randomized trials Serious1 No serious inconsistency No serious indirectness No serious imprecision None 50 52 – MD 0.01 lower

(0.29 lower to 0.27 higher)Moderate Critical

CM = collagen matrix; CTG = connective tissue graft; CI = confidence interval; MD = mean difference.1All studies showed unclear risk of bias in the evaluation of quality.



e142

surgeries. An obviously significant difference in postoperative discom-fort was also noted in MAGRs in the comparison of CM vs CTG in natural teeth. One study34 in this group re-ported insignificant results in SGR, but another study31 was associated with more-severe postoperative dis-comfort in the CM group of MAGRs. Most studies suggest that CM could effectively decrease postoperative pain and edema, but due to lim-ited information, there is limited evi-dence to support these conclusions. Besides, shorter surgery time in the CM group as compared with CTG group was also estimated from two studies30,32 treating MAGRs, and no available information was reported by studies treating SGRs.

A multicenter clinical trial after 3 years of observation concluded a long-term stability of CM with two of six centers (18/45 participants) remained.46 The MRC grew from 89.9% (at 6 months) up to 91.7% (at 3 years) after surgery in the CM group, while MRC in the CAF group dropped from 83.7% (at 6 months) to 82.8% (at 3 years). CRC of the two groups was the same after 3 years. Using a visual analog scale to as-sess overall satisfaction with the treatment showed better results in the CM group (9.75) than the CAF group (9.57). On the contrary, an-other clinical trial47 comparing the efficacy of CM and CTG treatments at the 5-year follow-up in 17 patients reported that the MRC of the CM group changed from 89.5% (at 6 months) to 77.6% (at 5 years), and in the CTG group changed from 97.5%

(at 6 months) to 95.5% (at 5 years). No significant difference in patient satisfaction was observed after 5 years. The two studies showed sta-ble long-term results of CM in both root coverage and patient satisfac-tion, though the changes were in-consistent, and demonstrated that the long-term stability of CM is infe-rior to CTG but superior to CAF.

In summary, not only can the addition of CM effectively improve the clinical efficacy of CAF alone, it is also related with potentially high-er patient-centered esthetic sat-isfaction and lower postoperative discomfort compared with CTG. From this review, it can be inferred that CM is a promising alternative for autogenous soft tissue grafts in periodontal plastic surgeries. In the future, more high-quality RCTs conducted with different defects, various techniques, and long-term follow-up periods are suggested to clarify the differences between CM and autogenous soft tissue grafts.

Conclusions

CM is a promising substitute relat-ed with advisable patient-centered outcomes. CM in combination with CAF is not superior to CTG plus CAF in CRC, MRC, and KTW pa-rameters, but CM can effectively im-prove the clinical efficiency of CAF alone in CRC, MRC, and KTW.

Acknowledgments

This paper was self-supported, and the au-thors have stated explicitly that this research did not receive any specific grant from fund-ing agencies in the public, commercial, or not-for-profit sectors. The authors declare no conflicts of interest.

References

1. Nieri M, Pini Prato GP, Giani M, Magnani N, Pagliaro U, Rotundo R. Patient per-ceptions of buccal gingival recessions and requests for treatment. J Clin Peri-odontol 2013;40:707–712.

2. Chambrone L, Chambrone D, Pustiglioni FE, Chambrone LA, Lima LA. Can sub-epithelial connective tissue grafts be considered the gold standard proce-dure in the treatment of Miller Class I and II recession-type defects? J Dent 2008; 36:659–671.

3. Lang NP, Löe H. The relationship be-tween the width of keratinized gingiva and gingival health. J Periodontol 1972; 43:623–627.

4. Agudio G, Nieri M, Rotundo R, Cortellini P, Pini Prato G. Free gingival grafts to increase keratinized tissue: A retro-spective long-term evaluation (10 to 25 years) of outcomes. J Periodontol 2008; 79:587–594.

5. Metin M, Dolanmaz D, Alkan A. Evalu-ation of autogenous grafts used in vestibuloplasty. J Int Med Res 2003;31: 335–339.

6. Camargo PM, Melnick PR, Kenney EB. The use of free gingival grafts for aes-thetic purposes. Periodontol 2000 2001;27:72–96.

7. Griffin TJ, Cheung WS, Zavras AI, Damoulis PD. Postoperative compli-cations following gingival augmenta-tion procedures. J Periodontol 2006; 77:2070–2079.

8. Wessel JR, Tatakis DN. Patient out-comes following subepithelial connec-tive tissue graft and free gingival graft procedures. J Periodontol 2008;79: 425–430.

9. Cairo F, Pagliaro U, Nieri M. Treatment of gingival recession with coronally ad-vanced flap procedures: A systematic review. J Clin Periodontol 2008;35(suppl 8):s136–s162.



e143

10. Chambrone L, Sukekava F, Araújo MG, Pustiglioni FE, Chambrone LA, Lima LA. Root-coverage procedures for the treatment of localized recession-type defects: A Cochrane systematic review. J Periodontol 2010;81:452–478.

11. Hofmänner P, Alessandri R, Laugisch O, et al. Predictability of surgical techniques used for coverage of mul-tiple adjacent gingival recessions—A systematic review. Quintessence Int 2012;43:545–554.

12. Sanz M, Simion M, Working Group 3 of the European Workshop on Peri-odontology. Surgical techniques on periodontal plastic surgery and soft tissue regeneration: Consensus report of Group 3 of the 10th European Work-shop on Periodontology. J Clin Peri-odontol 2014;41(suppl 15):s92–s97.

13. Madeley E, Duane B. Coronally ad-vanced flap combined with connective tissue graft; treatment of choice for root coverage following recession? Evid Based Dent 2017;18:6–7.

14. Guan W. Liao H, Guo L, Wang C, Cao Z. Root coverage using a coronally ad-vanced flap with or without acellular dermal matrix: A meta-analysis. J Peri-odontal Implant Sci 2016;46:22–34.

15. Cheng GL, Fu E, Tu YK, et al. Root cov-erage by coronally advanced flap with connective tissue graft and/or enamel matrix derivative: A meta-analysis. J Periodontal Res 2015;50:220–230.

16. Cairo F, Nieri M, Pagliaro U. Efficacy of periodontal plastic surgery procedures in the treatment of localized facial gin-gival recessions. A systematic review. J Clin Periodontol 2014;41(suppl 15):s44–s62.

17. Buti J, Baccini M, Nieri M, La Marca M, Pini-Prato GP. Bayesian network meta-analysis of root coverage procedures: Ranking efficacy and identification of best treatment. J Clin Periodontol 2013;40:372–386.

18. Hofmänner P, Alessandri R, Laugisch O, et al. Predictability of surgical techniques used for coverage of mul-tiple adjacent gingival recessions—A systematic review. Quintessence Int 2012;43:545–554.

19. Cairo F, Pagliaro U, Buti J, et al. Root coverage procedures improve patient aesthetics. A systematic review and Bayesian network meta-analysis. J Clin Periodontol 2016;43:965–975.

20. Ghanaati S, Schlee M, Webber MJ, et al. Evaluation of the tissue reaction to a new bilayered collagen matrix in vivo and its translation to the clinic. Biomed Mater 2011;6:015010.

21. Camelo M, Nevins M, Nevins ML, Sch-upbach P, Kim DM. Treatment of gin-gival recession defects with xenogenic collagen matrix: A histologic report. Int J Periodontics Restorative Dent 2012;32:167–173.

22. Schmitt CM, Tudor C, Kiener K, et al. Vestibuloplasty: Porcine collagen ma-trix versus free gingival graft: A clini-cal and histologic study. J Periodontol 2013;84:914–923.

23. Vignoletti F, Nuñez J, de Sanctis F, Lo-pez M, Caffesse R, Sanz M. Healing of a xenogeneic collagen matrix for kera-tinized tissue augmentation. Clin Oral Implants Res 2015;26:545–552.

24. Herford AS, Akin L, Cicciu M, Maio-rana C, Boyne PJ. Use of a porcine collagen matrix as an alternative to au-togenous tissue for grafting oral soft tissue defects. J Oral Maxillofac Surg 2010;68:1463–1470.

25. Sanz M, Lorenzo R, Aranda JJ, Martin C, Orsini M. Clinical evaluation of a new collagen matrix (Mucograft prototype) to enhance the width of keratinized tissue in patients with fixed prosthetic restorations: A randomized prospec-tive clinical trial. J Clin Periodontol 2009;36:868–876.

26. Atieh MA, Alsabeeha N, Tawse-Smith A, Payne AG. Xenogeneic collagen matrix for periodontal plastic sur-gery procedures: A systematic review and meta-analysis. J Periodontal Res 2016;51:438–452.

27. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. BMJ 2009;339:b2535.

28. Miller SA, Forrest JL. Enhancing your practice through evidence-based deci-sion making: PICO, learning how to ask good questions. J Evid Base Dent Pract 2001;1:136–141.

29. Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928.

30. Tonetti MS, Cortellini P, Pellegrini G, et al. Xenogenic collagen matrix or autologous connective tissue graft as adjunct to coronally advanced flaps for coverage of multiple adjacent gingival recession: Randomized trial assessing non-inferioirity in root coverage and su-periority in oral health-related quality of life. J Clin Periodontol 2018;45:78–88.

31. Cieslik-Wegemund M, Wierucka-Młynarczyk B, Tanasiewicz M, Gilowski Ł. Tunnel technique with collagen matrix compared with connective tissue graft for treatment of periodontal recession: A randomized clinical trial. J Periodontol 2016;87:1436–1443.

32. Aroca S, Molnár B, Windisch P, et al. Treatment of multiple adjacent Miller Class I and II gingival recessions with a modified coronally advanced tunnel (MCAT) technique and a collagen matrix or palatal connective tissue graft: A ran-domized, controlled clinical trial. J Clin Periodontol 2013;40:713–720.

33. Cardaropoli D, Tamagnone L, Roffredo A, Gaveglio L. Treatment of gingival recession defects using coronally ad-vanced flap with a porcine collagen matrix compared to coronally advanced flap with connective tissue graft: A ran-domized controlled clinical trial. J Peri-odontol 2012;83:321–328.

34. McGuire MK, Scheyer ET. Xenogeneic collagen matrix with coronally advanced flap compared to connective tissue with coronally advanced flap for the treat-ment of dehiscence-type recession de-fects. J Periodontol 2010;81:1108–1117.

35. Jepsen K, Jepsen S, Zucchelli G, et al. Treatment of gingival recession defects with a coronally advanced flap and a xenogeneic collagen matrix: A multi-center randomized clinical trial. J Clin Periodontol 2013;40:82–89.

36. Cardaropoli D, Tamagnone L, Roffredo A, Gaveglio L. Coronally advanced flap with and without a xenogenic collagen matrix in the treatment of multiple re-cessions: A randomized controlled clini-cal study. Int J Periodontics Restorative Dent 2014;34(suppl 3):s97–s102.

37. Stefanini M, Jepsen K, de Sanctis M, et al. Patient-reported outcomes and aesthetic evaluation of root coverage procedures: A 12-month follow-up of a randomized controlled clinical trial. J Clin Periodontol 2016;43:1132–1141.



e144

38. Sangiorgio JPM, Neves FLDS, Rocha Dos Santos M, et al. Xenogenous colla-gen matrix and/or enamel matrix deriva-tive for treatment of localized gingival recessions: A randomized clinical trial. Part I: Clinical outcomes. J Periodontol 2017;88:1309–1318.

39. Moreira ARO, Santamaria MP, Silvério KG, et al. Coronally advanced flap with or without porcine collagen matrix for root coverage: A randomized clinical tri-al. Clin Oral Investig 2016;20:2539–2549.

40. McGuire MK, Scheyer ET. Randomized, controlled clinical trial to evaluate a xe-nogeneic collagen matrix as an alter-native to free gingival grafting for oral soft tissue augmentation. J Periodontol 2014;85:1333–1341.

41. Cairo F, Barbato L, Tonelli P, Batalocco G, Pagavino G, Nieri M. Xenogeneic col-lagen matrix versus connective tissue graft for buccal soft tissue augmentation at implant site. A randomized, controlled clinical trial. J Clin Periodontol 2017; 44:769–776.

42. Lorenzo R, García V, Orsini M, Martin C, Sanz M. Clinical efficacy of a xeno-geneic collagen matrix in augmenting keratinized mucosa around implants: A randomized controlled prospective clin-ical trial. Clin Oral Implants Res 2012;23: 316–324.

43. Aguayo-Albasini JL, Flores-Pastor B, Soria-Aledo V. GRADE system: Clas-sification of quality of evidence and strength of recommendation [in Span-ish]. Cir Esp 2014;92:82–88.

44. Cairo F, Nieri M, Pagliaro U. Efficacy of periodontal plastic surgery procedures in the treatment of localized facial gin-gival recessions. A systematic review. J Clin Periodontol 2014;41(suppl 15): s44–s62.

45. Amine K, El Amrani Y, Chemlali S, Kissa J. Alternatives to connective tissue graft in the treatment of localized gingival re-cessions: A systematic review. J Stoma-tol Oral Maxillofac Surg 2018;119:25–32.

46. Jepsen K, Stefanini M, Sanz M, Zuc-chelli G, Jepsen S. Long-term stability of root coverage by coronally advanced flap procedures. J Periodontol 2017;88: 626–633.

47. McGuire MK, Scheyer ET. Long-term results comparing xenogeneic collagen matrix and autogenous connective tis-sue grafts with coronally advanced flaps for treatment of dehiscence-type reces-sion defects. J Periodontol 2016;87:221–227.



e145

Appendix 1 Comparison of CM vs CTG in Natural Teeth. (1) CRC = complete root coverage; (2) MRC = mean root coverage; (3) RD = recession reduction; (4) RW = changes of recession width; (5) KTW = width of keratinized tissue; (6) PPD = changes of probing pocket depth; (7) CAL = changes in clinical attachment level; (8) GT = changes in gingival tissue thickness; (9) Aesthetic satisfaction; (10) Postoperative discomfort; (11) Surgery time. CM = collagen matrix; CTG = connective tissue graft.



e146

Appendix 2 Comparison of CM vs CAF in Natural Teeth. (1) CRC = complete root coverage; (2) MRC = mean root coverage; (3) RD = recession reduction; (4) KTW = width of keratinized tissue; (5) GT = changes in gingival tissue thickness; (6) PPD = changes of probing pocket depth; (7) CAL = changes in clinical attachment level; (8) Aesthetic satisfaction. CM = collagen matrix; CAF = coronally advanced flap.



e147

Appendix 4 Heterogeneity Analysis for Comparison of CM vs CTG in Natural Teeth. (1) CRC = complete root coverage; (2) MRC = mean root coverage; (3) RD = recession reduction; (4) RW = changes of recession width. CM = collagen matrix; CTG = connective tissue graft.

Appendix 3 KTW (Comparison of CM vs CTG in Dental Implants). KTW = width of keratinized tissue; CM = collagen matrix; CTG = connective tissue graft.



e148

Appendix 5 Heterogeneity Analysis for Comparison of CM vs CAF in Natural Teeth. (1) MRC = mean root coverage; (2) RD = recession reduction; (3) GT = changes in gingival tissue thickness; (4) PPD = changes of probing pocket depth. CM= collagen matrix; CAF = coronally advanced flap.



e149

Appendix 6 Subgroup Analysis in CM vs CTG for MAGRs in Natural Teeth. (1) CRC = complete root coverage; (2) MRC = mean root coverage; (3) RD = recession reduction; (4) RW = changes of recession width; (5) KTW = width of keratinized tissue; (6) CAL = changes in clinical attachment level; (7) PPD = changes of probing pocket depth. CM = collagen matrix; CTG = connective tissue graft; MAGR = multiple adjacent gingival recession.



e150

Appendix 7 Subgroup Analysis in CM vs CTG for SGR in Natural Teeth. (1) CRC = complete root coverage; (2) MRC = mean root coverage; (3) RD = recession reduction; (4) KTW = width of keratinized tissue; (5) PPD = changes of probing pocket depth; (6) CAL = changes in clinical attachment level. CM = collagen matrix; CTG = connective tissue graft; SGR = single gingival recession.



e151

Appendix 8 Subgroup Analysis in CM vs CTG for the 6-Month Stage in Natural Teeth. (1) CRC = complete root coverage; (2) MRC = mean root coverage; (3) RD = recession reduction; (4) RW = changes of recession width; (5) CAL = changes in clinical attachment level; (6) KTW = width of keratinized tissue. CM = collagen matrix; CTG = connective tissue graft.



e152

Appendix 9 Subgroup Analysis in CM vs CTG for the 12-Month Stage in Natural Teeth. (1) CRC = complete root coverage; (2) MRC = mean root coverage; (3) RD = recession reduction; (4) CAL = changes in clinical attachment level; (5) KTW = width of keratinized tissue. CM = collagen matrix; CTG = connective tissue graft.



e153

Appendix 10 Subgroup Analysis in CM vs CAF Alone for SGR in Natural Teeth. (1) CRC = complete root coverage; (2) MRC = mean root coverage; (3) RD = recession reduction; (4) GT = changes in gingival tissue thickness; (5) PPD = changes of probing pocket depth. CM = collagen matrix; CAF = coronally advanced flap; SGR = single gingival recession.



e154

Appendix 11 Subgroup Analysis in CM vs CAF Alone for the 6-Month Stage in Natural Teeth. (1) CRC = complete root coverage; (2) MRC = mean root coverage; (3) GT = changes in gingival tissue thickness; (4) RD = recession reduction; (5) PPD = changes of probing pocket depth; (6) KTW = width of keratinized tissue; (7) CAL = changes in clinical attachment level. CM = collagen matrix; CAF = coronally advanced flap; SGR = single gingival recession.



e155

Appendix 12 Subgroup Analysis in CM vs CAF Alone for the 12-Month Stage in Natural Teeth. (1) CRC = complete root coverage; (2) MRC = mean root coverage; (3) RD = recession reduction; (4) GT = changes in gingival tissue thickness; (5) KTW = width of keratinized tissue; (6) PPD = changes of probing pocket depth; (7) CAL = changes in clinical attachment level. CM = collagen matrix; CAF = coronally advanced flap.


Documents

Collagen Matrix for Periodontal Plastic Surgery Procedures