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Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review
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Int. J. Oral Maxillofac. Surg. 2019; xxx: xxx–xxx https://doi.org/10.1016/j.ijom.2019.12.005, available online at https://www.sciencedirect.com
Systematic Review Dental Implants
Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review
W. Lu1,2, G. Qi1,2, Z. Ding3, X. Li1,2, W. Qi2,4, F. He2,4 1 Department of Periodontics, The Affiliated Stomatology Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; 2Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; 3Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, Zhejiang, China; 4Department of Oral Implantology and Prosthodontics, The Affiliated Stomatology Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
W. Lu, G. Qi, Z. Ding, X. Li, W. Qi, F. He: Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review. Int. J. Oral Maxillofac. Surg. 2019; xxx: xxx–xxx. ã 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Abstract. This review was performed to validate the clinical efficacy of acellular dermal matrix (ADM) for plastic periodontal and implant surgery. Four electronic databases and a manual search were utilized to select randomized clinical trials (RCTs) published until March 2019. Overall, 28 RCTs were included: 25 on teeth and three on implants. For plastic periodontal surgery, ADM exhibited a comparable gingival recession reduction (RecRed) and soft tissue thickness (STT) gain to connective tissue graft (CTG). Subgroup analyses revealed that ADM obtained a similar keratinized tissue width (KTW) gain to CTG within 3–6 months postoperative, but significantly less KTW gain at 1–5 years postoperative (P = 0.01, mean difference (MD) 0.86 mm). Analyses comparing ADM with free gingival graft (FGG) demonstrated similar RecRed but significantly more KTW/STT gain favouring FGG (KTW: P = 0.01, MD 1.78 mm; STT: P = 0.01, MD 0.77 mm). Significantly more RecRed and KTW/STT gain were verified in ADM + coronally advanced flap/laterally positioned flap compared with these flaps alone (RecRed: P < 0.00001, MD 0.65 mm; KTW: P = 0.001, MD 0.66 mm; STT: P < 0.00001, MD 0.59 mm). Limited data for implant surgery indicated a similar trend as for periodontal surgery. Concerning patient-reported outcomes, ADM achieved favourable aesthetic appearance, alleviation of dentinal hypersensitivity, and less surgical morbidity. In conclusion, ADM exerted comparable clinical efficacy to autogenous tissue for root coverage procedures, with good long-term stability. However, for soft tissue augmentation, ADM exhibited inferior 3–6-month postoperative outcomes compared with FGG and less long-term stability of KTW gain compared with CTG.
0901-5027/000001+010
Key words: acellular dermal matrix; plastic surgery; soft tissue augmentation; root coverage. Accepted for publication
ã 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Lu W, et al. Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.12.005
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Among all the mucogingival deformities, insufficient keratinized tissue and gingival recession are the most prevalent conditions that demand surgical correction1. Accordingly, soft tissue augmentation and root coverage procedures are essential parts of plastic surgery protocols. These procedures include coronally or laterally advanced flaps, double papillae repositioned flaps, sub-epithelial connective tissue grafts (CTG), free gingival grafts (FGG), the tunnel technique, and the bilaminar technique of pedicle flaps and grafts or barrier membranes. Undeniably, autogenous tissue grafts, including the CTG and FGG, remain the gold standard for both soft tissue augmentation and root coverage procedures2,3. Substantial evidence has confirmed that the CTG combined with a coronally advanced flap (CAF) achieves favourable root coverage of recession4 and that the FGG-based apically positioned flap/vestibuloplasty optimally widens the keratinized tissue zone5. Nevertheless, there are some noticeable disadvantages of harvesting autogenous tissue, such as postoperative bleeding and pain/discomfort at the donor site, a restricted supply of tissue, longer operative duration, increased morbidity, and additional expertise of the surgeon6. In order to overcome the drawbacks of autogenous tissue harvesting, several nonvital allograft substitutes have been produced as alternative options for plastic periodontal and implant surgery. An example is acellular dermal matrix (ADM), a dermal allograft derived from human skin7. During the processing of AlloDerm, one of the oldest and most utilized ADM products, the epithelium is first eliminated from the cadaveric skin using hypertonic saline and the cells are subsequently extracted using a series of detergents (0.1% glutaraldehyde, 0.5% sodium dodecyl sulphate, and 0.25% trypsin); this is done to prevent an antigenic response/ immunological rejection caused by HLA antigenicity, as well as to inactivate viruses8. The material is then cryoprotected, freeze-dried, and packaged in a proprietary process for immediate use. Since its initial use in the 20th century9,10, ADM has been used extensively in various areas of dental practice over the last two decades3,11. In particular, when the donor supply is inadequate and/or the patient is fearful of additional surgery, ADM has been proposed as an alternative option for plastic periodontal and implant surgery12. However, there remain concerns regarding the use of ADM, due to the associated ethical issues and the risk of
disease transmission. The manufacturer of AlloDerm (LifeCell) states that the donor blood sample is tested for infectious diseases, including HIV and hepatitis B and C viruses. The tissue samples are also screened for microbial contaminants and pathogenic bacteria. Moreover, the patented ADM process (U.S. Patent 5,336,616) demonstrates more than 99.9% viral reduction and that no cells or microbial pathogens are detected using professional tests. Nevertheless, it is difficult to entirely remove all cell remnants; thus there remains a low theoretical risk of disease transmission, which is the case for all preparations derived from allografts. Although ADM has yielded promising outcomes in numerous trials and its clinical efficacy has been discussed in several standard and commissioned reviews (i.e., European Federation of Periodontology, American Academy of Periodontology, and Cochrane), conclusions about the application of this material are still unclear and controversial. Moreover, evidence on the long-term clinical outcomes and patient-reported outcomes relevant to ADM is of low level. Therefore, the aim of this investigation was to conduct a comprehensive systematic review and meta-analysis with high methodological strength of evidence, focusing on clinical long-term stability and patient-centred parameters, in order to thoroughly verify the clinical efficacy of ADM for plastic periodontal and implant surgery.
Materials and methods Protocol and PICO (participants, intervention, comparison, outcomes) question
The protocol of this systematic review was developed in accordance with the PRISMA Statement (Preferred Reporting Items for Systematic Reviews and Meta-analyses)13,14 and was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42019111172). This review attempted to answer the following focused question: In systemically healthy patients with exposed roots or implants or lack of keratinized tissue (P, population), does ADM-based plastic periodontal and implant surgery (I, intervention), compared to conventional techniques for plastic periodontal and implant surgery (e.g. CAF or laterally positioned flap (LPF) or FGG or CTG + CAF) (C, control), result in a gain of keratinized tissue, resolution of gingival recession,
and improved patient-reported outcomes (O, outcomes)?
Eligibility criteria
Only randomized clinical trials (RCTs) of systemically healthy adult patients undergoing ADM-based plastic periodontal or implant surgery, with at least 3 months of follow-up, were eligible for inclusion. Primary clinical parameters (keratinized tissue width (KTW), soft tissue thickness (STT), and reduction of gingival recession (RecRed)) had to be evaluated quantitatively. If multiple studies with the same population were identified, the trial with the longest follow-up duration or with the lowest drop-out rate was selected for meta-analysis. Publications on in vitro studies and those investigating different incisions or surgical variations (e.g. with or without a vertical incision, CAF versus tunnel technique) with the same ADMbased surgical treatment in both groups were excluded. Studies in which it was not possible to identify the effect of ADM alone in plastic periodontal and implant surgery (e.g. those studying a combination of ADM with enamel matrix derivative, platelet-rich plasma, or guided bone regeneration) were also excluded.
Literature search strategy
Relevant RCTs published up until October 2004 that were included in a previous systematic review were identified12. Electronic searches of the literature, covering the period November 2004 to March 2019, were performed in the following databases: MEDLINE/PubMed, Google Scholar, Cochrane Library, and Web of Science. Moreover, an additional manual search of relevant journals was conducted (Fig. 1) and attempts were made to search the grey literature and unpublished data on the clinicaltrials.gov website. There was no restriction on publication language. The search terms, selection protocol, and data extraction are given in the Supplementary Material (Appendix S1).
Data items
Primary outcomes included KTW gain, STT gain, RecRed, and patient-reported outcomes. Secondary outcomes included mean root coverage, complete root coverage, clinical attachment level gain, probing depth reduction, wounding healing, complications, and clinicianassessed aesthetics.
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Fig. 1. Flowchart of the study selection process.
Quality assessment
Two reviewers (WL, ZD) independently assessed the methodological quality of all eligible RCTs with reference to the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The six domains/questions for evaluation included random sequence generation, allocation concealment, blinding of outcome assessment, incomplete outcome data, selected reporting, and other bias15. If the study met all criteria, the degree of bias was considered as low risk; if the study was missing fewer than three criteria, the degree of bias was ranked as moderate risk; otherwise (missing three or more criteria), the risk was categorized as high.
the individual effects of comparisons and the global estimation. The unit of analysis was the soft tissue defect site rather than the patient. Heterogeneity derived from the discrepant treatment effect of each study was evaluated using Cochran’s test16. The results of the Q statistic (significant at P < 0.10) and I2 test (25%: low; 50%: moderate; 75%: high heterogeneity) were utilized to assess the level of heterogeneity17. Sensitivity analyses and subgroup analyses were performed when necessary. Considering the power to detect publication bias, those analyses with fewer than 10 studies were not formally assessed18; otherwise publication bias was evaluated via funnel plots. The significant P-value level was defined as 0.05.
Statistical analyses
The statistical analyses were performed using RevMan 5.3 software (Cochrane Collaboration, Oxford, UK). The mean difference and standard deviation were used to describe the continuous outcomes from each trial, while dichotomous data such as complete root coverage were expressed as risk ratio estimates. Statistical quantitative outcomes were depicted as weighted mean differences (MD) with 95% confidence intervals (CI). In the case of unclear data for the standard deviation, the value was estimated as the square root of the sum of the variances of the measures12. The fixed-effects model was used in the event of low heterogeneity, while the random-effects model was used when moderate or high heterogeneity was present. Forest plots were drawn to illustrate
were on implants. A flowchart of the study selection process is displayed in Fig. 1. Included studies
A list of the 28 included RCTs and their respective characteristics is presented in the Supplementary Material (Appendix S3)19,21–47. Twenty-five studies reported the origin/manufacturer of the ADM, which was consistently found to be AlloDerm (a product of LifeCell). The selected RCTs conducted ADMbased plastic periodontal or implant surgery and these trials were further divided into the following comparisons: (1) around teeth (three comparisons): ADM versus CTG, ADM versus FGG, ADM + CAF/LPF versus CAF/LPF; (2) around implants (two comparisons): ADM versus CTG, ADM versus FGG.
Results Study selection and study characteristics
Quality assessment and publication bias
The electronic search yielded a total of 244 articles after the exclusion of duplicates. Following the reading of titles/ abstracts, 60 articles were included in the full-text assessment. Thirty-two of these were excluded for reasons based on the predetermined eligibility criteria (Supplementary Material, Appendix S2). Two trials conducted by Coˆrtes et al.19,20 referred to the same population but with two different follow-up durations (6 months and 5 years, respectively). Hence, the study with the longer follow-up duration was included in the analyses. Finally, 28 RCTs were eligible for statistical analysis, of which 25 were on teeth and three
The results of the quality assessment for the RCTs included are shown in the Supplementary Material (Appendix S4). In summary, four RCTs had a low risk of bias, 14 a moderate risk, and 10 a high risk. Funnel plots revealed consistent symmetry, which indicated a low risk of publication bias (Supplementary Material, Appendix S5). Results of the meta-analyses of primary outcomes
A total of 750 soft tissue deficient sites in 511 patients included in 28 eligible RCTs were assigned to specific comparisons for
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Fig. 2. Meta-analyses of keratinized tissue width (KTW) gain around teeth (millimetres). (A) Overall analysis of ADM versus CTG. (B) Subgroup analysis of ADM versus CTG with 3–6 months of follow-up. (C) Subgroup analysis of ADM versus CTG with 1–5 years of follow-up. (D) ADM versus FGG. (E) ADM + CAF/LPF versus CAF/LPF. (ADM, acellular dermal matrix; CTG, connective tissue graft; FGG, free gingival graft; CAF, coronally advanced flap; LPF, laterally positioned flap.).
Please cite this article in press as: Lu W, et al. Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.12.005
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Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review quantitative analysis and estimation of the effect size of all the parameters of interest. Analysis of plastic periodontal surgery— KTW gain
The comparison of ADM versus CTG around teeth (17 studies) included 16 trials using graft material combined with CAF22–26,28,30–33,35,37,40–43 [Au?1] and one trial with a double papillary flap34. The result indicated a significant mean difference of 0.46 mm favouring CTG (P = 0.002, 95% CI 0.75 to x2 = 43.02 (df = 16), 0.17 mm; P = 0.0003, I2 = 63%) (Fig. 2A). The sensitivity analysis excluding low-quality studies revealed similar heterogeneity, but no significant difference between the groups (P = 0.30) (Supplementary Material, Appendix S6A). Due to the substantial heterogeneity of the data and inconsistent follow-up durations, subgroup analyses were conducted. Subgroup one comprised 14 studies reporting KTW at 3–6 months postoperative; the meta-analysis revealed a borderline significant difference favouring CTG (P = 0.04, MD 0.30 mm, 95% CI 0.60 to 0.01 mm; x2 = 26.87 (df = 13), P = 0.01, I2 = 52%) (Fig. 2B). However, analysis of the eight high- and moderatequality studies of subgroup one exhibited no significant difference (P = 0.89) with low heterogeneity (x2 = 8.87 (df = 7), P = 0.26, I2 = 21%) (Supplementary Ma-
terial, Appendix S6B). Subgroup two comprised four studies recording KTW at 1–5 years postoperative; the results demonstrated significantly more KTW gain with CTG despite considerable heterogeneity (P = 0.01, MD 0.86 mm, 95% CI 1.54 to 0.17 mm; x2 = 11.91 (df = 3), P = 0.008, I2 = 75%) (Fig. 2C). Sensitivity analysis revealed that the large heterogeneity was mainly derived from one study41, without alteration of the result (Supplementary Material, Appendix S6C). Only three studies compared ADM versus FGG around teeth. The results indicated a significant difference favouring FGG (P = 0.01, MD 1.78 mm, 95% CI 3.16 to 0.40 mm; x2 = 18.40 (df = 2), P = 0.0001, I2 = 89%) (Fig. 2D). In detail, two studies favoured FGG, while the other study showed a similar result. Regarding the surgical technique, all relevant studies performed open graft healing with subtle differences21,22,39. In two studies22,39, ADM was left completely exposed, whereas in the other study21, it was partially covered by a split-thickness flap. Seven studies compared ADM + CAF/ LPF versus CAF/LPF around teeth (six studies combined ADM and CAF and one study combined ADM and LPF). The results showed a significant difference of 0.66 mm favouring ADM + CAF/LPF (P = 0.001, 95% CI 0.26 to 1.05 mm; x2 = 18.77 (df = 6), P = 0.005, I2 = 68%) (Fig. 2E). Bearing in mind that moderate
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heterogeneity may be derived from inconsistent flap techniques, a subgroup analysis was performed, in which the results revealed a significantly greater KTW gain with ADM + CAF compared with CAF alone (P = 0.0001, MD 0.44 mm, 95% CI 0.21 to 0.67 mm; x2 = 1.20 (df = 5), P = 0.94, I2 = 0%) (Supplementary Material, Appendix S6D). Analysis of plastic periodontal surgery— STT gain
Three studies on teeth compared ADM with CTG, which resulted in no statistically significant difference in STT gain (P = 0.31; x2 = 4.91 (df = 2), P = 0.09, I2 = 59%) (Fig. 3A). Three studies compared ADM + CAF/LPF with CAF/LPF around teeth, indicating a superior result favouring ADM + CAF (P < 0.00001, MD 0.59 mm, 95% CI 0.50 to 0.68 mm; x2 = 7.46 (df = 2), P = 0.02, I2 = 73%) (Fig. 3B). In all studies included in this analysis, ADM + CAF/LPF displayed significantly more STT gain than CAF/LPF alone. Only one study compared ADM versus FGG (Fig. 3C), and STT was evaluated using an ultrasound device positioned 1 mm apical to the gingival margin39. This study revealed a significant intergroup difference (P = 0.01), in which the STT gain was 0.42 mm in the ADM group and 1.19 mm in the FGG group at 6 months postoperative (MD 0.77 mm, 95% CI 1.37 to 0.17 mm).
Fig. 3. Meta-analyses of soft tissue thickness (STT) gain around teeth (millimetres). (A) ADM versus CTG. (B) ADM + CAF/LPF versus CAF/ LPF. (C) ADM versus FGG. (ADM, acellular dermal matrix; CTG, connective tissue graft; CAF, coronally advanced flap; LPF, laterally positioned flap; FGG, free gingival graft.).
Please cite this article in press as: Lu W, et al. Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.12.005
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Fig. 4. Meta-analyses of the reduction in gingival recession (RecRed) around teeth (millimetres). (A) ADM versus CTG. (B) ADM + CAF/LPF versus CAF/LPF. (C) ADM versus FGG. (ADM, acellular dermal matrix; CTG, connective tissue graft; CAF, coronally advanced flap; LPF, laterally positioned flap; FGG, free gingival graft.).
Analysis of plastic periodontal surgery— reduction in recession (RecRed)
Fourteen studies compared ADM versus CTG around teeth. The meta-analysis revealed no statistically significant difference in effect between them (P = 0.37; x2 = 21.78 (df = 13), P = 0.06, I2 = 40%) (Fig. 4A). A subgroup analysis of studies with 1–5 years of follow-up duration (four studies included) also displayed a similar result between ADM and CTG (P = 0.88; x2 = 0.71 (df = 3), P = 0.87, I2 = 0%) (Supplementary Material, Appendix S6E). Seven studies compared ADM + CAF/ LPF versus CAF/LPF around teeth. There was a robust significant difference between them favouring ADM + CAF/LPF (P < 0.00001, MD 0.65 mm, 95% CI 0.40 to 0.90 mm; x2 = 7.61 (df = 6), P = 0.27, I2 = 21%) (Fig. 4B). Only two studies compared ADM versus FGG around teeth. No significant difference in RecRed was
detected between them (P = 0.51; x2 = 0.02 (df = 1), P = 0.88 and I2 = 0%) (Fig. 4C). Analysis of plastic implant surgery
Considering plastic implant surgery, the data were rather limited as only three studies were included. The meta-analysis of KTW included two studies and revealed no significant difference (P = 0.57) with high heterogeneity (I2 = 84%) (Fig. 5A). One study revealed significantly greater KTW gain in FGG45, whereas the other study observed no statistical difference between ADM and CTG47. Regarding STT, two studies compared ADM with CTG, with one of these studies lacking quantitative data46. This latter study revealed greater STT gain in ADM, while the other study detected no statistical difference between ADM and
CTG at three different heights of STT47 (Fig. 5B–D). In terms of RecRed around implants, only one study conducted a comparison between ADM and CTG, but without reporting any quantitative data46. This study reported that RecRed increased over time in both groups, with no significant difference. Patient-reported outcomes of aesthetics, postoperative pain/discomfort, and dentinal hypersensitivity
With regard to patient-reported aesthetic outcomes, ADM achieved a more preferable aesthetic appearance compared with CTG24 and LPF44, or a similar level of aesthetic satisfaction compared with CTG46, CAF20,29, and FGG39 around teeth. Of note, the patient-reported and clinician-evaluated outcomes were inconsistent in two studies39,46.
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Fig. 5. Meta-analyses of plastic implant surgery. (A) Keratinized tissue width gain comparing ADM versus CTG/FGG (millimetres). (B) Soft tissue thickness gain at 1 mm apical to the gingival margin, comparing ADM versus CTG (millimetres). (C) Soft tissue thickness gain at 3 mm apical to the gingival margin, comparing ADM versus CTG (millimetres). (D) Soft tissue thickness gain at 5 mm apical to the gingival margin, comparing ADM versus CTG (millimetres). (ADM, acellular dermal matrix; CTG, connective tissue graft; FGG, free gingival graft.).
Seven studies assessed postoperative pain/discomfort22,24,29,42,45–47. No metaanalysis was conducted, owing to the limited and heterogeneous data. Postoperative was usually minimal or pain mild21,24,39,42, except for severe pain at the donor site45. Four studies revealed similar patient-reported comfort for ADM and CTG22,24,46,47, whereas other studies detected greater patient discomfort for ADM than for CAF29, but less postoperative discomfort for ADM than for CTG42 and FGG22,45. Only two studies evaluated dentinal hypersensitivity following surgical therapy, but without reporting quantitative data29,36; thus no meta-analysis was performed. Both studies reported less postoperative root sensitivity in favour of ADM + CAF compared with CAF alone. The results of the secondary outcomes and forest plots of these are presented in the Supplementary Material (Appendix S7, Appendix S8). Discussion Summary of the main results
This review demonstrated that ADM could achieve comparable clinical efficacy
for root coverage as autogenous tissue (i.e. CTG and FGG), with good long-term stability in terms of RecRed, mean root coverage, and complete root coverage. On the other hand, ADM-based soft tissue augmentation was found to have inferior clinical efficacy to FGG and lower longterm stability of KTW gain than CTG, despite insufficient long-term data. Nevertheless, ADM plus CAF/LPF showed significantly superior clinical efficacy than CAF/LPF alone for plastic periodontal surgery. Regarding patient-reported outcomes, ADM resulted in comparable or superior aesthetic satisfaction and less surgical morbidity than autogenous tissue, as well as favourable alleviation of dentinal hypersensitivity. However, due to limited data on ADM-based plastic implant surgery, it was not possible to draw any conclusions at this time. Agreement and disagreement with other studies or reviews
In terms of clinical efficacy in increasing KTW, ADM achieved significantly superior outcomes compared with CAF alone and similar outcomes to CTG with 3–6 months of follow-up. The results are in line with those of a recent systematic
review on multiple gingival recessions48, which verified ADM + CAF to be more effective for augmenting the keratinized tissue than enamel matrix derivative + CAF or CAF alone. This previous review also mentioned that ADM yielded stable grafting when combined with CAF for multiple recession defects and was comparable to CTG48,49. However, data from another systematic review favoured CTG for KTW gain12, although the number of studies was limited and the large heterogeneity decreased the statistical power. Of note, a recent systematic review reported greater KTW gain with ADM compared with CTG, despite low quality and substantial heterogeneity of the included studies50. On the other hand, the subgroup analysis in this review found less KTW gain for ADM compared with CTG after at least 1 year of follow-up, implying long-term instability of ADM. One study with 5 years of follow-up revealed stable KTW gain with CTG, but relapse to the presurgical KTW level with ADM32. That study attributed the relapse to a horizontal tooth brushing habit as the related factor. Hirsch et al.49 showed a stable KTW gain with both ADM and CTG after 2 years, while Coˆrtes et al.19 observed keratinized tissue
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loss with both ADM and CAF during 6 to 24 months postoperative. Despite the limited data, it is plausible that the instability of KTW gain is associated with postoperative material shrinkage. The reasons for the large shrinkage of ADM may be due to the fabrication process and specific histological features of healing51. In addition, operator expertise, flap thickness, patient recall intervals, and careful maintenance will also impact the long-term stability of soft tissue augmentation4,52. Concerning the surgical technique, apically positioned flap/vestibuloplasty plus autogenous tissue has been validated as the best evidence-based method to enhance KTW53. However, the majority of the studies included in the analyses in the present study used a bilaminar technique, which combined CAF/LPF with graft material. Although it is advisable to completely cover ADM in order to prevent resorption54, open graft healing of ADM still allowed consistent integration into the host tissue and a significant gain in KTW regardless of the 56–71% shrinkage rate22,39. With regard to the augmentation of STT, ADM exhibited a comparable STT gain to CTG and a more favourable result than CAF/LPF alone, but an inferior result to FGG, although the data were limited and there was large heterogeneity. Autogenous tissue has been fully verified to be reliable and predictable for augmenting STT4,51. Prominent tissue thickening and gingival biotype modification can also be obtained with ADM52, although the low level of evidence necessitates more well-designed RCTs in the future to substantiate this. As the universal desire for soft tissue recession is to completely cover the recession defect, RecRed, mean root coverage, and complete root coverage are proportional to root-coverage aesthetics. In the present meta-analysis, ADM exhibited comparable root coverage results to the ‘gold standard’ CTG, with favourable long-term stability, which is in agreement with the results of previous reviews11,12,50,55. One study reported that ADM resulted in better overall aesthetic outcomes compared with CTG, even though ADM displayed less complete root coverage24. The discrepancy was attributed to superior colour matches with the adjacent tissue for ADM and poor healing with CTG. Moreover, a Bayesian network meta-analysis corroborated that ADM/CTG/autologous fibroblasts + CAF resulted in the best aesthetic outcomes among the overall surgical techniques56. Unlike professional outcomes (surrogate end-points), patient-reported outcomes are true end-points that directly reflect a patient’s inner feelings, function, or life57,
and are individually tangible. In this review, very few studies evaluated patient-reported outcomes of aesthetics, morbidity, or dentinal hypersensitivity. Quantitative data were even more limited, and most merely recorded the patients’ opinions with empirical sentences. Interestingly, some clinician-related aesthetic judgements did not agree with the patient-reported outcomes, indicating that the professional rating may be inconsistent with patient preference39,46. In fact, patients are more sensitive to the change in gingival colour or thickness than incomplete root coverage, thus they tend to assess the aesthetic outcomes more favourably than the professional58. Considering surgical morbidity, the utilization of ADM markedly shortened the surgical duration and decreased the likelihood of swelling and bleeding compared with autogenous tissue6. Moreover, the present review revealed that ADM exerted a better resolution of dentinal hypersensitivity compared with CAF alone, which may be associated with the superior root coverage efficacy. Potential biases and limitations in the review process
Although a comprehensive search strategy was applied, including an additional search of clinicaltrials.gov to identify unpublished articles, no relevant data were obtained. Thirty-six percent (10/28) of the included RCTs had a high risk of bias, primarily due to the absence of allocation concealment, blinding of outcome data, and completeness of follow-up. No trial conducted blinding of participants to receive surgical procedures, due to the nature of the intervention, which could require a donor site to obtain autogenous tissue or simply apply ADM. As for the meta-analyses, nine RCTs did not provide the standard deviation value for parameters of interest (even after contacting the corresponding authors), which ultimately decreased the statistical power of the results. Furthermore, RevMan software does not allow data pooling from splitmouth and parallel-group studies in the ‘continuous mode’ for data synthesis, which may consequently result in a statistical error. From a methodological viewpoint, defect-level analysis would tend to underestimate the confidence intervals for the pooled estimate compared with patientlevel (parallel design) analysis, rendering an inflated type I error. Moreover, the span of soft tissue deficiency (single or multiple sites) may vastly affect the clinical outcomes, which was not investigated in the present analyses, since multiple adjacent deficiencies are more challenging and associated with more anatomical variations
(prominent roots, shallow vestibules, defect size, etc.)48. In addition, some of the results need to be interpreted carefully to a certain extent, given the small number of recruited RCTs and substantial heterogeneity. The considerable heterogeneity may relate to inconsistent surgical techniques, non-standardized measurement techniques, and evaluator sensitivity. With consideration to the limited evidence, it can be concluded that ADM showed comparable clinical efficacy to autogenous tissue for root coverage procedures, with good long-term stability. However, in regard to soft tissue augmentation, ADM exhibited inferior clinical efficacy compared to FGG within 3–6 months of follow-up and less long-term stability of KTW gain compared with CTG. Nevertheless, ADM-based periodontal plastic surgery can improve aesthetic outcomes, reduce surgical morbidity, and facilitate the resolution of dentinal hypersensitivity. Funding
This research was jointly supported by the National Natural Science Foundation of China (31670970), Zhejiang Provincial Key Developmental Project (2019C03081), and Zhejiang Provincial Natural Science Foundation of China (LY17H140003). Competing interests
No conflict of interest. Ethical approval
Not applicable. Patient consent
Not applicable.
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.ijom.2019. 12.005. References 1. Cortellini P, Bissada NF. Mucogingival conditions in the natural dentition: narrative review, case definitions, and diagnostic considerations. J Periodontol 2018;45: S190–8. 2. Chambrone L, Chambrone D, Pustiglioni FE, Chambrone LA, Lima LA. Can sube-
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14.
15.
pithelial connective tissue grafts be considered the gold standard procedure in the treatment of Miller class I and II recession-type defects? J Dent 2008;36:659–71. Scheyer ET, Sanz M, Dibart S, Greenwell H, John V, Kim DM, Langer L, Neiva R, Rasperini G. Periodontal soft tissue non-root coverage procedures: a consensus report from the AAP Regeneration Workshop. J Periodontol 2015;86:S73–6. Cairo F, Pagliaro U, Nieri M. Treatment of gingival recession with coronally advanced flap procedures: a systematic review. J Clin Periodontol 2008;35:136–62. Giancarlo A, Michele N, Roberto R, Pierpaolo C, Giovanpaolo PP. Free gingival grafts to increase keratinized tissue: a retrospective long-term evaluation (10 to 25 years) of outcomes. J Periodontol 2008;79:587–94. Griffin TJ, Cheung WS, Zavras AI, Damoulis PD. Postoperative complications following gingival augmentation procedures. J Periodontol 2006;77:2070–9. Rhee PH, Friedman CD, Ridge JA, Kusiak J. The use of processed allograft dermal matrix for intraoral resurfacing: an alternative to split-thickness skin graft. Arch Otolaryngol Head Neck Surg 1998;124:1201–4. Livesey SA, Herndon DN, Hollyoak MA, Atkinson YH, Nag A. Transplanted acellular allograft dermal matrix. Potential as a template for the reconstruction of viable dermis. Transplantation 1995;60:1. Wainwright DJ. Use of an acellular allograft dermal matrix (AlloDerm) in the management of full-thickness burns. Burns 1995;21: 243–8. Shulman J. Clinical evaluation of an acellular dermal allograft for increasing the zone of attached gingiva. Pract Periodontics Aesthet Dent 1996;8:201–8. Chambrone L, Tatakis DN. Periodontal soft tissue root coverage procedures: a systematic review from the AAP Regeneration Workshop. J Periodontol 2015;86(2 Suppl): S8–51. Gapski R, Parks CA, Wang HL. Acellular dermal matrix for mucogingival surgery: a meta-analysis. J Periodontol 2005;76: 1814–22. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 2009;151:W65–94. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. Open Med 2009;3:e123–30. Higgins JP, Altman DG. Assessing risk of bias in included studies. John Wiley & Sons; 2011.
16. Cochran WG. The combination of estimates from different experiments. Biometrics 1954;10:101–29. 17. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:1539–58. 18. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration. 2011 [Accessibility verified December 2018] https://handbook-5-1.cochrane.org/. 19. Coˆrtes Ade Q, Martins AG, Nociti Jr FH, Sallum AW, Casati MZ, Sallum EA. A twoyear prospective study of coronally positioned flap with or without acellular dermal matrix graft. J Clin Periodontol 2006;33: 683–9. 20. Coˆrtes Ade Q, Martins AG, Nociti Jr FH, Sallum AW, Casati MZ, Sallum EA. Coronally positioned flap with or without acellular dermal matrix graft in the treatment of class I gingival recessions: a randomized controlled clinical study. J Periodontol 2004;75:1137–44. 21. Wei PC, Laurell L, Geivelis M, Lingen MW, Maddalozzo D. Acellular dermal matrix allografts to achieve increased attached gingiva. Part 1. A clinical study. J Periodontol 2000;71:1297–305. 22. Harris RJ. Clinical evaluation of 3 techniques to augment keratinized tissue without root coverage. J Periodontol 2001;72:932–8. 23. Novaes AB, Grisi DC, Molina GO, Souza SLS, Taba M, Grisi MFM. Comparative 6month clinical study of a subepithelial connective tissue graft and acellular dermal matrix graft for the treatment of gingival recession. J Periodontol 2001;72:1477–84. 24. Aichelmann-Reidy ME, Yukna RA, Evans GH, Nasr HF, Mayer ET. Clinical evaluation of acellular allograft dermis for the treatment of human gingival recession. J Periodontol 2001;72:998–1005. 25. Tal H, Moses O, Zohar R, Meir H, Nemcovsky C. Root coverage of advanced gingival recession: a comparative study between acellular dermal matrix allograft and subepithelial connective tissue grafts. J Periodontol 2002;73:1405–11. 26. Thakare P, Baliga V, Bhongade ML. Comparative evaluation of the effectiveness of acellular dermal matrix allograft and subepithelial connective tissue to coronally advanced flap alone in the treatment of multiple gingival recessions: a clinical study. J Indian Soc Periodontol 2015;19:537–44. 27. Woodyard JG, Greenwell H, Hill M, Drisko C, Iasella JM, Scheetz J. The clinical effect of acellular dermal matrix on gingival thickness and root coverage compared to coronally positioned flap alone. J Periodontol 2004;75:44–56. 28. Rahmani ME, Lades MA. Comparative clinical evaluation of acellular dermal matrix allograft and connective tissue graft for the treatment of gingival recession. J Contemp Dent Pract 2006;7:63–70.
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29. Mahajan A, Dixit J, Verma UP. A patientcentered clinical evaluation of acellular dermal matrix graft in the treatment of gingival recession defects. J Periodontol 2007;78:2348–55. 30. Joly JC, Carvalho AM, Silva RCD, Ciotti DL, Cury PR. Root coverage in isolated gingival recessions using autograft versus allograft: a pilot study. J Periodontol 2007;78:1017–22. 31. Mansouri SS, Ayoubian N, Manouchehri ME. A comparative 6-month clinical study of acellular dermal matrix allograft and subepithelial connective tissue graft for root coverage. J Dent 2010;7:156–64. 32. Moslemi N, Jazi MM, Haghighati F, Morovati SP, Jamali R. Acellular dermal matrix allograft versus subepithelial connective tissue graft in treatment of gingival recessions: a 5-year randomized clinical study. J Clin Periodontol 2011;38:1122–9. 33. Koudale SB, Charde PA, Bhongade ML. A comparative clinical evaluation of acellular dermal matrix allograft and sub-epithelial connective tissue graft for the treatment of multiple gingival recessions. J Indian Soc Periodontol 2012;16:411–6. 34. Gholami GA, Saberi A, Kadkhodazadeh M, Amid R, Karami D. Comparison of the clinical outcomes of connective tissue and acellular dermal matrix in combination with double papillary flap for root coverage: a 6month trial. Dent Res J 2013;10:506–13. 35. Thomas LJ, Emmadi P, Thyagarajan R, Namasivayam A. A comparative clinical study of the efficacy of subepithelial connective tissue graft and acellular dermal matrix graft in root coverage: 6-month follow-up observation. J Indian Soc Periodontol 2013;17:478–83. 36. Ahmedbeyli C, Ipc¸i S¸D., Cakar G, Kuru BE, Yılmaz S. Clinical evaluation of coronally advanced flap with or without acellular dermal matrix graft on complete defect coverage for the treatment of multiple gingival recessions with thin tissue biotype. J Clin Periodontol 2014;41:303–10. 37. Paolantonio M, Dolci M, Esposito P, D’Archivio D, Lisanti L, Luccio AD, Perinetti G. Subpedicle acellular dermal matrix graft and autogenous connective tissue graft in the treatment of gingival recessions: a comparative 1-year clinical study. J Periodontol 2002;73:1299–307. 38. Thombre V, Koudale SB, Bhongade ML. Comparative evaluation of the effectiveness of coronally positioned flap with or without acellular dermal matrix allograft in the treatment of multiple marginal gingival recession defects. J Esthetic Restor Dent 2013;33: E88–94. 39. De Resende D, Greghi S, Siqueira AF, Benfatti C, Damante CA, Ragghianti MZ. Acellular dermal matrix allograft versus free gingival graft: a histological evaluation and split-mouth randomized clinical trial. Clin Oral Invest 2019;23:539–50.
Please cite this article in press as: Lu W, et al. Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.12.005
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Lu et al.
40. Taiyeb Ali TB, Shapeen IM, Ahmed HB, Javed F. Efficacy of acellular dermal matrix and autogenous connective tissue grafts in the treatment of gingival recession defects among Asians. J Investig Clin Dent 2015;6: 125–32. 41. Barros RRM, Macedo GO, Queiroz ACD, Novaes AB. A modified surgical flap for root coverage in association with grafting materials. J Esthetic Restor Dent 2015;27:84–91. 42. Goyal N, Gupta R, Nymphea P, Parveen D. Analysis of patient acceptance following treatment of Miller’s class II gingival recession with acellular dermal matrix and connective tissue graft. J Indian Soc Periodontol 2014;18:352–6. 43. Shori T, Kolte A, Kher V, Dharamthok S, Shrirao T. A comparative evaluation of the effectiveness of subpedicle acellular dermal matrix allograft with subepithelial connective tissue graft in the treatment of isolated marginal tissue recession: a clinical study. J Indian Soc Periodontol 2013;17:78–81. 44. Ahmedbeyli C, Ipci SD, Cakar G, Yilmaz S. Laterally positioned flap along with acellular dermal matrix graft in the management of maxillary localized recessions. Clin Oral Invest 2019;23:595–601. 45. Basegmez C, Karabuda ZC, Demirel K, Yalcin S. The comparison of acellular dermal matrix allografts with free gingival grafts in the augmentation of peri-implant attached mucosa: a randomised controlled trial. Eur J Oral Implantol 2013;6:145–52. 46. Anderson LE, Inglehart MR, Elkholy K, Eber R, Wang HL. Implant associated soft tissue defects in the anterior maxilla: a randomized control trial comparing subepithelial connective tissue graft and acellular
47.
48.
49.
50.
51.
52.
53.
54.
dermal matrix allograft. Implant Dent 2014;23:416–25. Hutton CG, Johnson GK, Barwacz CA, Allareddy V, Avila-Ortiz G. Comparison of two different surgical approaches to increase peri-implant mucosal thickness: a randomized controlled clinical trial. J Periodontol 2018;89:807–14. Graziani F, Gennai S, Discepoli N, Buti J, Madianos P, Herrera D. Efficacy of periodontal plastic procedures in the treatment of multiple gingival recessions. J Clin Periodontol 2014;41:S63–76. Hirsch A, Goldstein M, Goultschin J, Boyan BD, Schwartz Z. A 2-year follow-up of root coverage using subpedicle acellular dermal matrix allografts and subepithelial connective tissue autografts. J Periodontol 2005;76:1323–8. Gallagher SI, Matthews DC. Acellular dermal matrix and subepithelial connective tissue grafts for root coverage: a systematic review. J Indian Soc Periodontol 2017;21: 439–48. Thoma DS, Benic GI, Zwahlen M, Ha¨mmerle CHF, Jung RE. A systematic review assessing soft tissue augmentation techniques. Clin Oral Implants Res 2009;20: 146–65. Chambrone L, Pini Prato GP. Clinical insights about the evolution of root coverage procedures: the flap, the graft, and the surgery. J Periodontol 2019;90:9–15. Thoma DS, Buranawat B, Ha¨mmerle CHF, Held U, Jung RE. Efficacy of soft tissue augmentation around dental implants and in partially edentulous areas: a systematic review. J Clin Periodontol 2014;41:S77–S91. Ozenci I, Dirikan I.S¸, Cakar G, Yılmaz S. Tunnel technique versus coronally advanced
55.
56.
57.
58.
flap with acellular dermal matrix graft in the treatment of multiple gingival recessions. J Clin Periodontol 2016;42:1135–42. Chambrone L, Sukekava F, Arau´jo 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;81:452–78. Cairo F, Pagliaro U, Buti J, Baccini M, Graziani F, Tonelli P, Pagavino G, Tonetti MS. Root coverage procedures improve patient aesthetics. A systematic review and Bayesian network meta-analysis. J Clin Periodontol 2016;43:965–75. Fleming TR, Demets DL. Surrogate end points in clinical trials: are we being misled? Ann Intern Med 1996;125:605–13. Kim SM, Choi YH, Kim YG, Park JW, Lee JM, Suh JY. Analysis of the esthetic outcome after root coverage procedures using a comprehensive approach. J Esthetic Restor Dent 2014;26:107–18.
Address: Fuming He Department of Oral Implantology and Prosthodontics The Affiliated Stomatology Hospital School of Medicine Zhejiang University No. 395 Yan’an Road Hangzhou 310006 Zhejiang China Tel: +86 571 87215430 E-mail: [email protected]
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Int. J. Oral Maxillofac. Surg. 2019; xxx: xxx–xxx https://doi.org/10.1016/j.ijom.2019.12.005, available online at https://www.sciencedirect.com
Systematic Review Dental Implants
Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review
W. Lu1,2, G. Qi1,2, Z. Ding3, X. Li1,2, W. Qi2,4, F. He2,4 1 Department of Periodontics, The Affiliated Stomatology Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; 2Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; 3Zhejiang Provincial Centre for Disease Control and Prevention, Hangzhou, Zhejiang, China; 4Department of Oral Implantology and Prosthodontics, The Affiliated Stomatology Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
W. Lu, G. Qi, Z. Ding, X. Li, W. Qi, F. He: Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review. Int. J. Oral Maxillofac. Surg. 2019; xxx: xxx–xxx. ã 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Abstract. This review was performed to validate the clinical efficacy of acellular dermal matrix (ADM) for plastic periodontal and implant surgery. Four electronic databases and a manual search were utilized to select randomized clinical trials (RCTs) published until March 2019. Overall, 28 RCTs were included: 25 on teeth and three on implants. For plastic periodontal surgery, ADM exhibited a comparable gingival recession reduction (RecRed) and soft tissue thickness (STT) gain to connective tissue graft (CTG). Subgroup analyses revealed that ADM obtained a similar keratinized tissue width (KTW) gain to CTG within 3–6 months postoperative, but significantly less KTW gain at 1–5 years postoperative (P = 0.01, mean difference (MD) 0.86 mm). Analyses comparing ADM with free gingival graft (FGG) demonstrated similar RecRed but significantly more KTW/STT gain favouring FGG (KTW: P = 0.01, MD 1.78 mm; STT: P = 0.01, MD 0.77 mm). Significantly more RecRed and KTW/STT gain were verified in ADM + coronally advanced flap/laterally positioned flap compared with these flaps alone (RecRed: P < 0.00001, MD 0.65 mm; KTW: P = 0.001, MD 0.66 mm; STT: P < 0.00001, MD 0.59 mm). Limited data for implant surgery indicated a similar trend as for periodontal surgery. Concerning patient-reported outcomes, ADM achieved favourable aesthetic appearance, alleviation of dentinal hypersensitivity, and less surgical morbidity. In conclusion, ADM exerted comparable clinical efficacy to autogenous tissue for root coverage procedures, with good long-term stability. However, for soft tissue augmentation, ADM exhibited inferior 3–6-month postoperative outcomes compared with FGG and less long-term stability of KTW gain compared with CTG.
0901-5027/000001+010
Key words: acellular dermal matrix; plastic surgery; soft tissue augmentation; root coverage. Accepted for publication
ã 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Lu W, et al. Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.12.005
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Among all the mucogingival deformities, insufficient keratinized tissue and gingival recession are the most prevalent conditions that demand surgical correction1. Accordingly, soft tissue augmentation and root coverage procedures are essential parts of plastic surgery protocols. These procedures include coronally or laterally advanced flaps, double papillae repositioned flaps, sub-epithelial connective tissue grafts (CTG), free gingival grafts (FGG), the tunnel technique, and the bilaminar technique of pedicle flaps and grafts or barrier membranes. Undeniably, autogenous tissue grafts, including the CTG and FGG, remain the gold standard for both soft tissue augmentation and root coverage procedures2,3. Substantial evidence has confirmed that the CTG combined with a coronally advanced flap (CAF) achieves favourable root coverage of recession4 and that the FGG-based apically positioned flap/vestibuloplasty optimally widens the keratinized tissue zone5. Nevertheless, there are some noticeable disadvantages of harvesting autogenous tissue, such as postoperative bleeding and pain/discomfort at the donor site, a restricted supply of tissue, longer operative duration, increased morbidity, and additional expertise of the surgeon6. In order to overcome the drawbacks of autogenous tissue harvesting, several nonvital allograft substitutes have been produced as alternative options for plastic periodontal and implant surgery. An example is acellular dermal matrix (ADM), a dermal allograft derived from human skin7. During the processing of AlloDerm, one of the oldest and most utilized ADM products, the epithelium is first eliminated from the cadaveric skin using hypertonic saline and the cells are subsequently extracted using a series of detergents (0.1% glutaraldehyde, 0.5% sodium dodecyl sulphate, and 0.25% trypsin); this is done to prevent an antigenic response/ immunological rejection caused by HLA antigenicity, as well as to inactivate viruses8. The material is then cryoprotected, freeze-dried, and packaged in a proprietary process for immediate use. Since its initial use in the 20th century9,10, ADM has been used extensively in various areas of dental practice over the last two decades3,11. In particular, when the donor supply is inadequate and/or the patient is fearful of additional surgery, ADM has been proposed as an alternative option for plastic periodontal and implant surgery12. However, there remain concerns regarding the use of ADM, due to the associated ethical issues and the risk of
disease transmission. The manufacturer of AlloDerm (LifeCell) states that the donor blood sample is tested for infectious diseases, including HIV and hepatitis B and C viruses. The tissue samples are also screened for microbial contaminants and pathogenic bacteria. Moreover, the patented ADM process (U.S. Patent 5,336,616) demonstrates more than 99.9% viral reduction and that no cells or microbial pathogens are detected using professional tests. Nevertheless, it is difficult to entirely remove all cell remnants; thus there remains a low theoretical risk of disease transmission, which is the case for all preparations derived from allografts. Although ADM has yielded promising outcomes in numerous trials and its clinical efficacy has been discussed in several standard and commissioned reviews (i.e., European Federation of Periodontology, American Academy of Periodontology, and Cochrane), conclusions about the application of this material are still unclear and controversial. Moreover, evidence on the long-term clinical outcomes and patient-reported outcomes relevant to ADM is of low level. Therefore, the aim of this investigation was to conduct a comprehensive systematic review and meta-analysis with high methodological strength of evidence, focusing on clinical long-term stability and patient-centred parameters, in order to thoroughly verify the clinical efficacy of ADM for plastic periodontal and implant surgery.
Materials and methods Protocol and PICO (participants, intervention, comparison, outcomes) question
The protocol of this systematic review was developed in accordance with the PRISMA Statement (Preferred Reporting Items for Systematic Reviews and Meta-analyses)13,14 and was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42019111172). This review attempted to answer the following focused question: In systemically healthy patients with exposed roots or implants or lack of keratinized tissue (P, population), does ADM-based plastic periodontal and implant surgery (I, intervention), compared to conventional techniques for plastic periodontal and implant surgery (e.g. CAF or laterally positioned flap (LPF) or FGG or CTG + CAF) (C, control), result in a gain of keratinized tissue, resolution of gingival recession,
and improved patient-reported outcomes (O, outcomes)?
Eligibility criteria
Only randomized clinical trials (RCTs) of systemically healthy adult patients undergoing ADM-based plastic periodontal or implant surgery, with at least 3 months of follow-up, were eligible for inclusion. Primary clinical parameters (keratinized tissue width (KTW), soft tissue thickness (STT), and reduction of gingival recession (RecRed)) had to be evaluated quantitatively. If multiple studies with the same population were identified, the trial with the longest follow-up duration or with the lowest drop-out rate was selected for meta-analysis. Publications on in vitro studies and those investigating different incisions or surgical variations (e.g. with or without a vertical incision, CAF versus tunnel technique) with the same ADMbased surgical treatment in both groups were excluded. Studies in which it was not possible to identify the effect of ADM alone in plastic periodontal and implant surgery (e.g. those studying a combination of ADM with enamel matrix derivative, platelet-rich plasma, or guided bone regeneration) were also excluded.
Literature search strategy
Relevant RCTs published up until October 2004 that were included in a previous systematic review were identified12. Electronic searches of the literature, covering the period November 2004 to March 2019, were performed in the following databases: MEDLINE/PubMed, Google Scholar, Cochrane Library, and Web of Science. Moreover, an additional manual search of relevant journals was conducted (Fig. 1) and attempts were made to search the grey literature and unpublished data on the clinicaltrials.gov website. There was no restriction on publication language. The search terms, selection protocol, and data extraction are given in the Supplementary Material (Appendix S1).
Data items
Primary outcomes included KTW gain, STT gain, RecRed, and patient-reported outcomes. Secondary outcomes included mean root coverage, complete root coverage, clinical attachment level gain, probing depth reduction, wounding healing, complications, and clinicianassessed aesthetics.
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Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review
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Fig. 1. Flowchart of the study selection process.
Quality assessment
Two reviewers (WL, ZD) independently assessed the methodological quality of all eligible RCTs with reference to the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The six domains/questions for evaluation included random sequence generation, allocation concealment, blinding of outcome assessment, incomplete outcome data, selected reporting, and other bias15. If the study met all criteria, the degree of bias was considered as low risk; if the study was missing fewer than three criteria, the degree of bias was ranked as moderate risk; otherwise (missing three or more criteria), the risk was categorized as high.
the individual effects of comparisons and the global estimation. The unit of analysis was the soft tissue defect site rather than the patient. Heterogeneity derived from the discrepant treatment effect of each study was evaluated using Cochran’s test16. The results of the Q statistic (significant at P < 0.10) and I2 test (25%: low; 50%: moderate; 75%: high heterogeneity) were utilized to assess the level of heterogeneity17. Sensitivity analyses and subgroup analyses were performed when necessary. Considering the power to detect publication bias, those analyses with fewer than 10 studies were not formally assessed18; otherwise publication bias was evaluated via funnel plots. The significant P-value level was defined as 0.05.
Statistical analyses
The statistical analyses were performed using RevMan 5.3 software (Cochrane Collaboration, Oxford, UK). The mean difference and standard deviation were used to describe the continuous outcomes from each trial, while dichotomous data such as complete root coverage were expressed as risk ratio estimates. Statistical quantitative outcomes were depicted as weighted mean differences (MD) with 95% confidence intervals (CI). In the case of unclear data for the standard deviation, the value was estimated as the square root of the sum of the variances of the measures12. The fixed-effects model was used in the event of low heterogeneity, while the random-effects model was used when moderate or high heterogeneity was present. Forest plots were drawn to illustrate
were on implants. A flowchart of the study selection process is displayed in Fig. 1. Included studies
A list of the 28 included RCTs and their respective characteristics is presented in the Supplementary Material (Appendix S3)19,21–47. Twenty-five studies reported the origin/manufacturer of the ADM, which was consistently found to be AlloDerm (a product of LifeCell). The selected RCTs conducted ADMbased plastic periodontal or implant surgery and these trials were further divided into the following comparisons: (1) around teeth (three comparisons): ADM versus CTG, ADM versus FGG, ADM + CAF/LPF versus CAF/LPF; (2) around implants (two comparisons): ADM versus CTG, ADM versus FGG.
Results Study selection and study characteristics
Quality assessment and publication bias
The electronic search yielded a total of 244 articles after the exclusion of duplicates. Following the reading of titles/ abstracts, 60 articles were included in the full-text assessment. Thirty-two of these were excluded for reasons based on the predetermined eligibility criteria (Supplementary Material, Appendix S2). Two trials conducted by Coˆrtes et al.19,20 referred to the same population but with two different follow-up durations (6 months and 5 years, respectively). Hence, the study with the longer follow-up duration was included in the analyses. Finally, 28 RCTs were eligible for statistical analysis, of which 25 were on teeth and three
The results of the quality assessment for the RCTs included are shown in the Supplementary Material (Appendix S4). In summary, four RCTs had a low risk of bias, 14 a moderate risk, and 10 a high risk. Funnel plots revealed consistent symmetry, which indicated a low risk of publication bias (Supplementary Material, Appendix S5). Results of the meta-analyses of primary outcomes
A total of 750 soft tissue deficient sites in 511 patients included in 28 eligible RCTs were assigned to specific comparisons for
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Fig. 2. Meta-analyses of keratinized tissue width (KTW) gain around teeth (millimetres). (A) Overall analysis of ADM versus CTG. (B) Subgroup analysis of ADM versus CTG with 3–6 months of follow-up. (C) Subgroup analysis of ADM versus CTG with 1–5 years of follow-up. (D) ADM versus FGG. (E) ADM + CAF/LPF versus CAF/LPF. (ADM, acellular dermal matrix; CTG, connective tissue graft; FGG, free gingival graft; CAF, coronally advanced flap; LPF, laterally positioned flap.).
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Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review quantitative analysis and estimation of the effect size of all the parameters of interest. Analysis of plastic periodontal surgery— KTW gain
The comparison of ADM versus CTG around teeth (17 studies) included 16 trials using graft material combined with CAF22–26,28,30–33,35,37,40–43 [Au?1] and one trial with a double papillary flap34. The result indicated a significant mean difference of 0.46 mm favouring CTG (P = 0.002, 95% CI 0.75 to x2 = 43.02 (df = 16), 0.17 mm; P = 0.0003, I2 = 63%) (Fig. 2A). The sensitivity analysis excluding low-quality studies revealed similar heterogeneity, but no significant difference between the groups (P = 0.30) (Supplementary Material, Appendix S6A). Due to the substantial heterogeneity of the data and inconsistent follow-up durations, subgroup analyses were conducted. Subgroup one comprised 14 studies reporting KTW at 3–6 months postoperative; the meta-analysis revealed a borderline significant difference favouring CTG (P = 0.04, MD 0.30 mm, 95% CI 0.60 to 0.01 mm; x2 = 26.87 (df = 13), P = 0.01, I2 = 52%) (Fig. 2B). However, analysis of the eight high- and moderatequality studies of subgroup one exhibited no significant difference (P = 0.89) with low heterogeneity (x2 = 8.87 (df = 7), P = 0.26, I2 = 21%) (Supplementary Ma-
terial, Appendix S6B). Subgroup two comprised four studies recording KTW at 1–5 years postoperative; the results demonstrated significantly more KTW gain with CTG despite considerable heterogeneity (P = 0.01, MD 0.86 mm, 95% CI 1.54 to 0.17 mm; x2 = 11.91 (df = 3), P = 0.008, I2 = 75%) (Fig. 2C). Sensitivity analysis revealed that the large heterogeneity was mainly derived from one study41, without alteration of the result (Supplementary Material, Appendix S6C). Only three studies compared ADM versus FGG around teeth. The results indicated a significant difference favouring FGG (P = 0.01, MD 1.78 mm, 95% CI 3.16 to 0.40 mm; x2 = 18.40 (df = 2), P = 0.0001, I2 = 89%) (Fig. 2D). In detail, two studies favoured FGG, while the other study showed a similar result. Regarding the surgical technique, all relevant studies performed open graft healing with subtle differences21,22,39. In two studies22,39, ADM was left completely exposed, whereas in the other study21, it was partially covered by a split-thickness flap. Seven studies compared ADM + CAF/ LPF versus CAF/LPF around teeth (six studies combined ADM and CAF and one study combined ADM and LPF). The results showed a significant difference of 0.66 mm favouring ADM + CAF/LPF (P = 0.001, 95% CI 0.26 to 1.05 mm; x2 = 18.77 (df = 6), P = 0.005, I2 = 68%) (Fig. 2E). Bearing in mind that moderate
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heterogeneity may be derived from inconsistent flap techniques, a subgroup analysis was performed, in which the results revealed a significantly greater KTW gain with ADM + CAF compared with CAF alone (P = 0.0001, MD 0.44 mm, 95% CI 0.21 to 0.67 mm; x2 = 1.20 (df = 5), P = 0.94, I2 = 0%) (Supplementary Material, Appendix S6D). Analysis of plastic periodontal surgery— STT gain
Three studies on teeth compared ADM with CTG, which resulted in no statistically significant difference in STT gain (P = 0.31; x2 = 4.91 (df = 2), P = 0.09, I2 = 59%) (Fig. 3A). Three studies compared ADM + CAF/LPF with CAF/LPF around teeth, indicating a superior result favouring ADM + CAF (P < 0.00001, MD 0.59 mm, 95% CI 0.50 to 0.68 mm; x2 = 7.46 (df = 2), P = 0.02, I2 = 73%) (Fig. 3B). In all studies included in this analysis, ADM + CAF/LPF displayed significantly more STT gain than CAF/LPF alone. Only one study compared ADM versus FGG (Fig. 3C), and STT was evaluated using an ultrasound device positioned 1 mm apical to the gingival margin39. This study revealed a significant intergroup difference (P = 0.01), in which the STT gain was 0.42 mm in the ADM group and 1.19 mm in the FGG group at 6 months postoperative (MD 0.77 mm, 95% CI 1.37 to 0.17 mm).
Fig. 3. Meta-analyses of soft tissue thickness (STT) gain around teeth (millimetres). (A) ADM versus CTG. (B) ADM + CAF/LPF versus CAF/ LPF. (C) ADM versus FGG. (ADM, acellular dermal matrix; CTG, connective tissue graft; CAF, coronally advanced flap; LPF, laterally positioned flap; FGG, free gingival graft.).
Please cite this article in press as: Lu W, et al. Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.12.005
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Fig. 4. Meta-analyses of the reduction in gingival recession (RecRed) around teeth (millimetres). (A) ADM versus CTG. (B) ADM + CAF/LPF versus CAF/LPF. (C) ADM versus FGG. (ADM, acellular dermal matrix; CTG, connective tissue graft; CAF, coronally advanced flap; LPF, laterally positioned flap; FGG, free gingival graft.).
Analysis of plastic periodontal surgery— reduction in recession (RecRed)
Fourteen studies compared ADM versus CTG around teeth. The meta-analysis revealed no statistically significant difference in effect between them (P = 0.37; x2 = 21.78 (df = 13), P = 0.06, I2 = 40%) (Fig. 4A). A subgroup analysis of studies with 1–5 years of follow-up duration (four studies included) also displayed a similar result between ADM and CTG (P = 0.88; x2 = 0.71 (df = 3), P = 0.87, I2 = 0%) (Supplementary Material, Appendix S6E). Seven studies compared ADM + CAF/ LPF versus CAF/LPF around teeth. There was a robust significant difference between them favouring ADM + CAF/LPF (P < 0.00001, MD 0.65 mm, 95% CI 0.40 to 0.90 mm; x2 = 7.61 (df = 6), P = 0.27, I2 = 21%) (Fig. 4B). Only two studies compared ADM versus FGG around teeth. No significant difference in RecRed was
detected between them (P = 0.51; x2 = 0.02 (df = 1), P = 0.88 and I2 = 0%) (Fig. 4C). Analysis of plastic implant surgery
Considering plastic implant surgery, the data were rather limited as only three studies were included. The meta-analysis of KTW included two studies and revealed no significant difference (P = 0.57) with high heterogeneity (I2 = 84%) (Fig. 5A). One study revealed significantly greater KTW gain in FGG45, whereas the other study observed no statistical difference between ADM and CTG47. Regarding STT, two studies compared ADM with CTG, with one of these studies lacking quantitative data46. This latter study revealed greater STT gain in ADM, while the other study detected no statistical difference between ADM and
CTG at three different heights of STT47 (Fig. 5B–D). In terms of RecRed around implants, only one study conducted a comparison between ADM and CTG, but without reporting any quantitative data46. This study reported that RecRed increased over time in both groups, with no significant difference. Patient-reported outcomes of aesthetics, postoperative pain/discomfort, and dentinal hypersensitivity
With regard to patient-reported aesthetic outcomes, ADM achieved a more preferable aesthetic appearance compared with CTG24 and LPF44, or a similar level of aesthetic satisfaction compared with CTG46, CAF20,29, and FGG39 around teeth. Of note, the patient-reported and clinician-evaluated outcomes were inconsistent in two studies39,46.
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Fig. 5. Meta-analyses of plastic implant surgery. (A) Keratinized tissue width gain comparing ADM versus CTG/FGG (millimetres). (B) Soft tissue thickness gain at 1 mm apical to the gingival margin, comparing ADM versus CTG (millimetres). (C) Soft tissue thickness gain at 3 mm apical to the gingival margin, comparing ADM versus CTG (millimetres). (D) Soft tissue thickness gain at 5 mm apical to the gingival margin, comparing ADM versus CTG (millimetres). (ADM, acellular dermal matrix; CTG, connective tissue graft; FGG, free gingival graft.).
Seven studies assessed postoperative pain/discomfort22,24,29,42,45–47. No metaanalysis was conducted, owing to the limited and heterogeneous data. Postoperative was usually minimal or pain mild21,24,39,42, except for severe pain at the donor site45. Four studies revealed similar patient-reported comfort for ADM and CTG22,24,46,47, whereas other studies detected greater patient discomfort for ADM than for CAF29, but less postoperative discomfort for ADM than for CTG42 and FGG22,45. Only two studies evaluated dentinal hypersensitivity following surgical therapy, but without reporting quantitative data29,36; thus no meta-analysis was performed. Both studies reported less postoperative root sensitivity in favour of ADM + CAF compared with CAF alone. The results of the secondary outcomes and forest plots of these are presented in the Supplementary Material (Appendix S7, Appendix S8). Discussion Summary of the main results
This review demonstrated that ADM could achieve comparable clinical efficacy
for root coverage as autogenous tissue (i.e. CTG and FGG), with good long-term stability in terms of RecRed, mean root coverage, and complete root coverage. On the other hand, ADM-based soft tissue augmentation was found to have inferior clinical efficacy to FGG and lower longterm stability of KTW gain than CTG, despite insufficient long-term data. Nevertheless, ADM plus CAF/LPF showed significantly superior clinical efficacy than CAF/LPF alone for plastic periodontal surgery. Regarding patient-reported outcomes, ADM resulted in comparable or superior aesthetic satisfaction and less surgical morbidity than autogenous tissue, as well as favourable alleviation of dentinal hypersensitivity. However, due to limited data on ADM-based plastic implant surgery, it was not possible to draw any conclusions at this time. Agreement and disagreement with other studies or reviews
In terms of clinical efficacy in increasing KTW, ADM achieved significantly superior outcomes compared with CAF alone and similar outcomes to CTG with 3–6 months of follow-up. The results are in line with those of a recent systematic
review on multiple gingival recessions48, which verified ADM + CAF to be more effective for augmenting the keratinized tissue than enamel matrix derivative + CAF or CAF alone. This previous review also mentioned that ADM yielded stable grafting when combined with CAF for multiple recession defects and was comparable to CTG48,49. However, data from another systematic review favoured CTG for KTW gain12, although the number of studies was limited and the large heterogeneity decreased the statistical power. Of note, a recent systematic review reported greater KTW gain with ADM compared with CTG, despite low quality and substantial heterogeneity of the included studies50. On the other hand, the subgroup analysis in this review found less KTW gain for ADM compared with CTG after at least 1 year of follow-up, implying long-term instability of ADM. One study with 5 years of follow-up revealed stable KTW gain with CTG, but relapse to the presurgical KTW level with ADM32. That study attributed the relapse to a horizontal tooth brushing habit as the related factor. Hirsch et al.49 showed a stable KTW gain with both ADM and CTG after 2 years, while Coˆrtes et al.19 observed keratinized tissue
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loss with both ADM and CAF during 6 to 24 months postoperative. Despite the limited data, it is plausible that the instability of KTW gain is associated with postoperative material shrinkage. The reasons for the large shrinkage of ADM may be due to the fabrication process and specific histological features of healing51. In addition, operator expertise, flap thickness, patient recall intervals, and careful maintenance will also impact the long-term stability of soft tissue augmentation4,52. Concerning the surgical technique, apically positioned flap/vestibuloplasty plus autogenous tissue has been validated as the best evidence-based method to enhance KTW53. However, the majority of the studies included in the analyses in the present study used a bilaminar technique, which combined CAF/LPF with graft material. Although it is advisable to completely cover ADM in order to prevent resorption54, open graft healing of ADM still allowed consistent integration into the host tissue and a significant gain in KTW regardless of the 56–71% shrinkage rate22,39. With regard to the augmentation of STT, ADM exhibited a comparable STT gain to CTG and a more favourable result than CAF/LPF alone, but an inferior result to FGG, although the data were limited and there was large heterogeneity. Autogenous tissue has been fully verified to be reliable and predictable for augmenting STT4,51. Prominent tissue thickening and gingival biotype modification can also be obtained with ADM52, although the low level of evidence necessitates more well-designed RCTs in the future to substantiate this. As the universal desire for soft tissue recession is to completely cover the recession defect, RecRed, mean root coverage, and complete root coverage are proportional to root-coverage aesthetics. In the present meta-analysis, ADM exhibited comparable root coverage results to the ‘gold standard’ CTG, with favourable long-term stability, which is in agreement with the results of previous reviews11,12,50,55. One study reported that ADM resulted in better overall aesthetic outcomes compared with CTG, even though ADM displayed less complete root coverage24. The discrepancy was attributed to superior colour matches with the adjacent tissue for ADM and poor healing with CTG. Moreover, a Bayesian network meta-analysis corroborated that ADM/CTG/autologous fibroblasts + CAF resulted in the best aesthetic outcomes among the overall surgical techniques56. Unlike professional outcomes (surrogate end-points), patient-reported outcomes are true end-points that directly reflect a patient’s inner feelings, function, or life57,
and are individually tangible. In this review, very few studies evaluated patient-reported outcomes of aesthetics, morbidity, or dentinal hypersensitivity. Quantitative data were even more limited, and most merely recorded the patients’ opinions with empirical sentences. Interestingly, some clinician-related aesthetic judgements did not agree with the patient-reported outcomes, indicating that the professional rating may be inconsistent with patient preference39,46. In fact, patients are more sensitive to the change in gingival colour or thickness than incomplete root coverage, thus they tend to assess the aesthetic outcomes more favourably than the professional58. Considering surgical morbidity, the utilization of ADM markedly shortened the surgical duration and decreased the likelihood of swelling and bleeding compared with autogenous tissue6. Moreover, the present review revealed that ADM exerted a better resolution of dentinal hypersensitivity compared with CAF alone, which may be associated with the superior root coverage efficacy. Potential biases and limitations in the review process
Although a comprehensive search strategy was applied, including an additional search of clinicaltrials.gov to identify unpublished articles, no relevant data were obtained. Thirty-six percent (10/28) of the included RCTs had a high risk of bias, primarily due to the absence of allocation concealment, blinding of outcome data, and completeness of follow-up. No trial conducted blinding of participants to receive surgical procedures, due to the nature of the intervention, which could require a donor site to obtain autogenous tissue or simply apply ADM. As for the meta-analyses, nine RCTs did not provide the standard deviation value for parameters of interest (even after contacting the corresponding authors), which ultimately decreased the statistical power of the results. Furthermore, RevMan software does not allow data pooling from splitmouth and parallel-group studies in the ‘continuous mode’ for data synthesis, which may consequently result in a statistical error. From a methodological viewpoint, defect-level analysis would tend to underestimate the confidence intervals for the pooled estimate compared with patientlevel (parallel design) analysis, rendering an inflated type I error. Moreover, the span of soft tissue deficiency (single or multiple sites) may vastly affect the clinical outcomes, which was not investigated in the present analyses, since multiple adjacent deficiencies are more challenging and associated with more anatomical variations
(prominent roots, shallow vestibules, defect size, etc.)48. In addition, some of the results need to be interpreted carefully to a certain extent, given the small number of recruited RCTs and substantial heterogeneity. The considerable heterogeneity may relate to inconsistent surgical techniques, non-standardized measurement techniques, and evaluator sensitivity. With consideration to the limited evidence, it can be concluded that ADM showed comparable clinical efficacy to autogenous tissue for root coverage procedures, with good long-term stability. However, in regard to soft tissue augmentation, ADM exhibited inferior clinical efficacy compared to FGG within 3–6 months of follow-up and less long-term stability of KTW gain compared with CTG. Nevertheless, ADM-based periodontal plastic surgery can improve aesthetic outcomes, reduce surgical morbidity, and facilitate the resolution of dentinal hypersensitivity. Funding
This research was jointly supported by the National Natural Science Foundation of China (31670970), Zhejiang Provincial Key Developmental Project (2019C03081), and Zhejiang Provincial Natural Science Foundation of China (LY17H140003). Competing interests
No conflict of interest. Ethical approval
Not applicable. Patient consent
Not applicable.
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.ijom.2019. 12.005. References 1. Cortellini P, Bissada NF. Mucogingival conditions in the natural dentition: narrative review, case definitions, and diagnostic considerations. J Periodontol 2018;45: S190–8. 2. Chambrone L, Chambrone D, Pustiglioni FE, Chambrone LA, Lima LA. Can sube-
Please cite this article in press as: Lu W, et al. Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.12.005
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3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
pithelial connective tissue grafts be considered the gold standard procedure in the treatment of Miller class I and II recession-type defects? J Dent 2008;36:659–71. Scheyer ET, Sanz M, Dibart S, Greenwell H, John V, Kim DM, Langer L, Neiva R, Rasperini G. Periodontal soft tissue non-root coverage procedures: a consensus report from the AAP Regeneration Workshop. J Periodontol 2015;86:S73–6. Cairo F, Pagliaro U, Nieri M. Treatment of gingival recession with coronally advanced flap procedures: a systematic review. J Clin Periodontol 2008;35:136–62. Giancarlo A, Michele N, Roberto R, Pierpaolo C, Giovanpaolo PP. Free gingival grafts to increase keratinized tissue: a retrospective long-term evaluation (10 to 25 years) of outcomes. J Periodontol 2008;79:587–94. Griffin TJ, Cheung WS, Zavras AI, Damoulis PD. Postoperative complications following gingival augmentation procedures. J Periodontol 2006;77:2070–9. Rhee PH, Friedman CD, Ridge JA, Kusiak J. The use of processed allograft dermal matrix for intraoral resurfacing: an alternative to split-thickness skin graft. Arch Otolaryngol Head Neck Surg 1998;124:1201–4. Livesey SA, Herndon DN, Hollyoak MA, Atkinson YH, Nag A. Transplanted acellular allograft dermal matrix. Potential as a template for the reconstruction of viable dermis. Transplantation 1995;60:1. Wainwright DJ. Use of an acellular allograft dermal matrix (AlloDerm) in the management of full-thickness burns. Burns 1995;21: 243–8. Shulman J. Clinical evaluation of an acellular dermal allograft for increasing the zone of attached gingiva. Pract Periodontics Aesthet Dent 1996;8:201–8. Chambrone L, Tatakis DN. Periodontal soft tissue root coverage procedures: a systematic review from the AAP Regeneration Workshop. J Periodontol 2015;86(2 Suppl): S8–51. Gapski R, Parks CA, Wang HL. Acellular dermal matrix for mucogingival surgery: a meta-analysis. J Periodontol 2005;76: 1814–22. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 2009;151:W65–94. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. Open Med 2009;3:e123–30. Higgins JP, Altman DG. Assessing risk of bias in included studies. John Wiley & Sons; 2011.
16. Cochran WG. The combination of estimates from different experiments. Biometrics 1954;10:101–29. 17. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:1539–58. 18. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration. 2011 [Accessibility verified December 2018] https://handbook-5-1.cochrane.org/. 19. Coˆrtes Ade Q, Martins AG, Nociti Jr FH, Sallum AW, Casati MZ, Sallum EA. A twoyear prospective study of coronally positioned flap with or without acellular dermal matrix graft. J Clin Periodontol 2006;33: 683–9. 20. Coˆrtes Ade Q, Martins AG, Nociti Jr FH, Sallum AW, Casati MZ, Sallum EA. Coronally positioned flap with or without acellular dermal matrix graft in the treatment of class I gingival recessions: a randomized controlled clinical study. J Periodontol 2004;75:1137–44. 21. Wei PC, Laurell L, Geivelis M, Lingen MW, Maddalozzo D. Acellular dermal matrix allografts to achieve increased attached gingiva. Part 1. A clinical study. J Periodontol 2000;71:1297–305. 22. Harris RJ. Clinical evaluation of 3 techniques to augment keratinized tissue without root coverage. J Periodontol 2001;72:932–8. 23. Novaes AB, Grisi DC, Molina GO, Souza SLS, Taba M, Grisi MFM. Comparative 6month clinical study of a subepithelial connective tissue graft and acellular dermal matrix graft for the treatment of gingival recession. J Periodontol 2001;72:1477–84. 24. Aichelmann-Reidy ME, Yukna RA, Evans GH, Nasr HF, Mayer ET. Clinical evaluation of acellular allograft dermis for the treatment of human gingival recession. J Periodontol 2001;72:998–1005. 25. Tal H, Moses O, Zohar R, Meir H, Nemcovsky C. Root coverage of advanced gingival recession: a comparative study between acellular dermal matrix allograft and subepithelial connective tissue grafts. J Periodontol 2002;73:1405–11. 26. Thakare P, Baliga V, Bhongade ML. Comparative evaluation of the effectiveness of acellular dermal matrix allograft and subepithelial connective tissue to coronally advanced flap alone in the treatment of multiple gingival recessions: a clinical study. J Indian Soc Periodontol 2015;19:537–44. 27. Woodyard JG, Greenwell H, Hill M, Drisko C, Iasella JM, Scheetz J. The clinical effect of acellular dermal matrix on gingival thickness and root coverage compared to coronally positioned flap alone. J Periodontol 2004;75:44–56. 28. Rahmani ME, Lades MA. Comparative clinical evaluation of acellular dermal matrix allograft and connective tissue graft for the treatment of gingival recession. J Contemp Dent Pract 2006;7:63–70.
9
29. Mahajan A, Dixit J, Verma UP. A patientcentered clinical evaluation of acellular dermal matrix graft in the treatment of gingival recession defects. J Periodontol 2007;78:2348–55. 30. Joly JC, Carvalho AM, Silva RCD, Ciotti DL, Cury PR. Root coverage in isolated gingival recessions using autograft versus allograft: a pilot study. J Periodontol 2007;78:1017–22. 31. Mansouri SS, Ayoubian N, Manouchehri ME. A comparative 6-month clinical study of acellular dermal matrix allograft and subepithelial connective tissue graft for root coverage. J Dent 2010;7:156–64. 32. Moslemi N, Jazi MM, Haghighati F, Morovati SP, Jamali R. Acellular dermal matrix allograft versus subepithelial connective tissue graft in treatment of gingival recessions: a 5-year randomized clinical study. J Clin Periodontol 2011;38:1122–9. 33. Koudale SB, Charde PA, Bhongade ML. A comparative clinical evaluation of acellular dermal matrix allograft and sub-epithelial connective tissue graft for the treatment of multiple gingival recessions. J Indian Soc Periodontol 2012;16:411–6. 34. Gholami GA, Saberi A, Kadkhodazadeh M, Amid R, Karami D. Comparison of the clinical outcomes of connective tissue and acellular dermal matrix in combination with double papillary flap for root coverage: a 6month trial. Dent Res J 2013;10:506–13. 35. Thomas LJ, Emmadi P, Thyagarajan R, Namasivayam A. A comparative clinical study of the efficacy of subepithelial connective tissue graft and acellular dermal matrix graft in root coverage: 6-month follow-up observation. J Indian Soc Periodontol 2013;17:478–83. 36. Ahmedbeyli C, Ipc¸i S¸D., Cakar G, Kuru BE, Yılmaz S. Clinical evaluation of coronally advanced flap with or without acellular dermal matrix graft on complete defect coverage for the treatment of multiple gingival recessions with thin tissue biotype. J Clin Periodontol 2014;41:303–10. 37. Paolantonio M, Dolci M, Esposito P, D’Archivio D, Lisanti L, Luccio AD, Perinetti G. Subpedicle acellular dermal matrix graft and autogenous connective tissue graft in the treatment of gingival recessions: a comparative 1-year clinical study. J Periodontol 2002;73:1299–307. 38. Thombre V, Koudale SB, Bhongade ML. Comparative evaluation of the effectiveness of coronally positioned flap with or without acellular dermal matrix allograft in the treatment of multiple marginal gingival recession defects. J Esthetic Restor Dent 2013;33: E88–94. 39. De Resende D, Greghi S, Siqueira AF, Benfatti C, Damante CA, Ragghianti MZ. Acellular dermal matrix allograft versus free gingival graft: a histological evaluation and split-mouth randomized clinical trial. Clin Oral Invest 2019;23:539–50.
Please cite this article in press as: Lu W, et al. Clinical efficacy of acellular dermal matrix for plastic periodontal and implant surgery: a systematic review, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.ijom.2019.12.005
YIJOM-4339; No of Pages 10
10
Lu et al.
40. Taiyeb Ali TB, Shapeen IM, Ahmed HB, Javed F. Efficacy of acellular dermal matrix and autogenous connective tissue grafts in the treatment of gingival recession defects among Asians. J Investig Clin Dent 2015;6: 125–32. 41. Barros RRM, Macedo GO, Queiroz ACD, Novaes AB. A modified surgical flap for root coverage in association with grafting materials. J Esthetic Restor Dent 2015;27:84–91. 42. Goyal N, Gupta R, Nymphea P, Parveen D. Analysis of patient acceptance following treatment of Miller’s class II gingival recession with acellular dermal matrix and connective tissue graft. J Indian Soc Periodontol 2014;18:352–6. 43. Shori T, Kolte A, Kher V, Dharamthok S, Shrirao T. A comparative evaluation of the effectiveness of subpedicle acellular dermal matrix allograft with subepithelial connective tissue graft in the treatment of isolated marginal tissue recession: a clinical study. J Indian Soc Periodontol 2013;17:78–81. 44. Ahmedbeyli C, Ipci SD, Cakar G, Yilmaz S. Laterally positioned flap along with acellular dermal matrix graft in the management of maxillary localized recessions. Clin Oral Invest 2019;23:595–601. 45. Basegmez C, Karabuda ZC, Demirel K, Yalcin S. The comparison of acellular dermal matrix allografts with free gingival grafts in the augmentation of peri-implant attached mucosa: a randomised controlled trial. Eur J Oral Implantol 2013;6:145–52. 46. Anderson LE, Inglehart MR, Elkholy K, Eber R, Wang HL. Implant associated soft tissue defects in the anterior maxilla: a randomized control trial comparing subepithelial connective tissue graft and acellular
47.
48.
49.
50.
51.
52.
53.
54.
dermal matrix allograft. Implant Dent 2014;23:416–25. Hutton CG, Johnson GK, Barwacz CA, Allareddy V, Avila-Ortiz G. Comparison of two different surgical approaches to increase peri-implant mucosal thickness: a randomized controlled clinical trial. J Periodontol 2018;89:807–14. Graziani F, Gennai S, Discepoli N, Buti J, Madianos P, Herrera D. Efficacy of periodontal plastic procedures in the treatment of multiple gingival recessions. J Clin Periodontol 2014;41:S63–76. Hirsch A, Goldstein M, Goultschin J, Boyan BD, Schwartz Z. A 2-year follow-up of root coverage using subpedicle acellular dermal matrix allografts and subepithelial connective tissue autografts. J Periodontol 2005;76:1323–8. Gallagher SI, Matthews DC. Acellular dermal matrix and subepithelial connective tissue grafts for root coverage: a systematic review. J Indian Soc Periodontol 2017;21: 439–48. Thoma DS, Benic GI, Zwahlen M, Ha¨mmerle CHF, Jung RE. A systematic review assessing soft tissue augmentation techniques. Clin Oral Implants Res 2009;20: 146–65. Chambrone L, Pini Prato GP. Clinical insights about the evolution of root coverage procedures: the flap, the graft, and the surgery. J Periodontol 2019;90:9–15. Thoma DS, Buranawat B, Ha¨mmerle CHF, Held U, Jung RE. Efficacy of soft tissue augmentation around dental implants and in partially edentulous areas: a systematic review. J Clin Periodontol 2014;41:S77–S91. Ozenci I, Dirikan I.S¸, Cakar G, Yılmaz S. Tunnel technique versus coronally advanced
55.
56.
57.
58.
flap with acellular dermal matrix graft in the treatment of multiple gingival recessions. J Clin Periodontol 2016;42:1135–42. Chambrone L, Sukekava F, Arau´jo 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;81:452–78. Cairo F, Pagliaro U, Buti J, Baccini M, Graziani F, Tonelli P, Pagavino G, Tonetti MS. Root coverage procedures improve patient aesthetics. A systematic review and Bayesian network meta-analysis. J Clin Periodontol 2016;43:965–75. Fleming TR, Demets DL. Surrogate end points in clinical trials: are we being misled? Ann Intern Med 1996;125:605–13. Kim SM, Choi YH, Kim YG, Park JW, Lee JM, Suh JY. Analysis of the esthetic outcome after root coverage procedures using a comprehensive approach. J Esthetic Restor Dent 2014;26:107–18.
Address: Fuming He Department of Oral Implantology and Prosthodontics The Affiliated Stomatology Hospital School of Medicine Zhejiang University No. 395 Yan’an Road Hangzhou 310006 Zhejiang China Tel: +86 571 87215430 E-mail: [email protected]
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