The use of a xenogenic collagen matrix (Mucograft®) in the treatment of the implant site: a literature review
Review Article

The use of a xenogenic collagen matrix (Mucograft®) in the treatment of the implant site: a literature review

Lorenzo Bevilacqua, Giulia Pipinato, Giuseppe Perinetti, Fulvia Costantinides, Roberto Rizzo, Michele Maglione

Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy

Contributions: (I) Conception and design: L Bevilacqua, M Maglione; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: G Pipinato, F Costantinides; (V) Data analysis and interpretation: G Perinetti, F Costantinides; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Lorenzo Bevilacqua. Department of Medical, Surgical and Health Sciences, University of Trieste, Piazza dell’Ospitale 1, 34125 Trieste, Italy. Email: l.bevilacqua@fmc.units.it.

Abstract: Lack of adequate amount of keratinized gingiva around dental or implants is generally treated with coronally advanced flap in combination with connective tissue graft. The procedures of harvesting the soft tissue grafting are usually associated with a certain degree of morbidity; for this reason xenogenic collagen matrix was proposed to be used as an option to reduce morbidity. This collagen matrix quickly stabilizes the blood clot and promotes rapid vascularization. Moreover, this product promotes root coverage, reduction of recession and regeneration of keratinized gingiva both in width and thickness. Recently, xenogenic collagen matrix was also proposed as a biological material able to regenerate keratinized gingiva around implants. In this review, the role of xenogenic collagen matrix (Mucograft®) has been critically analyzed to evaluate its effectiveness and predictability in keratinized tissue augmentation around implants supporting prosthetic restorations. Most of the studies showed that xenogenic collagen matrix was effective in increasing the thickness of the peri-implant mucosa and in the gaining of keratinized gingiva with comparable or slightly lower results than autologous connective tissue grafts. From the aesthetics point of view, the gold standard appeared to be the autologous connective tissue graft. Histologic analysis showed a good integration of the collagen membrane that matures into a healthy tissue. Mucograft® seems an effective alternative to the autologous connective tissue graft with regard to the gain of keratinized tissue and the increase in thickness of peri-implant soft tissues, with less post-operative morbidity and reduced operative times.

Keywords: Xenogenic collagen matrix; implant; perimplantitis; soft tissue augmentation; recession


Received: 06 April 2020; Accepted: 26 August 2020; Published: 11 September 2020.

doi: 10.21037/fomm-20-25


Introduction

In 1957, the term of mucogingival surgery is introduced by Friedman in order to indicate “the surgical procedures aimed to preserve keratinized gingival tissue, remove aberrant frenulum or muscle attachments, and increase vestibular depth” (1). During the following years the promotion of periodontal health and the improvement of patient’s aesthetic become mucogingival surgery’s targets together with the preservation or creation of keratinized gingival tissue (2). However, only in 2012 Zucchelli introduced a more complete definition, including among the objectives of mucogingival surgery also the increased gingival height and thickness around prosthetic elements or implants (3). In general there were two schools of thought: the first, subsequently denied, believed the presence of a sufficient keratinized gingiva is necessary for the periodontal health (3,4) and the second one claimed that periodontal health is possible even if the amount of keratinized gingiva is poor or absent (3,5). However, the presence of keratinized gingiva is very important when dental implants are concerned. In fact, in 2009 Linkevicius et al. showed that the thickness of peri-implant mucosa was a critical factor for marginal bone stability, documenting the correlation between a thin mucosa and greater marginal bone loss (6). More recently the consensus report from the Osteology Foundation concluded that a sufficient peri-implant mucosa width is useful to guarantee a greater plaque control and a higher marginal bone stability when compared to sites lacking (or with minimal) mucosal thickness and keratinized mucosa (7). The aesthetic factor must also be considered; marginal tissue recession around dental implants is a functional but also an aesthetic problem. At least 2 mm of mucosal thickness is necessary to obtain better aesthetic outcomes (8). The peri-implant mucosa anatomically differs from periodontal soft tissue around teeth for the following characteristics: a longer junctional epithelium, parallel orientation of the connective tissue fibers, lower number of fibroblasts, and reduced vascularity (9). That’s why the soft tissue seal around dental implant is weaker than the natural teeth, thus making important having enough keratinized mucosa to maintaining peri-implant health (10). First of all, to successfully treat a recession defect, it's important to identify the etiology and remove it. There are anatomical factors (inadequate keratinized attached mucosa, buccally positioned implant platform, osseous dehiscence or fenestration, muscle pull, thin gingival biotype) and pathological factors (recurrent inflammation and iatrogenic factors such as vigorous toothbrushing or overcontoured prosthesis) which can cause gingival recession around dental implants (2). The conventional periodontal plastic surgical techniques commonly used to manage marginal tissue recession around dental implants can be divided into pedicle soft tissue grafts (rotational flap procedures and advanced flap procedures) and free soft tissue grafts (epithelialized and non-epithelialized grafts) or a combination of both (2). The success of the chosen surgical technique is influenced by patient-related factors, such as bad habits (smoking), systemic diseases and inadequate plaque control, or by defect-related factors, such as the presence of interproximal bone or the defect width and depth or by procedural-related factors (flap thickness) (2,11). Soft tissue grafts in particular, useful in increasing the thickness of the peri-implant mucosa, can be harvested from retromolar pad or from edentulous site, but the preferred site is the palate with free gingival grafts or sub-epithelial connective tissue grafts (12). Many limitations and complications are reported in association with soft tissue grafts harvested from the palate, including the need of a second surgical site with the donor site morbidity (bleeding, pain, infections, sensitivity disorders) (2,12,13). Alternative techniques have been explored to avoid these difficulties: allogenic grafts (acellular dermal matrix harvested from human dermis and processed to remove all the cellular and epidermal components), xenogeneic grafts (pure porcine collagen type I and III extracted and purified), guided tissue regeneration (a barrier membrane is used to exclude undesirable cells, such as epithelial cells), a tissue-engineered skin or gingival graft (living cellular construct that consists of purified type I bovine collagen and vial allogeneic neonatal keratinocytes and fibroblasts extracted from human foreskin) and growth factors (2). Among the soft tissue graft substitutes, recent studies have suggested that xenogeneic collagen matrix may provide outcomes comparable to the connective tissue graft (14,15), with the advantages of unlimited supply, less invasiveness, no donor site morbidity and less surgical time needed (16). Various options of xenogeneic grafts are available: MucoMatrixX, Alloderm®, Mucoderm®, Platelet rich fibrin, Puros® Dermis and Mucograft®. Mucograft® is a 3D pure porcine collagen matrix obtained by standardized, controlled manufacturing processes, consisting of a double functional layer: a compact layer and a spongy layer (17). The aim of this literature review is to investigate whether the use of xenogeneic collagen matrix, Mucograft® in particular, is an effective method for increasing soft tissue in patients with insufficient peri-implant mucosal width and thickness.


Methods

An electronic search is performed on the MEDLINE database, through PubMed (www.ncbi.nlm.nih.gov/pubmed), SCOPUS (www.scopus.com), Cochrane Library (www.thecochranelibrary.com) and Web of Science (www.webofknowledge.com) using the following key words connected by the boolean operators OR, AND: “xenogeneic collagen matrix”, “mucograft”, “dental implants”, “soft tissue augmentation” and “mucosal recession”. The last electronic search was carried out on 17 September 2019. No time restrictions and no restrictions regarding the classification of the studies were applied; both literature reviews, clinical trials and observational studies were considered. Only articles in English were considered. In vitro and animal studies were excluded. The selected articles were classified according to the study type and divided in three different tables (literature reviews, clinical trials, observational studies). The following data were extracted from each article: names of the authors, year of publication, study type, description of the sample size, follow-up period and outcomes.


Results

The electronic search provided a total of 88 articles. After examining the titles and abstracts, the articles that did not meet the inclusion criteria were excluded and 22 articles were selected, 21 from Pubmed and 1 from the Cochrane Library (2,9,10,12,14,15,18-33). Six literature reviews were selected (including two meta-analyzes), eight clinical trials (six randomized, one non-randomized, and one with unspecified randomization) and eight observational studies. The articles were divided according to the study type in Table 1, Table 2 and Table 3. The subjects considered in the various studies are mostly female. Age range of the subjects considered in the various studies is ≥18 and <88 years. Only one study considers the presence of differences in prognostic terms related to sex, age and gingival biotype of the patients. According to the study of Zuiderveld et al. no significant differences emerged (27). Where specified, only healthy patients from a systemic and periodontal point of view appear to have been considered, with optimal plaque control. The observational study of Lorenz et al. (24) selects patients suffering from head-neck cancer, but who have been cured for at least 1 year at the time of implant rehabilitation and with adequate oral hygiene. None of the analyzed studies, apart from one, takes into account the possible presence of differences related to the adopted type of implant. In the study of Zuiderveld et al. no significant differences were noted related to the length and diameter of the used implants (27). None of the studies analyzed consider the possible presence of differences linked to the site of intervention (mandible/maxilla, anterior sectors/posterior sectors). In the study of Zuiderveld et al. there are no significant differences related to the site of intervention (27). With regard to the gain of keratinized tissue in the apico-coronal sense, according to two studies the autologous connective tissue graft provides superior results to the collagen matrix (2,21). Eight studies support the superiority of the xenogenic matrix over collagen grafting (10,15,18,25,26,29,30,33). Five studies support the usefulness of the xenogenic matrix in the gain of peri-implant keratinized tissue (19,20,22,24,28). According to the review of Gargallo et al., the autologous connective tissue graft and the xenogenic collagen matrix are comparable in terms of increased thickness of peri-implant soft tissues (10). According to three studies the connective graft gives superior results compared to the collagen matrix (2,15,23). Two studies conclude by supporting the usefulness of the xenogenic matrix in increasing the thickness of peri-implant soft tissues (20,32). First (23) or contextually (19) implant insertion seems to be the most correct time to perform the graft, which gives better results in terms of keratinized tissue gain when combined with an apical limb with partial thickness (29,30). According to the Maiorana’s study a perfect integration of Mucograft® with the surrounding tissue was obtained (31). However, according to the majority of studies that take into consideration the aesthetic factor in terms of recession coverage and gray show-through (2,20,27,30), no significant improvements are obtained with Mucograft®. Almost all of the studies agree that the advantages of using Mucograft® include having less post-operative morbidity and complications, since the second surgical site is avoided altogether. In the observational study of Thoma et al., the frequent post-operative bleeding is found to be independent of the treatment used (29). Surgical chair time, if xenogenic collagen matrix is used, is reduced according to two clinical trials (15,21). The review of Gargallo et al. estimates a time reduction of 15.46 minutes when the collagen matrix is used instead of the autologous connective tissue graft (10). Only 4 studies (Table 4) consider the histological aspect (22,24,29,32) for a total of 21 samples analyzed. These studies conclude that 2 months after surgery the collagen membrane is well integrated and covered with epithelium; 4 months after surgery there is complete resorption of the collagen membrane and the tissue architecture is similar to that of a healthy gum.

Table 1
Table 1 Outcomes of reviews published following use of a xenogenic collagen matrix
Full table
Table 2
Table 2 Outcomes of clinical trials published following use of a xenogenic collagen matrix
Full table
Table 3
Table 3 Outcomes of observational studies published following use of a xenogenic collagen matrix
Full table
Table 4
Table 4 Histological outcomes following use of a xenogeneic collagen matrix
Full table

Discussion

A well-represented band of keratinized gingiva (at least 2 mm) has a positive influence on peri-implant health by establishing a seal around the implant which leads the reduction in tissue inflammation and plaque accumulation and, consequently, the reduction of development of perimplantitis. Having an adequate thickness of peri-implant mucosa is important not only to guarantee marginal bone stability over time, but also to mask the gray show-through. Adequate peri-implant mucosal thicknesses are therefore important both from the functional and aesthetic point of view. Most of the studies analyzed show that the xenogenic collagen matrix is effective in increasing the thickness of the peri-implant mucosa and in the gain of keratinized gingiva with comparable or slightly lower results than the autologous connective tissue graft. This difference could be attributed to the different years in which the studies were conducted; the most recent studies report more comforting results regarding the use of xenogenic collagen matrix (Mucograft®) and this could be due to the improvement of the matrix application technique and to the collection of more clinical cases to be compared. However, almost all studies conclude that the collagen matrix is a valid substitute for autologous connective tissue grafting in increasing the volume of peri-implant soft tissues, especially when the main concern is to reduce patient morbidity and operative surgical time. Despite the possible protocols to minimize post-operative pain after palatal collection, there is no doubt that the use of a non-autogenous graft, by avoiding a second surgical site, is less invasive, faster and more tolerable for the patient. From the aesthetics point of view, on the other hand, according to the studies analyzed, the preferred standard appears to be the autologous connective tissue graft, while the Mucograft® would not significantly improve the aesthetics in terms of recession coverage and gray show-through. Which procedure proves the most effective in terms of gaining keratinized gingiva and for the thickness of the soft tissues around the implants is one of the points investigated in the studies of Thoma et al. (29) and of Bassetti et al. (30), which conclude by suggesting the combination of graft (connective or Mucograft®) and partial thickness flap apically positioned. None of the selected studies, except for the one by Zuiderveld et al. (27), which find no statistically significant difference, considers the presence of differences in prognostic terms related to sex, age and gingival biotype of the patients, the type of implants used and the site of intervention. Almost all studies consider healthy patients from both a systemic and periodontal point of view, and a worsening of mucogingival treatment in prognostic terms can otherwise be easily hypothesized. We could as well hypothesize the possible indication of adopting collagen matrix instead of the autologous connective tissue graft in those patients who present pathologies compromising tolerance and pain threshold. Histological evaluation is performed only in 4 of the 22 studies considered, for a total of 21 analyzed samples. Within the limits of the reduced samples’ population, the histology shows a good integration of the collagen membrane that matures into a healthy tissue, similar to the native gingiva. Limitations to the present revision are to be attributed to the still relatively scarce available literature, in reason of which a broader range of study types were included, among which reviews, clinical trials and observational studies. This necessarily leads to an increased heterogeneity of results and the potential development of evaluation errors. Finally, the different surgical approaches chosen in the various studies and the different timing of the grafts (increase of soft tissues before, during or after implantology) cause heterogeneity of results as well. However, the revision of these articles seems to suggest the grafting of soft tissues using Mucograft®, before or at the same time as implant insertion, to counter post-surgical bone remodeling in the absence of adequate thickness.


Conclusions

The present systematic review of the literature, based on the analysis of six reviews, eight clinical trials and eight observational studies, suggests that Mucograft® is an effective alternative to the autologous connective tissue graft with regard to the gain of keratinized tissue and the increase in thickness of peri-implant soft tissues, and with less post-operative morbidity and less operating time required. However, new randomized clinical trials with an adequate follow-up period would be desirable for a histological evaluation of the collagen matrix graft samples, expanding the samples currently available.


Acknowledgments

Funding: None.


Footnote

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/fomm-20-25). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.


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doi: 10.21037/fomm-20-25
Cite this article as: Bevilacqua L, Pipinato G, Perinetti G, Costantinides F, Rizzo R, Maglione M. The use of a xenogenic collagen matrix (Mucograft®) in the treatment of the implant site: a literature review. Front Oral Maxillofac Med 2020;2:23.