Soft tissue augmentation with mucoderm®
On the occasion of the annual meeting of the German Society of Implantology (DGI) in Hamburg on November 26, 2016, seven leading experts with both a strong scientific and clinical background in the field of dental soft tissue reconstruction met to review the current status of peri-implant and periodontal soft tissue management. The discussion focused particularly on the clinical application and experience with the collagen matrix called mucoderm®, published data and data in preparation, as well as the potential limitations of its use, including in comparison with autologous soft tissue grafts.
mucoderm® – an acellular dermal matrix designed for soft tissue reconstruction
mucoderm® is a natural type I/III collagen matrix derived from porcine dermis that undergoes a multi-stage purification process to remove all non-collagenous proteins and cells, as well as potential bacteria and viruses. This processing results in a three-dimensional stable matrix consisting of a naturally cross-linked open porous collagen network that serves as a scaffold for the adhesion and migration of connective tissue cells and blood vessels (Pabst et al. 2015, Pabst et al. 2014). mucoderm® resembles the human dermis and is efficiently re-vascularized after implantation and subsequently remodeled stepwise into the patient’s own connective tissue (Barbeck et al. 2015, Rothamel et al. 2014, Ramachandra et al. 2014). Attracted by the signals from activated migrating and proliferating endothelial cells, blood vessels from the surrounding tissue then grow into the matrix. At the same time, fibroblasts adhere and spread onto the matrix. The simultaneous degradation of mucoderm® and the collagen production of adhering fibroblasts leads to its complete substitution by the newly formed host connective tissue within approx. 6-9 months (Rothamel et al. 2014). Thus, mucoderm® supports revascularization, fast soft tissue integration and offers a safe alternative to the autologous connective tissue. It is suitable for a diverse range of soft tissue grafting indications, such as the treatment of recession defects, peri-implant soft tissue thickening and vestibuloplasty (Schmitt et al. 2016, Zafiropoulos et al. 2016, Rossi et al. 2016, Konstantinova et al. 2015, Stricker et al. 2014).
Treatment of gingival recessions
Gingival recessions are associated with a high prevalence of soft tissue defects, which can manifest themselves as hypersensitive tooth roots or root caries (Sarfati et al. 2010). Root coverage procedures are predominantly indicated to improve tissue morphology for facilitating oral cleaning of the affected teeth and to enhance the esthetic score, thereby lowering the risk of further attachment loss.
Recently published studies on the treatment of maxillary Miller class I and II recessions using the modified coronally advanced tunnel (MCAT) technique in conjunction with the collagen matrix suggest that mucoderm® is a valid alternative to the autologous subepithelial connective tissue graft (SCTG) (Cieslik-Wegemund et al. 2016, Cosgarea et al. 2016). Mean root coverage values of 73.2% after 12 months (Cosgarea et al. 2016) and 91% after 6 months (Cieslik-Wegemund et al. 2016) of healing were observed. The successful improvement and treatment of Miller class III recessions using mucoderm® has also been reported (Cosgarea et al. 2016). The clinical outcome of Miller class III is, however, less predictable compared to the outcomes in Miller class I and II recessions. The experts agreed that mandibular recessions can be treated with mucoderm® and the tunneling technique, although the surgical procedure is more technique-sensitive, and the results in the lower jaw may be less predictable compared to the maxilla; furthermore, inserting muscles and frenula may adversely affect outcomes. In such cases, the use of mucoderm® should be considered only if a tension-free closure of the flap covering the graft can be achieved. In addition, the adjunctive use of Emdogain® may be considered.
Defect- and patient-related factors affecting successful outcomes in recession coverage
The experts agreed that (i) the coverage of the matrix, (ii) the flap design, (iii) the gingival biotype, and (iv) the immobilization of the matrix, are key factors in obtaining a stable and predictable outcome when mucoderm® is used in periodontal plastic surgery.
(i) Coverage of the matrix and (ii) Flap design
The optimal flap technique does not depend on the grafting material used, but rather on the anatomical situation and careful site assessment (biotype, width and amount of keratinized tissue present and recession classification). The expert group agreed that sufficient vascularization of the flap is extremely important. The revascularization strongly depends on the soft tissue thickness, flap design and flap fixation. The choice of the flap technique should be based on the goal of maintaining the vascularization of the overlying flap, which will provide nutrition to the underlying matrix. In the case of a shallow vestibulum, the modified coronally advanced flap (MCAF) may be preferred. If the coronally advanced flap (CAF) or MCAF is employed, a split-full-split preparation should be performed. Interestingly, a comparison of the two flap techniques in conjunction with mucoderm® revealed superior outcomes for the MCAF with respect to esthetics and patient satisfaction, while both flap designs resulted in successful root coverage (Ahmedbeyli et al. 2015). Prof. Kasaj emphasized that a tension-free primary closure of the flap by a split- or full-thickness flap over the graft is of utmost importance in maintaining an adequate vascular supply for the matrix.
(iii) Gingival biotype
With regard to the indicated flap technique, the evaluation of the gingival biotype is equally crucial for a successful treatment outcome since the overlying flap needs to be thick enough to support a blood supply. A thin biotype in the lower jaw requires a technique that is sensitive and demanding due to the risk of inadequate blood supply and the difficulty in achieving tension-free closure. Nevertheless, a thin biotype per se does not present a contraindication for the use of mucoderm®, but the surgical procedure is more demanding and a technique employing a full-thickness flap should be preferred. In the case of a thin biotype, the tunnel technique (MCAT) may be preferred, as it does not require splitting of the flap and the mucoderm® can be placed in direct contact with the bone.
(iv) Immobilization of the matrix
The immobilization of the mucoderm® graft is another crucial point in promoting matrix integration. If the mucoderm® is not sufficiently stabilized by the flap, the matrix should be fixed/sutured to avoid micro-movements during the early healing period. The expert group stressed that the need for fixation of the collagen matrix depends on the flap technique employed. If possible mucoderm® should be tightly sutured to the periosteum (CAF or MCAF) to avoid hematoma formation. If mucoderm® cannot be fixed to the periosteum it should be fixed to the flap. If the tunnel technique is used the mucoderm® should be fixed to the inner aspects of the flap.
A plane adaptation at the recipient site is essential. Dr. Cosgarea and Dr. Horváth referred to fixation by sling sutures when MCAT procedures are used, i.e. the lateral ends of mucoderm® can be sutured to the flap or the periosteum, while the coronal parts are best fixed with sling sutures around teeth/splints. For CAF or MCAF, cross sutures can be used for plane adaptation of the graft over the entire area.
All fields of dental soft tissue management were discussed, such as recession coverage at teeth, peri-implant soft tissue thickening, broadening of the attached mucosa and socket management.
The following experts were invited to the meeting:
Prof. Dr. Dr. Adrian Kasaj
(University of Mainz, Germany),
PD Dr. Dr. Peer Kämmerer
(University Medical Centre Rostock, Germany),
Dr. Raluca Cosgarea
(University of Cluij-Napocca, Romania and University of Marburg, Germany),
Dr. Dominiki Chazopoulou
(Queen Mary University of London, UK),
Dr. Attila Horváth
(Semmelweis University Budapest, Hungary),
Dr. Alessandro Rossi
(University of Milan, Italy)
and Dr. Christian Schmitt
(University of Erlangen, Germany).
Patient-related success factors
Further factors impacting on the clinical success are preoperative low plaque scores and good plaque control, as well as proper pre-surgical preparation of the exposed root surfaces to eliminate inflammation and remove local factors, including plaque and stains. Some modification of the root surface may be advised, and composite restorations will need to be removed. In addition, patient care is extremely important, and recommendations should be given for the postoperative care, avoiding brushing and flossing of, and mechanical trauma to, the surgical sites for 2 to 3 weeks, daily rinsing with 0.1-0.2% chlorhexidine or local application of antiseptic chlorhexidine gel for 2 to 3 weeks, prescription of anti-inflammatory drugs and pain control medications. Suture removal is recommended 2 to 4 weeks after surgery.
Healing and long-term stability of mucoderm®
Observations and recently published data refer to the specific healing pattern and long-term stability of the clinical outcome. In the early healing phase bulgy tissue or ‘edges’ may be visible in the coronal area of the matrix, but these will gradually disappear. The esthetic result will improve over time, and leveling of the tissue accompanied by creeping substitution may be observed. It has also been noticed that the treatment with mucoderm® will lead to no, or only a minimal, increase in the width of the keratinized tissue. Nevertheless, the treatment will lead to an increase in tissue thickness and to dense connective tissue beneath the mucosal surface, which will help stabilize the periodontium. The overall outcome is good even if the surface is not extensively keratinized. On the other hand, keratinization of the tissue is not essential for a successful treatment outcome, whereas a band of attached gingiva of, ideally, 2 mm is essential for the maintenance of periodontal health and to enable patients to maintain good oral hygiene (Marquez et al. 2004).
The stability of the clinical outcome when mucoderm is used to treat gingival recessions is currently being investigated by means of a retrospective analysis (Gaal, Hangyasi et al., unpublished). In this study 198 defects with a mean follow-up period of 28 months were examined, and preliminary results indicate that mucoderm® is a suitable alternative to autologous SCTG. The results are being prepared for publication, and a long-term follow-up of the patients is planned. Another retrospective analysis of 12 patients with 54 recessions involves 3-year data on the MCAT technique in conjunction with mucoderm® (Cosgarea, Sculean et al., in preparation). The clinical outcomes indicate stable results over time; publication is planned in 2017. Moreover, clinical cases with follow-up periods of up to 5 years show highly stable results, although further confirmatory long-term studies are needed.
Deciding between mucoderm® and SCTG
The experts concluded that mucoderm® can be a genuine alternative to SCTG and, in certain clinical situations, the use of mucoderm® is particularly beneficial. In the case of multiple recessions it is sometimes not possible to harvest autologous grafts in sufficient quantity or quality, thus requiring a soft tissue substitute such as mucoderm®, which offers unlimited availability. By using a dermal matrix, multiple recessions can be treated in a single session. Moreover, mucoderm® offers the advantages of fewer surgical interventions and postoperative complications, as tissue harvesting from the palate is not needed, and reduced surgical time. The treatment is also less painful if the collagen matrix is used instead of an autograft, as patients complain mostly about the pain at the donor site. mucoderm® may also be preferable for anxious patients, as the surgery is more complicated and time-consuming if an SCTG has to be harvested. It was pointed out that, if the situation is viable for both autograft and mucoderm®, the patient should be asked about their preference, which is considered to be the most important aspect in a private practice setting. Compared to the SCTG, mucoderm® has to be covered, which means that the coronal repositioning of the flap can cause flattening of the vestibule in specific situations. An autologous soft tissue graft should also be considered the method of choice for mandibular recessions in the frontal area in conjunction with a thin biotype.
Combining mucoderm® and enamel matrix derivative – a novel approach to recession coverage
A new attractive approach to treat gingival recessions is the combination of mucoderm® and enamel matrix derivative (EMD, Straumann® Emdogain®), which can improve the clinical outcome and postoperative healing (Kasaj et al. 2015). Recent findings indicate that collagen products can absorb and release the biological activity of the enamel matrix proteins, thus promoting regeneration (Miron et al. 2016, Stähli et al. 2016, Shirakata et al. 2016). A recent in vivo study demonstrated the combined use of mucoderm® and EMD for recession coverage employed with the CAF technique. Most of the clinical parameters, such as bone gain and cementum formation, favored the EMD/collagen matrix group (Shirakata et al. 2016). Adding Straumann® Emdogain® to a root coverage procedure with mucoderm® can thus improve the quality of the attachment (Shirakata et al. 2016, McGuire et al. 2003) and stimulate angiogenesis (Kasaj et al. 2012), which may improve revascularization and integration of the collagen matrix. Furthermore, the combination of Emdogain® with mucoderm® can improve the quantity of the keratinized tissue (Shin et al. 2007, Pilloni et al. 2006), which may be beneficial if there is less, or no, residual keratinized gingiva. Emdogain® can therefore be advantageous in thin gingival biotypes to improve the vascularization of the flap and thus mucoderm® integration and tissue remodeling. The experts broadly agreed that genuine periodontal regeneration may be achieved by combining mucoderm® with Emdogain®. Dr. Chatzopoulou and Prof. Kasaj stressed that this combination was specifically beneficial for smokers and other medically compromised groups (e.g. diabetic patients), since Emdogain® has been shown to be capable of promoting wound healing (Alves et al. 2012). Adding Emdogain® might also improve the clinical outcome in Miller class III recession-type defects (Shin et al. 2007, Cueva et al. 2004), although complete root coverage remains less predictable in this indication. As regards the correct procedure, the expert group pointed out that the Emdogain® gel should be applied beneath and on top of the mucoderm®. Clinical experience has also shown that Emdogain® improves wound healing and is more comfortable for the patient.
In summary, the mucoderm® matrix can be a valid alternative to the autologous soft tissue graft for recession coverage. For a successful clinical outcome, appropriate patient selection based on the Miller class is required, as well as a surgical technique that enables efficient revascularization and complete coverage of the matrix. The combined use of mucoderm® and Emdogain® in this indication may be an attractive approach to induce the formation of a natural attachment, gain new soft tissue volume and, at the same time, improve postoperative healing.
Soft tissue thickening around teeth and implants
Sufficient peri-implant soft tissue is crucial to prevent crestal bone loss following implant placement, as indicated by recent studies (Akcali et al. 2016, Linkevicius et al. 2009). mucoderm® is indicated to augment the soft tissue around teeth and dental implants (Zafiropoulos et al. 2016, Puisys et al. 2015, Schmitt et al. 2015).
Current in vivo data highlight the volume stability of the mucoderm® matrix in tissue thickening procedures. Volume loss was observed within the first 3 months after tissue thickening around teeth in an animal model comparing mucoderm® with a palatal SCTG (Schmitt et al. 2015). This is in accordance with various cases operated on by the experts, where a volume loss of about 50% was observed within the first 3 months. After 3 months, stabilization with equal results up to 10 months was observed in the animal study (Schmitt et al. 2015). Histological quantitative analyses after tissue thickening with mucoderm® vs. SCTG showed significantly increased tissue thickness in the SCTG group after 10 months (Schmitt et al., unpublished). Interestingly, the immunohistological quantification of the matrix proteins collagen and VEGF showed no significant differences between the mucoderm® and SCTG groups after 10 months in the augmented regions (Schmitt et al., unpublished).
Interim results of an ongoing clinical trial show volume losses of 84% for mucoderm® and 53% for the SCTG after tissue thickening around dental implants following an evaluation period of 6 months (Schmitt et al., unpublished). However, the treatment resulted in comparable increases in tissue thickness after 6 months (about 1.5 mm for mucoderm® and 1.46 mm for the SCTG). These results are in line with various cases and studies showing an average gain in soft tissue of about 1.0 – 1.5 mm after 6 to 10 months following tissue augmentation (Zafiropoulos et al. 2016, Schmitt et al., unpublished, Rossi et al., unpublished). With respect to soft tissue thickening, it was also demonstrated that the collagen matrix can improve the esthetic score in early implant placement procedures (Puisys et al. 2015). The expert group stated that a soft tissue thickness gain of about 1.0 – 1.5 mm can be regarded as a satisfactory clinical result, and that over-contouring might be useful to account for the volume loss.
In conclusion, thickening of the soft tissues around implants or natural teeth may be achieved by applying mucoderm® instead of an autograft, although the volume loss in the early phase seems to be more pronounced compared to the autologous soft tissue graft. However, a recently published study (Zafiropoulos et al. 2016) and preliminary results of ongoing clinical studies indicate a comparable soft tissue volume gain following augmentation with mucoderm®. Notably, the stability of the clinical results up to at least 5 years after soft tissue thickening with mucoderm® was demonstrated in a retrospective study (Puisys et al. 2015).
An adequate width of the attached mucosa around teeth and implants provides protection against the penetration of microorganisms and food particles. The attached gingiva absorbs the mechanical strain from the lip and cheek muscles, shielding the teeth from the strain. A reduction in, or lack of, attached gingiva may increase susceptibility to recession and inflammation (periodontitis or peri-implantitis), potentially leading respectively to bone resorption and tooth or implant loss (Bassetti et al. 2015). The experts broadly agreed that less than 2 mm of keratinized tissue around a tooth or an implant may cause discomfort when brushing, potentially leading to poor oral hygiene, plaque accumulation and inflammation (Lin et al. 2013).
mucoderm® is indicated to augment the attached gingiva in vestibuloplasty procedures (Hegedüs et al. 2015, Konstantinova et al. 2015, Soytürk et al. 2015, Horvath et al. 2014, Nocini et al. 2014). In this indication a close contact between the periosteum and mucoderm® is necessary to ensure fast integration and revitalization of the matrix by the ingrowth of blood vessels and cells. mucoderm® should be closely fixed to the underlying periosteum by modified periosteal mattress sutures in order to attain tight contact between the graft and the periosteum. In addition, it may be beneficial to try to tuck the matrix under the remaining keratinized mucosa. A continuous sling suture can be applied to fix the mobile mucosa.
Ongoing studies are investigating the healing and volume stability of the collagen matrix in vestibuloplasty procedures (Horváth et al., Kämmerer et al., unpublished). Dr. Horváth reported rapid vascularization in the early healing phase which, in many cases, appears to be even faster than the revitalization of the free gingival graft (FGG). Moreover, in the early healing phase a fibrin-like exudation may be observed 2 weeks after the augmentation (Kämmerer et al., unpublished). Re-epithelialization of the augmented site takes about 4 weeks, and the site generally heals without scaring. Thus, the esthetic results are favorable compared to a skin graft or FGG. Mean increases of 2.1 mm and 2.7 mm in the width of the attached gingiva with shrinkage of about 25% were observed by Hegedűs et al and Kämmerer et al., respectively. In addition, results from Dr. Horváth and coworkers indicate that shrinkage can reach 50% after 6 months (Hegedűs et al.). These results are either more favorable than, or in accordance with, the findings for other collagen matrices available on the market (Horváth et al 2014, Schmitt et al. 2016). The experts concluded that an over-augmentation, i.e. twice the desired width, can be recommended in order to produce a desirable band of attached gingiva of 2 – 3 mm, which may not be considered as a drawback, due to the unlimited source of the xenograft.
With regard to clinical success, the expert group further stated that a more stable and predictable clinical outcome can be expected in the maxilla compared to the mandible. This may be the result of the greater tension of inserting muscle fibers. Naturally, postoperative care and plaque control are key points for a successful outcome. Patients should refrain from brushing the recipient site for at least 2 weeks and use antiseptics e.g. chlorhexidine 0.1-0.2% or antiseptic gel. Furthermore, a soft diet is recommended, and excessive physical activities should be avoided.
In summary, mucoderm® may be a viable alternative to FGG/CTG for broadening the keratinized mucosa, especially in cases of insufficient quantity and/or color mismatch of the FGG/CTG, without the concomitant postoperative discomfort associated with the harvesting of an autologous graft.
Soft tissue management before or during implant placement
mucoderm® may be used to improve the soft tissue contour in case of immediate implantation or sealing extractions sockets after tooth removal (Rossi et al. 2016). The coverage of an extraction socket with mucoderm® can be applied to maintain the soft tissue volume, to augment the keratinized tissue and to protect the socket or biomaterials in the socket. One of the main benefits of mucoderm® for socket sealing is that its application helps to avoid the compromising coronal shift of the mucogingival junction caused by forced primary closure of the flaps.
The expert group pointed out that mucoderm® can be applied to cover extraction sockets without any filling or after grafting the socket with a bone substitute material or collagen sponge. However, the application of a xenogeneic or synthetic bone graft can help maintaining the volume of the alveolar ridge, but systematic reviews have shown various results of socket seal and ridge preservation techniques with or without the use of grafts especially in histological evaluations (MacBeth et al. 2016, Horváth et al. 2013). The findings of an ongoing study indicate that predictable results can be obtained if two-third of the matrix is secured under the periosteum, so that only one-third is exposed (Rossi et al.). In this study 10 intact sockets with intact buccal walls were sealed by mucoderm®, and two-thirds of the surface of the mucoderm® matrix were stabilized under the marginal tissue, with a mean exposure area of 26 mm2. The follow-up revealed that closure of the socket after 8 weeks was maintained in 9 out of 10 sites. The authors emphasized that releasing incisions are not needed in these cases, while the space under the periosteum can be created by tunneling. Thereafter, mucoderm® can be placed under the periosteum buccally and lingually and immobilized by cross sutures over the matrix.
Thus, mucoderm® offers an attractive approach to seal extraction sockets. Ongoing studies are investigating the healing in socket preservation procedures where the sockets are grafted with allogenic or synthetic biomaterials.
Following a fruitful discussion of published clinical studies and case series, as well as ongoing, recently published clinical data, on the use of mucoderm® as a soft tissue replacement, the experts concluded that the present xenogenic dermal matrix could be used successfully in periodontal and implant-related procedures without the need for autograft harvesting. However, all participants stressed the significance of revascularization as the most crucial point when mucoderm® is used in periodontal plastic surgery, peri-implant soft tissue thickening, vestibuloplasty or socket sealing procedures. The experts further deemed the clinical manageability of mucoderm® to be excellent and straightforward, requiring no material-specific modifications. There was also broad consensus on the need for further clinical data, specifically with respect to the long-term stability of the clinical outcome, although promising results have demonstrated stable soft tissue situations following augmentation with mucoderm® (Zafiropoulos et al. 2016, Cosgarea et al. 2016, Puisys et al. 2015). Further studies should also evaluate the advantages of the combination therapy with Emdogain® and/or other growth factors. The experts accordingly proposed potential study designs so that, together with currently running studies, new insights into the clinical use of mucoderm® will be gained in the future.