Resumen de Generation of Site-Appropriate Tissue by a Living Cellular Sheet in the Treatment of Mucogingival Defects
Background: Generation of site-appropriate tissue in the oral cavity includes the restoration of the correct anatomic type, amount, and distribution of the tissue. This study is a post hoc analysis of data collected during previously published results from two randomized clinical trials of a living cellular sheet (LCS; allogenic cultured keratinocytes and fibroblasts in bovine collagen) versus a free gingival graft (FGG), evaluating their ability to augment keratinized tissue or gingiva.
Methods: Post hoc histologic and clinical (photographic) comparisons of the outcomes of treatment were performed on histologic and photographic data gathered in the two randomized clinical trials.
Results: Histologic findings showed that LCS-treated sites resembled gingiva rather than alveolar mucosa. Photographic analysis indicated that LCS treatment resulted in more site-appropriate tissue than FGG in terms of tissue color, with adjacent untreated tissue, absence of scar formation or keloid-like appearance, and mucogingival junction alignment.
Conclusion: Treatment of mucogingival defects with LCS resulted in the generation of tissue that is more site appropriate than tissue transplanted from the palate.
The optimal goal for treating oral mucosal defects is to restore function while preserving esthetic appearance. Current options are limited and rely predominantly on grafting techniques; i.e., free gingival graft (FGG), subepithelial connective tissue grafts, and rotated pedicle and papillae flaps.1,2 Unfortunately, FGG techniques cause patient morbidity as a result of graft harvesting, and they may not restore tissue that is as esthetically pleasing as native tissue.1,2 Previous research has shown that gingival and palatal grafts retain their tissue characteristics after transplantation to an ectopic site.3-5 Because of these limitations, alternative or adjunctive treatments, such as dermal substitutes, growth factors, and other biomimetics, are being considered.5-7 The goal of many of these technologies is to repair mucogingival tissue and to restore function and esthetics in a site-appropriate manner, while reducing patient morbidity.5-7 Although this living cellular sheet (LCS) has been used for >14 years to treat patients with cutaneous chronic wounds and has also been evaluated in patients with acute cutaneous wounds, its application in oral soft-tissue therapy is relatively recent.2,8-12 LCS is composed of living allogenic human cells, bovine collagen, and human extracellular proteins. The LCS does not engraft but produces a wide array of growth factors and cytokines13-16 that are thought to improve the course of wound healing and tissue regeneration by influencing, transiently and locally, the way that the patient�s own cells differentiate into site-appropriate tissue.2 Two randomized, within-patient controlled clinical trials have demonstrated that LCS can stimulate the patient�s own cells to predictably generate a clinically significant amount of keratinized tissue (KT) and attached gingiva (AG) surrounding teeth that do not require root coverage.2,12 A hallmark of tissue regeneration is the formation of site-appropriate tissue (e.g., correct anatomic type, amount, and distribution).17 In addition to demonstrating the generation of KT, results from these trials showed that tissue generated at LCS-treated sites was superior (P <0.001) to FGG-treated sites in terms of color and texture match with adjacent, untreated tissue.12 In addition to differences in gross clinical morphology, histology may be used to differentiate gingiva, palatal mucosa, and alveolar mucosa (Table 1).3-5 Hematoxylin and eosin staining can be used to evaluate the presence and formation of rete ridges, whereas additional histologic stains may be used to evaluate the arrangement and distribution of collagen, elastin, and reticulin. The specific aim of the present post hoc analysis is to evaluate whether changes in histology and extracellular protein expression correlated with the observed clinical differences in appearance between FGG- and LCS-treated sites from the two clinical trials. 2,12
