Tissue-Engineered Gingival Augmentation

Background:  The oral cavity contains 2 main types of soft tissue: keratinized tissue (KT) and alveolar mucosa (AM). KT, particularly attached gingiva (AG), and AM have distinct functions in the mouth. Adequate KT is believed necessary to maintain a healthy periodontium.  Developmental or acquired mucogingival defects must be surgically corrected. The most widely used technique to augment KT without root coverage is a free gingival graft (FGG). Morbidity at the donor site, lack of sufficient donor tissue and esthetics of the final tissue are disadvantages of FGG. A novel living cellular sheet (LCS) containing allogeneic keratinocytes and fibroblasts in bovine collagen was studied for the treatment of recession-type defects not requiring root coverage in a 6 month, pivotal, multicenter, randomized, within-patient control trial. LCS does not function as a graft. In vitro, LCS secretes human growth factors and cytokines and contains extracellular matrix proteins which are known to be involved in wound repair and regeneration.   Methods: Patients were ≥18 years with 2 nonadjacent teeth in contralateral quadrants the same jaw with an insufficient zone (<1 mm) of AG requiring soft tissue grafting. LCS (in a z-fold) and FGG were applied to a treatment site in 2 separate quadrants respectively.  Ninety-six patients enrolled in and completed the study; 11 were training subjects and included in the safety analysis only. Safety measures included collection of adverse events (AEs); efficacy measures included amount of KT generated and other periodontal health measures, esthetic evaluation, post-surgical subject comfort, and subject preference.  Study visits occurred at screening/baseline, days 0 (surgery), 2, 3, weeks 1 and 4, and months 3 and 6. Results: At 6 months, 95% of patients generated ≥2 mm of KT, significantly superior (P<0.0001) to a predefined standard (50% success) for a 2 mm KT threshold.  A mean of 3.2 ± 1.0 mm of KT was generated at LCS-treated sites. Compared with FGG, LCS-treated tissue was more consistent in color and texture to adjacent tissue (P < 0.0001 for both parameters) and preferred by patients after 6 months. Both treatments were well tolerated with typical oral surgery AEs reported.

Conclusion: LCS can be used to predictably generate site appropriate KT in the oral cavity without the morbidities and tissue limitation associated with FGGs. LCS does not function as a tissue graft. The use of LCS represents a treatment option for surgeons.