Treatment of intractable oral ulceration with an oral mucosa equivalent

The current use of steroids or pharmacological immunomodulators for the treatment of intractable oral ulceration is ineffective, necessitating newer cell-based therapeutic approaches. We examined the potential efficacy of an oral mucosa equivalent developed in this study in an in vivo model of repeat major oral ulceration mimicking the intractable oral ulceration observed clinically. Oral mucosal samples and plasma fibrin were obtained from Sprague-Dawley rats. The oral mucosa equivalents were prepared with cultured mucosal keratinocytes and plasma fibrin mixed with cultured fibroblasts. Ulcers were chemically induced on the rat buccal mucosa thrice in 3 weeks and covered with or without mucosa equivalents. Gross and microscopic findings and mRNA expression levels were compared between the ulcer control and mucosa equivalent groups. Oral mucosal keratinocytes and fibroblasts were cultured in vitro to achieve high viability and colony-forming efficiency. The equivalents showed epithelial and subepithelial structures similar to those of oral mucosa and exhibited high p63 positivity. In the in vivo study, ulceration was resolved earlier without significant granulation or scarring in the equivalent group than in control group (p < 0.05). Microscopic examinations revealed rapid re-epithelialization and less fibrosis in the equivalent group than in the control group (p < 0.05). Mucosa equivalent-covered ulcers showed histological characteristics similar to those of the normal buccal mucosa and exhibited lower expression of TGFB1, ACTA2, and FN1 mRNAs than the control group. The in vitro-engineered oral mucosa equivalent promotes ulcer healing without scarring and functional deficits. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1779-1785, 2019.