029 Differential Angiogenic Responses in Oral Mucosal and Cutaneous Wounds

Abstract

Wound healing in adults is a multi‐step process that concludes with scar formation. A common clinical observation is that intra‐oral wounds demonstrate privileged healing when compared to wounds at extra‐oral sites. Oral mucosa heals faster and with less scar formation than skin does. We have shown that oral mucosal wounds exhibit decreased inflammation and faster reepithelialization than skin wounds. The present study compares angiogenesis in oral mucosal and skin wounds, and examines in vitro VEGF production by oral and epidermal keratinocytes. Two 1 mm diameter excisional full‐thickness wounds were placed on lateral sides of the tongue and on the dorsal skin of anesthetized BALB/C mice. At 0, 2, 4, 12, 24, 36 hours and 2, 3, 5, and 7 days after injury, wound tissue was harvested for analysis. VEGF and FGF‐2 levels were measured by ELISA, and normalized for protein content. The level of VEGF in oral mucosal wounds was less than that of cutaneous wounds at all time points. At 24 hours, VEGF levels peaked in oral wounds, yet were much lower than comparable skin wounds (106.6 +/− 19 vs. 194.0 +/− 23.6 pg/mg protein, p < 0.001). At 36 hours, wound VEGF levels had declined in oral mucosa, while reaching peak levels in skin (82.7 +/− 8.9 vs. 374.2 +/− 27 pg/mg protein, p < 0.001). No differences in FGF‐2 levels were seen. The relative increase in tissue vascularization during wound repair, analyzed by CD 31 immunostaining, was lower in oral mucosal wounds than in skin (3.4 +/− 0.2% vs. 11.5 +/− 0.5%, p < 0.001). For in vitro experiments, normal human epidermal and oral mucosal keratinocytes were grown for 12 h under hpoxic conditions. In response to hypoxia, VEGF protein production, determined by ELISA, increased 2.3‐fold in oral keratinocytes vs. 3.3‐fold in epidermal keratinocytes. RT‐PCR analysis revealed that relative VEGF mRNA expression increased 2‐fold in oral vs. 4‐fold in epidermal keratinocytes. This study demonstrates that the differential repair of skin and oral mucosal wounds involves distinct patterns of angiogenesis, and that keratinocytes exhibit intrinsic site‐specific differences in VEGF production.