Figure 2.

Progression of the healing cascade in cutaneous and oral wounds. Healthy skin and oral mucosa maintain barrier function and satisfy local physiologic functions (top panels). Progression of healing and tissue remodeling after wound closure differentiate the two tissues (middle panels). (1) The oral mucosa keratinocytes migrate and proliferate more rapidly into the wound bed. (2) The overall inflammatory response to wounding is far more transient in oral wounds with less immune infiltrate and rapid resolution of the active inflammatory state. (3) Pro-fibrotic fibroblasts are largely absent in the healing oral mucosa and different lineages contribute to earlier and more rapid extracellular matrix reorganization (ECM) than in the skin. (4) Although the oral mucosa is more vascularized in the healthy state (top panels), oral wounds have less neovascularization/angiogenesis into the wound bed than cutaneous wounds. Healed wounds in the skin contrast significantly with regenerated wounds in the oral mucosa (bottom panels). Adnexal structures in the skin (hair follicles, sebaceous glands, sweat glands, nerves, etc.) are lost in healed wounds that leave a deep scar. The fibrotic ECM and inability of adult cutaneous cells to transdifferentiate into the necessary adnexal precursors precludes the reformation of these structures in extensive wounds and may inhibit full tissue recovery in more superficial wounds. In contrast, oral wounds regenerate to their physiologic baseline (top panel, right) without the formation of fibrotic ECM and with the return of site-dependent adnexal structures.