Non-Healing Perianal Fistulas: A Clinical Model of Tissue Senescence Impairing Both Tissue Fibrosis and Regenerative Potential

Senescent cells and fibrosis are important components that impact the regenerative capacity of skin, particularly when considering chronic non-healing wounds. Anoderm and perianal fistulas in the setting of Crohn’s disease are clinically pathophysiological extremes with consequently different healing processes which impact treatment modalities. This study describes the implications of potential senescence reversing techniques including autologous fat grafting and pharmacologic and immunomodulating agents. Given these findings, the authors propose a future direction of study involving exosomes loaded with senolytics as a method for potentially improving chronic wound healing. In conclusion, this manuscript explores the diversity of skin healing and healing outcomes which supports the future investigation of senotherapeutic agents promoting regenerative processes for non-healing wounds.