Novel and Experimental Therapies for Anal Fistula

Abstract Anal fistula is a challenging clinical entity primarily due to complex anatomy, the risk of recurrence, and the potential for incontinence resulting from treatment. Traditional surgical approaches, such as fistulotomy, seton placement, advancement flap, and ligation of the intersphincteric fistula tract, offer effective solutions for numerous cases but may carry the risk of sphincter damage or suboptimal healing in complex fistulas. As a result, multiple minimally invasive and biologics-based therapies have emerged, including video-assisted anal fistula treatment, laser fistula closure, endoscopic closure devices such as over-the-scope clips, next-generation biomaterial scaffolds, platelet-rich plasma, and mesenchymal stem cell therapy. Each of these approaches has distinct mechanisms, clinical evidence, and limitations. More recent innovations include next-generation biomaterials and the integration of artificial intelligence for optimized diagnostic and treatment planning. This chapter reviews the mechanisms, clinical trial evidence, outcomes, and future directions for these novel therapies in both cryptoglandular and Crohn's disease–associated anal fistulas, emphasizing clinical relevance and decision-making.