Abstract
Background: The treatment of perianal fistulas remains challenging, with low healing and high recurrence rates. Autologous adipose-derived regenerative therapies and platelet-rich plasma (PRP) have emerged as adjuncts to surgical intervention for cryptoglandular and Crohn’s disease (CD)-related perianal fistulas (PAF). This systematic review evaluates the outcomes of these therapies as an add-on to surgical intervention. Methods: A systematic search was conducted in several online databases up to December 2025. Studies with ≥10 patients reporting on the use of intraoperative autologous adipose-derived therapies and/or PRP for the treatment of cryptoglandular or CD-related PAF, and clinical healing rates, were included. Other outcomes comprised radiologic healing (as defined in the study), recurrence rates and complications. The study quality was assessed with the Effective Public Health Practice Tool. Results: In total, 28 studies on individual cases were included (n = 1017 patients, range 10–219) (17 in cryptoglandular PAF, 8 in CD-related PAF and 3 in both entities). A total of 57% of the studies were rated low quality. In cryptoglandular PAF, reported healing rates with adipose-derived therapies ranged from 50% to 90% across studies of low to good methodological quality. For PRP, three of the four randomized trials demonstrated no superiority over standard care. In CD-related PAF, healing rates after treatment with adipose-derived therapies ranged from 40% to 80%. For PRP, three studies, of which two were low quality, reported highly variable healing rates (33–80%). Radiologic healing, reported in 10 studies, ranged from 38 to 76% in cryptoglandular and 33–75% in CD-related PAF. Recurrence rates remained <17% for adipose-derived therapies and <31% following treatment with PRP. Major complications occurred in <15% of the patients. Conclusions: High heterogeneity with regard to fistula complexities, outcome definitions and surgical method was observed in the available studies on autologous add-on therapies. This hinders an overall effectiveness analysis. The promising healing rates, low recurrence rates after healing and low complication rates warrant high-quality trials.