Bridging the gap in ligament healing: A systematic review of secretome-derived therapies

Background and Aims: This systematic review evaluates the benefits of secretome application in ligament healing. Materials and Methods: Secretome treatment is shown to enhance graft revascularization, collagen deposition, and biomechanical strength in preclinical investigations. Clinical investigations indicated improved functional recovery, diminished inflammation, and decreased graft failure rates relative to traditional anterior cruciate ligament (ACL) reconstruction. Nevertheless, variability in secretome preparation and application techniques restricts direct comparisons. Our study has been registered at PROSPERO ID CRD420251001614. Results: The comprehensive review consolidates findings from qualifying investigations, emphasizing enhancements in collagen organization, vascularization, biomechanical strength, and clinical functional scores. Variations in the source, dosage, and application method of the secretome affected the outcomes. Conclusion: Secretome treatment seems to improve ACL autograft healing by facilitating biological integration and functional recovery. Although pre-clinical and initial clinical findings are encouraging, additional high-quality randomized controlled studies are essential to establish standardized techniques and validate long-term efficacy.