Anti-adhesive agents in tendon repair: mechanisms, preclinical evidence, clinical challenges, and future perspectives—a narrative review

Tendon injuries constitute a significant challenge to musculoskeletal health, comprising approximately 50% of all related injuries in the United States and resulting in considerable treatment expenditures. Conventional conservative and surgical interventions frequently do not succeed in mitigating peritendinous adhesions, resulting in compromised functionality, pain, and an increased risk of re-rupture. This analysis investigates the underlying mechanisms of adhesion formation in the context of tendon healing, highlighting the disparity between intrinsic and extrinsic factors throughout the phases of inflammation, proliferation, and remodeling. The restoration of tendon gliding and mobility underscores the significance of adhesion prevention. This review concentrates on anti-adhesive compounds, encompassing physical barriers such as collagen and chitosan, as well as pharmacological agents including 5-fluorouracil and platelet-rich plasma. The analysis covers their mechanisms of action and preclinical efficacy demonstrated in vitro and in animal models, along with their diverse bioactivities, which include anti-inflammatory and antibacterial effects. The principal findings indicate significant reductions in adhesions; however, they also highlight challenges such as inconsistent degradation rates, potential toxicity, and a paucity of clinical evidence. Future directions encompass the implementation of randomized controlled trials, the establishment of standardized protocols, and the development of multifunctional biomaterials aimed at addressing research gaps and improving patient outcomes in the field of orthopedic surgery.