Postoperative abdominal adhesions: pathogenesis and advances in hydrogel-based multimodal prevention strategies.

Postoperative abdominal adhesions (PAA) occur frequently (> 90%) after abdominal surgery and commonly lead to various serious postoperative complications. Adhesiolysis remains the sole effective clinical method to release adhesions; however, recurrence rates are as high as 80%. Current clinical strategies for preventing PAA primarily rely on applying anti-adhesion barriers. However, the limited functionality of physical barriers results in suboptimal clinical outcomes. Among biomaterials, hydrogels are considered one of the most promising physical barriers due to their satisfactory wound coverage and tunable mechanical properties. Therefore, this review aims to provide guidance for the rational design of multifunctional anti-adhesion hydrogels by combining the pathophysiological mechanisms of PAA. A systematic review of the latest reviews and original research articles searched from PubMed and Web of Science databases was performed. We first introduce the structure of the peritoneum and the normal healing process after peritoneal injury. Next, we analyze the key events and immune cell behaviors in the development of PAA and elucidate the main influencing factors. Based on the interplay between the pathogenesis of PAA and current clinical practice, we propose six hydrogel-based adhesion prevention strategies. These hydrogels can be fabricated by physical cross-linking, chemical cross-linking, physical/chemical cross-linking, self-assembly or 3D printing, and applied to the wound surface by pre-preparation or in situ cross-linking. Finally, the relevant applications of each strategy are summarized and their future potential is discussed. STATEMENT OF SIGNIFICANCE: Postoperative abdominal adhesions (PAA) affect >90% of patients undergoing abdominal operations and cause serious complications. Compared to conventional liquid or film-based physical barriers, hydrogels have various advantages and become a promising alternative that attracted widespread attention from researchers. This review aims to provide guidance for the rational design of multifunctional anti-adhesion hydrogels by aligning with the pathophysiological mechanisms of PAA. First, the mechanisms driving PAA formation are outlined, with particular attention to critical pathological steps and immune cells contributions. Next, several hydrogel optimization strategies developed in latest years aligned with mechanistic insights and clinical demands are systematically summarized. For each strategy, recent advances and limitations are critically analyzed. Finally, existing limitations and future research priorities are discussed to guide next-generation barrier development.