Sprayable extracellular matrix hydrogel reduces postoperative adhesion formation and protects healing tissues in preclinical models

Tissue trauma initiates inflammation that can lead to fibrotic complications such as postoperative peritoneal adhe-sions, which contribute to chronic pain, infertility, and bowel obstruction. Despite their prevalence and impact,effective interventions to prevent adhesion formation remain limited. In this study, we evaluated a sprayableextracellular matrix (ECM) hydrogel as a barrier to protect healing tissues and reduce adhesion formation after ab-dominal surgery. In both mouse and rabbit models of colorectal and gynecologic procedures, ECM hydrogel ap-plication resulted in a substantial reduction in adhesion severity. Mechanistic studies demonstrated that thehydrogel promotes preservation or restoration of the mesothelial lining while modulating early local inflammation.Treated tissues exhibited reduced expression of inflammatory cytokines, including IL-1β, and maintained an intactmesothelial surface with fewer activated myofibroblasts compared with synthetic hydrogel and controls. Immuno-histochemical analysis, transcriptomic profiling of mesothelial cells, and in vitro mechanical stretch experimentsrevealed that the ECM hydrogel mitigates mesothelial-to-mesenchymal transition. These findings suggest that thehydrogel not only provides a physical barrier but also serves as a biological modulator, shielding tissue from me-chanical and inflammatory cues that drive adhesion formation. Overall, this study identifies a dual-function, bio-logically active ECM hydrogel capable of protecting healing tissues and reducing adhesion development inpreclinical surgical models. These results support the potential of ECM hydrogel as a clinically translatable, biocom-patible strategy for improving postsurgical healing outcomes and reducing adhesion-related complications