Tissue trauma initiates inflammation that can lead to fibrotic complications such as postoperative peritoneal adhesions, 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 sprayable extracellular matrix (ECM) hydrogel as a barrier to protect healing tissues and reduce adhesion formation after abdominal surgery. In both mouse and rabbit models of colorectal and gynecologic procedures, ECM hydrogel application resulted in a substantial reduction in adhesion severity. Mechanistic studies demonstrated that the hydrogel 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 intact mesothelial surface with fewer activated myofibroblasts compared with synthetic hydrogel and controls. Immunohistochemical analysis, transcriptomic profiling of mesothelial cells, and in vitro mechanical stretch experiments revealed that the ECM hydrogel mitigates mesothelial-to-mesenchymal transition. These findings suggest that the hydrogel not only provides a physical barrier but also serves as a biological modulator, shielding tissue from mechanical and inflammatory cues that drive adhesion formation. Overall, this study identifies a dual-function, biologically active ECM hydrogel capable of protecting healing tissues and reducing adhesion development in preclinical surgical models. These results support the potential of ECM hydrogel as a clinically translatable, biocompatible strategy for improving postsurgical healing outcomes and reducing adhesion-related complications.

Carcinoma-associated fibroblasts (CAFs) are highly accumulated in the tumor-surrounding stroma of primary epithelial ovarian cancer (OC). CAFs exert important functions for the vascularization, growth, and progression of OC cells. However, the origin of CAFs in primary OC had not yet been studied, and they were assumed to arise from the activation of resident fibroblasts. Here, we compared CAFs in the ovary to CAFs found in peritoneal metastases from patients with advanced OC. Our findings show that CAFs from primary tumors and peritoneal metastases share the expression of mesothelial markers. Therefore, similar to peritoneal carcinomatosis, CAFs in primary ovarian carcinomas may originate from mesothelial cells via a mesothelial-to-mesenchymal transition. The detection of mesothelial-derived CAFs in tumors confined to the ovary and identification of biomarkers could be the key to the early detection of OC and peritoneal spread.

: Carcinoma-associated fibroblasts (CAFs) are highly accumulated in the tumor surrounding stroma of primary epithelial ovarian cancer (OC). CAFs exert important functions for the vascularization, growth and progression of ovarian tumor cells. However, no attention has been shown to their origin so far. It has been mainly assumed that CAFs in primary OC arise from the activation of resident fibroblasts. Here, we compare CAFs with ovarian location to CAFs found in peritoneal implants from patients with advanced OC. Our findings show that CAFs from primary tumors and peritoneal metastases share the expression of mesothelial-related markers. Therefore, as in peritoneal carcinomatosis, CAFs in primary ovarian carcinomas could be originated via a mesothelia-to-mesenchymal transition (MMT) process. The detection of mesothelial-derived CAFs in tumors confined to the ovary and associated biomarkers could be the key to early detection of peritoneal spread in affected patients.