Project Summary Over 7 million abdominal and pelvic operations are performed each year in the US and adhesions—the leading cause of post-operative morbidity—form in nearly 90% of patients following these surgeries. Adhesions are bands of scar tissue that contribute to the manifestation of myriad life-long complications (e.g., chronic pelvic pain, small bowel obstruction, and infertility) and the annual healthcare burden exceeds $2.5 billion, but current options to mitigate adhesion formation are limited and flawed. Based on nearly a decade of research, we have developed a sprayable adhesion barrier derived from extracellular matrix (ECM Spray), which serves as a mechanical barrier that elicits a healing response from the patient’s own body to prevent adhesions and regulate tissue repair. The ECM Spray is thermally responsive and forms a thin film hydrogel over the tissue where it’s applied and prevents adhesions by acting as a mechanical barrier between adjacent tissues. In two separate pre-clinical studies using validated small and large animal models, post-operative application of ECM Spray has resulted in >75% reduction in adhesion incidence and tenacity. A major limitation of currently available adhesion barriers is that they are contraindicated for use in procedures that involve a bowel resection and re-connection (i.e., bowel anastomosis) because the adhesion barriers have been shown to inhibit healing which can cause leakage. Interestingly, we’ve shown that when applied to surgically injured peritoneum, ECM Spray acts as a scaffold to support re-epithelialization and healing of the peritoneum. However, it is unknown how ECM Spray will interact with more complex wound healing processes which occur in intestinal anastomosis procedures. Therefore, the objective of the present study is to determine the efficacy of ECM Spray’s for preventing adhesions while safely maintaining bowel healing following anastomosis procedures. In Aim 1, we will determine the efficacy of ECM Spray on adhesion prevention and characterize the effect of ECM Spray on intestinal healing. In Aim 2, we will determine whether ECM Spray may promote anastomotic healing in a high-risk model of intestinal repair. Results of the proposed work will lead to a key research and development milestone necessary for establishing safety and efficacy of ECM Spray for use in abdominal and pelvic operations and increase the technological and commercial potential of ECM Spray. In addition, if we show potential for ECM Spray to limit anastomotic leaks, this will broaden the scope for use and dramatically increase the patient and clinical impact, as well as encourage surgeon adoption in colorectal surgeries.