Abdominal surgery is an important treatment for many diseases. A frequent and serious side effect of abdominal surgery is the formation of post-surgical adhesions. Post-surgical adhesions can cause pain as well as other serious complications such as infertility and bowel obstruction. These complications affect many patients and the management of post-surgical adhesions can costs billions of dollars each year. Therefore, there has been strong interest in the development of strategies and agents that can prevent post-surgical adhesion formation. Current strategies to minimize adhesions generally involve the use of adhesion reducing liquids and large physical barriers. However, clinical studies have shown that the benefits of existing agents in reducing adhesions are quite limited. Thus, there is a strong need for the development of novel agents and strategies to reduce post- surgical adhesions. A key challenge in this effort is to provide barrier function and reduce inflammation at sites of tissue injury only while avoiding normal peritoneal surfaces. Recent advances in nanotechnology have enabled the development of nanoparticles (NPs) that can target specific molecules or tissue, such as collagen. We have shown that we can utilize these nanoparticles to form targeted microscopic barriers at sites of surgical injury. We hypothesize that we optimize our targeted NPs and the 2-NP system to enable a biologically targeted barrier for adhesion prevention. We further theorize that we can encapsulate and deliver anti-inflammatory therapeutics using these NPs and these drug containing NPs can further reduce risk of post-surgical adhesion formation. The central goal of this application is to engineer and optimize biologically targeted biodegradable NPs that can bind to sites of peritoneal injury, form a robust barrier and prevent surgical adhesion. To accomplish this goal, we plan to utilize our existing BM-targeted NP platform and formulate NPs with different sizes, compositions, binding chemistries, and encapsulate different anti-inflammatory therapeutics. These NPs will be evaluated for adhesion prevention using rat models of pelvic post-surgical adhesion. In summary, our application aims to apply advances in nanomedicine to develop novel agents for adhesion prevention. Our proposed work has potential to reduce the risk of post-surgical adhesion which will directly translate into improvement in patients’ quality of life.