Anti-Adhesive Bioresorbable Elastomer Coating That Reduce Intraperitoneal Adhesions in Abdominal Repair Procedures

Intraperitoneal adhesions (IAs) are a major complication arising from abdominal repair surgeries and affects thousands of patients (&gt;100,000) per year in the US with total treatment cost estimated upward of $1 Billion.<br/>IAs can cause small-bowel obstruction, fistula, infection, chronic pain and inflammation, which often require high-risk re-operation with prolonged hospitalization and sometimes leading to chronically debilitated patients.<br/>Herein, we fabricated a composite mesh using a macroporous monofilament polypropylene mesh and a degradable elastomer coating designed to meet the requirements of this clinical application. The degradable elastomer was synthesized using an organo-base catalyzed thiol-yne addition polymerization. The polymer design affords independent control of degradation rate and mechanical properties. The elastomeric coating was further enhanced by the covalent tethering of antifouling zwitterionic molecules on its surface using ‘Click Chemistry’ which was confirmed by XPS measurements. Quartz crystal microbalance measurements showed the zwitterionic functionalized elastomer further reduced fibrinogen adsorption by 73% <i>in vitro</i> when compared to unfunctionalized elastomer controls. Mechanical testing demonstrated the elastomer forms a robust coating on the polypropylene mesh that does not exhibit micro-fractures, cracks or mechanical delamination under cyclic fatigue testing that exceeds peak abdominal loads (50 N/cm). The elastomer exhibited degradation with limited tissue response in a 10-week murine subcutaneous implantation model. We also evaluated the composite mesh in a 12-week study in a rabbit hernia adhesion model. The zwitterionic composite mesh significantly reduced the extent and tenacity of IAs by 94% and 90% respectively with respect to uncoated polypropylene mesh. The resulting composite mesh device is an excellent candidate to reduce complications related to abdominal repair through suppressed fouling and adhesion formation, reduced tissue inflammation, and appropriate degradation rate.