Synthetic Barrier Material for the Prevention of Surgical Adhesions

<b>Background</b><br/>Adhesions, abnormal tissue bridges that form between adjacent organs or tissues following surgery, can lead to significant morbidity and complications for patients. To prevent surgical adhesions (SAs), barrier membranes have been developed to prevent the occurrence of SAs and improve patient outcomes. Conventional adhesion barrier membranes are made of biopolymers and biological materials that rapidly degrade within a few days while the synthetic membranes are nonbiodegradable and cause adverse effects, that necessitate surgical removal and pose risks of long-term complications. In this study, we developed an anti-adhesion membrane (Anti-Mater) using phosphate crosslinked polyvinyl alcohol (PVA) and showed the impact of physicochemical properties of Anti-Mater on SAs prevention. Based on our previous findings that the negative surface charge of biopolymer could modulate inflammatory responses in tissues, we studied the effect of Anti-Mater and its properties on preventing adhesions. <br/><b>Methods</b><br/>To fabricate Anti-Mater, we first prepared PVA solutions of different concentrations (5-15% w/v) in water and we then added sodium trimetaphosphate to the solutions. The PVA solutions were either dried overnight as a thin film on a flat, smooth surface or used as a bioink for 3D-printing. We characterized their physicochemical and mechanical properties by FT-IR, tensile testing, water contact angle, surface energy measurements, and surface pH. We also evaluated swelling capacity and degradation of Anti-Mater. We confirmed the hemocompatibility, biocompatibility, and immune modulation of Anti-Mater using fresh porcine blood, mouse bone marrow-derived macrophages, and human peripheral blood mononuclear cells. We evaluated in vivo anti-adhesion effects of Anti-Mater and Seprafilm, a commercially available membrane, by surgically implanting Anti-Mater in mice for 1-4 weeks. After the study, we harvested tissues and studied immune responses, adhesion and scar formation. <br/><b>Results</b><br/>This study confirmed that the crosslinking not only increased the mechanical stability of Anti-Mater but also yielded a negatively charged surface. The 3D printing method allowed us to fabricate membranes with more uniform thickness and modify their elasticity and mechanical strength by adjusting the number of layers printed. We demonstrated that the degradation of Anti-Mater could be tuned from 4 to 8 weeks, by varying the crosslinking density, i.e., low crosslinking density accelerated degradation compared to high crosslinking density in vitro. In cell lines, we showed that Anti-Mater is biocompatible and hemocompatible with more than 85% cell viability and no hemolysis. We observed that LPS-induced cells showed lower proinflammatory cytokine levels after incubation with Anti-Mater. After 1-4 weeks of implantation, we observed Anti-Mater did not cause inflammation or scar formation in the surrounding tissues in mice. <br/><b>Conclusions</b><br/>This study demonstrated the feasibility of synthetic adhesion barrier membranes and their effect on preventing SAs by manipulating physicochemical and mechanical properties. In addition, the phosphate crosslinking enhanced Anti-Mater’s mechanical properties and functionalized the surface that modulates inflammatory responses, thus preventing adhesion formation. Therefore, Anti-Mater is a promising barrier membrane with tunable properties that can effectively prevent SAs.