Serograft: A bioinspired acellular biomaterial for combating tissue adhesions - PROJECT SUMMARY Postoperative abdominal adhesions are a major economic and medical burden and remains a significant clinical issue due to the lack of effective treatments. Estimates suggest more than 25% of laparotomy patients are re- hospitalized due to formation of abdominal adhesions within 5 years of the initiating event, leading to annual healthcare costs in the US upwards of $2.3 billion. Despite attention to this issue and the development of a variety of commercially available treatments made from a variety of materials, these products are generally considered only partially effective and there remains an unmet need for effective approaches to limit and prevent postoperative adhesions. We have developed Serograft, a novel bio-inspired and bio-derived membrane to reduce / eliminate formation of post-surgical abdominal adhesions. Serograft is a decellularized, regenerated membrane derived from intestinal serosa and is thus composed of the same lubricating constituents found in endogenous serosa – the native lubricating layer on visceral organs. Ex vivo testing indicates a significant reduction in adhesion measured by shear test and a pilot study in induced abdominal adhesions in rats demonstrated that Serograft outperforms both commercially available cellulose-based membranes and fibrin patches on blinded scoring of degree of adhesion formation at 7 days post-op. This proposal will focus on the further engineering of Serograft in a Janus format to achieve two overall goals: enhancement of anti-adhesive properties on the peritoneal cavity-facing side of the material, and increased tissue adhesivity on the target organ-facing side of the material. Aim 1 will focus on the development of porcine- and bovine- serosa-derived variants of Serograft with conjugation to different forms and densities of poly(ethylene glycol) (PEG), to enhance the anti-adhesive properties of the membrane. Aim 2 will focus on the Janus format of Serograft by incorporated a chitosan methacrylate layer on one side of the material which will impart increased tissue adhesivity to the target tissue in a wet environment. Both aims will employ ex vivo, in vitro, and in vivo studies to systematically characterize the properties, performance, and biocompatibility of the materials. The success of the research is supported by a strong, diverse team with complementary scientific expertise in biomaterials, inflammation and tissue responses, and animal models with additional support from expert colorectal surgeons with extensive clinical experience in the real-word relevance of the proposed application. Using the design-build-test biomaterials development principles and well-established bioengineering methods, this proposal will leverage the innovative and scientifically robust environment at Arizona State University and neighboring institutions to develop a novel therapeutic intervention for abdominal adhesion prevention, with a strong path to clinical translation.
