SUMMARY BioAesthetics is developing a novel acellular graft for improved abdominal wall reconstruction (AWR). A hernia is a condition in which an internal organ pushes through an opening in the muscle or tissue that holds it in place. More than one million hernia repair surgeries occur annually in the US, corresponding to healthcare costs of $48 billion annually. Hernia repair is the most common operation performed by general surgeons. Inguinal hernias – in which the lower abdominal wall is breached – are the most common type of hernias requiring repair. AWR is typically performed for treating recurring or severe inguinal hernias. Typical challenges observed with AWR include hernia recurrence, infections and trauma, and repair material failures. Recently, state-of-the- art dermal substitutes have been utilized that consist of acellular biologic grafts (ABGs). ABGs are widely used for wound repair, including AWR, but suffer from complication rates up to 40% due to infection, necrosis, and mechanical failure. There is a significant unmet need to identify novel, innovative approaches to safely treat patients undergoing AWR. BioAesthetics is developing a transformative antibiotic-loaded, polymer-strengthened ABG that delivers drugs to the surgical site during healing and provides an optimal regenerative scaffold. Our approach and application differ from competitive products on the market and should provide superior performance for improved patient outcomes. Our preliminary data demonstrate increased ABG mechanical strength as well as release of a model molecule from the ABG over 2 weeks. In this Phase I proposal, porcine ABGs will be impregnated with poly(lactide-co-glycolide) (PLGA) polymer loaded with the antibiotics rifampin and minocycline. We intend to (a) demonstrate release of the antibiotics in vitro, (b) evaluate mechanical properties of our product, and (c) assess in vivo efficacy of the product in a rodent model of AWR. If successful, we will thus generate proof-of-concept data demonstrating that our antibiotic- and polymer-impregnated ABGs are capable of reducing infection and promoting wound healing.

NARRATIVE Abdominal wall reconstruction (AWR) is a type of hernia repair surgery, which may use surgical mesh or acellular biologic grafts – current products in these categories suffer from significant drawbacks like mechanical failure and infection. BioAesthetics is developing a drug-loaded, polymer-strengthened acellular graft that delivers antibiotics to the surgical site and provides an optimal regenerative scaffold. This project will demonstrate that our approach is capable of reducing infection and promoting wound healing.