Novel peptide-impregnated hydrogel as a wound healing device

PROJECT SUMMARY / ABSTRACT Wounds healing with exuberant fibrotic scarring or wounds that fail to heal represent two opposing ends of the wound repair spectrum. Fibrotic scarring in highly visible areas after craniofacial reconstruction can result in severe functional and cosmetic disability. Similarly, wound dehiscence—wound tissue separation due to a failure to heal with adequate tensile strength—can be life-threatening if it exposes vital structures such as viscera, brain, or blood vessels. Even if non-life-threatening, dehiscence can disrupt critical repairs such as in tendons, hernias, cleft lips and palates (one of the most prevalent congenital craniofacial conditions with post-repair dehiscence rates up to 22.76%). Additionally, ~43% of abdominal incisional hernia cases are secondary to wound dehiscence. More importantly, wound dehiscence mortality rates can be as high as 14%-50%. Unfortunately, all available tissue approximation devices (e.g., sutures, staples, adhesives) only bring tissues together in a purely mechanical fashion. There are no devices to actively promote fibroblast migration and myofibroblast contraction to increase wound tensile strength. To address current device limitations, we developed an SLI-F06 peptide-containing hyaluronic acid (HA) hydrogel (HA-SLI-F06). SLI-F06 promotes fibroblast migration, contraction, and collagen cross-linking to accelerate wound tensile strength reestablishment while HA provides a “bridge” to facilitate cellular migration. An injectable SLI-F06 first-in-class drug is currently in a Phase 1/2a clinical trial to minimize dermal scar formation. However, injecting the liquid SLI-F06 is time- consuming for larger wounds and impractical for thin tissues such as fascia. This PAR-19-333 Commercialization Readiness Pilot (CRP) Program directly continues the Direct-to-Phase II SBIR award R44DE026080, and is designed to accelerate the Clinical Trial Application for the novel bioactive HA-SLI-F06 hydrogel. HA-SLI-F06 can be applied contemporaneously with most any tissue approximation devices during surgery to enhance wound healing. Pig efficacy data showed a significant wound tensile strength increase in wounds treated with HA-SLI-F06 compared to controls. To expedite and derisk technical, regulatory/clinical, and business milestone activities that could impact or delay HA-SLI-F06 commercialization, we propose: AIM 1 to develop the Chemistry, Manufacturing, and Controls (CMC) to minimize technical HA-SLI-F06 production risks; AIM 2 to conduct essential safety studies to support HA-SLI-F06 application in a broad range of soft tissues; AIM 3 to expedite clinical development and minimize regulatory risks by incorporating quantifiable tools to ensure optimal clinical study design and efficient clinical methods to assess safety and efficacy to meet the FDA requirements; and AIM 4 to fully integrate our intellectual property, market focus, and business strategies to maximize valuation. If successful, this product will represent a new paradigm enabling surgeons to easily convert most any mechanical tissue approximation device (e.g., sutures, staples, mesh, adhesives) into a bioactive tissue approximation device to accelerate tensile reestablishment and reduce wound dehiscence, while also decreasing scarring.