Plasmid-seeded aligned nanofibrillar scaffold for acute muscle injury treatment

Based on encouraging Phase I feasibility results, we propose developing a novel gene therapy approach to promote guided vascular regeneration in treating extremities after traumatic injury. Our approach is to provide thread-like implants comprised of aligned nanofibrillar collagen scaffolds loaded with Hepatocyte Growth Factor (HGF) vectors (e.g., HGF DNA plasmid, modified mRNA) designed to enhance and guide neovascularization. Such scaffolds are produced using a proprietary process and fabricated to mimic native structure of the blood vessels inner wall, which promotes cell attachment, migration and can be used for delivering transcripts that are translated into therapeutic proteins with sustained biological effect in vivo. This local secretion of the HGF protein attracts endothelial cells (EC) and stimulates EC proliferation, helping to bridge the gap(s) in the vasculature caused by vascular and soft tissue trauma. Phase II will build on this programs earlier accomplishments, with a focus on further development, optimization and testing prototypes of both HGF DNA plasmid and modified mRNA, using these constructs in small animal models for both hind limb ischemia (HLI) and volumetric muscle loss, with the final optimized product defined and tested in a large animal model pilot study for HLI.