Enhancing Peripheral Nerve Repair with an Injectable Recombinant Polypeptide Scaffold

PROJECT SUMMARY The objective of this proposal is to investigate the ability of an injectable polypeptide scaffold -- inSoma Bio’s proprietary elastin-derived biomaterial FractomerTM -- to improve outcomes after peripheral nerve repair. This objective is motivated by the observation that peripheral nerve injuries (PNI) affect >20 million people in the US alone, with $150 billion in healthcare costs annually, and is a cause of devastating functional disability and chronic pain in those affected. The gold-standard treatment for PNI is primary neurorrhaphy when a tension-free repair approach is feasible; otherwise, secondary options such as interposition autografts, decellularized allografts, or nerve conduits are used. However, regardless of approach, only about 50% patients achieve meaningful sensorimotor recovery and the majority of patients continue to experience chronic pain. Lack of success is generally attributed to a poor microenvironment for neuroregeneration which must simultaneously be able to provide neovascularization, low inflammation, cell infiltration, and successful neuroaxonal migration. Current treatment strategies fail to address all these needs. Motivated by this clear clinical need, we will investigate the applicability of Fractomer to improve outcomes after peripheral nerve repair. Fractomer is a unique biomaterial that transitions from an injectable liquid at room temperature to a physically crosslinked, porous network. Fractomer has been shown to be highly biocompatible, integrating into the surrounding tissue, initiating remodeling, cell infiltration, and vascularization. Further, its ability to phase transition under the action of body temperature, letting it be injected as a low-viscosity liquid, allows for its easy handling and integration in the operating room, and its scalable manufacturing process means that it has the capability to be a commercially viable product. Our central goal will be to demonstrate that Fractomer is uniquely suited to provide the needed mechanical support and well-vascularized microenvironment essential for successful neuroaxonal regeneration. Our strategy will include tailoring the Fractomer formulation to have the correct porous microarchitecture and mechanical properties for peripheral nerve repair applications. We will then investigate the ability of Fractomer to augment outcomes following peripheral nerve repair in models of rat sciatic nerve injury. Functional and histological testing will be performed and compared to current gold-standard primary neurorrhaphy and commercially available products from Avance and Integra. If this proposal is successful, it will provide a strong foundation to commence large animal testing and begin scale-up for translation into clinical application, and ultimately for commercialization into what is currently a $7B market opportunity. The improvement of surgical outcomes following peripheral nerve repair by application of Fractomer has the potential for a transformative impact for patients with peripheral nerve injuries by reducing long-term disability and chronic pain.