PFI:AIR-TT: Biocompatibility and Biomechanical Validation of Cellulose-Based Hydrogels for Intervertebral Disc Repair

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This PFI: AIR Technology Translation project focuses on translating a novel injectable biomaterial derived from the plant polysaccharide, cellulose, to treat injuries or degeneration of the intervertebral disc (IVD).   These materials are important because they address a clinical problem (IVD degeneration) that is the most common diagnosis for lower back pain, a debilitating condition that affects 15-30% of the United States population, with associated annual costs of $100 billion. The project will result in valuable proof-of-concept data demonstrating safety and efficacy of these cellulosic biomaterials in a small animal in vivo model and a large animal explant model. Successful completion will motivate further validation in a large animal preclinical injury model prior to clinical studies. The cellulosic materials are unique in that they are plant-derived, gel in situ via a dual coupling mechanism and allow for the incorporation of cells and growth factors for combination therapies.  These features provide the advantages of an extensive safety profile, cost effectiveness, minimally invasive delivery, enhanced stability and therapeutic versatility when compared to the leading competing materials under development in this market space.  This project addresses several technology gaps as it translates from research discovery toward commercial application of a novel material for IVD repair. Current surgical treatment options (i.e., discectomy) are inadequate for long-term disease management, and existing commercial implants (i.e., total disc replacement) do not sufficiently restore disc structure and function. Replacing the gelatinous nucleus pulposus tissue of the IVD with an injectable material may help restore IVD mechanical functionality. Several products are under development for nucleus pulposus replacement, with none approved for use in the United States. This project focuses on the use of injectable cellulose-based hydrogels that form in situ in the intradiscal space to replace resected nucleus pulposus tissue. The proposed validation experiments will characterize an optimized cellulosic gel formulation previously shown to be stable and restore disc properties under axial compression. The studies will determine the foreign body reaction in a small animal model as well as the mechanical properties and failure mechanisms under cyclic loading in bending using a large animal spine motion segment injury model. Many of the competing products under development have been found to have poor biocompatibility or exhibited migration and reherniation. Also, few prior studies have been capable of evaluating candidate materials under such "worst-case-scenario" bending conditions. As such, they have met with limited success. In addition, personnel involved in this project include undergraduate and graduate students who will receive training in innovation and technology commercialization through translational medicine courses, and via regular interactions with potential strategic partners, participation in innovation and commercialization conferences and symposia, and small business grant proposal preparation.The project engages experts in orthopaedic surgery from the Icahn School of Medicine at Mount Sinai and an experienced biomedical device industry professional to guide the biomechanical evaluation studies and commercialization aspects, respectively, in this effort to translate the proposed technology from research discovery toward commercial reality.