Diversity Supplement for: Mechanisms for Regenerative Healing in Intervertebral Discs

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PROJECT SUMMARY Back pain is a leading cause of global disability impacting >100 million US adults. Poor IVD healing results in structural IVD defects that accumulate to result in herniation, degeneration, and anatomical disruptions that cause disability and pain. A critical unmet need is to develop annulus fibrosus (AF) repair strategies since no treatments exist and discectomy, the gold standard treatment for nucleus pulposus (NP) herniation, leaves AF defects unrepaired with complications including reherniation and recurrent pain. The parent grant focuses on understanding fundamental cellular and mechanobiological factors that enable regenerative healing in neonatal IVDs. The Diversity Supplement expands the scope of the parent grant in 2 highly significant ways. First, the Diversity Supplement is translational focusing on developing an optimized 3D biomaterial carrier to deliver cells that can promote adult IVD healing. Second, the career development activities of Ms. Sabrina Delva are considered highly significant. By focusing the Aims of the Diversity Supplement on AF repair, this project allows Ms. Delva to join the team of scientists involved in the parent grant enabling her to rapidly learn new methods, gain confidence and advance her career with training activities. Aim 1 is to determine the effect of biomaterial stiffness on IVD deformations and herniation risk. Our first biomaterial which is a newly developed two-part repair strategy comprising a dual-modified (MethAcrylated and oxidized) Hyaluronic Acid (HAMA) and injectable interpenetrating network hydrogel composed of fibronectin-conjugated fibrin and poly (ethylene glycol) diacrylate (PEGDA), or HAMA-PEGDA. This material was selected since the HAMA chemically adsorbs the PEGDA to integrate with the native AF tissue by covalently bonding to collagen. Our second biomaterial adhesive is a newly developed Methacrylated and oxidized carboxymethylcellulose (MoCMC) which was selected to be a thermogeling adhesive with hydrolytic stability and cytocompatibility. Aim 2 then adds complexity by determining which biomaterial sealant strategy most effectively retains biomechanical and biological function of large animal IVDs in organ culture injury models with biomechanical and biological assessments. Aim 3 is to engineer mechanically optimized cell delivery biomaterials by modulating type and concentration of cell adhesion molecules and macromer concentrations. The research and mentoring plans are designed to provide Ms. Sabrina Delva with a rigorous, inspiring, and well-mentored PhD program. Key elements are to provide Ms. Delva with substantial scientific training, extensive mentoring, coursework, and professional development & networking. We expect Ms. Delva to present at least annually at annual meetings, and to establish many collaborations across Mount Sinai and the City College of New York.