Diversity Supplement for: Mechanisms for Regenerative Healing in Intervertebral Discs

多样性补充：椎间盘再生愈合机制

• 批准号: 10631488
• 负责人: James C. Iatridis
• 金额: $ 3.13万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631488
• 关键词: 3-Dimensional; Adhesives; Adult; Anatomy; Animals; Back Pain; Biocompatible Materials; Biological; Biological Process; Biomechanics; Biomedical Engineering; Carboxymethylcellulose; Cell Adhesion Molecules; Cells; Chemicals; Cities; Collaborations; Collagen; Defect; Development; Doctor of Philosophy; Elements; Engineering; Fibrin; Fibronectins; Gold; Human Anti-Mouse Antibody; Hyaluronic Acid; Hydrogels; Injectable; Injury; Intervertebral disc structure; Joints; Learning; Mechanics; Mentors; Methacrylates; Methods; Modeling; Neonatal; New York; Organ Culture Techniques; Oxides; Pain; Recurrent pain; Research; Risk; Scientist; Tissues; Training; Training Activity; Underrepresented Students; career; career development; college; covalent bond; design; disability; disability impact; disc regeneration; healing; injury and repair; intervertebral disk degeneration; meetings; nucleus pulposus; parent grant; poly(ethylene glycol)diacrylate; pre-doctoral; programs; recruit; regenerative; repair strategy; repaired; sealant; standard care

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.

项目总结