Diversity Supplement for: Mechanisms for Regenerative Healing in Intervertebral Discs

项目摘要 背痛是全球残疾的主要原因，影响超过1亿美国成年人。IVD愈合不良导致 结构性IVD缺陷累积导致疝、变性和解剖结构破坏， 造成残疾和疼痛。一个关键的未满足的需求是开发纤维环（AF）修复策略，因为没有 椎间盘切除术是治疗髓核（NP）突出的金标准， 缺损未修复，并发症包括再疝和复发性疼痛。父母补助金的重点是 了解使新生儿再生愈合的基本细胞和机械生物学因素 体外诊断多样性补充以两种非常重要的方式扩大了父母补助金的范围。一是 Diversity Supplement致力于开发一种优化的3D生物材料载体， 可以促进成人IVD愈合。第二，Sabrina Delva女士的职业发展活动是 被认为非常重要。通过将多样性补充的目标集中在AF修复上，该项目 允许德尔瓦女士加入参与母基金的科学家团队，使她能够迅速学习新的知识。 方法，获得信心，并通过培训活动推动她的职业生涯。目的1是确定 生物材料硬度对IVD变形和疝风险的影响。我们的第一种生物材料是一种新开发的 两部分修复策略，包括双重修饰的（甲基丙烯酸化和氧化）透明质酸（HAMA）和 由纤连蛋白结合纤维蛋白和聚乙烯组成的可注射互穿网络水凝胶 乙二醇）二丙烯酸酯（PEGDA）或HAMA-PEGDA。选择这种材料是因为HAMA化学吸附 PEGDA通过与胶原共价结合而与天然AF组织整合。我们的第二种生物材料 粘合剂是一种新开发的甲基丙烯酸酯化和氧化羧甲基纤维素（MoCMC）， 选择为具有水解稳定性和细胞相容性的热凝胶粘合剂。Aim 2随后补充道 通过确定哪种生物材料密封剂策略最有效地保留生物力学和 大动物体外引流物在器官培养损伤模型中的生物力学和生物学功能 评估。目的3是通过调节类型和结构来设计机械优化的细胞递送生物材料。 细胞粘附分子浓度和大分子单体浓度。研究和指导计划 旨在为Sabrina Delva女士提供严格，鼓舞人心和精心指导的博士课程。关键 要素是为德尔瓦女士提供大量的科学培训，广泛的指导，课程， 专业发展和网络。我们希望德尔瓦女士至少每年在年会上发言， 并在西奈山和纽约城市学院建立了许多合作关系。

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.