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.

项目概要 背痛是影响超过 1 亿美国成年人的全球残疾的主要原因。 IVD 愈合不良会导致 结构性 IVD 缺陷累积导致疝出、变性和解剖结构破坏， 导致残疾和疼痛。一个未满足的关键需求是开发纤维环（AF）修复策略，因为没有 存在治疗方法，椎间盘切除术是治疗髓核 (NP) 突出症的金标准，可消除 AF 未修复的缺陷并伴有并发症，包括再疝气和复发性疼痛。家长补助金的重点是 了解促进新生儿再生愈合的基本细胞和机械生物学因素 体外诊断设备。多元化补充计划通过两个非常重要的方式扩大了家长补助金的范围。首先， Diversity Supplement 是一个转化性项目，专注于开发优化的 3D 生物材料载体来输送细胞 可以促进成人 IVD 愈合。其次，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重点放在房颤修复上，该项目 允许德尔瓦女士加入参与家长资助的科学家团队，使她能够快速学习新知识 方法，通过培训活动获得信心并推进她的职业生涯。目标 1 是确定效果 生物材料硬度对 IVD 变形和疝气风险的影响。我们的第一种生物材料是新开发的 两部分修复策略包括双重修饰（甲基丙烯酸化和氧化）透明质酸 (HAMA) 和 由纤连蛋白缀合的纤维蛋白和聚（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 会化学吸附 PEGDA 通过与胶原蛋白共价结合而与天然 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和氧化羧甲基纤维素（MoCMC）， 选择具有水解稳定性和细胞相容性的热凝胶粘合剂。目标 2 然后添加 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复杂性 大型动物IVD在器官培养损伤模型中的生物力学和生物学功能 评估。目标 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 细胞粘附分子的浓度和大分子单体的浓度。研究和指导计划 旨在为 Sabrina Delva 女士提供严谨、鼓舞人心且指导良好的博士课程。钥匙 要素是为德尔瓦女士提供大量的科学培训、广泛的指导、课程作业和 专业发展和网络。我们期望 Delva 女士至少每年出席年会， 并在西奈山和纽约城市学院建立许多合作关系。