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.

项目摘要 背痛是全球残疾影响> 1亿美国成年人的主要原因。 IVD愈合不佳会导致 累积的结构IVD缺陷会导致疝气，变性和解剖干扰 导致残疾和疼痛。一个关键的未满足需求是开发纤维纤维（AF）维修策略，因为没有 存在治疗和椎间盘切除术，牙髓核（NP）催眠的金标准治疗 缺陷未经修复，并发症，包括重新连接和复发性疼痛。父母赠款专注于 了解基本的细胞和机械生物学因素，使新生儿的再生愈合 IVD。多样性补充剂以两种非常重要的方式扩大了父母赠款的范围。首先， 多样性补充是转化的重点，致力于开发优化的3D生物材料载体以提供细胞 可以促进成人IVD愈合。第二，萨布丽娜·德尔瓦女士的职业发展活动是 被认为很重要。通过将多样性补充剂的目的集中在AF维修上，该项目 允许Delva女士加入参与父母赠款的科学家团队，使她能够迅速学习新的 方法，获得信心并通过培训活动提高职业生涯。目标1是确定 IVD变形和疝气风险的生物材料刚度。我们的第一个生物材料是新开发的 两部分修复策略包括双重修饰（甲基丙烯酸和氧化）透明质酸（HAMA）和 可注射的互穿网络水凝胶由纤连蛋白偶联的纤维蛋白和聚乙烯组成 甘油）二氟酸酯（PEGDA）或HAMA-PEGDA。自哈马化学吸附以来，选择了此材料 PEGDA通过共价键合胶原蛋白与天然AF组织整合。我们的第二个生物材料 粘合剂是一种新开发的甲基丙烯酸和氧化羧甲基纤维素（MOCMC），是 被选为具有水解稳定性和细胞相容性的热凝胶粘合剂。 AIM 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 大型动物IVD在器官培养损伤模型中的生物学功能与生物力学和生物学 评估。 AIM 3是通过调节类型和 细胞粘附分子和宏观浓度的浓度。研究和指导计划 旨在为Sabrina Delva女士提供严格，鼓舞人心且精通的博士学位计划。钥匙 要素将为Delva女士提供大量的科学培训，广泛的指导，课程和 专业发展与网络。我们希望Delva女士至少每年在年度会议上介绍 并在西奈山和纽约城市学院建立许多合作。