Intervertebral Disc Degeneration and Cross-Talk with the Nervous System

椎间盘退变和与神经系统的交互作用

• 批准号: 10412615
• 负责人: Lori A. Setton
• 金额: $ 5.62万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10412615
• 关键词: Alginates; Attenuated; Azides; Biocompatible Materials; Biomedical Engineering; Cardiovascular system; Cell Culture Techniques; Chemistry; Coupling; Development; Development Plans; Disease model; Drug Delivery Systems; Education; Educational workshop; Engineering; Environment; Gel; Goals; Hydrogels; Individual; Injectable; Intervertebral disc structure; Kinetics; Knowledge; Low Back Pain; Mentors; Mentorship; Modification; Musculoskeletal; Nerve Growth Factors; Nervous system structure; Neurons; Pain; Pharmaceutical Preparations; Plant Roots; Post Graduate Year; Pre-Clinical Model; Regenerative Medicine; Research; Research Activity; Research Project Grants; Resources; Schools; Scientist; Spinal Ganglia; Training Activity; Universities; Washington; Work; afferent nerve; calcium indicator; design; experience; graduate student; intervertebral disk degeneration; medical schools; mouse model; novel; pain relief; parent grant; perineural; skills; spinal nerve posterior root; success; symposium; transmission process

Intervertebral disc (IVD) degeneration is one of the greatest contributors to low back pain, yet how the IVD can generate pain remains poorly understood. The parent grant will pursue Specific Aims to study the development of temporal and spatial changes in neuronal function and their “cross-talk” with changes in the degenerating IVD in a mouse model of lumbar IVD degeneration. Here, we propose a supplemental project called “Novel Injectable Hydrogels for Localized Pain Relief in the Dorsal Root Ganglion (DRG)” that will support Ms. Sydney Neal in the design of a novel injectable drug depot in order to attenuate neuronal sensitivity with lumbar IVD degeneration. The overall goal is for Ms. Neal, a graduate student in biomedical engineering, to develop a novel chemistry that will couple the nerve growth factor (NGF) antagonist, Tanuzemab, to an injectable, gelling alginate to provide for local release of an NGF antagonist at the lumbar DRGs with IVD degeneration. In Supplemental Aim 1, Ms. Neal will modify binary mixtures of alginate and evaluate gelation kinetics and localization to the DRGs following simulated perineural delivery. In Supplemental Aim 2, Ms. Neal will develop a strategy to couple Tanezumab to alginate using an azide modification and evaluate the efficiency of coupling. In Supplemental Aim 3, Ms. Neal will evaluate the bioactivity of the drug-conjugated alginate hydrogels in isolated DRG neurons subjected to periods of incubation with NGF. Ms. Neal will be co-sponsored by Dr. Nate Huebsch who brings experience with biomaterials and drug delivery to the team, and Dr. Lori Setton who brings experience with IVD degeneration and perineural drug delivery to the team. During the period of this project, Ms. Neal will gain new and valuable skills in neuronal cell culture, genetically-encoded calcium indicators, pre-clinical models of disease development, and work closely with clinicians to increase her knowledge of treatment relevance for engineered biomaterials. Ms. Neal will further prepare an Individual Development Plan, participate in workshops for research success at Washington University, attend national conferences to present her work, and have an opportunity to participate in a national conference to mentor Black scientists. Washington University provides an excellent environment for the completion of this research project and continued professional development of Ms. Sydney Neal. Ms. Neal will work within the McKelvey School of Engineering and the School of Medicine and participate in resources of the Musculoskeletal Research Center, the Cardiovascular Research Center, and the Center for Regenerative Medicine. In all, these combined research and training activities are designed to prepare Ms. Neal for continued academic research in her post-graduate years.

椎间盘（IVD）变性是导致腰痛的最大因素之一，但是IVD如何 产生的疼痛仍然很少理解。父母赠款将追求特定的目标来研究发展 神经元功能的临时和空间变化及其“串扰”随着变化IVD的变化 在腰部IVD变性的小鼠模型中。在这里，我们提出了一个名为“新型注射型的补充项目” 背侧根神经节（DRG）的局部疼痛缓解的水凝胶将支持悉尼尼尔女士 新型可注射药物仓库的设计，以通过腰椎IVD变性来减轻神经元灵敏度。 总的来说，生物医学工程研究生尼尔女士是开发小说的 将神经生长因子（NGF）拮抗剂Tanuzemab与可注射的，胶凝算法相结合的化学性质 提供IVD变性的腰部DRG的NGF拮抗剂的局部释放。补充 AIM 1，Neal女士将修改藻酸盐的二元混合物，并评估凝胶化动力学和本地化 模拟周围传递后的DRG。在补充目标2中，尼尔女士将制定一项战略 将Tanezumab夫妇使用叠氮化物修饰和评估耦合效率。在 补充目标3，尼尔女士将评估分离的药物偶联藻酸盐氢的生物活性 DRG神经元与NGF孵育时期。尼尔女士将由Nate Huebsch博士共同赞助 谁为团队带来了生物材料和药物提供的经验，以及带来经验的洛里·塞顿（Lori Setton）博士 IVD变性并向团队输送周期药物。 在这个项目期间，尼尔女士将获得神经元细胞培养的新技能， 遗传编码的钙指标，疾病发展前临床模型，并与 临床医生增加她对工程生物材料相关的治疗知识。尼尔女士将进一步 准备一个个人发展计划，参加华盛顿的研究成功研讨会 大学，参加全国会议以展示她的作品，并有机会参加国家 会议指导黑人科学家。华盛顿大学为 悉尼尼尔女士的研究项目和持续的专业发展完成。尼尔女士 在麦凯维工程学院和医学院工作，并参与 肌肉骨骼研究中心，心血管研究中心和再生中心 药品。总之，这些合并的研究和培训活动旨在为尼尔女士做准备 在她的研究生时期的学术研究。