Neurotransmitter-based poly(aminoglycerol ester)s

基于神经递质的聚（氨基甘油酯）

• 批准号: 7382731
• 负责人: Yadong Wang
• 金额: $ 20.83万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382731
• 关键词: Adult; Affect; American; Animal Model; Autologous; Autologous Transplantation; Behavioral; Biocompatible Materials; Biological; Brain; Chemicals; Clinical; Coupling; Data; Defect; Development; Dopamine; Electrophysiology (science); Embryonic Development; Environment; Equipment; Esters; Extracellular Matrix; Family; Fibrin; Figs - dietary; Foundations; Funding; Gel; Goals; In Vitro; Injury; Laboratories; Medicine; Methods; Mitotic; Molecular; Morbidity - disease rate; Natural regeneration; Nerve; Nerve Regeneration; Nerve Tissue; Neurites; Neurons; Neurotransmitter Receptor; Neurotransmitters; Operative Surgical Procedures; Outcome; Peripheral Nerves; Play; Pliability; Polymers; Prevention approach; Principal Investigator; Publishing; Range; Rate; Rattus; Recovery of Function; Regenerative Medicine; Research; Research Personnel; Role; Site; Standards of Weights and Measures; Structure; Structure-Activity Relationship; Testing; Vertebral column; Work; axon growth; base; biodegradable polymer; cost; density; design; experience; functional group; functional restoration; hydrophilicity; improved; in vivo; innovation; insight; macromolecule; morphogens; multidisciplinary; nanofiber; nanoscale; nerve injury; nervous system disorder; neurogenesis; neurotrophic factor; novel; novel strategies; painful neuropathy; research study; response; sciatic nerve; tool

DESCRIPTION: Neurological disorders affect 20% of Americans, with an estimated annual cost of $400 billion. Current clinical approaches are unable to effectively restore the functions in damaged nerves. Our long-term goal is to use neuro-inductive biomaterials to restore functions in damaged nervous tissues. The objective of this proposal is to elucidate the structure-function relationship of a unique family of neurotransmitter-based biomaterials and explore their potential to regenerate peripheral nerves. The central hypothesis is that rationally-designed biodegradable materials with neurotransmitter functional groups can induce precise responses from neurons through their specific neurotransmitter receptors, and enhance their survival and regenerative capability. Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: (1) Control neuron-material interactions by systematically varying the structure of neurotransmitter-based polymers; and (2) Regenerate peripheral nerves using electrospun neurotransmitter-based polymer nanofibers. Under the first aim, an already proven synthesis strategy will be used to systematically vary the structure of the polymer regarding the backbone flexibility and hydrophilicity, and the type and density of neurotransmitters. We will examine the effects of a structural perturbation on a material's interactions with neurons in vitro and nerves in vivo. Under the second aim, we will create nerve guidance conduits using electrospun nanofibers with equipment that is already in our laboratory. The efficacy of these conduits in regenerating transected sciatic nerve will be evaluated using behavioral, electrophysiological, histological, and immunohistochemical methods. This approach is innovative because it uses chemical messengers to impart bioactivity to synthetic biodegradable polymers. The combination of work in aims 1 and 2 is expected to create a biomaterial platform capable of presenting defined density of neurotransmitter functional groups and nano-scale contact guidance to control neuronal activities. This multidisciplinary proposal combines the complementary expertise of the Principal Investigator in biomaterial design and regenerative medicine, and the Collaborators in neuropathic pain and electrophysiology. When successful, the proposed research will represent a significant advance in the rational design of biomaterials, and may enable new approaches in functional nerve regeneration. Current clinical approaches are unable to effectively restore the functions in damaged nerves. The proposed research seeks to determine the structure-function relationship of a family of novel neurotransmitter-based biomaterials and to apply these materials in functional nerve regeneration.

神经系统疾病影响20%的美国人，估计每年花费4000亿美元。目前的临床方法无法有效地恢复受损神经的功能。我们的长期目标是使用神经诱导生物材料来恢复受损神经组织的功能。该提案的目的是阐明基于神经递质的生物材料的独特家族的结构-功能关系，并探索其再生周围神经的潜力。其核心假设是，合理设计的具有神经递质功能基团的可生物降解材料可以通过其特定的神经递质受体诱导神经元的精确反应，并增强其存活和再生能力。在强有力的初步数据的指导下，这一假设将通过追求两个具体目标进行测试：（1）通过系统地改变基于神经递质的聚合物的结构来控制神经元-材料相互作用;（2）使用基于神经递质的电纺聚合物纳米纤维再生周围神经。在第一个目标下，已经证明的合成策略将用于系统地改变聚合物的骨架柔性和亲水性以及神经递质的类型和密度的结构。我们将研究结构扰动对材料与体外神经元和体内神经元相互作用的影响。在第二个目标下，我们将使用我们实验室中已经存在的设备使用静电纺丝纳米纤维创建神经引导导管。将使用行为学、电生理学、组织学和免疫组织化学方法评价这些导管在再生横断坐骨神经中的功效。这种方法是创新的，因为它使用化学信使赋予生物活性的合成生物可降解聚合物。目标1和目标2中的工作组合有望创建一种生物材料平台，该平台能够呈现神经递质官能团的定义密度和纳米级接触引导以控制神经元活动。这个多学科的建议结合了生物材料设计和再生医学的主要研究者的互补专业知识，以及神经性疼痛和电生理学的合作者。如果成功，这项研究将代表生物材料合理设计的重大进展，并可能实现功能性神经再生的新方法。目前的临床方法无法有效地恢复受损神经的功能。该研究旨在确定一系列新型神经递质生物材料的结构-功能关系，并将这些材料应用于功能性神经再生。