Neurotransmitter-based poly(aminoglycerol ester)s

描述：神经系统疾病影响了20%的美国人，估计每年的成本为4000亿美元。目前的临床方法还不能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。本研究的目的是阐明一类独特的神经递质生物材料的结构-功能关系，并探索其再生周围神经的潜力。该研究的核心假设是，合理设计具有神经递质功能基团的可生物降解材料，可以通过特定的神经递质受体诱导神经元的精确反应，从而提高神经元的存活和再生能力。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来验证：(1)通过系统地改变神经递质聚合物的结构来控制神经元与物质的相互作用；(2)利用电纺神经递质聚合物纳米纤维再生周围神经。在第一个目标下，一个已经被证明的合成策略将被用于系统地改变聚合物的结构，包括主链的柔韧性和亲水性，以及神经递质的类型和密度。我们将研究结构扰动对材料与体外神经元和体内神经相互作用的影响。第二个目标是，我们将利用实验室已有的设备，利用静电纺纳米纤维制造神经引导导管。使用行为学、电生理、组织学和免疫组织化学方法评估这些导管再生横断坐骨神经的效果。这种方法是创新的，因为它使用化学信使赋予合成的可生物降解聚合物生物活性。目标1和目标2的结合有望创建一个生物材料平台，能够呈现神经递质功能群的定义密度和纳米级接触引导，以控制神经元活动。这项多学科提案结合了生物材料设计和再生医学首席研究员以及神经性疼痛和电生理学合作者的互补专业知识。如果成功，该研究将代表着生物材料合理设计的重大进步，并可能为功能性神经再生提供新方法。目前的临床方法还不能有效地恢复受损神经的功能。该研究旨在确定一类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。

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.