Neurotransmitter-based poly(aminoglycerol ester)s

描述：神经性疾病影响20%的美国人，估计每年造成4000亿美元的损失。目前的临床治疗方法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。该建议的目的是阐明一类独特的神经递质生物材料的结构与功能关系，并探索其再生周围神经的潜力。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，可以通过神经元特有的神经递质受体诱导神经元做出精确的反应，提高神经元的生存和再生能力。在强大的初步数据的指导下，这一假说将通过追求两个具体目标来检验：(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与材料的相互作用；(2)使用静电纺丝的基于神经递质的聚合物纳米纤维再生周围神经。在第一个目标下，将使用已经得到验证的合成策略来系统地改变聚合物的结构，包括骨架的柔韧性和亲水性，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。在第二个目标下，我们将使用已经在实验室中的设备，使用静电纺丝纳米纤维来创建神经引导管道。我们将用行为学、电生理学、组织学和免疫组织化学的方法来评估这些导管在再生横断坐骨神经方面的效果。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。AIMS 1和AIMS 2的工作结合有望创建一个生物材料平台，能够呈现定义密度的神经递质功能基团和纳米级接触指导，以控制神经元活动。这一多学科的建议结合了生物材料设计和再生医学方面的首席研究人员以及神经病理性疼痛和电生理学方面的合作者的互补专业知识。如果成功，这项拟议的研究将代表着生物材料合理设计方面的重大进步，并可能使功能神经再生的新方法成为可能。目前的临床治疗方法不能有效地恢复受损神经的功能。这项研究旨在确定一类基于神经递质的新型生物材料的结构与功能关系，并将其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.