SILICON BIOCAPSULES-- DELIVERY OF NEUROSECRETORY CELLS

硅生物胶囊——神经分泌细胞的输送

• 批准号: 6394748
• 负责人: John P Welsh
• 金额: $ 8.65万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394748
• 关键词: albino rat; biomaterial development /preparation; brain stem; cell transplantation; dosage forms; drug delivery systems; medical implant science; neurochemistry; neuroendocrine system; neurons; neurophysiology; neurotransmitter transport; silicon; tissue /cell culture; xenotransplantation

DESCRIPTION (Adapted from the applicant's abstract): The purpose of this exploratory grant proposal is to develop and test a novel silicon-based biocapsule system for implanting neuronal xenografts. The proposal represents an interdisciplinary effort in which the fundamental problem of immunorejection of xenogeneic brain transplantation is approached from an engineering perspective and tested with functional paradigms in neuroscience. Biocapsules for neurosecretory cells will be micromachined from silicon to possess pores in the tens of nanometer range that will allow for free diffusion of neurotransmitter and essential nutrients but not antibodies and complement components. The ability of such permselective biocapsules to function as neurosecretory elements will be tested within the olivocerebellar system maintained under highly-controlled conditions in vitro, in which well- defined biophysical parameters can be used to assess the functionality of neurotransmitter release from encapsulated cell cultures. The specific aims of the proposal are: 1) to determine whether and how long chemically-specific neuronal populations can be cultured in micro fabricated permselective environments and retain function; 2) to integrate an active element into micro fabricated biocapsules in order to depolarize encapsulated neurons and induce neurotransmitter release on demand; 3) to determine whether and how long GABAergic or serotonergic neurons encapsulated within micro fabricated biocapsules can functionally affect extra-capsular neurons maintained in vitro; and 4) to determine whether delivery of specific neurotransmitters using stimulation biocapsules implanted into the brain in vivo can remediate a neurological disorder in an animal model. It is anticipated that the successful development of this silicon biocapsule for neuronal encapsulation and neurotransmitter release will provide a new paradigm for xenogeneic transplantation of tissue into the brain and other organ systems.

描述（改编自申请人的摘要）：本申请的目的 探索性赠款提案是开发和测试一种新的硅基 用于植入神经元异种移植物的生物支架系统。 该提案代表了 一个跨学科的努力，其中的基本问题， 异种脑移植的免疫排斥反应是从一个 工程的角度和测试与功能范式在神经科学。 神经分泌细胞的生物胶囊将由硅微加工而成， 拥有数十纳米范围内的孔隙， 神经递质和必需营养素的扩散，而不是抗体的扩散， 互补成分 这种选择性渗透生物载体的能力， 作为神经分泌成分的功能将在橄榄小脑内进行测试。 在体外高度受控的条件下维持的系统，其中良好- 定义的生物物理参数可用于评估 神经递质从包封的细胞培养物释放。 具体目标 该提案的要点是：1）确定是否具有化学特异性以及持续多久 神经元群体可以在微制造的选择性渗透的环境中培养， 环境和保留功能; 2）将活性元素集成到微 制造生物胶囊，以使被包裹的神经元脱髓鞘并诱导 神经递质按需释放; 3）确定是否和多长时间 封装在微结构中的GABA能或多巴胺能神经元 生物囊膜可以在功能上影响维持在神经元中的囊外神经元。 体外;以及4）确定是否递送特定的神经递质 使用刺激生物胶囊植入体内大脑可以修复 在动物模型中的神经障碍。 预计该 成功开发用于神经元包封硅生物膜 神经递质的释放将为异种 组织移植到大脑和其他器官系统。