SILICON BIOCAPSULES-- DELIVERY OF NEUROSECRETORY CELLS

硅生物胶囊——神经分泌细胞的输送

• 批准号: 6095986
• 负责人: John P Welsh
• 金额: $ 10.34万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 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 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6095986
• 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）：此目的 探索性拨款提案旨在开发和测试一种新型硅基 用于植入神经元异种移植物的生物胶囊系统。 该提案代表 一项跨学科的努力，其中的基本问题是 异种脑移植的免疫排斥是从 工程视角并通过神经科学的功能范式进行测试。 用于神经分泌细胞的生物胶囊将通过硅微机械加工成 具有数十纳米范围的孔隙，可以自由 神经递质和必需营养素的扩散，但抗体和 补充成分。 这种选择性渗透生物胶囊的能力 作为神经分泌元件的功能将在橄榄小脑内进行测试 系统在体外高度控制的条件下维持，其中良好 定义的生物物理参数可用于评估 神经递质从封装的细胞培养物中释放。 具体目标 该提案的内容是： 1) 确定化学特异性是否以及持续多久 神经元群可以在微制造的选择性渗透中培养 环境和保留功能； 2）将有源元件集成到微 制造生物胶囊以使封装的神经元去极化并诱导 神经递质按需释放； 3）确定是否以及持续多久 GABA 能或血清素能神经元封装在微制造中 生物胶囊可以在功能上影响维持在 体外； 4) 确定是否输送特定的神经递质 使用植入大脑体内的刺激生物胶囊可以修复 动物模型中的神经系统疾病。 预计 成功开发用于神经元封装的硅生物胶囊 神经递质的释放将为异种提供新的范例 将组织移植到大脑和其他器官系统中。