SILICON BIOCAPSULES-- DELIVERY OF NEUROSECRETORY CELLS

描述(改编自申请人的摘要)：本报告的目的 探索性拨款建议是开发和测试一种新型的硅基 植入异种神经细胞的生物包囊系统。该提案代表了 一个跨学科的努力，其中的根本问题是 异种脑移植的免疫排斥反应 从工程学的角度出发，并用神经科学中的功能范例进行测试。 用于神经分泌细胞的生物胶囊将从硅微机械加工到 拥有几十纳米范围的孔洞，这将允许自由 神经递质和必需营养素的扩散，但不是抗体和 补充成分。这种透过性生物胶囊的能力 作为神经分泌元件的功能将在橄榄小脑内进行测试 系统在体外维持在高度可控的条件下，在其中良好- 已定义的生物物理参数可用于评估 微囊化细胞培养释放神经递质。具体目标 该提案的主要内容是：1)确定是否具有化学特性以及持续多长时间 神经元群可以在微细加工的经膜选择性培养中培养 环境和保留功能；2)将活性元素融入微观 制造生物胶囊以去极化被包裹的神经元并诱导 神经递质按需释放；3)确定是否释放以及释放多长时间 封装在微细加工中的GABA能或5-羟色胺能神经元 生物胶囊可以功能性地影响维持在被膜外的神经元 以及4)确定特定神经递质的传递是否 利用体内植入脑内的刺激性生物胶囊可以修复 动物模型中的神经紊乱。据预计， 成功研制成功用于神经元包埋的硅胶生物胶囊 神经递质的释放将为异种移植提供新的范式 将组织移植到大脑和其他器官系统。

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.