A hybrid nanosack for the enhanced islet engraftment in the omentum

用于增强大网膜中胰岛移植的混合纳米袋

• 批准号: 8568304
• 负责人: Ho-Wook Jun
• 金额: $ 7.15万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8568304
• 关键词: Abdomen; Adhesives; Affect; Attention; Blindness; Blood; Blood Vessels; Cardiovascular system; Cell Death; Cell Survival; Cells; Characteristics; Complex; Computers; Dithizone; Encapsulated; Engraftment; Enzymes; Exposure to; Extracellular Matrix; Extrahepatic; Extravasation; Fibroblast Growth Factor 2; Fluorescein; Gastrointestinal tract structure; Gel; Glucose; Goals; Graft Survival; Hybrids; Immunosuppressive Agents; Implant; In Vitro; Infiltration; Inflammatory; Insulin-Dependent Diabetes Mellitus; Islet Cell; Islets of Langerhans Transplantation; Kidney Failure; Kinetics; Ligands; Liver; Mechanics; Mediating; Mission; Nerve; Omentum; Operative Surgical Procedures; Outcome; Peptides; Pharmaceutical Preparations; Property; Propidium Diiodide; Rat-1; Rattus; Reaction; Risk; Site; Staging; Staining method; Stains; Structure; Toxic effect; Transplantation; caprolactone; controlled release; design; implantation; improved; in vivo; innovation; insulin secretion; intrahepatic; islet; nanofiber; public health relevance; scaffold; tomography

DESCRIPTION (provided by applicant): Pancreatic islet transplantation (PIT) has been tried with consistent and sustained type 1 diabetes reversal. However, the substantial loss of islet cells during the peritransplant period which limits islet graft survival represents a major problem for practical implementation of PIT. Two significant factors associated with this problem are: 1) loss of natural islet extracellular matrix (ECM) microenvironment during islet isolation and 2) the inherent characteristics of particular surgical implantation site for PIT The goal of this proposalis to develop an innovative strategy to provide an ECM mimicking microenvironment that enhances islet survival, function, and engraftment in the omentum. Our proposed hybrid nanosack will serve as a clinically-applicable innovative strategy, as it will be designed for both reconstructing islet-ECM microenvironment and inducing islet revasculazation in the omentum. The hybrid nanosack will consist of 1) a self-assembled peptide amphiphile (PA) nanomatrix gel capable of encapsulating islets with a nurturing microenvironment and 2) a poly (¿-caprolactone) electrospun (ePCL) nanofiber sheet with a craterlike porous structure for infiltration of blood vessels and a mechanically stable structure for surgical manipulation. Outcomes from this proposal will support feasibility of the hybrid nanosack for enhanced islet engraftments in the omuntum through following two Specific Aims. Specific Aim 1: To demonstrate enhanced survival and function of islets encapsulated in a self-assembled peptide amphiphile nanomatrix gel in vitro. Specific Aim 2: To fabricate a hybrid nanosack for extrahepatic islet transplantation and determine revascularization around the omentum in vivo.

描述（由申请人提供）：胰岛移植（PIT）已被尝试用于一致且持续的 1 型糖尿病逆转，然而，移植期间胰岛细胞的大量损失限制了胰岛移植物的存活。 与此问题相关的两个重要因素是：1）胰岛分离过程中天然胰岛细胞外基质（ECM）微环境的损失；2） PIT 特定手术植入部位的特征 该提案的目标是开发一种创新策略，以提供模拟 ECM 的微环境，从而增强胰岛在大网膜中的存活、功能和植入。我们提出的混合纳米袋将作为一种固有的临床适用创新。策略，因为它将针对两者而设计 重建胰岛-ECM 微环境并诱导大网膜中的胰岛血运重建。混合纳米袋将由 1) 能够用培育微环境封装胰岛的自组装肽两亲物 (PA) 纳米基质凝胶和 2) 聚（己内酯）组成。电纺（ePCL）纳米纤维片具有火山口状多孔结构，可渗透血管，并具有机械性能该提案的结果将支持混合纳米袋通过以下两个具体目标增强胰岛植入的可行性：具体目标1：证明封装在自组装肽两亲物中的胰岛的存活率和功能增强。具体目标 2：制造用于肝外胰岛移植的混合纳米袋。 并确定体内大网膜周围的血运重建。