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

基本信息

批准号：
8701294
负责人：
Ho-Wook Jun
金额：
$ 7.13万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-15 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8701294
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

项目摘要

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（由适用提供）：胰岛移植（PIT）已尝试使用一致且持续的1型糖尿病逆转。但是，胰岛植物周期中胰岛细胞的大量损失限制了胰岛移植的存活率代表了一个主要问题用于实际实施坑。与此问题相关的两个重要因素是：1）胰岛分离期间天然胰岛细胞外基质（ECM）微环境的丧失，2）特定外科手术实施地点的固有特征是该提案的目标，以制定一种创新策略，以提供模仿Mimick的微环境，从而增强胰岛的生存，功能和植入Omentum。我们拟议的混合动力Nanosack将作为临床上适用的创新策略，因为它将针对这两者设计重建胰岛ECM微环境和诱导的胰岛相比是在omentum中的相比。杂化纳米袋将由1）自组装的肽两亲物（PA）纳米质凝胶，能够用养育的微环境封装胰岛和2）poly（ - 丙糖酮）型（EPCL）静电材料（EPCL）纳尼诺弗材料，具有丝状造成骨膜的刺激性，均为动作效果的机构。该提案的结果将通过遵循两个特定的目标来支持混合纳米袋在omuntum中增强胰岛植入的可行性。具体目的1：在体外封装在自组装肽两亲纳米纳米质凝胶中的胰岛的生存和功能增强。特定目的2：用于制造杂种纳米毛包，用于外膜外胰岛移植并确定体内网骨周围的血运重建。