A hybrid nanosack for the enhanced islet engraftment in the omentum

描述（由申请人提供）：胰岛移植（PIT）已被尝试与一致和持续的1型糖尿病逆转。然而，在围移植期胰岛细胞的大量丢失限制了胰岛移植物的存活，这是一个主要问题 PIT的实际应用。与该问题相关的两个重要因素是：1）在胰岛分离期间天然胰岛细胞外基质（ECM）微环境的损失，以及2）在胰岛细胞分离期间， PIT特定手术植入部位的固有特征本提案的目标是开发一种创新策略，以提供ECM模拟微环境，增强胰岛存活、功能和网膜中的植入。我们提出的混合纳米袋将作为一个临床适用的创新战略，因为它将是专为这两个 重建胰岛-ECM微环境并诱导网膜中的胰岛再血管化。混合纳米袋将由1）自组装的肽两亲物（PA）纳米基质凝胶和2）聚（ε-己内酯）电纺（ePCL）纤维片组成，该凝胶能够用培养微环境封装胰岛，该纤维片具有用于血管渗透的火山口状多孔结构和用于手术操作的机械稳定结构。该提案的结果将支持混合纳米袋通过以下两个特定目标在网膜中增强胰岛植入的可行性。具体目的1：证明体外自组装肽两亲物纳米基质凝胶包封的胰岛的存活和功能增强。具体目标2：制备用于肝外胰岛移植的混合纳米囊 并在体内确定网膜周围的血管再生。

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.