A hybrid nanosack for the enhanced islet engraftment in the omentum

描述(申请人提供)：胰岛移植(PIT)已经尝试了一致和持续的1型糖尿病逆转。然而，胰岛细胞在移植周期间的大量丢失限制了胰岛移植物的存活，这是一个主要问题。 为IT的实际实施提供参考。与这个问题相关的两个重要因素是：1)在胰岛分离过程中失去自然的胰岛细胞外基质(ECM)微环境；2)胰岛分离过程中 本研究的目的是开发一种创新的策略，提供一种模拟胰岛微环境的ECM，以提高胰岛的存活、功能和在大网膜的植入率。我们提出的混合纳米袋将作为一种临床适用的创新策略，因为它将为两者设计 重建胰岛-细胞外基质微环境，诱导大网膜胰岛血运重建。这种混合纳米袋将由1)自组装肽两亲性(PA)纳米基质凝胶和2)聚己内酯电纺(EPCL)纳米纤维片组成，该凝胶能够将胰岛包裹在滋养微环境中，该纳米纤维片具有用于血管渗透的火山口状多孔结构和用于外科操作的机械稳定结构。这项提议的结果将通过以下两个具体目标支持在脐部植入强化胰岛的混合纳米袋的可行性。具体目的1：证实自组装肽两亲性纳米基质凝胶包裹的胰岛在体外增强存活和功能。特定目的2：制备用于肝外胰岛移植的杂交纳米袋 并在体内确定大网膜周围的血运重建。

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.