Bioengineered Vascularized Insulin Producing Endocrine Tissues

Islet transplantation is a promising treatment for type 1 diabetes (T1D), but limited islet engraftment hampers its success. In vivo, islets require time to remodel the hepatic parenchyma and establish their own microenvironment, but they face challenges such as ischemic reperfusion injury and immune reactions that hinder engraftment process. Bioengineering approaches are emerging as a solution to overcome these limitations. Specifically, ex vivo engineering of the islet niche microenvironment prior to implantation is gaining interest. These approaches aim to address challenges faced during isolation and in vivo engraftment, including the avascular phase, extracellular matrix (ECM) interactions, and mechanical/inflammatory stress. Alternative cell sources and native/synthetic materials are used to reshape the niche architecture, maximizing the cell-to-scaffold ratio. Meticulous design of the endocrine microenvironment, considering the endocrine, vasculature, and ECM compartments, has shown promise in improving engraftment and function. The generation of an endocrine vascularized pancreas platform enables ex vivo assembly of the essential building blocks, facilitating connection between the endocrine and vascular compartments. This approach has the potential to prevent inflammation, promote rapid vascularization, and enhance graft function. Here, we will discuss the up-to-date approaches in bioengineering the vascularized endocrine tissues based on reshaping all endocrine niche building blocks: ECM, vascular and endocrine compartments that are critical for successful assembly of an efficient vascularized endocrine insulin-producing tissue.