Degradable methacrylic acid-based synthetic hydrogel for subcutaneous islet transplantation

Abstract

Islet transplantation is a promising regenerative therapy that would reduce the dependence of type 1 diabetic patients on insulin injections. However, islet transplantation is not yet widely available, in part because there is no ideal transplant site. The subcutaneous space has been highlighted as a promising transplant site, but it does not have the vasculature required to support an islet graft. In this study we demonstrate that islets engraft in the subcutaneous space when injected in an inherently vascularizing, degradable methacrylic acid-polyethylene glycol (MAA-PEG) hydrogel; no vascularizing cells or growth factors were required. In streptozotocin-induced diabetic mice, injection of 600 rodent islet equivalents in MAA-PEG hydrogels was sufficient to reverse diabetes for 70 days; a PEG gel without MAA had no benefit. MAA-PEG hydrogel scaffolds degraded over the course of a week and were replaced by a host-derived, vascularized, innervated matrix that supported subcutaneous islets. The survival of islet grafts through the inflammatory events of subcutaneous transplantation, hydrogel degradation, and islet revascularization underscore the benefits of the MAA biomaterial. Our findings establish the MAA-PEG hydrogel as a platform for subcutaneous islet transplantation.

Keywords: Injectable hydrogel; Innervation; Islet transplantation; Methacrylic acid; Tissue engineering; Vascularization.