Abstract Type 1 diabetes (T1D) arises from autoimmune destruction of pancreatic β-cells, leading to lifelong dependence on exogenous insulin. Clinical islet transplantation offers a potential cure by restoring endogenous insulin secretion; however, its success is critically limited by poor post-transplant vascularization and oxygen deprivation, which cause over 70% of transplanted islets to undergo early necrosis or apoptosis. To address these challenges, we developed an injectable, biodegradable dual-functional hydrogel composed of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMC). This polysaccharide-based platform co-delivers vascular endothelial growth factor (VEGF) and an oxygen-carrying perfluorotributylamine (PFTBA) nanoemulsion, enabling simultaneous enhancement of angiogenesis and oxygenation within the graft microenvironment. The OHA/CMC hydrogel exhibited excellent biocompatibility, tunable gelation, and sustained release of both oxygen and VEGF. In vitro, hydrogel-encapsulated islets demonstrated markedly improved resilience under hypoxic stress, exhibiting an 8.6-fold increase in viability after 6 hours and a 4.0-fold enhancement in glucose-stimulated insulin secretion (GSIS) after 48 hours under 0% O2. In streptozotocin-induced diabetic mice, transplantation with the OHA/CMC–PFTBA–VEGF hydrogel enabled rapid restoration of endogenous insulin secretion, reversal of severe hyperglycemia, prolonged graft function, and enhanced neovascularization at the implant site. Collectively, this multifunctional hydrogel represents a promising and translatable therapeutic platform for improving islet transplantation outcomes in T1D and potentially advancing broader applications in regenerative medicine and complex tissue engineering.
Zhang et al. (Mon,) studied this question.