Background: Islet transplantation is a promising approach for diabetes management, but clinical application is limited by poor engraftment and immune-mediated rejection. Microporous Annealed Particle (MAP) gels are injectable, granular scaffolds formed by annealing microgels into a porous network. Unlike traditional hydrogels, MAP gels permit rapid cell infiltration and vascularization due to their interconnected microporosity, and their modular chemistry enables tunable immunomodulation. This study investigates the utility of MAP gel as a scaffold to enhance islet viability, promote engraftment, and modulate immune responses in transplantation settings.

Methods: Dissociated murine islets, whole human islets, or Beta TC-6 cells were mixed with MAP gel and transplanted into diabetic syngeneic or xenogeneic recipients. Blood glucose (BG) was monitored daily. Additionally, MAP or nanoporous (NP) gels were implanted in non-diabetic mice with or without Beta TC-6 cells. Cytokine profiling was performed at 7 and 14 days post-transplantation.

Results: In diabetic C57BL/6 mice, transplantation of 100 dissociated islets with MAP gel under the kidney capsule restored normoglycemia (BG <200 mg/dL) within 18 days and maintained control for 40 days, while islets transplanted without MAP gel failed to reverse hyperglycemia. In the epididymal fat pad, 400 dissociated islets with MAP gel sustained normoglycemia for 44 days in two mice, whereas MAP gel alone, whole islets alone, or dissociated islets alone did not.

A pilot study using xenogeneic (human) islets at the SC site demonstrated MAP gel’s efficacy: mice receiving 800 IEQ human islets exhibited the greatest glucose reduction, while 400 IEQ showed a moderate effect. Unlike persistently hyperglycemic controls, MAP-supported transplants exhibited glucose changes indicative of islet activity.

Additionally, MAP gel demonstrated immunomodulatory properties. At 7 days post-implantation of 1 million Beta TC-6 cells with MAP or NP gels, cytokine profiling revealed reduced pro-inflammatory cytokines (IFNγ, IL-6, IL-1α, IL-1β, IL-10, IL-17, TNFα). Notably, IL-10 levels were lower in the MAP scaffold group, suggesting a less inflammatory microenvironment conducive to cell survival.

Conclusions: MAP gel significantly enhances islet engraftment, maintains glycemic control, and creates a more favorable immune environment in both syngeneic and xenogeneic transplantation models. These results highlight MAP gel’s potential as an innovative scaffold to improve the efficacy of cell-based therapies, particularly in diabetes management.