A durable immuno-protective core-shell microgel for the enhanced pancreatic islet transplantation in diabetes therapy

Type 1 diabetes mellitus (T1DM) remains a significant therapeutic challenge due to the autoimmune destruction of insulin-producing β-cells. Islet transplantation offers promise but faces hurdles like immune rejection and poor cell survival. Here, we engineered an innovative core-shell microgel system for durable immune-protective islet cell encapsulation. The microgels were fabricated in our home-made droplet-based microfluidic device, with gelatin methacrylate (GelMA) and chitosan methacrylate (CHMA) as the core, and polyethylene glycol diacrylate (PEGDA) and alginate (Alg) as the shell materials to make core-shell structure. This design demonstrated excellent immuno-isolation properties, permitting nutrient exchange but blocking immune components. In vitro assessments revealed the sustained cell viability and glucose-responsive insulin secretion. The transplantation of these microgels into diabetic rat models exhibited the normalized blood glucose levels for 60 days. Notably, the microgels facilitated host tissue integration and angiogenesis. The animals achieved weight recovery but minimal fibrotic encapsulation. These findings position our core-shell microgels as a transformative platform for cell-based diabetes therapy, potentially eliminating the need for chronic immunosuppression.