Decellularized matrix-based hydrogel for targeted beta cell islet delivery in type I diabetes treatment

Introduction: Type 1 Diabetes Mellitus (T1DM) affects over 9 million people worldwide and is marked by autoimmune destruction of pancreatic β-cells, which produce insulin. Current treatment relies on exogenous insulin, but inaccurate delivery often causes poor glycemic control or hypoglycemia. Islet transplantation offers a promising alternative, though long-term graft survival remains a challenge. This work proposes a permeable, pro-angiogenic immune-isolation hydrogel to improve cell- based therapies. The design uses pancreatic decellularized extracellular matrix (dECM) to mimic native tissue, supporting cell growth and insulin release. Riboflavin (Vitamin B2), with antioxidant and anti-inflammatory properties, and Ruthenium, providing photophysical crosslinking, are employed as photocrosslinkers. Objectives: Development of a: permeable, pro-angiogenic, immune-isolation hydrogel using decellularized pancreatic extracellular matrix (dECM), crosslinked with Riboflavin or Ruthenium for beta cells encapsulation. Conclusions: This study established a supercritical CO₂–based decellularization protocol as a robust and reproducible method for generating pancreatic dECM, achieving consistent DNA removal despite inter-organ variability. The process led to a reduction in glycosaminoglycans (GAGs) and soluble collagen while enriching insoluble collagen, and also revealed regional compositional differences across pancreatic zones. Two hydrogel formulations were investigated: riboflavin-mediated hydrogels exhibited limited stiffness, whereas ruthenium-mediated hydrogels provided enhanced crosslinking and mechanical stability. Preliminary cell studies demonstrated distinct metabolic responses, with ruthenium hydrogels derived from the pancreatic body supporting the highest activity. Future efforts will aim to optimize mechanical properties, minimize residual crosslinkers, and broaden cellular evaluation. Collectively, these results highlight pancreatic dECM hydrogels as a promising platform for β-cell replacement strategies in diabetes therapy.