Supercritical CO decellularized-ECM derived coreshell hydrogel for functional β-cell encapsulation and immune protection

Introduction: Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease that destroys insulinproducing pancreatic cells, affecting over 9 million people worldwide. While insulin therapy is standard, it often leads to poor glucose control or hypoglycemia. Pancreatic islet transplantation shows promise but faces graft survival challenges. This study develops a permeable, pro-angiogenic immune-isolation hydrogel using pancreatic decellularized extracellular matrix (dECM) to mimic native tissue and support insulin production, with ruthenium as crosslinker surrounded by an Alginate shell aiming to reduce oxidative stress and inflammation. Conclusions: This study validated a supercritical CO₂ decellularization protocol as a robust and effective method for pancreatic dECM preparation, achieving reliable DNA removal across organ variability. Decellularization reduced GAGs and soluble collagen while increasing insoluble collagen, results also highlighted regional differences within the pancreas. A core-shell hydrogel for B cell spheroids seeding was developed. The core, ruthenium-based hydrogels showed desired crosslinking but low stability after 7 days which will need to be improved. The core-shell construct showed no signs of cytotoxicity and allowed cell seeding before alginate crosslinking. Preliminary cell studies showed similar metabolic activity along the timepoints tested. Future work will focus on optimizing stiffness, reducing residual of crosslinkers in hydrogels, and expanding cellular assays. Overall, these findings establish pancreatic dECM hydrogels as promising scaffolds for β-cell replacement therapies in diabetes.