Carboxymethyl chitosan/oxidized carboxymethyl starch Schiff base hydrogels containing fasudil for islet encapsulation and transplantation

Islet transplantation offers a promising therapeutic strategy for type 1 diabetes patients with inadequate glycemic control or severe complications. Islet encapsulation using biocompatible materials presents a potential solution to reduce immune rejection. This study fabricated and characterized Schiff base hydrogels (CMOCs) composed of varying ratios of carboxymethyl chitosan (CMCS) and oxidized carboxymethyl starch (OCMS). CMOCs exhibited desirable mechanical properties, injectability, self-healing properties, antibacterial properties, biocompatibility, and controlled-release capabilities. CMOC3, with the highest CMCS content, was selected for loading Fasudil and further islet encapsulation experiments. In vitro studies demonstrated that CMOC3 and CMOC3-Fasudil hydrogel (CMOC3-Fas) not only supported islet survival and insulin secretion but also increased insulin bioavailability through chelating the zinc ions from the insulin hexamers. CMOC3-Fas exhibited pro-angiogenic and anti-inflammatory properties, and effectively reduced islet cell death under hypoxic conditions. Finally, transplantation of islets encapsulated within CMOC3-Fas achieved prolonged normoglycemia and increased body weight in diabetic mice. This study demonstrates the synergistic protective effect of Schiff-base hydrogel co-delivering fasudil for islet encapsulation, potentially paving the way for improved islet transplantation therapy in type 1 diabetes.