Engineering superstable islets-laden chitosan microgels with carboxymethyl cellulose coating for long-term blood glucose regulation in vivo

Islet transplantation to restore endogenous insulin secretion is a promising therapy for type 1 diabetes in clinic. However, host immune rejection seriously limits the survival of transplanted islets. Despite of the various encapsulation strategies and materials developed so far to provide immune isolation for transplanted islets, long-term blood glucose regulation is still difficult due to the inherent defects of the encapsulation materials. Herein, a novel islet-encapsulation composite material with low immunogenicity, good biocompatibility and excellent stability is reported. Specifically, chitosan (CS) microgels (diameter: ~302 μm) are prepared via Michael addition reaction between maleimide grafted chitosan (CS-Mal) and thiol grafted chitosan (CS-NAC) in droplet-based microfluidic device, and then zwitterionic surface layer is constructed on CS microgel surface by covalent binding between maleimide groups on CS and thiol groups on thiol modified carboxymethyl cellulose (CMC-SH). The as-formed carboxymethyl cellulose coated chitosan (CS@CMC) microgels show not only long-term stability in vivo owing to the non-biodegradability of CMC, but also fantastic anti-adsorption and antifibrosis because of the stable zwitterionic surface layer. As a result, islets encapsulated in the CS@CMC microgels exhibit high viability and good insulin secretion function in vivo, and long-term blood glucose regulation is achieved for 180 days in diabetic mice post-transplantation.