Microfluidic Production of Zwitterion Coating Microcapsules with Low Foreign Body Reactions for Improved Islet Transplantation

Islet transplantation is a promising strategy for type 1 diabetes mellitus (T1DM) treatment, whereas implanted‐associated foreign body reaction (FBR) usually induces the necrosis of transplanted islets and leads to the failure of glycemic control. Benefiting from the excellent anti‐biofouling property of zwitterionic materials and their successful application in macroscopic implanted devices, microcapsules with zwitterionic coatings may be promising candidates for islet encapsulation. Herein, a series of zwitterion‐coated core–shell microcapsules is fabricated (including carboxybetaine methacrylate [CBMA]‐coated gelatin methacrylate [GelMA] [CBMA‐GelMA], sulfobetaine methacrylate [SBMA]‐coated GelMA [SBMA‐GelMA], and phosphorylcholine methacrylate [MPC]‐coated GelMA [MPC‐GelMA]) by one‐step photopolymerization of inner GelMA and outer zwitterionic monomers via a handmade two‐fluid microfluidic device and it is demonstrated that they can effectively prevent protein adsorption, cell adhesion, and inflammation in vitro. Interestingly, the zwitterionic microcapsules successfully resist FBR in C57BL/6 mice after intraperitoneal implantation for up to 4 months. After successfully encapsulating xenogeneic rat islets in the SBMA‐GelMA microcapsules, sustained normoglycemia is further validated in streptozotocin (STZ)‐induced mice for up to 3 months. The zwitterion‐modified microcapsule using a microfluidic device may represent a platform for cell encapsulation treatment for T1DM and other hormone‐deficient diseases. Core–shell microcapsules with zwitterionic coatings are fabricated by a designed microfluidic device exhibiting excellent foreign body reaction (FBR)‐mitigating properties and protective effects of islets. After transplantation, such islet‐encapsulated microcapsules can successfully restore the glucose of diabetic mice and maintain their normoglycemia for up to 3 months.