Microfluidic Generation of Thin-Shelled Polyethylene Glycol-Tyramine Microgels for Non-Invasive Delivery of Immunoprotected Β-Cells.

Transplantation of microencapsulated pancreatic cells is emerging as a promising therapy to replenish β-cell mass lost from auto-immune nature of Type I diabetes mellitus (T1DM). This strategy intends to use micrometer-sized microgels to provide immunoprotection to transplanted cells to avoid chronic application of immunosuppression. Clinical application of encapsulation has remained elusive due to often limited production throughputs and body's immunological reactions to the implanted materials. We here present high-throughput fabrication of monodisperse, non-immunogenic, non-degradable, immunoprotective, semi-permeable, enzymatically-crosslinkable polyethylene glycol-tyramine (PEG-TA) microgels for β-cell microencapsulation. Monodisperse β-cell laden microgels of ∼120 μm, with a shell thickness of 20 μm were produced using an outside-in crosslinking strategy. Microencapsulated β-cells rapidly self-assembled into islet-sized spheroids. Immunoprotection of the microencapsulated was demonstrated by inability of FITC-IgG antibodies to diffuse into cell-laden microgels and inability of NK-cells to kill microencapsulated β-cells. Multiplexed ELISA analysis on live blood immune reactivity confirmed limited immunogenicity. Microencapsulated MIN6β1 spheroids remained glucose responsive for at least 28 days in vitro, and was able to restore normoglycemia 5 days post-implantation in diabetic mice without notable amounts of cell death. In short, PEG-TA microgels can effectively protect implanted cells from the host's immune system while being viable and functional, validating this strategy for the treatment of T1DM. This article is protected by copyright. All rights reserved.