Microfluidic Generation of Thin‐Shelled Polyethylene Glycol‐Tyramine Microgels for Non‐Invasive Delivery of Immunoprotected β‐Cells

• DOI: 10.1002/adhm.202301552
• Publication Date: 2023-08-07T08:55:52Z
• Authors: Nuno Araújo‐Gomes; Barbara Zoetebier...; Bas van Loo; Malin Becker; Suzanne Nijhuis; Alexandra M. Smink; Bart J. de Haan; Paul de Vos; Marcel Karperien; Jeroen Leijten
• Keywords: Tyramine

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