A Bioartificial Pancreas with “Immune Stealth” and Continuous Oxygen Supply for Islet Transplantation

Transplantation of microencapsulated islet cells remains a promising strategy for the normalization of glucose metabolism control in type 1 diabetes mellitus. However, vigorous host immunologic rejection, fibrotic overgrowth around the microcapsules, and poor oxygen supply often lead to graft failur...

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Veröffentlicht in:Macromolecular rapid communications. 2023-12, Vol.44 (23), p.e2300383-n/a
Hauptverfasser: Zheng, Yin, Yang, Wenyi, Gao, Weisong, Zhang, Xinge, Wu, Zhongming, Wang, Mo
Format: Artikel
Sprache:eng
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Zusammenfassung:Transplantation of microencapsulated islet cells remains a promising strategy for the normalization of glucose metabolism control in type 1 diabetes mellitus. However, vigorous host immunologic rejection, fibrotic overgrowth around the microcapsules, and poor oxygen supply often lead to graft failure. Herein, a bioartificial pancreas is constructed, which incorporates the “stealth effect” based on polyethylene glycol copolymers and the high oxygen‐carrying performance of fluorinated nanoparticles. Polycationic poly(l‐lysine)‐grafted‐poly(ethylene glycol) is successfully coated on the surface of alginate microcapsules through electrostatic interaction, which can not only resist fibrinogen adhesion and avoid excessive fibrosis around the microcapsules but also isolate the host immune system from attacking, achieving a “stealth effect” of microencapsulated islet cells. Furthermore, the coloading of fluoride‐based O2 nanocarriers gives them enhanced oxygen‐carrying and continuous oxygen supply capabilities, thereby effectively prolonging the survival of islet cells. The intracapsular islet cells still display similar cell viability and almost normal insulin secretion function even in long‐term culture under hypoxic conditions. Collectively, here a new approach is opened for microencapsulated islets to efficiently evade host immune attack and improve oxygen supply and a promising strategy is provided for islet transplantation in type 1 diabetes mellitus. A bioartificial pancreas is constructed, which incorporates the “stealth effect” and the high oxygen‐carrying performance. Polycationic poly(l‐lysine)‐grafted‐PEG coating on the surface of microcapsules forms a brush‐like structure that resists fibrinogen adhesion and isolates immunity. Perfluorohexane/poly(lactic‐co‐glycolic acid)@nanoparticles act as O2 carriers leading to continuous O2 supply for islet cells and normalization of insulin release.
ISSN:1022-1336
1521-3927
DOI:10.1002/marc.202300383