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

Author:

Zheng Yin123,Yang Wenyi123,Gao Weisong123,Zhang Xinge4ORCID,Wu Zhongming123,Wang Mo5

Affiliation:

1. Key Laboratory of Endocrine Glucose and Lipids Metabolism and Brain Aging Ministry of Education Department of Endocrinology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong 250021 China

2. Shandong Key Laboratory of Endocrinology and Lipid Metabolism Jinan Shandong 250021 China

3. Jinan Key Laboratory of Translational Medicine on Metabolic Diseases Shandong Institute of Endocrine and Metabolic Diseases Endocrine and Metabolic Diseases Hospital of Shandong First Medical University Jinan Shandong 250012 China

4. Key Laboratory of Functional Polymer Materials of Ministry of Education Institute of Polymer Chemistry College of Chemistry Nankai University Tianjin 300071 China

5. Vascular Surgury Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong 250021 China

Abstract

AbstractTransplantation 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.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

Materials Chemistry,Polymers and Plastics,Organic Chemistry

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