Staphylococcal protein A-modified hydrogel facilitates in situ immunomodulation by capturing anti-HMGB1 for islet grafts

作者全名："Bai, Xue; Wang, Dan; Wang, Bin; Zhang, Xiao; Bai, Yan; Zhang, Xinying; Tian, Ruoyuan; Li, Caihua; Yi, Qiying; Cheng, Yao; He, Sirong"

作者地址："[Bai, Xue; Zhang, Xiao; Zhang, Xinying; Tian, Ruoyuan; Li, Caihua; He, Sirong] Chongqing Med Univ, Coll Basic Med, Dept Immunol, Chongqing 400016, Peoples R China; [Bai, Xue; Zhang, Xiao; Zhang, Xinying; Tian, Ruoyuan; Li, Caihua; He, Sirong] Chongqing Med Univ, Coll Basic Med, Chongqing Key Lab Basic & Translat Res Tumor Immun, Chongqing 400016, Peoples R China; [Wang, Dan] Chongqing Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Wang, Bin] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Bai, Yan] Chongqing Med Univ, Sch Pharm, Chongqing 400016, Peoples R China; [Yi, Qiying] Chongqing Med Univ, Lab Anim Ctr, Chongqing 400016, Peoples R China; [Cheng, Yao] Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Chongqing 400016, Peoples R China; [Bai, Xue; He, Sirong] Chongqing Med Univ, Coll Basic Med, Dept Immunol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Bai, X; He, SR (通讯作者)，Chongqing Med Univ, Coll Basic Med, Dept Immunol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：ACTA BIOMATERIALIA

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:001033248000001

JCR分区：Q1

影响因子：9.4

年份：2023

卷号：166

期号：　

开始页：95

结束页：108

文献类型：Article

关键词：Islet transplantation; Hydrogel; Staphylococcus aureus protein A; Immunomodulation; Revascularization

摘要："Islet transplantation is regarded as the most promising therapy for type 1 diabetes. However, both hy-poxia and immune attack impair the grafted islets after transplantation, eventually failing the islet graft. Although many studies showed that biomaterials with nanoscale pores, like hydrogels, could protect islets from immune cells, the pores on biomaterials inhibited vascular endothelial cells (VECs) to creep in, which resulted in poor revascularization. Thus, a hydrogel device that can facilitate in situ immune mod-ulations without the cost of poor revascularization should be put forward. Accordingly, we designed a spA-modified hydrogel capturing anti-HMGB1 mAB (mAB-spA Gel): the Staphylococcus aureus protein A (spA) was conjugated on the network of hydrogel to capture anti-HMGB1mAB which can inactivate immune cells, while the pore sizes of the hydrogel were more than 100 & mu;m which allows vascular en-dothelial cells (VECs) to creep in. In this study, we screened the optimal spA concentration in mAB-spA Gel according to the physical properties and antibody binding capability, then demonstrated that it could facilitate in situ immunomodulation without decreasing the vessel reconstruction in vitro . Further, we transplanted islet graft in vivo and showed that the survival of islets was elongated. In conclusion, mAB-spA Gel provided an alternative islet encapsulation strategy for type 1 diabetes.Statement of significanceAlthough various studies have shown that the backbone of the hydrogels can isolate islets grafts from immune cells and the survival of the islets can be prolonged by this way, it is also reported that when the pore size of the backbone is too small the revascularization will be adversely affected. According to this point, it is hard to adjust hydrogel's pore size to protect the islets from the immune attack while allowing endothelial vascular cells to creep in. To solve this dilemma, we designed an immunomodu-latory hydrogel inhibiting the activation of T cells by immunosuppressive IgGs instead of the backbone network, so the hydrogel can prolong the survival of islets without the sacrifice of revascularization.& COPY; 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved."

基金机构："Program of Natural Science Foundation of China [81701950, 82172135]; Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0058]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202200436]; Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing [20210120]; CQMU Program for Youth Innovation in Future Medicine [W0100]; Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University [KY2019Y002]"

基金资助正文："The work was supported by the Program of Natural Science Foundation of China [Nos. 81701950 ; 82172135] ; the Natural Science Foundation of Chongqing (No. CSTB2022NSCQ-MSX0058) ; the Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJQN202200436) ; the Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing [No. 20210120] ; the CQMU Program for Youth Innovation in Future Medicine [No. W0100] and the Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University [Grant No. KY2019Y002] ."