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Sustained release of hepatocyte growth factor by cationic self-assembling peptide/heparin hybrid hydrogel improves β-cell survival and function through modulating inflammatory response.

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机构： [1]Key Laboratory of Transplant Engineering and Immunology, West China Hospital. [2]Institute for Nanobiomedical Technology and Membrane Biology, Sichuan University, Chengdu, People's Republic of China.

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关键词： self-assembling peptide islet transplantation inflammation HGF slow release

摘要：

Inflammatory response is a major cause of grafts dysfunction in islet transplantation. Hepatocyte growth factor (HGF) had shown anti-inflammatory activity in multiple diseases. In this study, we aim to deliver HGF by self-assembling peptide/heparin (SAP/Hep) hybrid gel to protect β-cell from inflammatory injury. The morphological and slow release properties of SAPs were analyzed. Rat INS-1 β-cell line was treated with tumor necrosis factor α in vitro and transplanted into rat kidney capsule in vivo, and the viability, apoptosis, function, and inflammation of β-cells were evaluated. Cationic KLD1R and KLD2R self-assembled to nanofiber hydrogel, which showed higher binding affinity for Hep and HGF because of electrostatic interaction. Slow release of HGF from cationic SAP/Hep gel is a two-step mechanism involving binding affinity with Hep and molecular diffusion. In vitro and in vivo results showed that HGF-loaded KLD2R/Hep gel promoted β-cell survival and insulin secretion, and inhibited cell apoptosis, cytokine release, T-cell infiltration, and activation of NFκB/p38 MAPK pathways in β-cells. This study suggested that SAP/Hep gel is a promising carrier for local delivery of bioactive proteins in islet transplantation.

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出版当年[2016]版：

大类 | 1 区

工程技术

小类 | 2 区药学 3 区纳米科技

最新[2023]版：

大类 | 2 区

医学

小类 | 2 区药学 3 区纳米科技

第一作者：

第一作者机构： [1]Key Laboratory of Transplant Engineering and Immunology, West China Hospital.

通讯作者：

通讯机构： [1]Key Laboratory of Transplant Engineering and Immunology, West China Hospital. [*1]Key Laboratory of Transplant Engineering and Immunology, West China Hospital, No 1 Keyuan 4th Road, Gaopeng Avenue, Chengdu 610041, People’s Republic of China

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