VEGF-Modified PVA/Silicone Nanofibers Enhance Islet Function Transplanted in Subcutaneous Site Followed by Device-Less Procedure

Abstract

Bin Yang,1,* Guodong Cao,1,2,* Kailun Cai,1,* Gang Wang,2 Pengping Li,3 Lei Zheng,1 Haolei Cai,1 Yi Zhu,1 Xiang Li,2 Yulian Wu1 1Department of Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310009, People’s Republic of China; 2State Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou, 310027, People’s Republic of China; 3Department of Surgery, The First People’s Hospital of Xiaoshan District, Hangzhou, Zhejiang Province 310009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yulian WuDepartment of Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, Zhejiang Province 310009, People’s Republic of ChinaTel/Fax [phone]Email [email protected] LiState Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou 310027, People’s Republic of ChinaEmail [email protected]: As heterologous islets or islet-like stem cells become optional sources for islet transplantation, the subcutaneous site appears to be an acceptable replacement of the intrahepatic site due to its graft retrievability. The device-less (DL) procedure improves the feasibility; however, some limitations such as fibrotic overgrowth or immunodeficiency still exist. Nanofibers could mimic the extracellular matrix to improve the vitality of transplanted islets. Therefore, we designed a vascular endothelial growth factor (VEGF)-modified polyvinyl alcohol (PVA)/silicone nanofiber (SiO2-VEGF) to optimize the DL procedure.Methods: SiO2-VEGF nanofibers were designed by nano-spinning and characterized the physical-chemical properties before subcutaneous islet transplantation. Cell viability, vessel formation, and glucose-stimulated insulin secretion were tested in vitro to ensure biocompatibility; and blood glucose level (BGL), transplanted islet function, and epithelial–mesenchymal transition (EMT)-related biomarker expression were analyzed in vivo.Results: The intensity of inflammatory reaction induced by SiO2 nanofibers was between nylon and silicone, which did not bring out excessive fibrosis. The vascularization could be enhanced by VEGF functionalization both in vitro and in vivo. The BGL control was better in the DL combined with SiO2-VEGF group. The percentage of recipients that achieved normoglycemia was higher and earlier (71% at day 57), and the intraperitoneal glucose tolerance test (IPGTT) also confirmed better islet function. The expressions of vimentin, α-SMA, and twist-1 were upregulated, which indicated that SiO2-VEGF nanofibers might promote islet function by regulating the EMT pathway.Discussion: In summary, our new SiO2-VEGF combined with DL procedure might improve the feasibility of subcutaneous islet transplantation for clinical application.Keywords: islet transplantation, subcutaneous site, VEGF modified nanofibers, device-less procedure

Keywords

• islet transplantation
• subcutaneous site
• vegf modified nanofibers
• device-less procedure