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

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; 2Stat...

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Autores principales:	Yang B, Cao G, Cai K, Wang G, Li P, Zheng L, Cai H, Zhu Y, Li X, Wu Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	islet transplantation subcutaneous site vegf modified nanofibers device-less procedure Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/dfe12756eb32408f8cca7c9268441389
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spelling	oai:doaj.org-article:dfe12756eb32408f8cca7c92684413892021-12-02T04:16:18ZVEGF-Modified PVA/Silicone Nanofibers Enhance Islet Function Transplanted in Subcutaneous Site Followed by Device-Less Procedure1178-2013https://doaj.org/article/dfe12756eb32408f8cca7c92684413892020-01-01T00:00:00Zhttps://www.dovepress.com/vegf-modified-pvasilicone-nanofibers-enhance-islet-function-transplant-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Bin 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 +86 571 87783563Email yulianwu@zju.edu.cnXiang LiState Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou 310027, People’s Republic of ChinaEmail xiang.li@zju.edu.cnIntroduction: 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 procedureYang BCao GCai KWang GLi PZheng LCai HZhu YLi XWu YDove Medical Pressarticleislet transplantationsubcutaneous sitevegf modified nanofibersdevice-less procedureMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 587-599 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	islet transplantation subcutaneous site vegf modified nanofibers device-less procedure Medicine (General) R5-920
spellingShingle	islet transplantation subcutaneous site vegf modified nanofibers device-less procedure Medicine (General) R5-920 Yang B Cao G Cai K Wang G Li P Zheng L Cai H Zhu Y Li X Wu Y VEGF-Modified PVA/Silicone Nanofibers Enhance Islet Function Transplanted in Subcutaneous Site Followed by Device-Less Procedure
description	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 +86 571 87783563Email yulianwu@zju.edu.cnXiang LiState Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou 310027, People’s Republic of ChinaEmail xiang.li@zju.edu.cnIntroduction: 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
format	article
author	Yang B Cao G Cai K Wang G Li P Zheng L Cai H Zhu Y Li X Wu Y
author_facet	Yang B Cao G Cai K Wang G Li P Zheng L Cai H Zhu Y Li X Wu Y
author_sort	Yang B
title	VEGF-Modified PVA/Silicone Nanofibers Enhance Islet Function Transplanted in Subcutaneous Site Followed by Device-Less Procedure
title_short	VEGF-Modified PVA/Silicone Nanofibers Enhance Islet Function Transplanted in Subcutaneous Site Followed by Device-Less Procedure
title_full	VEGF-Modified PVA/Silicone Nanofibers Enhance Islet Function Transplanted in Subcutaneous Site Followed by Device-Less Procedure
title_fullStr	VEGF-Modified PVA/Silicone Nanofibers Enhance Islet Function Transplanted in Subcutaneous Site Followed by Device-Less Procedure
title_full_unstemmed	VEGF-Modified PVA/Silicone Nanofibers Enhance Islet Function Transplanted in Subcutaneous Site Followed by Device-Less Procedure
title_sort	vegf-modified pva/silicone nanofibers enhance islet function transplanted in subcutaneous site followed by device-less procedure
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/dfe12756eb32408f8cca7c9268441389
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VEGF-Modified PVA/Silicone Nanofibers Enhance Islet Function Transplanted in Subcutaneous Site Followed by Device-Less Procedure

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