Hybrid heart valves with VEGF-loaded zwitterionic hydrogel coating for improved anti-calcification and re-endothelialization

With the aging of the population in worldwide, valvular heart disease has become one of the most prominent life-threatening diseases in human health, and heart valve replacement surgery is one of the therapeutic methods for valvular heart disease. Currently, commercial bioprosthetic heart valves (BH...

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Main Authors: Qi Tong, Ao Sun, Zhengjie Wang, Tao Li, Xinye He, Yongjun Qian, Zhiyong Qian
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Materials Today Bio
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2590006422002575
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author Qi Tong
Ao Sun
Zhengjie Wang
Tao Li
Xinye He
Yongjun Qian
Zhiyong Qian
author_facet Qi Tong
Ao Sun
Zhengjie Wang
Tao Li
Xinye He
Yongjun Qian
Zhiyong Qian
author_sort Qi Tong
collection DOAJ
description With the aging of the population in worldwide, valvular heart disease has become one of the most prominent life-threatening diseases in human health, and heart valve replacement surgery is one of the therapeutic methods for valvular heart disease. Currently, commercial bioprosthetic heart valves (BHVs) for clinical application are prepared with xenograft heart valves or pericardium crosslinked by glutaraldehyde. Due to the residual cell toxicity from glutaraldehyde, heterologous antigens, and immune response, there are still some drawbacks related to the limited lifespan of bioprosthetic heart valves, such as thrombosis, calcification, degeneration, and defectiveness of re-endothelialization. Therefore, the problems of calcification, defectiveness of re-endothelialization, and poor biocompatibility from the use of bioprosthetic heart valve need to be solved. In this study, hydrogel hybrid heart valves with improved anti-calcification and re-endothelialization were prepared by taking decellularized porcine heart valves as scaffolds following grafting with double bonds. Then, the anti-biofouling zwitterionic monomers 2-methacryloyloxyethyl phosphorylcholine (MPC) and vascular endothelial growth factor (VEGF) were utilized to obtain a hydrogel-coated hybrid heart valve (PEGDA-MPC-DHVs@VEGF). The results showed that fewer platelets and thrombi were observed on the surface of the PEGDA-MPC-DHVs@VEGF. Additionally, the PEGDA-MPC-DHVs@VEGF exhibited excellent collagen stability, biocompatibility and re-endothelialization potential. Moreover, less calcification deposition and a lower immune response were observed in the PEGDA-MPC-DHVs@VEGF compared to the glutaraldehyde-crosslinked DHVs (Glu-DHVs) after subcutaneous implantation in rats for 30 days. These studies demonstrated that the strategy of zwitterionic hydrogels loaded with VEGF may be an effective approach to improving the biocompatibility, anti-calcification and re-endothelialization of bioprosthetic heart valves.
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spelling doaj.art-22ea628231d544238243c44b565c42232022-12-22T02:34:40ZengElsevierMaterials Today Bio2590-00642022-12-0117100459Hybrid heart valves with VEGF-loaded zwitterionic hydrogel coating for improved anti-calcification and re-endothelializationQi Tong0Ao Sun1Zhengjie Wang2Tao Li3Xinye He4Yongjun Qian5Zhiyong Qian6Department of Cardiovascular Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR ChinaState Key Laboratory of Biotherapy, State Key Laboratory and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR ChinaDepartment of Cardiovascular Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR ChinaDepartment of Cardiovascular Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR ChinaState Key Laboratory of Biotherapy, State Key Laboratory and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR ChinaDepartment of Cardiovascular Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China; Corresponding author. Department of Cardiovascular Surgery, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China.State Key Laboratory of Biotherapy, State Key Laboratory and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR China; Corresponding author. State Key Laboratory of Biotherapy, State Key Laboratory and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, PR ChinaWith the aging of the population in worldwide, valvular heart disease has become one of the most prominent life-threatening diseases in human health, and heart valve replacement surgery is one of the therapeutic methods for valvular heart disease. Currently, commercial bioprosthetic heart valves (BHVs) for clinical application are prepared with xenograft heart valves or pericardium crosslinked by glutaraldehyde. Due to the residual cell toxicity from glutaraldehyde, heterologous antigens, and immune response, there are still some drawbacks related to the limited lifespan of bioprosthetic heart valves, such as thrombosis, calcification, degeneration, and defectiveness of re-endothelialization. Therefore, the problems of calcification, defectiveness of re-endothelialization, and poor biocompatibility from the use of bioprosthetic heart valve need to be solved. In this study, hydrogel hybrid heart valves with improved anti-calcification and re-endothelialization were prepared by taking decellularized porcine heart valves as scaffolds following grafting with double bonds. Then, the anti-biofouling zwitterionic monomers 2-methacryloyloxyethyl phosphorylcholine (MPC) and vascular endothelial growth factor (VEGF) were utilized to obtain a hydrogel-coated hybrid heart valve (PEGDA-MPC-DHVs@VEGF). The results showed that fewer platelets and thrombi were observed on the surface of the PEGDA-MPC-DHVs@VEGF. Additionally, the PEGDA-MPC-DHVs@VEGF exhibited excellent collagen stability, biocompatibility and re-endothelialization potential. Moreover, less calcification deposition and a lower immune response were observed in the PEGDA-MPC-DHVs@VEGF compared to the glutaraldehyde-crosslinked DHVs (Glu-DHVs) after subcutaneous implantation in rats for 30 days. These studies demonstrated that the strategy of zwitterionic hydrogels loaded with VEGF may be an effective approach to improving the biocompatibility, anti-calcification and re-endothelialization of bioprosthetic heart valves.http://www.sciencedirect.com/science/article/pii/S2590006422002575Zwitterionic hydrogelHybrid heart valveAnti-CalcificationRe-endothelializationBiocompatibility
spellingShingle Qi Tong
Ao Sun
Zhengjie Wang
Tao Li
Xinye He
Yongjun Qian
Zhiyong Qian
Hybrid heart valves with VEGF-loaded zwitterionic hydrogel coating for improved anti-calcification and re-endothelialization
Materials Today Bio
Zwitterionic hydrogel
Hybrid heart valve
Anti-Calcification
Re-endothelialization
Biocompatibility
title Hybrid heart valves with VEGF-loaded zwitterionic hydrogel coating for improved anti-calcification and re-endothelialization
title_full Hybrid heart valves with VEGF-loaded zwitterionic hydrogel coating for improved anti-calcification and re-endothelialization
title_fullStr Hybrid heart valves with VEGF-loaded zwitterionic hydrogel coating for improved anti-calcification and re-endothelialization
title_full_unstemmed Hybrid heart valves with VEGF-loaded zwitterionic hydrogel coating for improved anti-calcification and re-endothelialization
title_short Hybrid heart valves with VEGF-loaded zwitterionic hydrogel coating for improved anti-calcification and re-endothelialization
title_sort hybrid heart valves with vegf loaded zwitterionic hydrogel coating for improved anti calcification and re endothelialization
topic Zwitterionic hydrogel
Hybrid heart valve
Anti-Calcification
Re-endothelialization
Biocompatibility
url http://www.sciencedirect.com/science/article/pii/S2590006422002575
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