Long-term in vivo study of biodegradable Zn-Cu stent: A 2-year implantation evaluation in porcine coronary artery

Chao Zhou, Hua-Fang Li, Yu-Xia Yin, Zhang-Zhi Shi, Ting Li, Xiang-Yi Feng, Jun-Wei Zhang, Cai-Xia Song, Xiao-Shan Cui, Kai-Li Xu, Yan-Wei Zhao, Wen-Bo Hou, Shou-Tao Lu, Guang Liu, Mao-Quan Li, Jian-Ying Ma, Egon Toft, Alex A Volinsky, Min Wan, Xiu-Jun YaoChang-Bin Wang, Kang Yao, Shi-Kun Xu, Hao Lu, Shu-Fu Chang, Jun-Bo Ge, Lu-Ning Wang, Hai-Jun Zhang

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24 months. Micro-CT analysis showed that the implanted stent was able to maintain structural integrity after 6 months, while its disintegration occurred after 9 months of implantation. After 24 months of implantation, approximately 28 ± 13 vol% of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24 months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24 months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications. Statement of Significance: Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research.

Original languageEnglish
JournalActa Biomaterialia
Volume97
Pages (from-to)657-670
ISSN1742-7061
DOIs
Publication statusPublished - Oct 2019

Fingerprint

Stents
varespladib methyl
Coronary Vessels
Swine
Thrombosis
Translational Medical Research
Inflammation
Degradation
Blood Vessels
Equipment and Supplies
Disintegration
Struts
Optical tomography
Optical Coherence Tomography
Structural integrity
Cardiovascular System
Ion implantation
Medicine
Zinc
Animals

Bibliographical note

Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Keywords

  • Biodegradation performance
  • Coronary artery stent
  • In vivo evaluation
  • Medical device performance
  • Zn-based biodegradable stent

Cite this

Zhou, Chao ; Li, Hua-Fang ; Yin, Yu-Xia ; Shi, Zhang-Zhi ; Li, Ting ; Feng, Xiang-Yi ; Zhang, Jun-Wei ; Song, Cai-Xia ; Cui, Xiao-Shan ; Xu, Kai-Li ; Zhao, Yan-Wei ; Hou, Wen-Bo ; Lu, Shou-Tao ; Liu, Guang ; Li, Mao-Quan ; Ma, Jian-Ying ; Toft, Egon ; Volinsky, Alex A ; Wan, Min ; Yao, Xiu-Jun ; Wang, Chang-Bin ; Yao, Kang ; Xu, Shi-Kun ; Lu, Hao ; Chang, Shu-Fu ; Ge, Jun-Bo ; Wang, Lu-Ning ; Zhang, Hai-Jun. / Long-term in vivo study of biodegradable Zn-Cu stent : A 2-year implantation evaluation in porcine coronary artery. In: Acta Biomaterialia. 2019 ; Vol. 97. pp. 657-670.
@article{dc58a38593b747c2901a350013ac6359,
title = "Long-term in vivo study of biodegradable Zn-Cu stent: A 2-year implantation evaluation in porcine coronary artery",
abstract = "In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24 months. Micro-CT analysis showed that the implanted stent was able to maintain structural integrity after 6 months, while its disintegration occurred after 9 months of implantation. After 24 months of implantation, approximately 28 ± 13 vol{\%} of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24 months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24 months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications. Statement of Significance: Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research.",
keywords = "Biodegradation performance, Coronary artery stent, In vivo evaluation, Medical device performance, Zn-based biodegradable stent",
author = "Chao Zhou and Hua-Fang Li and Yu-Xia Yin and Zhang-Zhi Shi and Ting Li and Xiang-Yi Feng and Jun-Wei Zhang and Cai-Xia Song and Xiao-Shan Cui and Kai-Li Xu and Yan-Wei Zhao and Wen-Bo Hou and Shou-Tao Lu and Guang Liu and Mao-Quan Li and Jian-Ying Ma and Egon Toft and Volinsky, {Alex A} and Min Wan and Xiu-Jun Yao and Chang-Bin Wang and Kang Yao and Shi-Kun Xu and Hao Lu and Shu-Fu Chang and Jun-Bo Ge and Lu-Ning Wang and Hai-Jun Zhang",
note = "Copyright {\circledC} 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.",
year = "2019",
month = "10",
doi = "10.1016/j.actbio.2019.08.012",
language = "English",
volume = "97",
pages = "657--670",
journal = "Acta Biomaterialia",
issn = "1742-7061",
publisher = "Elsevier",

}

Zhou, C, Li, H-F, Yin, Y-X, Shi, Z-Z, Li, T, Feng, X-Y, Zhang, J-W, Song, C-X, Cui, X-S, Xu, K-L, Zhao, Y-W, Hou, W-B, Lu, S-T, Liu, G, Li, M-Q, Ma, J-Y, Toft, E, Volinsky, AA, Wan, M, Yao, X-J, Wang, C-B, Yao, K, Xu, S-K, Lu, H, Chang, S-F, Ge, J-B, Wang, L-N & Zhang, H-J 2019, 'Long-term in vivo study of biodegradable Zn-Cu stent: A 2-year implantation evaluation in porcine coronary artery', Acta Biomaterialia, vol. 97, pp. 657-670. https://doi.org/10.1016/j.actbio.2019.08.012

Long-term in vivo study of biodegradable Zn-Cu stent : A 2-year implantation evaluation in porcine coronary artery. / Zhou, Chao; Li, Hua-Fang; Yin, Yu-Xia; Shi, Zhang-Zhi; Li, Ting; Feng, Xiang-Yi; Zhang, Jun-Wei; Song, Cai-Xia; Cui, Xiao-Shan; Xu, Kai-Li; Zhao, Yan-Wei; Hou, Wen-Bo; Lu, Shou-Tao; Liu, Guang; Li, Mao-Quan; Ma, Jian-Ying; Toft, Egon; Volinsky, Alex A; Wan, Min; Yao, Xiu-Jun; Wang, Chang-Bin; Yao, Kang; Xu, Shi-Kun; Lu, Hao; Chang, Shu-Fu; Ge, Jun-Bo; Wang, Lu-Ning; Zhang, Hai-Jun.

In: Acta Biomaterialia, Vol. 97, 10.2019, p. 657-670.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Long-term in vivo study of biodegradable Zn-Cu stent

T2 - A 2-year implantation evaluation in porcine coronary artery

AU - Zhou, Chao

AU - Li, Hua-Fang

AU - Yin, Yu-Xia

AU - Shi, Zhang-Zhi

AU - Li, Ting

AU - Feng, Xiang-Yi

AU - Zhang, Jun-Wei

AU - Song, Cai-Xia

AU - Cui, Xiao-Shan

AU - Xu, Kai-Li

AU - Zhao, Yan-Wei

AU - Hou, Wen-Bo

AU - Lu, Shou-Tao

AU - Liu, Guang

AU - Li, Mao-Quan

AU - Ma, Jian-Ying

AU - Toft, Egon

AU - Volinsky, Alex A

AU - Wan, Min

AU - Yao, Xiu-Jun

AU - Wang, Chang-Bin

AU - Yao, Kang

AU - Xu, Shi-Kun

AU - Lu, Hao

AU - Chang, Shu-Fu

AU - Ge, Jun-Bo

AU - Wang, Lu-Ning

AU - Zhang, Hai-Jun

N1 - Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

PY - 2019/10

Y1 - 2019/10

N2 - In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24 months. Micro-CT analysis showed that the implanted stent was able to maintain structural integrity after 6 months, while its disintegration occurred after 9 months of implantation. After 24 months of implantation, approximately 28 ± 13 vol% of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24 months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24 months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications. Statement of Significance: Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research.

AB - In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24 months. Micro-CT analysis showed that the implanted stent was able to maintain structural integrity after 6 months, while its disintegration occurred after 9 months of implantation. After 24 months of implantation, approximately 28 ± 13 vol% of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24 months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24 months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications. Statement of Significance: Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research.

KW - Biodegradation performance

KW - Coronary artery stent

KW - In vivo evaluation

KW - Medical device performance

KW - Zn-based biodegradable stent

UR - http://www.scopus.com/inward/record.url?scp=85071398531&partnerID=8YFLogxK

U2 - 10.1016/j.actbio.2019.08.012

DO - 10.1016/j.actbio.2019.08.012

M3 - Journal article

VL - 97

SP - 657

EP - 670

JO - Acta Biomaterialia

JF - Acta Biomaterialia

SN - 1742-7061

ER -