Vascular scaffolds with enhanced antioxidant activity inhibit graft calcification

Bin Jiang; Rachel Suen; Jiao Jing Wang; Zheng J. Zhang; Jason A. Wertheim; Guillermo A. Ameer

doi:10.1016/j.biomaterials.2017.08.014

Vascular scaffolds with enhanced antioxidant activity inhibit graft calcification

Bin Jiang, Rachel Suen, Jiao Jing Wang, Zheng J. Zhang, Jason A. Wertheim^*, Guillermo A. Ameer

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

Abstract

There is a need for off-the-shelf, small-diameter vascular grafts that are safe and exhibit high long-term patency. Decellularized tissues can potentially be used as vascular grafts; however, thrombogenic and unpredictable remodeling properties such as intimal hyperplasia and calcification are concerns that hinder their clinical use. The objective of this study was to investigate the long-term function and remodeling of extracellular matrix (ECM)-based vascular grafts composited with antioxidant poly(1, 8-octamethylene-citrate-co-cysteine) (POCC) with or without immobilized heparin. Rat aortas were decellularized to create the following vascular grafts: 1) ECM hybridized with POCC (Poly-ECM), 2) Poly-ECM subsequently functionalized with heparin (Poly-ECM-Hep), and 3) non-modified vascular ECM. Grafts were evaluated as interposition grafts in the abdominal aorta of adult rats at three months. All grafts displayed antioxidant activity, were patent, and exhibited minimal intramural cell infiltration with varying degrees of calcification. Areas of calcification co-localized with osteochondrogenic differentiation of vascular smooth muscle cells, lipid peroxidation, oxidized DNA damage, and cell apoptosis, suggesting an important role for oxidative stress in the calcification of grafts. The extent of calcification within grafts was inversely proportional to their antioxidant activity: Poly-ECM-Hep > ECM > Poly-ECM. The incorporation of antioxidants into vascular grafts may be a viable strategy to inhibit degenerative changes.

Original language	English (US)
Pages (from-to)	166-175
Number of pages	10
Journal	Biomaterials
Volume	144
DOIs	https://doi.org/10.1016/j.biomaterials.2017.08.014
State	Published - Nov 2017

Funding

Research reported in this publication was supported by the National Institute of Biomedical Imaging and Bioengineering and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers 5R01EB017129 to GA and K08DK101757 to JAW. This work is also supported by the McCormick Foundation via Northwestern Memorial Hospital, the Dixon Translational Research Grants Innovation Award from the Northwestern Memorial Foundation , American Heart Association (AHA) Midwest Affiliate Postdoctoral Fellowship ( 14POST20160091 ) to BJ, and the Chicago Biomedical Consortium (CBC ) Postdoctoral Award ( PDR-008 ) to BJ. The authors would also like to thank the Northwestern University Microsurgical Core (Chicago, IL) for performing animal surgeries, and Dr. Tracy Gluckman for training and technical assistance in ultrasound imaging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Appendix A

Keywords

Antioxidant
Calcification
Extracellular matrix
Oxidative stress
Vascular grafts

ASJC Scopus subject areas

Mechanics of Materials
Ceramics and Composites
Bioengineering
Biophysics
Biomaterials

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10.1016/j.biomaterials.2017.08.014

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@article{5753036773f54123ad57fa11e4a46265,

title = "Vascular scaffolds with enhanced antioxidant activity inhibit graft calcification",

abstract = "There is a need for off-the-shelf, small-diameter vascular grafts that are safe and exhibit high long-term patency. Decellularized tissues can potentially be used as vascular grafts; however, thrombogenic and unpredictable remodeling properties such as intimal hyperplasia and calcification are concerns that hinder their clinical use. The objective of this study was to investigate the long-term function and remodeling of extracellular matrix (ECM)-based vascular grafts composited with antioxidant poly(1, 8-octamethylene-citrate-co-cysteine) (POCC) with or without immobilized heparin. Rat aortas were decellularized to create the following vascular grafts: 1) ECM hybridized with POCC (Poly-ECM), 2) Poly-ECM subsequently functionalized with heparin (Poly-ECM-Hep), and 3) non-modified vascular ECM. Grafts were evaluated as interposition grafts in the abdominal aorta of adult rats at three months. All grafts displayed antioxidant activity, were patent, and exhibited minimal intramural cell infiltration with varying degrees of calcification. Areas of calcification co-localized with osteochondrogenic differentiation of vascular smooth muscle cells, lipid peroxidation, oxidized DNA damage, and cell apoptosis, suggesting an important role for oxidative stress in the calcification of grafts. The extent of calcification within grafts was inversely proportional to their antioxidant activity: Poly-ECM-Hep > ECM > Poly-ECM. The incorporation of antioxidants into vascular grafts may be a viable strategy to inhibit degenerative changes.",

keywords = "Antioxidant, Calcification, Extracellular matrix, Oxidative stress, Vascular grafts",

author = "Bin Jiang and Rachel Suen and Wang, {Jiao Jing} and Zhang, {Zheng J.} and Wertheim, {Jason A.} and Ameer, {Guillermo A.}",

note = "Funding Information: Research reported in this publication was supported by the National Institute of Biomedical Imaging and Bioengineering and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers 5R01EB017129 to GA and K08DK101757 to JAW. This work is also supported by the McCormick Foundation via Northwestern Memorial Hospital, the Dixon Translational Research Grants Innovation Award from the Northwestern Memorial Foundation , American Heart Association (AHA) Midwest Affiliate Postdoctoral Fellowship ( 14POST20160091 ) to BJ, and the Chicago Biomedical Consortium (CBC ) Postdoctoral Award ( PDR-008 ) to BJ. The authors would also like to thank the Northwestern University Microsurgical Core (Chicago, IL) for performing animal surgeries, and Dr. Tracy Gluckman for training and technical assistance in ultrasound imaging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Appendix A Publisher Copyright: {\textcopyright} 2017",

year = "2017",

month = nov,

doi = "10.1016/j.biomaterials.2017.08.014",

language = "English (US)",

volume = "144",

pages = "166--175",

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AU - Jiang, Bin

AU - Suen, Rachel

AU - Wang, Jiao Jing

AU - Zhang, Zheng J.

AU - Wertheim, Jason A.

AU - Ameer, Guillermo A.

N1 - Funding Information: Research reported in this publication was supported by the National Institute of Biomedical Imaging and Bioengineering and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers 5R01EB017129 to GA and K08DK101757 to JAW. This work is also supported by the McCormick Foundation via Northwestern Memorial Hospital, the Dixon Translational Research Grants Innovation Award from the Northwestern Memorial Foundation , American Heart Association (AHA) Midwest Affiliate Postdoctoral Fellowship ( 14POST20160091 ) to BJ, and the Chicago Biomedical Consortium (CBC ) Postdoctoral Award ( PDR-008 ) to BJ. The authors would also like to thank the Northwestern University Microsurgical Core (Chicago, IL) for performing animal surgeries, and Dr. Tracy Gluckman for training and technical assistance in ultrasound imaging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Appendix A Publisher Copyright: © 2017

PY - 2017/11

Y1 - 2017/11

N2 - There is a need for off-the-shelf, small-diameter vascular grafts that are safe and exhibit high long-term patency. Decellularized tissues can potentially be used as vascular grafts; however, thrombogenic and unpredictable remodeling properties such as intimal hyperplasia and calcification are concerns that hinder their clinical use. The objective of this study was to investigate the long-term function and remodeling of extracellular matrix (ECM)-based vascular grafts composited with antioxidant poly(1, 8-octamethylene-citrate-co-cysteine) (POCC) with or without immobilized heparin. Rat aortas were decellularized to create the following vascular grafts: 1) ECM hybridized with POCC (Poly-ECM), 2) Poly-ECM subsequently functionalized with heparin (Poly-ECM-Hep), and 3) non-modified vascular ECM. Grafts were evaluated as interposition grafts in the abdominal aorta of adult rats at three months. All grafts displayed antioxidant activity, were patent, and exhibited minimal intramural cell infiltration with varying degrees of calcification. Areas of calcification co-localized with osteochondrogenic differentiation of vascular smooth muscle cells, lipid peroxidation, oxidized DNA damage, and cell apoptosis, suggesting an important role for oxidative stress in the calcification of grafts. The extent of calcification within grafts was inversely proportional to their antioxidant activity: Poly-ECM-Hep > ECM > Poly-ECM. The incorporation of antioxidants into vascular grafts may be a viable strategy to inhibit degenerative changes.

AB - There is a need for off-the-shelf, small-diameter vascular grafts that are safe and exhibit high long-term patency. Decellularized tissues can potentially be used as vascular grafts; however, thrombogenic and unpredictable remodeling properties such as intimal hyperplasia and calcification are concerns that hinder their clinical use. The objective of this study was to investigate the long-term function and remodeling of extracellular matrix (ECM)-based vascular grafts composited with antioxidant poly(1, 8-octamethylene-citrate-co-cysteine) (POCC) with or without immobilized heparin. Rat aortas were decellularized to create the following vascular grafts: 1) ECM hybridized with POCC (Poly-ECM), 2) Poly-ECM subsequently functionalized with heparin (Poly-ECM-Hep), and 3) non-modified vascular ECM. Grafts were evaluated as interposition grafts in the abdominal aorta of adult rats at three months. All grafts displayed antioxidant activity, were patent, and exhibited minimal intramural cell infiltration with varying degrees of calcification. Areas of calcification co-localized with osteochondrogenic differentiation of vascular smooth muscle cells, lipid peroxidation, oxidized DNA damage, and cell apoptosis, suggesting an important role for oxidative stress in the calcification of grafts. The extent of calcification within grafts was inversely proportional to their antioxidant activity: Poly-ECM-Hep > ECM > Poly-ECM. The incorporation of antioxidants into vascular grafts may be a viable strategy to inhibit degenerative changes.

KW - Antioxidant

KW - Calcification

KW - Extracellular matrix

KW - Oxidative stress

KW - Vascular grafts

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JF - Biomaterials

ER -

Vascular scaffolds with enhanced antioxidant activity inhibit graft calcification

Abstract

Funding

Keywords

ASJC Scopus subject areas

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