Hybrid small-diameter vascular grafts: Anti-expansion effect of electrospun poly ε-caprolactone on heparin-coated decellularized matrices

Gong, Wei; Lei, Dong; Li, Sen; Huang, Peng; Qi, Quan; Sun, Yu; Zhang, Yijie; Wang, Zhe; You, Zhengwei; Ye, Xiaofeng; Zhao, Qiang

doi:10.1016/j.biomaterials.2015.10.066

Cited by 143 publications

(99 citation statements)

References 41 publications

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“…Especially, PCL has demonstrated to be suitable for the design of implantable material in vascular tissue engineering because their appropriate biodegradability (> 1 year) proved to minimize infection risk/inflammatory response, and promoted favorable endothelialization for blood vessel reconstruction. [34, 35]. …”

Section: Resultsmentioning

confidence: 99%

Heparin-functionalized polymer graft surface eluting MK2 inhibitory peptide to improve hemocompatibility and anti-neointimal activity

Lee

Thi

Seon

et al. 2017

Journal of Controlled Release

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The leading cause of synthetic graft failure includes thrombotic occlusion and intimal hyperplasia at the site of vascular anastomosis. Herein, we report a co- immobilization strategy of heparin and potent anti-neointimal drug (Mitogen Activated Protein Kinase II inhibitory peptide; MK2i) by using a tyrosinase-catalyzed oxidative reaction for preventing thrombotic occlusion and neointimal formation of synthetic vascular grafts. The binding of heparin–tyramine polymer (HT) onto the polycarprolactone (PCL) surface enhanced blood compatibility with significantly reduced protein absorption (64.7% decrease) and platelet adhesion (82.2% decrease) compared to bare PCL surface. When loading MK2i, 1) the HT depot surface gained high MK2i- loading efficiency through charge-charge interaction, and 2) this depot platform enabled long-term, controlled release over 4 weeks (92–272 μg/mL of MK2i). The released MK2i showed significant inhibitory effects on VSMC migration through down-regulated phosphorylation of target proteins (HSP27 and CREB) associated with intimal hyperplasia. In addition, it was found that the released MK2i infiltrated into the tissue with a cumulative manner in ex vivo human saphenous vein (HSV) model. This present study demonstrates that enzymatically HT-coated surface modification is an effective strategy to induce long-term MK2i release as well as hemocompatibility, thereby improving anti- neointimal activity of synthetic vascular grafts.

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Section: Resultsmentioning

confidence: 99%

Heparin-functionalized polymer graft surface eluting MK2 inhibitory peptide to improve hemocompatibility and anti-neointimal activity

Lee

Thi

Seon

et al. 2017

Journal of Controlled Release

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“…[63, 64] Strategies to stabilize ECM-based vascular grafts to prevent dilation include chemical crosslinking using carbodiimide chemistry to reduce ECM degradation[63] and perivascular polymer coating with electrospun PCL to prevent expansion. [65] However, stabilization of the ECM scaffold with either chemical crosslinking or polymer coating could also lead to increased stiffness and compliance mismatch between native arteries and vascular grafts and result in a severe inflammatory response and increased neointimal hyperplasia. [9] Therefore, balancing matrix degradation and minimizing new tissue formation remains an important challenge in vascular tissue engineering to minimize graft failure in the clinical setting.…”

Section: Discussionmentioning

confidence: 99%

Vascular scaffolds with enhanced antioxidant activity inhibit graft calcification

et al. 2017

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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-octamethylenecitrate-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.

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“…In the current work, mechanical tests revealed that uncoated decellularized arteries ruptured at a lower pressure than native arteries, as previously reported 43 and coating with the 8g7 polymer enhanced the mechanical properties of the decellularized vessels. Combination of decellularized vessels with polymers such as poly ε-caprolactone (PCL) 44 and poly(D,L-lactide) (PDLLA) 45 has been reported to improve the biomechanical properties of the graft. Due to their diverse mechanical properties, a wide range of biocompatible polyacrylates has found varied applications in biomedicine ranging from poly(methyl methacrylate) (PMMA) used in artificial teeth and bone cements to polyhydroxyethyl methacrylate used in soft contact lenses, drug delivery systems and dressings 46–50 .…”

Section: Discussionmentioning

confidence: 99%

“…fabricated a hybrid tissue engineered vascular graft by the application of an electrospun nano-polycaprolactone coating on the outside of a decellularized rat aorta, which improved the biomechanics of the decellularized vessel. However, they also needed to incorporate exogenous heparin to modify the acellular vascular intimal surfaces 44 . In another study, the anticoagulant lepirudin was added to a Poly-(D,L-lactide) coating applied in decellularized arteries.…”

Section: Discussionmentioning

confidence: 99%

Poly(ethylmethacrylate-co-diethylaminoethyl acrylate) coating improves endothelial re-population, bio-mechanical and anti-thrombogenic properties of decellularized carotid arteries for blood vessel replacement

López‐Ruiz

Venkateswaran

Perán

et al. 2017

Sci Rep

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Decellularized vascular scaffolds are promising materials for vessel replacements. However, despite the natural origin of decellularized vessels, issues such as biomechanical incompatibility, immunogenicity risks and the hazards of thrombus formation, still need to be addressed. In this study, we coated decellularized vessels obtained from porcine carotid arteries with poly (ethylmethacrylate-co-diethylaminoethylacrylate) (8g7) with the purpose of improving endothelial coverage and minimizing platelet attachment while enhancing the mechanical properties of the decellularized vascular scaffolds. The polymer facilitated binding of endothelial cells (ECs) with high affinity and also induced endothelial cell capillary tube formation. In addition, platelets showed reduced adhesion on the polymer under flow conditions. Moreover, the coating of the decellularized arteries improved biomechanical properties by increasing its tensile strength and load. In addition, after 5 days in culture, ECs seeded on the luminal surface of 8g7-coated decellularized arteries showed good regeneration of the endothelium. Overall, this study shows that polymer coating of decellularized vessels provides a new strategy to improve re-endothelialization of vascular grafts, maintaining or enhancing mechanical properties while reducing the risk of thrombogenesis. These results could have potential applications in improving tissue-engineered vascular grafts for cardiovascular therapies with small caliber vessels.

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Hybrid small-diameter vascular grafts: Anti-expansion effect of electrospun poly ε-caprolactone on heparin-coated decellularized matrices

Cited by 143 publications

References 41 publications

Heparin-functionalized polymer graft surface eluting MK2 inhibitory peptide to improve hemocompatibility and anti-neointimal activity

Heparin-functionalized polymer graft surface eluting MK2 inhibitory peptide to improve hemocompatibility and anti-neointimal activity

Vascular scaffolds with enhanced antioxidant activity inhibit graft calcification

Poly(ethylmethacrylate-co-diethylaminoethyl acrylate) coating improves endothelial re-population, bio-mechanical and anti-thrombogenic properties of decellularized carotid arteries for blood vessel replacement

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