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Dexter DJ, O'Neill F, Neville RF. Systematic literature review comparing clinical utility of heparin-bonded expanded polytetrafluoroethylene graft with autologous saphenous vein graft for the management of below-the-knee peripheral arterial disease. J Vasc Surg 2024; 80:1863-1870.e6. [PMID: 39025282 DOI: 10.1016/j.jvs.2024.07.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 06/19/2024] [Accepted: 07/10/2024] [Indexed: 07/20/2024]
Abstract
BACKGROUND This systematic literature review compares the clinical outcomes of heparin-bonded expanded polytetrafluoroethylene with autologous saphenous vein in the management of patients undergoing below-the-knee bypass to treat peripheral arterial disease. METHODS An electronic literature search was conducted in MEDLINE and Embase to identify comparative studies in patients who underwent below-the-knee surgical bypass. Studies were screened at abstract and full text review using predefined inclusion criteria by two independent reviewers and critically appraised for risk of bias. Meta-analyses were conducted using Review Manager 5 software (Nordic Cochrane Centre). RESULTS Eight retrospective cohort studies were identified. Meta-analysis of primary patency demonstrated no significant difference between heparin-bonded expanded polytetrafluoroethylene and autologous saphenous vein grafts after 1 (odds ratio: 0.91, 95% confidence interval: [0.52-1.59]; P = .74), 2 (1.12 [0.60-2.10]; P = .77), 3 (0.62 [0.26-1.48]; P = .28), and 4 years (0.70 [0.36-1.39]; P = .31). Similarly, for secondary patency, no significant difference was detected at 1 (0.62 [0.33-1.15]; P = .13), 2 (0.83 [0.32-2.13]; P = .69), 3 (0.60 [0.27-1.32]; P = .20), and 4 years (0.66 [0.32-1.36]; P = .26). There was no significant difference between autologous veins and heparin-bonded expanded polytetrafluoroethylene for limb salvage and mortality at all time points. A sensitivity analysis to compare outflow vessels was conducted in only tibial bypass and identified no differences. All analyses were considered at high-risk bias because of heterogeneity in study populations and attrition in follow-up. CONCLUSIONS This meta-analysis demonstrates similar outcomes between autologous saphenous vein and heparin-bonded expanded polytetrafluoroethylene for patency, limb salvage, and mortality through 4 years. The use of heparin-bonded expanded polytetrafluoroethylene synthetic grafts is a satisfactory option to prevent amputation, particularly when autologous saphenous vein grafts are not available. Controlled clinical studies are needed to further inform future decision-making and economic modeling related to the choice of conduit for below-the-knee graft construction.
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Affiliation(s)
- David J Dexter
- Division of Vascular Surgery, Eastern Virginia Medical School, Norfolk, VA.
| | - Frank O'Neill
- Health Economics, W.L. Gore & Associates, Inc., Flagstaff, AZ
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Chen C, Ai Q, Tian H, Wei Y. CKLF1 in cardiovascular and cerebrovascular diseases. Int Immunopharmacol 2024; 139:112718. [PMID: 39032474 DOI: 10.1016/j.intimp.2024.112718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 07/14/2024] [Accepted: 07/15/2024] [Indexed: 07/23/2024]
Abstract
Chemokine like factor 1 (CKLF1) is a novel atypical chemokine, playing a crucial role in cardiovascular and cerebrovascular diseases (CCVDs) demonstrated by a growing body of works. In cardiovascular diseases including atherosclerosis and myocardial infarction, meanwhile in cerebrovascular diseases such as ischemic stroke and hemorrhagic stroke, the expression levels of CKLF1 change markedly, which triggers downstream signaling pathways by binding with its functional receptors, and then exerts multiple effects to participate in the occurrence and development of these CCVDs. The functional roles of CKLF1 are dynamic and CKLF1 may act as a double-edged sword. The CCVDs-promoting role is related to recruiting inflammatory cells, enhancing the proliferation of vascular smooth muscle cells and endothelial cells, while the CCVDs-suppressing role may correlate with migration of nerve cells and promotion of hematopoietic stem cell proliferation which contributes to disease recovery. Based on this, the paper intends to review expression shifts, potential roles, and molecular mechanisms of CKLF1 in CCVDs, and the current status of CKLF1 targeted therapeutic strategies is also included. We hope this review may provide a valuable reference for using CKLF1 as a diagnostic and prognostic biomarker for CCVDs or developing novel treatments.
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Affiliation(s)
- Chen Chen
- Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China.
| | - Qidi Ai
- Hunan University of Traditional Chinese Medicine, Changsha 410208, China
| | - Haiyan Tian
- Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China
| | - Yuhui Wei
- Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou 730000, China
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Das A, Nikhil A, Kumar A. Antioxidant and Trilayered Electrospun Small-Diameter Vascular Grafts Maintain Patency and Promote Endothelialisation in Rat Femoral Artery. ACS Biomater Sci Eng 2024; 10:1697-1711. [PMID: 38320085 DOI: 10.1021/acsbiomaterials.4c00006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2024]
Abstract
Vascular grafts with a small diameter encounter inadequate patency as a result of intimal hyperplasia development. In the current study, trilayered electrospun small-diameter vascular grafts (PU-PGACL + GA) were fabricated using a poly(glycolic acid) and poly(caprolactone) blend as the middle layer and antioxidant polyurethane with gallic acid as the innermost and outermost layers. The scaffolds exhibited good biocompatibility and mechanical properties, as evidenced by their 6 MPa elastic modulus, 4 N suture retention strength, and 2500 mmHg burst pressure. Additionally, these electrospun grafts attenuated cellular oxidative stress and demonstrated minimal hemolysis (less than 1%). As a proof-of-concept, the preclinical evaluation of the grafts was carried out in the femoral artery of rodents, where the conduits demonstrated satisfactory patency. After 35 days of implantation, ultrasound imaging depicted adequate blood flow through the grafts, and the computed vessel diameter and histological staining showed no significant stenosis issue. Immunohistochemical analysis confirmed matrix deposition (38% collagen I and 16% elastin) and cell infiltration (42% for endothelial cells and 55% for smooth muscle cells) in the explanted grafts. Therefore, PU-PGACL + GA showed characteristics of a clinically relevant small-diameter vascular graft, facilitating re-endothelialization while preserving the anticoagulant properties of the synthetic blood vessels.
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Affiliation(s)
- Ankita Das
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur 208016, U.P., India
| | - Aman Nikhil
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur 208016, U.P., India
| | - Ashok Kumar
- Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur 208016, U.P., India
- Centre for Environmental Science and Engineering, Indian Institute of Technology Kanpur, Kanpur 208016, U.P., India
- The Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur, Kanpur 208016, U.P., India
- Centre of Excellence in Orthopaedics and Prosthetics, Gangwal School of Medical Sciences and Technology, Indian Institute of Technology Kanpur, Kanpur 208016, U.P., India
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Mota L, Zhu M, Li J, Contreras M, Aridi T, Tomeo JN, Stafford A, Mooney DJ, Pradhan-Nabzdyk L, Ferran C, LoGerfo FW, Liang P. Perivascular CLICK-gelatin delivery of thrombospondin-2 small interfering RNA decreases development of intimal hyperplasia after arterial injury. FASEB J 2024; 38:e23321. [PMID: 38031974 PMCID: PMC10726962 DOI: 10.1096/fj.202301359r] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 10/25/2023] [Accepted: 11/05/2023] [Indexed: 12/01/2023]
Abstract
Bypass graft failure occurs in 20%-50% of coronary and lower extremity bypasses within the first-year due to intimal hyperplasia (IH). TSP-2 is a key regulatory protein that has been implicated in the development of IH following vessel injury. In this study, we developed a biodegradable CLICK-chemistry gelatin-based hydrogel to achieve sustained perivascular delivery of TSP-2 siRNA to rat carotid arteries following endothelial denudation injury. At 21 days, perivascular application of TSP-2 siRNA embedded hydrogels significantly downregulated TSP-2 gene expression, cellular proliferation, as well as other associated mediators of IH including MMP-9 and VEGF-R2, ultimately resulting in a significant decrease in IH. Our data illustrates the ability of perivascular CLICK-gelatin delivery of TSP-2 siRNA to mitigate IH following arterial injury.
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Affiliation(s)
- Lucas Mota
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston MA
| | - Max Zhu
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston MA
| | - Jennifer Li
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston MA
| | - Mauricio Contreras
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston MA
| | - Tarek Aridi
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston MA
| | - John N. Tomeo
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston MA
| | - Alexander Stafford
- John A. Paulson School of Engineering and Applied Science, Harvard University, Cambridge, MA
| | - David J. Mooney
- John A. Paulson School of Engineering and Applied Science, Harvard University, Cambridge, MA
| | - Leena Pradhan-Nabzdyk
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston MA
| | - Christiane Ferran
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston MA
- The Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston MA
- Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston MA
| | - Frank W. LoGerfo
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston MA
| | - Patric Liang
- Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston MA
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West-Livingston L, Lim JW, Lee SJ. Translational tissue-engineered vascular grafts: From bench to bedside. Biomaterials 2023; 302:122322. [PMID: 37713761 DOI: 10.1016/j.biomaterials.2023.122322] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 09/01/2023] [Accepted: 09/09/2023] [Indexed: 09/17/2023]
Abstract
Cardiovascular disease is a primary cause of mortality worldwide, and patients often require bypass surgery that utilizes autologous vessels as conduits. However, the limited availability of suitable vessels and the risk of failure and complications have driven the need for alternative solutions. Tissue-engineered vascular grafts (TEVGs) offer a promising solution to these challenges. TEVGs are artificial vascular grafts made of biomaterials and/or vascular cells that can mimic the structure and function of natural blood vessels. The ideal TEVG should possess biocompatibility, biomechanical mechanical properties, and durability for long-term success in vivo. Achieving these characteristics requires a multi-disciplinary approach involving material science, engineering, biology, and clinical translation. Recent advancements in scaffold fabrication have led to the development of TEVGs with improved functional and biomechanical properties. Innovative techniques such as electrospinning, 3D bioprinting, and multi-part microfluidic channel systems have allowed the creation of intricate and customized tubular scaffolds. Nevertheless, multiple obstacles must be overcome to apply these innovations effectively in clinical practice, including the need for standardized preclinical models and cost-effective and scalable manufacturing methods. This review highlights the fundamental approaches required to successfully fabricate functional vascular grafts and the necessary translational methodologies to advance their use in clinical practice.
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Affiliation(s)
- Lauren West-Livingston
- Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA; Department of Vascular and Endovascular Surgery, Duke University, Durham, NC, 27712, USA
| | - Jae Woong Lim
- Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA; Department of Thoracic and Cardiovascular Surgery, Soonchunhyang University Hospital, Bucheon-Si, Gyeonggi-do, 420-767, Republic of Korea
| | - Sang Jin Lee
- Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
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Parikh KS, Josyula A, Inoue T, Fukunishi T, Zhang H, Omiadze R, Shi R, Yazdi Y, Hanes J, Ensign LM, Hibino N. Nanofiber-coated, tacrolimus-eluting sutures inhibit post-operative neointimal hyperplasia in rats. J Control Release 2023; 353:96-104. [PMID: 36375620 PMCID: PMC9892275 DOI: 10.1016/j.jconrel.2022.11.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 10/13/2022] [Accepted: 11/08/2022] [Indexed: 11/24/2022]
Abstract
Post-operative complications of vascular anastomosis procedures remain a significant clinical challenge and health burden globally. Each year, millions of anastomosis procedures connect arteries and/or veins in vascular bypass, vascular access, organ transplant, and reconstructive surgeries, generally via suturing. Dysfunction of these anastomoses, primarily due to neointimal hyperplasia and the resulting narrowing of the vessel lumen, results in failure rates of up to 50% and billions of dollars in costs to the healthcare system. Non-absorbable sutures are the gold standard for vessel anastomosis; however, damage from the surgical procedure and closure itself causes an inflammatory cascade that leads to neointimal hyperplasia at the anastomosis site. Here, we demonstrate the development of a novel, scalable manufacturing system for fabrication of high strength sutures with nanofiber-based coatings composed of generally regarded as safe (GRAS) polymers and either sirolimus, tacrolimus, everolimus, or pimecrolimus. These sutures provided sufficient tensile strength for maintenance of the vascular anastomosis and sustained drug delivery at the site of the anastomosis. Tacrolimus-eluting sutures provided a significant reduction in neointimal hyperplasia in rats over a period of 14 days with similar vessel endothelialization in comparison to conventional nylon sutures. In contrast, systemically delivered tacrolimus caused significant weight loss and mortality due to toxicity. Thus, drug-eluting sutures provide a promising platform to improve the outcomes of vascular interventions without modifying the clinical workflow and without the risks associated with systemic drug delivery.
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Affiliation(s)
- Kunal S Parikh
- Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Center for Bioengineering Innovation & Design, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Aditya Josyula
- Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Takahiro Inoue
- Department of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Takuma Fukunishi
- Department of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Huaitao Zhang
- Department of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Revaz Omiadze
- Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Richard Shi
- Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Youseph Yazdi
- Center for Bioengineering Innovation & Design, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Justin Hanes
- Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
| | - Laura M Ensign
- Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA; Department of Gynecology and Obstetrics and Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
| | - Narutoshi Hibino
- Department of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Cardiac Surgery, University of Chicago/Advocate Children's Hospital, Chicago, IL 60637, USA.
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Hong Q, Que D, Zhong C, Huang G, Zhai W, Chen D, Yan J, Yang P. Trimethylamine-N-oxide (TMAO) promotes balloon injury-induced neointimal hyperplasia via upregulating Beclin1 and impairing autophagic flux. Biomed Pharmacother 2022; 155:113639. [PMID: 36088853 DOI: 10.1016/j.biopha.2022.113639] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/25/2022] [Accepted: 08/30/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND AND AIMS TMAO is a microbiota-dependent metabolite associated with increased risk of various cardiovascular diseases. However, the relationship between TMAO and vascular injury-related neointimal hyperplasia is unclear. This study aimed to explore whether TMAO promotes neointimal hyperplasia after balloon injury and elucidate the underlying mechanism. METHODS AND RESULTS Through hematoxylin and eosin staining and immunohistochemistry staining, we found that supplementary TMAO promoted balloon injury-induced neointimal hyperplasia, while reducing TMAO by antibiotic administration produced the opposite result. TMAO showed limited effect on rat aortic vascular smooth muscle cells (RAOSMCs) proliferation and migration. However, TMAO notably induced dysfunction of rat aortic vascular endothelial cells (RAOECs) in vitro and attenuated reendothelialization of carotid arteries after balloon injury in vivo. Autophagic flux was measured by fluorescent mRFP-GFP-LC3, transmission electron microscopy, and western blot. TMAO impaired autophagic flux, as evidenced by the accumulation of p62 and LC3II and high autophagosome to autolysosome ratios. Furthermore, we confirmed that Beclin1 level increased in TMAO-treated RAOECs and carotid arteries. Knocking down Beclin1 alleviated TMAO-induced autophagic flux impairment and neointimal hyperplasia. CONCLUSIONS TMAO promoted neointimal hyperplasia through Beclin1-induced autophagic flux blockage, suggesting that TMAO is a potential target for improvement of vascular remodeling after injury.
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Affiliation(s)
- Qingqing Hong
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangzhou, Guangdong, China
| | - Dongdong Que
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangzhou, Guangdong, China
| | - Chongbin Zhong
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangzhou, Guangdong, China
| | - Guanlin Huang
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangzhou, Guangdong, China
| | - Weicheng Zhai
- Department of Cardiology, Huizhou Third People's Hospital, Guangzhou Medical University, Huizhou City, China
| | - Deshu Chen
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangzhou, Guangdong, China
| | - Jing Yan
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangzhou, Guangdong, China.
| | - Pingzhen Yang
- Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangzhou, Guangdong, China.
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Cuenca JP, Kang HJ, Fahad MAA, Park M, Choi M, Lee HY, Lee BT. Physico-mechanical and biological evaluation of heparin/VEGF-loaded electrospun polycaprolactone/decellularized rat aorta extracellular matrix for small-diameter vascular grafts. JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2022; 33:1664-1684. [PMID: 35446751 DOI: 10.1080/09205063.2022.2069398] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 04/19/2022] [Accepted: 04/20/2022] [Indexed: 06/14/2023]
Abstract
Although the continuous development of small-diameter vascular grafts (SDVGs) (D < 5 mm) continues, most vascular grafts are made from synthetic polymers, which lead to serious complications from arteriosclerosis, thrombosis, and vascular ischemia. Here, to address these shortcomings, we combine synthetic polymers with natural decellularized small-diameter vessels and loaded with growth factor. We fabricated vascular grafts by electrospinning polycaprolactone (PCL) to decellularized rat aorta matrix (ECM) followed by heparin and vascular endothelial growth factor (VEGF) loading. In- vitro studies showed that PCL/ECM/VEGF vascular grafts, showed excellent hemocompatibility and biocompatibility properties. The vascular grafts implanted into the rat aorta revealed that the PCL/ECM/VEGF grafts promotes endothelial cells and smooth-muscle cells infiltration with a rate of FLK-1, ICAM1, and a-SMA distribution higher than that of the PCL and PCL/ECM vascular grafts at 2 weeks and 4 weeks after implantation. The PCL/ECM/VEGF vascular graft should be considered for potential small-diameter vascular grafts in clinical fields.
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Affiliation(s)
- John Patrick Cuenca
- Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan, South Korea
| | - Hoe-Jin Kang
- Institute of Tissue Regeneration, Soonchunhyang University, Cheonan, South Korea
| | - Md Abdullah Al Fahad
- Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan, South Korea
| | - Myeongki Park
- Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan, South Korea
| | - Minji Choi
- Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan, South Korea
| | - Hyun-Yong Lee
- Department of Surgery, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
| | - Byong-Taek Lee
- Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan, South Korea
- Institute of Tissue Regeneration, Soonchunhyang University, Cheonan, South Korea
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Using Graphene-Based Materials for Stiff and Strong Poly(ethylene glycol) Hydrogels. Int J Mol Sci 2022; 23:ijms23042312. [PMID: 35216431 PMCID: PMC8880715 DOI: 10.3390/ijms23042312] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/04/2022] [Accepted: 02/10/2022] [Indexed: 11/17/2022] Open
Abstract
Blood-contacting devices are increasingly important for the management of cardiovascular diseases. Poly(ethylene glycol) (PEG) hydrogels represent one of the most explored hydrogels to date. However, they are mechanically weak, which prevents their use in load-bearing biomedical applications (e.g., vascular grafts, cardiac valves). Graphene and its derivatives, which have outstanding mechanical properties, a very high specific surface area, and good compatibility with many polymer matrices, are promising candidates to solve this challenge. In this work, we propose the use of graphene-based materials as nanofillers for mechanical reinforcement of PEG hydrogels, and we obtain composites that are stiffer and stronger than, and as anti-adhesive as, neat PEG hydrogels. Results show that single-layer and few-layer graphene oxide can strengthen PEG hydrogels, increasing their stiffness up to 6-fold and their strength 14-fold upon incorporation of 4% w/v (40 mg/mL) graphene oxide. The composites are cytocompatible and remain anti-adhesive towards endothelial cells, human platelets and Staphylococcus aureus, similar to neat hydrogels. To the best of our knowledge, this is the first work to report such an increase of the tensile properties of PEG hydrogels using graphene-based materials as fillers. This work paves the way for the exploitation of PEG hydrogels as a backbone material for load-bearing applications.
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Abstract
Pediatric hemodialysis access is a demanding field. Procedures are infrequent, technically challenging, and associated with high complication and failure rates. Each procedure affects subsequent access and transplants sites. The choice is made easier and outcomes improved when access decisions are made by a multidisciplinary, pediatric, hemodialysis access team. This manuscript reviews the current literature and offers technical suggestions to improve outcomes.
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11
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Lampridis S, George SJ. Nonautologous Grafts in Coronary Artery Bypass Surgery: A Systematic Review. Ann Thorac Surg 2021; 112:2094-2103. [PMID: 33340520 DOI: 10.1016/j.athoracsur.2020.11.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 10/17/2020] [Accepted: 11/02/2020] [Indexed: 10/22/2022]
Abstract
BACKGROUND Suitable autologous conduits may be lacking when performing coronary artery bypass grafting. The aim of this review is to determine the status of nonautologous grafts in coronary artery bypass grafting. METHODS We conducted a literature search on MEDLINE All, Embase Classic, and Embase through Ovid from 1960 to April 2020. RESULTS Of the 1579 records identified, 21 studies were included in the review. The following grafts were assessed for patency: 109 homologous saphenous veins (patency rates ranged from 66.7% at a median follow-up of 8.5 months to 0% at 6-12 months and 7-18 months, respectively), 29 expanded polytetrafluoroethylene grafts (from 80% at a median follow-up of 5 months to 14.3% at 45 months), 12 human umbilical veins (50% at a median follow-up of 6 months), 50 Bioflow bovine internal mammary arteries (from 15.8% to 0% at a mean follow-up of 9.5 months and 19 months, respectively), 39 Perma-Flow grafts (80% and 76.9% at 1-3 months and 12 months, respectively), 20 No-React bovine internal mammary arteries (57.1% at a median follow-up of 28 months and 23.1% at a mean follow-up of 7 months), 40 autologous venous endothelial cell-seeded expanded polytetrafluoroethylene grafts (94.7% and 81% at a mean follow-up of 27 months and 60 months, respectively), and 12 autologous venous endothelial cell-seeded cryopreserved homologous veins (83.3% at a mean follow-up of 8.5 months). CONCLUSIONS The goal of an alternative conduit with patency and attributes that match those of autografts remains elusive. Autologous endothelial cell-seeded synthetic grafts have demonstrated promising results but require further investigation.
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Affiliation(s)
- Savvas Lampridis
- Bristol Medical School, University of Bristol, Bristol, United Kingdom.
| | - Sarah J George
- Bristol Medical School, University of Bristol, Bristol, United Kingdom
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12
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Yu L, Newton ER, Gillis DC, Sun K, Cooley BC, Keith AN, Sheiko SS, Tsihlis ND, Kibbe MR. Coating small-diameter ePTFE vascular grafts with tunable poly(diol-co-citrate-co-ascorbate) elastomers to reduce neointimal hyperplasia. Biomater Sci 2021; 9:5160-5174. [PMID: 34312627 PMCID: PMC12036540 DOI: 10.1039/d1bm00101a] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Lack of long-term patency has hindered the clinical use of small-diameter prosthetic vascular grafts with the majority of these failures due to the development of neointimal hyperplasia. Previous studies by our laboratory revealed that small-diameter expanded polytetrafluoroethylene (ePTFE) grafts coated with antioxidant elastomers are a promising localized therapy to inhibit neointimal hyperplasia. This work is focused on the development of poly(diol-co-citrate-co-ascorbate) (POCA) elastomers with tunable properties for coating ePTFE vascular grafts. A bioactive POCA elastomer (@20 : 20 : 8, [citrate] : [diol] : [ascorbate]) coating was applied on a 1.5 mm diameter ePTFE vascular graft as the most promising therapeutic candidate for reducing neointimal hyperplasia. Surface ascorbate density on the POCA elastomer was increased to 67.5 ± 7.3 ng mg-1 cm-2. The mechanical, antioxidant, biodegradable, and biocompatible properties of POCA demonstrated desirable performance for in vivo use, inhibiting human aortic smooth muscle cell proliferation, while supporting human aortic endothelial cells. POCA elastomer coating number was adjusted by a modified spin-coating method to prepare small-diameter ePTFE vascular grafts similar to natural vessels. A significant reduction in neointimal hyperplasia was observed after implanting POCA-coated ePTFE vascular grafts in a guinea pig aortic interposition bypass graft model. POCA elastomer thus offers a new avenue that shows promise for use in vascular engineering to improve long-term patency rates by coating small-diameter ePTFE vascular grafts.
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Affiliation(s)
- Lu Yu
- Department of Surgery, University of North Carolina at Chapel Hill, 4001 Burnett-Womack Building, CB #7050, Chapel Hill, NC 27599-7050, USA.
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13
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Aslani S, Kabiri M, HosseinZadeh S, Hanaee-Ahvaz H, Taherzadeh ES, Soleimani M. The applications of heparin in vascular tissue engineering. Microvasc Res 2020; 131:104027. [DOI: 10.1016/j.mvr.2020.104027] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 06/01/2020] [Accepted: 06/02/2020] [Indexed: 02/06/2023]
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14
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Grainger DW. Fluorinated Biomaterials. Biomater Sci 2020. [DOI: 10.1016/b978-0-12-816137-1.00012-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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15
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Maitz MF, Martins MCL, Grabow N, Matschegewski C, Huang N, Chaikof EL, Barbosa MA, Werner C, Sperling C. The blood compatibility challenge. Part 4: Surface modification for hemocompatible materials: Passive and active approaches to guide blood-material interactions. Acta Biomater 2019; 94:33-43. [PMID: 31226481 DOI: 10.1016/j.actbio.2019.06.019] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 05/29/2019] [Accepted: 06/13/2019] [Indexed: 12/22/2022]
Abstract
Biomedical devices in the blood flow disturb the fine-tuned balance of pro- and anti-coagulant factors in blood and vessel wall. Numerous technologies have been suggested to reduce coagulant and inflammatory responses of the body towards the device material, ranging from camouflage effects to permanent activity and further to a responsive interaction with the host systems. However, not all types of modification are suitable for all types of medical products. This review has a focus on application-oriented considerations of hemocompatible surface fittings. Thus, passive versus bioactive modifications are discussed along with the control of protein adsorption, stability of the immobilization, and the type of bioactive substance, biological or synthetic. Further considerations are related to the target system, whether enzymes or cells should be addressed in arterial or venous system, or whether the blood vessel wall is addressed. Recent developments like feedback controlled or self-renewing systems for drug release or addressing cellular regulation pathways of blood platelets and endothelial cells are paradigms for a generation of blood contacting devices, which are hemocompatible by cooperation with the host system. STATEMENT OF SIGNIFICANCE: This paper is part 4 of a series of 4 reviews discussing the problem of biomaterial associated thrombogenicity. The objective was to highlight features of broad agreement and provide commentary on those aspects of the problem that were subject to dispute. We hope that future investigators will update these reviews as new scholarship resolves the uncertainties of today.
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Affiliation(s)
- Manfred F Maitz
- Institute Biofunctional Polymer Materials, Max Bergmann Center of Biomaterials, Leibniz-Institut für Polymerforschung Dresden e.V., Dresden, Germany; Key Laboratory of Advanced Technology for Materials of Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
| | - M Cristina L Martins
- i3S, Instituto de Investigação e Inovação em Saúde, Portugal; INEB, Instituto de Engenharia Biomédica, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | - Niels Grabow
- Institut für Biomedizinische Technik, Universitätsmedizin Rostock, Friedrich-Barnewitz-Str. 4, 18119 Rostock, Germany
| | - Claudia Matschegewski
- Institut für Biomedizinische Technik, Universitätsmedizin Rostock, Friedrich-Barnewitz-Str. 4, 18119 Rostock, Germany; Institute for ImplantTechnology and Biomaterials (IIB) e.V., Friedrich-Barnewitz-Str. 4, 18119 Rostock, Germany
| | - Nan Huang
- Key Laboratory of Advanced Technology for Materials of Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
| | - Elliot L Chaikof
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02115, United States; Wyss Institute for Biologically Inspired Engineering at Harvard University, 3 Blackfan Circle, Boston, MA 02115, United States; Harvard-MIT Division of Health Sciences and Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, United States
| | - Mário A Barbosa
- i3S, Instituto de Investigação e Inovação em Saúde, Portugal; INEB, Instituto de Engenharia Biomédica, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | - Carsten Werner
- Institute Biofunctional Polymer Materials, Max Bergmann Center of Biomaterials, Leibniz-Institut für Polymerforschung Dresden e.V., Dresden, Germany
| | - Claudia Sperling
- Institute Biofunctional Polymer Materials, Max Bergmann Center of Biomaterials, Leibniz-Institut für Polymerforschung Dresden e.V., Dresden, Germany
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16
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Sologashvili T, Saat SA, Tille JC, De Valence S, Mugnai D, Giliberto JP, Dillon J, Yakub A, Dimon Z, Gurny R, Walpoth BH, Moeller M. Effect of implantation site on outcome of tissue-engineered vascular grafts. Eur J Pharm Biopharm 2019; 139:272-278. [DOI: 10.1016/j.ejpb.2019.04.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 04/15/2019] [Accepted: 04/16/2019] [Indexed: 01/31/2023]
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Ilanlou S, Khakbiz M, Amoabediny G, Mohammadi J, Rabbani H. Carboxymethyl kappa carrageenan-modified decellularized small-diameter vascular grafts improving thromboresistance properties. J Biomed Mater Res A 2019; 107:1690-1701. [PMID: 30920157 DOI: 10.1002/jbm.a.36684] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 12/05/2018] [Accepted: 02/21/2019] [Indexed: 11/10/2022]
Abstract
The development of decellularized small-diameter vascular grafts is a potential solution for patients requiring vascular reconstructive procedures. However, there is a limitation for acellular scaffolds due to incomplete recellularization and exposure of extracellular matrix components to whole blood resulting in platelet adhesion. To address this issue, a perfusion decellularization method was developed using a custom-designed set up which completely removed cell nuclei and preserved three-dimensional structure and mechanical properties of native tissue (sheep carotid arteries). Afterwards, carboxymethyl kappa carrageenan (CKC) was introduced as a novel anticoagulant in vascular tissue engineering which can inhibit thrombosis formation. The method enabled uniform immobilization of CKC on decellularized arteries as a result of interaction between amine functional groups of decellularized arteries and carboxyl groups of CKC. The CKC modified graft significantly reduced platelet adhesion from 44.53 ± 2.05% (control) to 19.57 ± 1.37% (modified) and supported endothelial cells viability, proliferation, and nitric oxide production. Overall, the novel CKC modified scaffold provides a promising solution for thrombosis formation of small-diameter vessels and could be a potent graft for future in vivo applications in vascular bypass procedures. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1690-1701, 2019.
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Affiliation(s)
- Shervin Ilanlou
- Division of Biomedical Engineering, Faculty of New Sciences and Technologies, University of Tehran, North Karegar Ave., PO Box 14395-1561, Tehran, Iran
| | - Mehrdad Khakbiz
- Division of Biomedical Engineering, Faculty of New Sciences and Technologies, University of Tehran, North Karegar Ave., PO Box 14395-1561, Tehran, Iran
| | - Ghasem Amoabediny
- Division of Biomedical Engineering, Faculty of New Sciences and Technologies, University of Tehran, North Karegar Ave., PO Box 14395-1561, Tehran, Iran.,Research Center for New Technologies in Life Science Engineering, University of Tehran, Tehran, Iran.,Faculty of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran
| | - Javad Mohammadi
- Division of Biomedical Engineering, Faculty of New Sciences and Technologies, University of Tehran, North Karegar Ave., PO Box 14395-1561, Tehran, Iran
| | - Hodjattallah Rabbani
- Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
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18
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Wu Y, Yu C, Xing M, Wang L, Guan G. Surface modification of polyvinyl alcohol (PVA)/polyacrylamide (PAAm) hydrogels with polydopamine and REDV for improved applicability. J Biomed Mater Res B Appl Biomater 2019; 108:117-127. [PMID: 30912304 DOI: 10.1002/jbm.b.34371] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2018] [Revised: 03/01/2019] [Accepted: 03/05/2019] [Indexed: 02/03/2023]
Abstract
Developing a small-diameter vascular graft with a satisfactory performance in terms of mechanical and biological properties remains a challenging issue because of comprehensive requirements from clinical applications. Polyvinyl alcohol (PVA)/polyacrylamide (PAAm) hydrogels exhibit many desirable characteristics for small-diameter vascular grafts because of their tunable mechanical properties, especially high compliance. However, poor cells adhesion hinders their application for endothelialization in situ. Therefore, in the present work, polydopamine (PDA) and tetrapeptide Arg-Glu-Asp-Val (REDV) were used to functionalize the hydrogels surface and improve cells adhesion. A series of characterizations were systematically conducted to examine the applicability of coated hydrogels to small-diameter vascular grafts. Results showed that bare and coated hydrogels have appropriate structural stability, and no significant differences in tensile properties could be found after being coated with PDA or PDA-REDV. The hydrophilicity of the hydrogels decreased with the coatings of PDA and especially PDA-REDV to improve protein adsorption, porcine iliac artery endothelial cells (PIECs) adhesion, viability, proliferation, and spreading on the hydrogels. Lower hemolysis percentages and higher blood clotting index values were attained for the hydrogels, suggesting their satisfactory hemocompatibility. Overall, the present work provided insights into the development of a novel hydrogel-based small-diameter vascular graft. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:117-127, 2020.
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Affiliation(s)
- Yufen Wu
- Key Laboratory of Textile Science & Technology, Ministry of Education, College of Textiles, Donghua University, Shanghai, 201620, China
| | - Chenglong Yu
- Key Laboratory of Textile Science & Technology, Ministry of Education, College of Textiles, Donghua University, Shanghai, 201620, China
| | - Meiyi Xing
- Key Laboratory of Textile Science & Technology, Ministry of Education, College of Textiles, Donghua University, Shanghai, 201620, China
| | - Lu Wang
- Key Laboratory of Textile Science & Technology, Ministry of Education, College of Textiles, Donghua University, Shanghai, 201620, China
| | - Guoping Guan
- Key Laboratory of Textile Science & Technology, Ministry of Education, College of Textiles, Donghua University, Shanghai, 201620, China
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19
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Nguyen TU, Shojaee M, Bashur CA, Kishore V. Electrochemical fabrication of a biomimetic elastin-containing bi-layered scaffold for vascular tissue engineering. Biofabrication 2018; 11:015007. [PMID: 30411718 DOI: 10.1088/1758-5090/aaeab0] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Biomimetic tissue-engineered vascular grafts (TEVGs) have immense potential to replace diseased small-diameter arteries (<4 mm) for the treatment of cardiovascular diseases. However, biomimetic approaches developed thus far only partially recapitulate the physicochemical properties of the native vessel. While it is feasible to fabricate scaffolds that are compositionally similar to native vessels (collagen and insoluble elastic matrix) using freeze-drying, these scaffolds do not mimic the aligned topography of collagen and elastic fibers found in native vessels. Extrusion-based scaffolds exhibit anisotropic collagen orientation but these scaffolds are compositionally dissimilar (cannot incorporate insoluble elastic matrix). In this study, an electrochemical fabrication technique was employed to develop a biomimetic elastin-containing bi-layered collagen scaffold which is compositionally and structurally similar to native vessels and the effect of insoluble elastin incorporation on scaffold mechanics and smooth muscle cell (SMC) response was investigated. Further, the functionality of human umbilical vein endothelial cells (HUVECs) on the scaffold lumen surface was assessed via immunofluorescence. Results showed that incorporation of insoluble elastin maintained the overall collagen alignment within electrochemically aligned collagen (ELAC) fibers and this underlying aligned topography can direct cellular orientation. Ring test results showed that circumferential orientation of ELAC fibers significantly improved scaffold mechanics. Real-time PCR revealed that the expression of α-smooth muscle actin (Acta2) and myosin heavy chain (MyhII) was significantly higher on elastin containing scaffolds suggesting that the presence of insoluble elastin can promote contractility in SMCs. Further, mechanical properties of the scaffolds significantly improved post-culture indicating the presence of a mature cell-synthesized and remodeled matrix. Finally, HUVECs expressed functional markers on collagen lumen scaffolds. In conclusion, electrochemical fabrication is a viable method for the generation of a functional biomimetic TEVG with the potential to be used in bypass surgery.
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Affiliation(s)
- Thuy-Uyen Nguyen
- Department of Chemical Engineering, Florida Institute of Technology, Melbourne, FL 32901, United States of America
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20
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Zaredar Z, Askari F, Shokrolahi P. Polyurethane synthesis for vascular application. Prog Biomater 2018; 7:269-278. [PMID: 30349979 PMCID: PMC6304180 DOI: 10.1007/s40204-018-0101-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 10/03/2018] [Indexed: 12/11/2022] Open
Abstract
Abstract Three polyurethane formulations were prepared on the basis of siloxane; two formulations contained 1% and 3% of a hydroxyl functionalized polyhedral oligomeric silsesquioxane [POSS (ROH)2] nano-particles (as a co-chain extender) and one was without nano-particle. Structures of the polyurethanes were characterized by FTIR and SEM. The effect of POSS nano-particles on properties of the synthesized PUs was examined for vascular applications by tensile test, contact angle, SEM, AFM and endothelial cells viability evaluation. Properties of the polyurethane with 1% POSS were compared with those of PU without POSS and the results showed 66% increase in the elongation-at-break, 53% increase in tensile strength and 33% increase in modulus, 9.45% increase in contact angle, 76.7% reduction in surface roughness and 9.46% increase in cell viability. It was also shown that a polyurethane containing 1% of POSS nano-particles in its structure developed the highest hydrophobicity, which resulted in its lowest potential for thrombosis. Graphical Abstract ![]()
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Affiliation(s)
- Zahra Zaredar
- Polymer Science Department, Iran Polymer and Petrochemical Institute, Tehran-Karaj Hwy, Tehran, 14977-13115, Iran
| | - Fahimeh Askari
- Polymer Science Department, Iran Polymer and Petrochemical Institute, Tehran-Karaj Hwy, Tehran, 14977-13115, Iran.
| | - Parvin Shokrolahi
- Biomaterials Department, Iran Polymer and Petrochemical Institute, Tehran-Karaj Hwy, Tehran, 14977-13115, Iran
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21
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Rajab TK. Anastomotic techniques for rat lung transplantation. World J Transplant 2018; 8:38-43. [PMID: 29696104 PMCID: PMC5915375 DOI: 10.5500/wjt.v8.i2.38] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 03/06/2018] [Accepted: 04/01/2018] [Indexed: 02/05/2023] Open
Abstract
The first lung transplantation in the rat was achieved by Asimacopoulos et al using sutured anastomoses in 1971. Subsequent development of a cuffed technique to construct the anastomoses by Mizuta and colleagues in 1989 represented a breakthrough that resulted in simplification of the procedure and shorter warm ischemic times. Since then, a number of further variations on the technique of rat lung transplantation have been described. In spite of this, the procedure remains technically demanding and involves a long learning curve. This minireview describes the following new technical safeguards to further evolve the technique for cuffed anastomoses in rat lung transplantation: the use of anatomical landmarks to avoid twisting of the everted donor pulmonary vein and bronchus in the cuff, the use of the cuff tie as a landmark to avoid twisting of the anastomotic cuffs relative to the recipient vessels, distal ties on the recipient vessels to achieve a bloodless field and triangulation of the venotomy to avoid pulmonary vein tearing.
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Affiliation(s)
- Taufiek Konrad Rajab
- Division of Cardiac Surgery, Brigham and Women’s Hospital, Boston, MA 02115, United States
- Department of Surgery, Harvard Medical School, Boston, MA 02115, United States
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22
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Gregory EK, Webb A, Vercammen JM, Kelly ME, Akar B, van Lith R, Bahnson EM, Jiang W, Ameer GA, Kibbe MR. Inhibiting intimal hyperplasia in prosthetic vascular grafts via immobilized all-trans retinoic acid. J Control Release 2018; 274:69-80. [PMID: 29391231 PMCID: PMC5847482 DOI: 10.1016/j.jconrel.2018.01.020] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Revised: 12/15/2017] [Accepted: 01/22/2018] [Indexed: 12/24/2022]
Abstract
Peripheral arterial disease is a leading cause of morbidity and mortality. The most commonly utilized prosthetic material for peripheral bypass grafting is expanded polytetrafluoroethylene (ePTFE) yet it continues to exhibit poor performance from restenosis due to neointimal hyperplasia, especially in femoral distal bypass procedures. Recently, we demonstrated that periadventitial delivery of all-trans retinoic acid (atRA) immobilized throughout porous poly(1,8 octamethylene citrate) (POC) membranes inhibited neointimal formation in a rat arterial injury model. Thus, the objective of this study was to investigate whether atRA immobilized throughout the lumen of ePTFE vascular grafts would inhibit intimal formation following arterial bypass grafting. Utilizing standard ePTFE, two types of atRA-containing ePTFE vascular grafts were fabricated and evaluated: grafts whereby all-trans retinoic acid was directly immobilized on ePTFE (atRA-ePTFE) and grafts where all-trans retinoic acid was immobilized onto ePTFE grafts coated with POC (atRA-POC-ePTFE). All grafts were characterized by SEM, HPLC, and FTIR and physical characteristics were evaluated in vitro. Modification of these grafts, did not significantly alter their physical characteristics or biocompatibility, and resulted in inhibition of intimal formation in a rat aortic bypass model, with atRA-POC-ePTFE inhibiting intimal formation at both the proximal and distal graft sections. In addition, treatment with atRA-POC-ePTFE resulted in increased graft endothelialization and decreased inflammation when compared to the other treatment groups. This work further confirms the biocompatibility and efficacy of locally delivered atRA to inhibit intimal formation in a bypass setting. Thus, atRA-POC-ePTFE grafts have the potential to improve patency rates in small diameter bypass grafts and warrant further investigation.
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Affiliation(s)
- Elaine K Gregory
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States
| | - Antonio Webb
- The University of Florida, Gainesville, FL 32611, United States
| | - Janet M Vercammen
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States
| | - Megan E Kelly
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States
| | - Banu Akar
- Biomedical Engineering Department, McCormick School of Engineering, Northwestern University, Evanston, IL 60201, United States
| | - Robert van Lith
- Biomedical Engineering Department, McCormick School of Engineering, Northwestern University, Evanston, IL 60201, United States; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States
| | - Edward M Bahnson
- Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
| | - Wulin Jiang
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States
| | - Guillermo A Ameer
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States; Biomedical Engineering Department, McCormick School of Engineering, Northwestern University, Evanston, IL 60201, United States; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States
| | - Melina R Kibbe
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL 60611, United States; Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
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23
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Unnikrishnan M, Umashankar PR, Viswanathan S, Savlania A, Joseph R, Muraleedharan CV, Agrawal V, Shenoy SJ, Krishnan LK, Mohanan PV, Sabareeswaran A. Preclinical evaluation of hydrogel sealed fluropassivated indigenous vascular prosthesis. Indian J Med Res 2018; 146:646-653. [PMID: 29512608 PMCID: PMC5861477 DOI: 10.4103/ijmr.ijmr_1933_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Background & objectives: Polyethylene terephthalate (PET) graft, designed and developed at our institute for vascular reconstruction, is porous to promote optimal incorporation and neointima formation, requiring pre-clotting or biomodification by sealing the pores before implantation. The objective of this study was to characterize, test and perform preclinical evaluation of hydrogel (alginate dialdehyde cross-linked gelatin) sealed fluoropassivated PET vascular prosthesis in pig model, so as to avoid pre-clotting, for its safety and efficacy before employing the indigenous and less expensive graft for clinical use. Methods: Hydrogel sealed, fluoropassivated PET vascular prosthesis were tested for haemocompatibility and toxicity followed by small animal toxicology tests and in vivo experiments in pigs receiving implantation at thoracic aorta. All 33 animals received test as well as control grafts with a plan for phased explantation at 2, 12 and 26 weeks. All animals underwent completion angiogram at the end of procedure as well as before graft explantation. Results: Haemocompatibility tests for haemolysis and toxicity tests showed no adverse events in tested mice and rabbits. Completion angiogram showed intact anastamosis and patent graft in each animal in post-operative period and at explantation. Gross and histopathological examination showed well-encapsulated grafts, clean glistening neointima and no evidence of thrombus in both test and control grafts. Interpretation & conclusions: Hydrogel sealed, fluoropassivated PET vascular prosthesis was found non-toxic, haemocompatible and remained patent in in vivo studies at planned intervals.
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Affiliation(s)
- Madathipat Unnikrishnan
- Division of Vascular Surgery, Department of Cardiovascular & Thoracic Surgery, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - P R Umashankar
- Division of In Vivo Models & Testing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - Sidharth Viswanathan
- Division of Vascular Surgery, Department of Cardiovascular & Thoracic Surgery, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - Ajay Savlania
- Division of Vascular Surgery, Department of Cardiovascular & Thoracic Surgery, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - Roy Joseph
- Polymer Processing Laboratory, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - C V Muraleedharan
- Division of Artificial Organs, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - Vivek Agrawal
- Division of Vascular Surgery, Department of Cardiovascular & Thoracic Surgery, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - Sachin J Shenoy
- Division of Artificial Organs, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - Lissy K Krishnan
- Thrombosis Research Unit, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - P V Mohanan
- Division of Toxicology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - A Sabareeswaran
- Division of Implant Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
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24
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La Francesca S, Aho JM, Barron MR, Blanco EW, Soliman S, Kalenjian L, Hanson AD, Todorova E, Marsh M, Burnette K, DerSimonian H, Odze RD, Wigle DA. Long-term regeneration and remodeling of the pig esophagus after circumferential resection using a retrievable synthetic scaffold carrying autologous cells. Sci Rep 2018; 8:4123. [PMID: 29515136 PMCID: PMC5841275 DOI: 10.1038/s41598-018-22401-x] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 02/21/2018] [Indexed: 02/07/2023] Open
Abstract
Treatment of esophageal disease can necessitate resection and reconstruction of the esophagus. Current reconstruction approaches are limited to utilization of an autologous conduit such as stomach, small bowel, or colon. A tissue engineered construct providing an alternative for esophageal replacement in circumferential, full thickness resection would have significant clinical applications. In the current study, we demonstrate that regeneration of esophageal tissue is feasible and reproducible in a large animal model using synthetic polyurethane electro-spun grafts seeded with autologous adipose-derived mesenchymal stem cells (aMSCs) and a disposable bioreactor. The scaffolds were not incorporated into the regrown esophageal tissue and were retrieved endoscopically. Animals underwent adipose tissue biopsy to harvest and expand autologous aMSCs for seeding on electro-spun polyurethane conduits in a bioreactor. Anesthetized pigs underwent full thickness circumferential resection of the mid-lower thoracic esophagus followed by implantation of the cell seeded scaffold. Results from these animals showed gradual structural regrowth of endogenous esophageal tissue, including squamous esophageal mucosa, submucosa, and smooth muscle layers with blood vessel formation. Scaffolds carrying autologous adipose-derived mesenchymal stem cells may provide an alternative to the use of a gastro-intestinal conduit for some patients following resection of the esophagus.
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Affiliation(s)
| | - Johnathon M Aho
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, 55905, USA
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, 55905, USA
| | - Matthew R Barron
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, 55905, USA
| | - Ellen W Blanco
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, 55905, USA
| | | | | | | | | | | | | | | | - Robert D Odze
- Department of Pathology, Harvard Medical School, Boston, MA, 02115, USA
| | - Dennis A Wigle
- Division of Thoracic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, 55905, USA.
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, 55905, USA.
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25
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Liu RH, Ong CS, Fukunishi T, Ong K, Hibino N. Review of Vascular Graft Studies in Large Animal Models. TISSUE ENGINEERING PART B-REVIEWS 2017; 24:133-143. [PMID: 28978267 DOI: 10.1089/ten.teb.2017.0350] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
As the incidence of cardiovascular disease continues to climb worldwide, there is a corresponding increase in demand for surgical interventions involving vascular grafts. The current gold standard for vascular grafts is autologous vessels, an option often excluded due to disease circumstances. As a result, many patients must resort to prosthetic options. While widely available, prosthetic grafts have been demonstrated to have inferior patency rates compared with autologous grafts due to inflammation and thrombosis. In an attempt to overcome these limitations, many different materials for constructing vascular grafts, from modified synthetic nondegradable polymers to biodegradable polymers, have been explored, many of which have entered the translational stage of research. This article reviews these materials in the context of large animal models, providing an outlook on the preclinical potential of novel biomaterials as well as the future direction of vascular graft research.
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Affiliation(s)
- Rui Han Liu
- 1 Division of Cardiac Surgery, The Johns Hopkins Hospital , Baltimore, Maryland
| | - Chin Siang Ong
- 1 Division of Cardiac Surgery, The Johns Hopkins Hospital , Baltimore, Maryland
| | - Takuma Fukunishi
- 1 Division of Cardiac Surgery, The Johns Hopkins Hospital , Baltimore, Maryland
| | - Kingsfield Ong
- 2 Department of Cardiac, Thoracic and Vascular Surgery, National University Health System , Singapore, Singapore
| | - Narutoshi Hibino
- 1 Division of Cardiac Surgery, The Johns Hopkins Hospital , Baltimore, Maryland
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26
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Huang AH, Balestrini JL, Udelsman BV, Zhou KC, Zhao L, Ferruzzi J, Starcher BC, Levene MJ, Humphrey JD, Niklason LE. Biaxial Stretch Improves Elastic Fiber Maturation, Collagen Arrangement, and Mechanical Properties in Engineered Arteries. Tissue Eng Part C Methods 2017; 22:524-33. [PMID: 27108525 DOI: 10.1089/ten.tec.2015.0309] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Tissue-engineered blood vessels (TEVs) are typically produced using the pulsatile, uniaxial circumferential stretch to mechanically condition and strengthen the arterial grafts. Despite improvements in the mechanical integrity of TEVs after uniaxial conditioning, these tissues fail to achieve critical properties of native arteries such as matrix content, collagen fiber orientation, and mechanical strength. As a result, uniaxially loaded TEVs can result in mechanical failure, thrombus, or stenosis on implantation. In planar tissue equivalents such as artificial skin, biaxial loading has been shown to improve matrix production and mechanical properties. To date however, multiaxial loading has not been examined as a means to improve mechanical and biochemical properties of TEVs during culture. Therefore, we developed a novel bioreactor that utilizes both circumferential and axial stretch that more closely simulates loading conditions in native arteries, and we examined the suture strength, matrix production, fiber orientation, and cell proliferation. After 3 months of biaxial loading, TEVs developed a formation of mature elastic fibers that consisted of elastin cores and microfibril sheaths. Furthermore, the distinctive features of collagen undulation and crimp in the biaxial TEVs were absent in both uniaxial and static TEVs. Relative to the uniaxially loaded TEVs, tissues that underwent biaxial loading remodeled and realigned collagen fibers toward a more physiologic, native-like organization. The biaxial TEVs also showed increased mechanical strength (suture retention load of 303 ± 14.53 g, with a wall thickness of 0.76 ± 0.028 mm) and increased compliance. The increase in compliance was due to combinatorial effects of mature elastic fibers, undulated collagen fibers, and collagen matrix orientation. In conclusion, biaxial stretching is a potential means to regenerate TEVs with improved matrix production, collagen organization, and mechanical properties.
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Affiliation(s)
- Angela H Huang
- 1 Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University , New Haven, Connecticut
| | - Jenna L Balestrini
- 1 Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University , New Haven, Connecticut
| | | | - Kevin C Zhou
- 1 Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University , New Haven, Connecticut
| | - Liping Zhao
- 2 School of Medicine, Yale University , New Haven, Connecticut
| | - Jacopo Ferruzzi
- 1 Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University , New Haven, Connecticut
| | - Barry C Starcher
- 3 Department of Biochemistry, The University of Texas Health Science Center at Tyler , Tyler, Texas
| | - Michael J Levene
- 1 Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University , New Haven, Connecticut
| | - Jay D Humphrey
- 1 Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University , New Haven, Connecticut
| | - Laura E Niklason
- 1 Department of Biomedical Engineering, School of Engineering and Applied Science, Yale University , New Haven, Connecticut.,2 School of Medicine, Yale University , New Haven, Connecticut
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27
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Kaplan O, Hierlemann T, Krajewski S, Kurz J, Nevoralová M, Houska M, Riedel T, Riedelová Z, Zárubová J, Wendel HP, Brynda E. Low-thrombogenic fibrin-heparin coating promotes in vitro endothelialization. J Biomed Mater Res A 2017. [PMID: 28646555 DOI: 10.1002/jbm.a.36152] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Long-term performance of implanted cardiovascular grafts can be ensured if living endothelium overgrows their surface. Surface modifications to implants are therefore being sought that can encourage endothelialization while preventing thrombus formation until the natural endothelium is formed. In the present study, heparin was covalently attached to a fibrin mesh grown from a polyvinyl chloride (PVC) substrate surface by the catalytic action of surface immobilized thrombin on a fibrinogen solution. The coating prevented platelet activation, thrombin generation and clot formation, and reduced inflammatory reactions when exposed to fresh human whole blood circulating in a Chandler loop model. In addition, in vitro seeded human umbilical vein and human saphenous vein endothelial cells showed considerably enhanced attachment and proliferation on the coating. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2995-3005, 2017.
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Affiliation(s)
- Ondřej Kaplan
- Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Prague, CZ-162 06, Czech Republic
| | - Teresa Hierlemann
- Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Tuebingen, DE-72076, Germany
| | - Stefanie Krajewski
- Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Tuebingen, DE-72076, Germany
| | - Julia Kurz
- Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Tuebingen, DE-72076, Germany
| | - Martina Nevoralová
- Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Prague, CZ-162 06, Czech Republic
| | - Milan Houska
- Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Prague, CZ-162 06, Czech Republic
| | - Tomáš Riedel
- Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Prague, CZ-162 06, Czech Republic
| | - Zuzana Riedelová
- Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Prague, CZ-162 06, Czech Republic
| | - Jana Zárubová
- Institute of Physiology of the Czech Academy of Sciences, Prague, CZ-142 20, Czech Republic
| | - Hans P Wendel
- Department of Thoracic, Cardiac and Vascular Surgery, Clinical Research Laboratory, University Hospital Tuebingen, Tuebingen, DE-72076, Germany
| | - Eduard Brynda
- Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Prague, CZ-162 06, Czech Republic
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28
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Kondyurina I, Wise SG, Ngo AKY, Filipe EC, Kondyurin A, Weiss AS, Bao S, Bilek MMM. Plasma mediated protein immobilisation enhances the vascular compatibility of polyurethane with tissue matched mechanical properties. Biomed Mater 2017; 12:045002. [DOI: 10.1088/1748-605x/aa6eb6] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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29
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Brockman KS, Lai BFL, Kizhakkedathu JN, Santerre JP. Hemocompatibility of Degrading Polymeric Biomaterials: Degradable Polar Hydrophobic Ionic Polyurethane versus Poly(lactic-co-glycolic) Acid. Biomacromolecules 2017. [PMID: 28621927 DOI: 10.1021/acs.biomac.7b00456] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The use of degradable polymers in vascular tissue regeneration has sparked the need to characterize polymer biocompatibility during degradation. While tissue compatibility has been frequently addressed, studies on polymer hemocompatibility during degradation are limited. The current study evaluated the differences in hemocompatibility (platelet response, complement activation, and coagulation cascade initiation) between as-made and hydrolyzed poly(lactic-co-glycolic) acid (PLGA) and degradable polar hydrophobic ionic polyurethane (D-PHI). Platelet activation decreased (in whole blood) and platelet adhesion decreased (in blood without leukocytes) for degraded versus as-made PLGA. D-PHI showed minimal hemocompatibility changes over degradation. Leukocytes played a major role in mediating platelet activation for samples and controls, as well as influencing platelet-polymer adhesion on the degraded materials. This study demonstrates the importance of assessing the blood compatibility of biomaterials over the course of degradation since the associated changes in surface chemistry and physical state could significantly change biomaterial hemocompatibility.
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Affiliation(s)
- Kathryne S Brockman
- Department of Chemical Engineering and Applied Chemistry, University of Toronto , Toronto, Ontario M5S 3R5, Canada.,Institute of Biomaterials and Biomedical Engineering, Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, University of Toronto , Toronto, Ontario M5G 1M1, Canada
| | - Benjamin F L Lai
- Department of Pathology and Laboratory Medicine and Centre for Blood Research, University of British Columbia , Vancouver, British Columbia V6T 1Z3, Canada
| | - Jayachandran N Kizhakkedathu
- Department of Pathology and Laboratory Medicine and Centre for Blood Research, University of British Columbia , Vancouver, British Columbia V6T 1Z3, Canada.,Department of Chemistry, University of British Columbia , Vancouver, British Columbia V6T 1Z1, Canada
| | - J Paul Santerre
- Department of Chemical Engineering and Applied Chemistry, University of Toronto , Toronto, Ontario M5S 3R5, Canada.,Institute of Biomaterials and Biomedical Engineering, Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, University of Toronto , Toronto, Ontario M5G 1M1, Canada.,Faculty of Dentistry, University of Toronto , Toronto, Ontario M5G 1G6, Canada
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30
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Gerrah R, Haller SJ, George I. Mechanical Concepts Applied in Congenital Heart Disease and Cardiac Surgery. Ann Thorac Surg 2017; 103:2005-2014. [DOI: 10.1016/j.athoracsur.2017.01.068] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Revised: 01/04/2017] [Accepted: 01/16/2017] [Indexed: 11/30/2022]
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31
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Abstract
The development of new methods for drug elution of graft material, biofiber films and resurfacing of prosthetic graft surfaces offers new opportunities for improvement of graft function in arteriovenous (AV) access. Three areas of research include developing grafts that reduce the development of neointimal hyperplasia, reducing infection and reducing thrombogenicity. The only drug eluting graft presently being used, is the heparin coated expanded polytetrafluoroethylene (ePTFE) graft, which has been shown to decrease the incidence of early thrombosis. New drug eluting grafts include those with paclitaxel and those with antibiotics. The development of a hybrid coated prosthetic graft that can deliver targeted gene therapies holds great promise in the field.
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32
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Albaghdadi MS, Yang J, Brown JH, Mansukhani NA, Ameer GA, Kibbe MR. A Tailorable In-Situ Light-Activated Biodegradable Vascular Scaffold. ADVANCED MATERIALS TECHNOLOGIES 2017; 2:1600243. [PMID: 29578542 PMCID: PMC5860681 DOI: 10.1002/admt.201600243] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Biodegradable vascular scaffolds (BVS) are novel treatments for obstructive atherosclerotic cardiovascular disease that have been developed to overcome the limitations of traditional metallic drug-eluting stents (DES). The mechanical properties of bioabsorbable polymers used for the production of novel BVS are a key consideration for the clinical translation of this emerging technology. Herein, we describe the engineering of an in situ light-activated vascular scaffold (ILVS) comprised of a biodegradable citric acid-based elastomeric polymer, referred to as methacrylated poly-diol citrate (mPDC), and a diazeniumdiolate chitosan nitric oxide donor (chitoNO). In vitro studies demonstrate that the mechanical properties of the ILVS can be tailored to meet or exceed those of commercially available self-expanding bare metal stents (BMS). The radial compression strength of the ILVS is higher than that of a BMS despite undergoing degradation at physiologic conditions for 7 months. ILVS containing chitoNO provides sustained supraphysiologic levels of NO release. Lastly, ILVS were successfully cast in porcine arteries ex vivo using a custom designed triple balloon catheter, demonstrating translational potential. In conclusion, these data demonstrate the ability of an ILVS to provide tunable mechanical properties and drug-delivery capabilities for the vasculature, and thereby support mPDC as a promising material for the development of novel BVS platforms.
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Affiliation(s)
- Mazen S. Albaghdadi
- Department of Medicine, Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago Illinois
| | - Jian Yang
- Biomedical Engineering Department, Northwestern University, Evanston, Illinois
| | - Jessica H. Brown
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago Illinois
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Neel A. Mansukhani
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago Illinois
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Guillermo A. Ameer
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago Illinois
- Biomedical Engineering Department, Northwestern University, Evanston, Illinois
- Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
- International Institute for Nanotechnology, Northwestern University, Evanston, Illinois
| | - Melina R. Kibbe
- Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago Illinois
- Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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33
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Askari F, Shafieian M, Solouk A, Hashemi A. A comparison of the material properties of natural and synthetic vascular walls. J Mech Behav Biomed Mater 2017; 71:209-215. [PMID: 28347955 DOI: 10.1016/j.jmbbm.2017.03.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 03/12/2017] [Accepted: 03/22/2017] [Indexed: 10/19/2022]
Abstract
Characterization of the mechanical properties of native and synthetic vascular grafts is an essential task in the process of designing novel vascular constructs. The aim in this study was to compare the mechanical behavior of ovine left Subclavian artery with that of POSS-PCU (a commercial biomaterial which is currently under clinical investigation. ClinicalTrials.gov Identifier: NCT02301312). We used Delfino's strain energy potential within the framework of quasilinear viscoelasticity theory to capture the viscoelastic response of the considered materials. The material parameters of the quasilinear viscoelastic constitutive equation were determined through a combination of experimental and computational method. First, a uniaxial tensile testing device was used to perform a series of stress relaxation tests on ring samples. Then, the derived quasilinear viscoelastic models were implemented into finite element system. With the aid of mechanical experimentation and finite element simulation, the material parameters were obtained, modified and used for comparison of the mechanical properties of vascular walls. The results showed that the stiffness and the long term viscoelastic parameters of POSS-PCU may lead to different stress responses of the vascular walls. These two factors can be improved by modifications in manufacturing parameters of the synthetic vessel.
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Affiliation(s)
- Forough Askari
- Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), 424 Hafez Ave, Tehran, Iran
| | - Mehdi Shafieian
- Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), 424 Hafez Ave, Tehran, Iran.
| | - Atefeh Solouk
- Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), 424 Hafez Ave, Tehran, Iran
| | - Ata Hashemi
- Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), 424 Hafez Ave, Tehran, Iran
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34
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Lavery KS, Rhodes C, Mcgraw A, Eppihimer MJ. Anti-thrombotic technologies for medical devices. Adv Drug Deliv Rev 2017; 112:2-11. [PMID: 27496703 DOI: 10.1016/j.addr.2016.07.008] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Revised: 06/03/2016] [Accepted: 07/26/2016] [Indexed: 01/08/2023]
Abstract
Thrombosis associated with medical devices may lead to dramatic increases in morbidity, mortality and increased health care costs. Innovative strategies are being developed to reduce this complication and provide a safe biocompatible interface between device and blood. This article aims to describe the biological phenomena underlying device-associated thrombosis, and surveys the literature describing current and developing technologies designed to overcome this challenge. To reduce thrombosis, biomaterials with varying topographical properties and incorporating anti-thrombogenic substances on their surface have demonstrated potential. Overall, there is extensive literature describing technical solutions to reduce thrombosis associated with medical devices, but clinical results are required to demonstrate significant long-term benefits.
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Affiliation(s)
- Karen S Lavery
- Preclinical Sciences, Boston Scientific Corporation, 100 Boston Scientific Way, Marlborough, MA 01752-1234, United States
| | - Candace Rhodes
- Preclinical Sciences, Boston Scientific Corporation, 100 Boston Scientific Way, Marlborough, MA 01752-1234, United States
| | - Adam Mcgraw
- Preclinical Sciences, Boston Scientific Corporation, 100 Boston Scientific Way, Marlborough, MA 01752-1234, United States
| | - Michael J Eppihimer
- Preclinical Sciences, Boston Scientific Corporation, 100 Boston Scientific Way, Marlborough, MA 01752-1234, United States
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35
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Van de Vyver H, Bovenkamp PR, Hoerr V, Schwegmann K, Tuchscherr L, Niemann S, Kursawe L, Grosse C, Moter A, Hansen U, Neugebauer U, Kuhlmann MT, Peters G, Hermann S, Löffler B. A Novel Mouse Model of Staphylococcus aureus Vascular Graft Infection: Noninvasive Imaging of Biofilm Development in Vivo. THE AMERICAN JOURNAL OF PATHOLOGY 2017; 187:268-279. [PMID: 28088288 DOI: 10.1016/j.ajpath.2016.10.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Revised: 09/20/2016] [Accepted: 10/04/2016] [Indexed: 10/20/2022]
Abstract
Staphylococcus aureus causes very serious infections of vascular grafts. Knowledge of the molecular mechanisms of this disease is largely lacking because of the absence of representable models. Therefore, the aim of this study was to set up a mouse model of vascular graft infections that closely mimics the human situation. A catheter was inserted into the right carotid artery of mice, which acted as a vascular graft. Mice were infected i.v. using 8 different S. aureus strains, and development of the infection was followed up. Although all strains had varying abilities to form biofilm in vitro and different levels of virulence in mice, they all caused biofilm formation on the grafts. This graft infection was monitored using magnetic resonance imaging (MRI) and 18F-fluordeoxyglucose positron emission tomography (FDG-PET). MRI allowed the quantification of blood flow through the arteries, which was decreased in the catheter after infection. FDG-PET revealed high inflammation levels at the site of the catheter after infection. This model closely resembles the situation in patients, which is characterized by a tight interplay between pathogen and host, and can therefore be used for the testing of novel treatment, diagnosis, and prevention strategies. In addition, combining MRI and PET with microscopic techniques provides an appropriate way to characterize the course of these infections and to precisely analyze biofilm development.
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Affiliation(s)
- Hélène Van de Vyver
- Institute of Medical Microbiology, University Hospital Muenster, Muenster, Germany.
| | - Philipp R Bovenkamp
- Department of Clinical Radiology, University Hospital Muenster, Muenster, Germany
| | - Verena Hoerr
- Department of Clinical Radiology, University Hospital Muenster, Muenster, Germany; Institute of Medical Microbiology, Jena University Hospital, Jena, Germany
| | - Katrin Schwegmann
- European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany
| | - Lorena Tuchscherr
- Institute of Medical Microbiology, Jena University Hospital, Jena, Germany
| | - Silke Niemann
- Institute of Medical Microbiology, University Hospital Muenster, Muenster, Germany
| | - Laura Kursawe
- Biofilmcenter, German Heart Institute Berlin, Berlin, Germany
| | - Christina Grosse
- Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany; Leibniz Institute of Photonic Technology, Jena, Germany
| | - Annette Moter
- Biofilmcenter, German Heart Institute Berlin, Berlin, Germany
| | - Uwe Hansen
- Institute of Experimental Musculoskeletal Medicine, University Hospital Muenster, Muenster, Germany
| | - Ute Neugebauer
- Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany; Leibniz Institute of Photonic Technology, Jena, Germany; Institute of Physical Chemistry, University of Jena, Jena, Germany
| | - Michael T Kuhlmann
- European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany
| | - Georg Peters
- Institute of Medical Microbiology, University Hospital Muenster, Muenster, Germany; Cells-in-Motion Cluster of Excellence (EXC 1003 - CiM), University of Münster, Münster, Germany
| | - Sven Hermann
- European Institute for Molecular Imaging, University Hospital Muenster, Muenster, Germany
| | - Bettina Löffler
- Institute of Medical Microbiology, Jena University Hospital, Jena, Germany
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36
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Liu K, Wang N, Wang W, Shi L, Li H, Guo F, Zhang L, Kong L, Wang S, Zhao Y. A bio-inspired high strength three-layer nanofiber vascular graft with structure guided cell growth. J Mater Chem B 2017; 5:3758-3764. [DOI: 10.1039/c7tb00465f] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
A bio-inspired three-layer vascular graft with strong mechanical properties and good cell biocompatibility was fabricated by electrospinning. It will play an important role in vessel remodeling and regeneration.
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37
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Wise SG, Liu H, Kondyurin A, Byrom MJ, Bannon PG, Edwards GA, Weiss AS, Bao S, Bilek MM. Plasma Ion Activated Expanded Polytetrafluoroethylene Vascular Grafts with a Covalently Immobilized Recombinant Human Tropoelastin Coating Reducing Neointimal Hyperplasia. ACS Biomater Sci Eng 2016; 2:1286-1297. [DOI: 10.1021/acsbiomaterials.6b00208] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Steven G. Wise
- The Heart Research Institute, 7 Eliza Street, Newtown, Sydney, New South Wales 2042, Australia
- Sydney
Medical School, University of Sydney, Edward Ford Building (A27), Fisher
Road, Sydney, New South Wales 2006, Australia
- School
of Molecular Bioscience, University of Sydney, Biochemistry Building (G08), Butlin
Avenue, Sydney, New South
Wales 2006, Australia
| | - Hongjuan Liu
- Department
of Pathology, University of Sydney, Blackburn Building (D06), Blackburn Circuit, Sydney, New South Wales 2006, Australia
| | - Alexey Kondyurin
- School
of Physics (A28), University of Sydney, Physics Road, Sydney, New South Wales 2006, Australia
| | - Michael J. Byrom
- The Heart Research Institute, 7 Eliza Street, Newtown, Sydney, New South Wales 2042, Australia
- The Baird Institute, Suite 305, 100 Carillon Avenue, Newtown, Sydney, New South Wales 2042, Australia
| | - Paul G. Bannon
- Sydney
Medical School, University of Sydney, Edward Ford Building (A27), Fisher
Road, Sydney, New South Wales 2006, Australia
- The Baird Institute, Suite 305, 100 Carillon Avenue, Newtown, Sydney, New South Wales 2042, Australia
| | - Glenn A. Edwards
- School
of Veterinary Science, University of Melbourne, 757 Swanston Street, Parkville, Victoria 3030, Australia
| | - Anthony S. Weiss
- School
of Molecular Bioscience, University of Sydney, Biochemistry Building (G08), Butlin
Avenue, Sydney, New South
Wales 2006, Australia
- Bosch
Institute, University of Sydney, Anderson Stuart Building (F13), Fisher Road, Sydney, New
South Wales 2006, Australia
- Charles
Perkins Centre (D17), University of Sydney, John Hopkins Drive, Sydney, New South Wales 2006, Australia
| | - Shisan Bao
- Department
of Pathology, University of Sydney, Blackburn Building (D06), Blackburn Circuit, Sydney, New South Wales 2006, Australia
| | - Marcela M. Bilek
- School
of Physics (A28), University of Sydney, Physics Road, Sydney, New South Wales 2006, Australia
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38
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Lamichhane S, Anderson JA, Remund T, Sun H, Larson MK, Kelly P, Mani G. Responses of endothelial cells, smooth muscle cells, and platelets dependent on the surface topography of polytetrafluoroethylene. J Biomed Mater Res A 2016; 104:2291-304. [PMID: 27119260 DOI: 10.1002/jbm.a.35763] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Revised: 04/19/2016] [Accepted: 04/25/2016] [Indexed: 11/09/2022]
Abstract
In this study, the effect of different structures (flat, expanded, and electrospun) of polytetrafluoroethylene (PTFE) on the interactions of endothelial cells (ECs), smooth muscle cells (SMCs), and platelets was investigated. In addition, the mechanisms that govern the interactions between ECs, SMCs, and platelets with different structures of PTFE were discussed. The surface characterizations showed that the different structures of PTFE have the same surface chemistry, similar surface wettability and zeta potential, but uniquely different surface topography. The viability, proliferation, morphology, and phenotype of ECs and SMCs interacted with different structures of PTFE were investigated. Expanded PTFE (ePTFE) provided a relatively better surface for the growth of ECs. In case of SMC interactions, although all the different structures of PTFE inhibited SMC growth, a maximum inhibitory effect was observed for ePTFE. In case of platelet interactions, the electrospun PTFE provided a better surface for preventing the adhesion and activation of platelets. Thus, this study demonstrated that the responses of ECs, SMCs, and platelets strongly dependent on the surface topography of the PTFE. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2291-2304, 2016.
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Affiliation(s)
- Sujan Lamichhane
- Biomedical Engineering Program, The University of South Dakota, 4800 N. Career Avenue, Sioux Falls, South Dakota, 57107
| | - Jordan A Anderson
- Biomedical Engineering Program, The University of South Dakota, 4800 N. Career Avenue, Sioux Falls, South Dakota, 57107
| | - Tyler Remund
- Sanford Research, 2301 East 60th Street North, Sioux Falls, South Dakota, 57104
| | - Hongli Sun
- Biomedical Engineering Program, The University of South Dakota, 4800 N. Career Avenue, Sioux Falls, South Dakota, 57107
| | - Mark K Larson
- Department of Biology, Augustana University, 2001 S. Summit Avenue, Sioux Falls, South Dakota, 57197
| | - Patrick Kelly
- Sanford Health, 1305 West 18th Street, Sioux Falls, South Dakota, 57105
| | - Gopinath Mani
- Biomedical Engineering Program, The University of South Dakota, 4800 N. Career Avenue, Sioux Falls, South Dakota, 57107
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Elastomers in vascular tissue engineering. Curr Opin Biotechnol 2016; 40:149-154. [PMID: 27149017 DOI: 10.1016/j.copbio.2016.04.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Revised: 03/25/2016] [Accepted: 04/05/2016] [Indexed: 11/23/2022]
Abstract
Elastomers are popular in vascular engineering applications, as they offer the ability to design implants that match the compliance of native tissue. By mimicking the natural tissue environment, elastic materials are able to integrate within the body to promote repair and avoid the adverse physiological responses seen in rigid alternatives that often disrupt tissue function. The design of elastomers has continued to evolve, moving from a focus on long term implants to temporary resorbable implants that support tissue regeneration. This has been achieved through designing chemistries and processing methodologies that control material behavior and bioactivity, while maintaining biocompatibility in vivo. Here we review the latest developments in synthetic and natural elastomers and their application in cardiovascular treatments.
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Choi WS, Joung YK, Lee Y, Bae JW, Park HK, Park YH, Park JC, Park KD. Enhanced Patency and Endothelialization of Small-Caliber Vascular Grafts Fabricated by Coimmobilization of Heparin and Cell-Adhesive Peptides. ACS APPLIED MATERIALS & INTERFACES 2016; 8:4336-4346. [PMID: 26824876 DOI: 10.1021/acsami.5b12052] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
The clinical utility of a small-caliber vascular graft is still limited, owing to the occlusion of graft by thrombosis and restenosis. A small-caliber vascular graft (diameter, 2.5 mm) fabricated by electrospinning with a polyurethane (PU) elastomer (Pellethane) and biofunctionalized with heparin and two cell-adhesive peptides, GRGDS and YIGSR, was developed for the purpose of preventing the thrombosis and restenosis through antithrombogenic activities and endothelialization. The vascular grafts showed slightly reduced adhesion of platelets and significantly decreased adsorption of fibrinogen. In vitro studies demonstrated that peptide treatment on a vascular graft enhanced the attachment of human umbilical vein endothelial cells (HUVECs), and the presence of heparin and peptides on the graft significantly increased the proliferation of HUVECs. In vivo implantation of heparin/peptides coimmobilized graft (PU-PEG-Hep/G+Y) and PU (control) grafts was performed using an abdominal aorta rabbit model for 60 days followed by angiographic monitoring and explanting for histological analyses. The patency was significantly higher for the modified PU grafts (71.4%) compared to the PU grafts (46.2%) at 9 weeks after implantation. The nontreated PU grafts showed higher levels of α-SMA expression compared to the modified grafts, and for both samples, the proximal and distal regions expressed higher levels compared to the middle region of the grafts. Moreover, immobilization of heparin and peptides and adequate porous structure were found to play important roles in endothelialization and cellular infiltration. Our results strongly encourage that the development of small-caliber vascular grafts is feasible.
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Affiliation(s)
- Won Sup Choi
- Department of Molecular Science and Technology, Ajou University , Suwon 443-749, Republic of Korea
| | - Yoon Ki Joung
- Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology , Seoul 136-791, Republic of Korea
| | - Yunki Lee
- Department of Molecular Science and Technology, Ajou University , Suwon 443-749, Republic of Korea
| | - Jin Woo Bae
- Department of Molecular Science and Technology, Ajou University , Suwon 443-749, Republic of Korea
| | | | | | | | - Ki Dong Park
- Department of Molecular Science and Technology, Ajou University , Suwon 443-749, Republic of Korea
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Development of nitric oxide catalytic coatings by conjugating 3,3-disulfodipropionic acid and 3,3-diselenodipropionic acid for improving hemocompatibility. Biointerphases 2015; 10:04A303. [DOI: 10.1116/1.4932195] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Lachaud CC, Rodriguez-Campins B, Hmadcha A, Soria B. Use of Mesothelial Cells and Biological Matrices for Tissue Engineering of Simple Epithelium Surrogates. Front Bioeng Biotechnol 2015; 3:117. [PMID: 26347862 PMCID: PMC4538307 DOI: 10.3389/fbioe.2015.00117] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Accepted: 08/03/2015] [Indexed: 12/13/2022] Open
Abstract
Tissue-engineering technologies have progressed rapidly through last decades resulting in the manufacture of quite complex bioartificial tissues with potential use for human organ and tissue regeneration. The manufacture of avascular monolayered tissues such as simple squamous epithelia was initiated a few decades ago and is attracting increasing interest. Their relative morphostructural simplicity makes of their biomimetization a goal, which is currently accessible. The mesothelium is a simple squamous epithelium in nature and is the monolayered tissue lining the walls of large celomic cavities (peritoneal, pericardial, and pleural) and internal organs housed inside. Interestingly, mesothelial cells can be harvested in clinically relevant numbers from several anatomical sources and not less important, they also display high transdifferentiation capacities and are low immunogenic characteristics, which endow these cells with therapeutic interest. Their combination with a suitable scaffold (biocompatible, degradable, and non-immunogenic) may allow the manufacture of tailored serosal membranes biomimetics with potential spanning a wide range of therapeutic applications, principally for the regeneration of simple squamous-like epithelia such as the visceral and parietal mesothelium vascular endothelium and corneal endothelium among others. Herein, we review recent research progresses in mesothelial cells biology and their clinical sources. We make a particular emphasis on reviewing the different types of biological scaffolds suitable for the manufacture of serosal mesothelial membranes biomimetics. Finally, we also review progresses made in mesothelial cells-based therapeutic applications and propose some possible future directions.
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Affiliation(s)
- Christian Claude Lachaud
- Andalusian Center for Molecular Biology and Regenerative Medicine - Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER) , Seville , Spain ; Centro de Investigación en Red sobre Diabetes y Enfermedades Metabólicas (CIBERDEM) , Madrid , Spain
| | - Berta Rodriguez-Campins
- Departamento de I+D, New Biotechnic S.A. , Seville , Spain ; Fundación Andaluza de Investigación y Desarrollo (FAID) , Seville , Spain
| | - Abdelkrim Hmadcha
- Andalusian Center for Molecular Biology and Regenerative Medicine - Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER) , Seville , Spain ; Centro de Investigación en Red sobre Diabetes y Enfermedades Metabólicas (CIBERDEM) , Madrid , Spain
| | - Bernat Soria
- Andalusian Center for Molecular Biology and Regenerative Medicine - Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER) , Seville , Spain ; Centro de Investigación en Red sobre Diabetes y Enfermedades Metabólicas (CIBERDEM) , Madrid , Spain
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Bastijanic JM, Kligman FL, Marchant RE, Kottke-Marchant K. Dual biofunctional polymer modifications to address endothelialization and smooth muscle cell integration of ePTFE vascular grafts. J Biomed Mater Res A 2015; 104:71-81. [DOI: 10.1002/jbm.a.35541] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2015] [Revised: 07/10/2015] [Accepted: 07/14/2015] [Indexed: 01/02/2023]
Affiliation(s)
| | - Faina L. Kligman
- Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic; Cleveland Ohio
| | - Roger E. Marchant
- Department of Biomedical Engineering; Case Western Reserve University; Cleveland Ohio
| | - Kandice Kottke-Marchant
- Department of Biomedical Engineering; Case Western Reserve University; Cleveland Ohio
- Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic; Cleveland Ohio
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Koens MJW, Krasznai AG, Hanssen AEJ, Hendriks T, Praster R, Daamen WF, van der Vliet JA, van Kuppevelt TH. Vascular replacement using a layered elastin-collagen vascular graft in a porcine model: one week patency versus one month occlusion. Organogenesis 2015; 11:105-21. [PMID: 26060888 DOI: 10.1080/15476278.2015.1038448] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
A persistent clinical demand exists for a suitable arterial prosthesis. In this study, a vascular conduit mimicking the native 3-layered artery, and constructed from the extracellular matrix proteins type I collagen and elastin, was evaluated for its performance as a blood vessel equivalent. A tubular 3-layered graft (elastin-collagen-collagen) was prepared using highly purified type I collagen fibrils and elastin fibers, resembling the 3-layered native blood vessel architecture. The vascular graft was crosslinked and heparinised (37 ± 4 μg heparin/mg graft), and evaluated as a vascular graft using a porcine bilateral iliac artery model. An intra-animal comparison with clinically-used heparinised ePTFE (Propaten®) was made. Analyses included biochemical characterization, duplex scanning, (immuno)histochemistry and scanning electron microscopy. The tubular graft was easy to handle with adequate suturability. Implantation resulted in pulsating grafts without leakage. One week after implantation, both ePTFE and the natural acellular graft had 100% patencies on duplex scanning. Grafts were partially endothelialised (Von Willebrand-positive endothelium with a laminin-positive basal membrane layer). After one month, layered thrombi were found in the natural (4/4) and ePTFE graft (1/4), resulting in occlusion which in case of the natural graft is likely due to the porosity of the inner elastin layer. In vivo application of a molecularly-defined tubular graft, based on nature's matrix proteins, for vascular surgery is feasible.
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Affiliation(s)
- M J W Koens
- a Department of Biochemistry ; NCMLS; Radboud University Medical Centre ; Nijmegen , HB , The Netherlands.,b Department of Urology ; Radboud University Medical Centre ; Nijmegen , HB , The Netherlands
| | - A G Krasznai
- c Department of Surgery ; Radboud University Medical Centre ; Nijmegen , HB , The Netherlands
| | - A E J Hanssen
- d Central Animal Laboratory; Radboud University Medical Centre ; Nijmegen , HB , The Netherlands
| | - T Hendriks
- c Department of Surgery ; Radboud University Medical Centre ; Nijmegen , HB , The Netherlands
| | - R Praster
- c Department of Surgery ; Radboud University Medical Centre ; Nijmegen , HB , The Netherlands
| | - W F Daamen
- a Department of Biochemistry ; NCMLS; Radboud University Medical Centre ; Nijmegen , HB , The Netherlands
| | - J A van der Vliet
- c Department of Surgery ; Radboud University Medical Centre ; Nijmegen , HB , The Netherlands
| | - T H van Kuppevelt
- a Department of Biochemistry ; NCMLS; Radboud University Medical Centre ; Nijmegen , HB , The Netherlands
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Jiang B, Akgun B, Lam RC, Ameer GA, Wertheim JA. A polymer-extracellular matrix composite with improved thromboresistance and recellularization properties. Acta Biomater 2015; 18:50-8. [PMID: 25712388 PMCID: PMC4395555 DOI: 10.1016/j.actbio.2015.02.015] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2014] [Revised: 01/30/2015] [Accepted: 02/13/2015] [Indexed: 01/21/2023]
Abstract
Organ engineering using decellularized scaffolds is a potential long-term solution to donor organ shortage. However, this technology is severely limited by small vessel thrombosis due to incompletely recellularized vessels, resulting in exposure of extracellular matrix (ECM) components to platelets and clotting factors in flowing blood. To address this limitation, we designed a polymer-ECM composite and demonstrated its potential to reduce thrombosis and facilitate re-endothelialization in a vascular graft model. Rat aortas were decellularized using a sequential combination of weak detergents followed by a nuclease treatment that resulted in 96.5±1.3% DNA removal, while ECM components and mechanical properties were well maintained. A biodegradable and biocompatible elastomer poly(1,8 octanediol citrate) (POC, 1wt.%) was infused throughout the ECM at mild conditions (37°C and 45°C) and was functionalized with heparin using carbodiimide chemistry. The polymer-ECM composite significantly reduced platelet adhesion (67.4±8.2% and 82.7±9.6% reduction relative to untreated ECM using one of two processing temperatures, 37°C or 45°C, respectively); inhibited whole blood clotting (85.9±4.3% and 87.0±11.9% reduction relative to untreated ECM at 37°C or 45°C processing temperature, respectively); and supported endothelial cell-and to a lesser extent smooth muscle cell-adhesion in vitro. Taken together, this novel POC composite may provide a solution for thrombosis of small vessel conduits commonly seen in decellularized scaffolds used in tissue engineering applications.
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Affiliation(s)
- Bin Jiang
- Biomedical Engineering Department, Northwestern University, Evanston, IL 60201, United States; Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States
| | - Berke Akgun
- Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States
| | - Ryan C Lam
- Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL, United States
| | - Guillermo A Ameer
- Biomedical Engineering Department, Northwestern University, Evanston, IL 60201, United States; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States; Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60201, United States; Simpson Querrey Institute for BioNanotechnology in Medicine, Northwestern University, Chicago, IL 60611, United States.
| | - Jason A Wertheim
- Biomedical Engineering Department, Northwestern University, Evanston, IL 60201, United States; Comprehensive Transplant Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States; Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60201, United States; Simpson Querrey Institute for BioNanotechnology in Medicine, Northwestern University, Chicago, IL 60611, United States; Department of Surgery, Jesse Brown VA Medical Center, Chicago, IL 60612, United States.
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Böer U, Hurtado-Aguilar LG, Klingenberg M, Lau S, Jockenhoevel S, Haverich A, Wilhelmi M. Effect of Intensified Decellularization of Equine Carotid Arteries on Scaffold Biomechanics and Cytotoxicity. Ann Biomed Eng 2015; 43:2630-41. [PMID: 25921001 DOI: 10.1007/s10439-015-1328-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 04/20/2015] [Indexed: 12/26/2022]
Abstract
Decellularized equine carotid arteries (dEAC) are suggested to represent an alternative for alloplastic vascular grafts in haemodialysis patients to achieve vascular access. Recently it was shown that intensified detergent treatment completely removed cellular components from dEAC and thereby significantly reduced matrix immunogenicity. However, detergents may also affect matrix composition and stability and render scaffolds cytotoxic. Therefore, intensively decellularized carotids (int-dEAC) were now evaluated for their biomechanical characteristics (suture retention strength, burst pressure and circumferential compliance at arterial and venous systolic and diastolic pressure), matrix components (collagen and glycosaminoglycan content) and indirect and direct cytotoxicity (WST-8 assay and endothelial cell seeding) and compared with native (n-EAC) and conventionally decellularized carotids (con-dEAC). Both decellularization protocols comparably reduced matrix compliance (venous pressure compliance: 32.2 and 27.4% of n-EAC; p < 0.01 and arterial pressure compliance: 26.8 and 23.7% of n-EAC, p < 0.01) but had no effect on suture retention strength and burst pressure. Matrix characterization revealed unchanged collagen contents but a 39.0% (con-dEAC) and 26.4% (int-dEAC, p < 0.01) reduction of glycosaminoglycans, respectively. Cytotoxicity was not observed in either dEAC matrix which was also displayed by an intact endothelial lining after seeding. Thus, even intensified decellularization generates matrix scaffolds highly suitable for vascular tissue engineering purposes, e.g., the generation of haemodialysis shunts.
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Affiliation(s)
- Ulrike Böer
- GMP-Model Laboratory for Tissue Engineering, Feodor-Lynen-Str. 31, 30625, Hannover, Germany.
- Division for Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
| | - Luis G Hurtado-Aguilar
- Department of Tissue Engineering and Textile Implants, AME - Institute of Applied Medical Engineering, Helmholtz Institute, Pauwelsstr. 20, 52074, Aachen, Germany
| | - Melanie Klingenberg
- GMP-Model Laboratory for Tissue Engineering, Feodor-Lynen-Str. 31, 30625, Hannover, Germany
- Division for Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Skadi Lau
- GMP-Model Laboratory for Tissue Engineering, Feodor-Lynen-Str. 31, 30625, Hannover, Germany
- Division for Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Stefan Jockenhoevel
- Department of Tissue Engineering and Textile Implants, AME - Institute of Applied Medical Engineering, Helmholtz Institute, Pauwelsstr. 20, 52074, Aachen, Germany
| | - Axel Haverich
- GMP-Model Laboratory for Tissue Engineering, Feodor-Lynen-Str. 31, 30625, Hannover, Germany
- Division for Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Mathias Wilhelmi
- GMP-Model Laboratory for Tissue Engineering, Feodor-Lynen-Str. 31, 30625, Hannover, Germany
- Division for Cardiac-, Thoracic-, Transplantation- and Vascular Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
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Assadian A, Eckstein HH, Assadian A, Härtl F, Lulay GR, Storck M, Berg P, Gahlen J, Hupp T, Ghotbi R, Adili F, Schmitz-Rixen T, Eckstein HH. Outcome of the FUSION vascular graft for above-knee femoropopliteal bypass. J Vasc Surg 2015; 61:713-9.e1. [DOI: 10.1016/j.jvs.2014.10.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2014] [Accepted: 10/01/2014] [Indexed: 12/22/2022]
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Chong DST, Turner LA, Gadegaard N, Seifalian AM, Dalby MJ, Hamilton G. Nanotopography and plasma treatment: redesigning the surface for vascular graft endothelialisation. Eur J Vasc Endovasc Surg 2015; 49:335-43. [PMID: 25579872 DOI: 10.1016/j.ejvs.2014.12.008] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2014] [Accepted: 12/05/2014] [Indexed: 11/18/2022]
Abstract
INTRODUCTION Vascular graft materials in clinical use, such as polytetrafluoroethylene (PTFE) and Dacron, do not endothelialise and have low patency rates. The importance of an endothelial cell layer on the luminal surface of a vascular graft is well-known with surface topography and chemistry playing an important role. The aim of this study was to investigate the potential of plasma treatment and topographical structures on the luminal graft surface to enhance the self-endothelialisation potential of a nanocomposite vascular graft. METHODS POSS-PCU is a polycarbonate urea urethane (PCU) with a nanoparticle, polyhedral oligomeric silsesquioxane (POSS) incorporated within it. Planar, microgrooved, and nanopit patterned polymer films were fabricated using photolithography, electron beam lithography, reactive ion etching, and replication by solvent casting. Films were then exposed to oxygen plasma treatment at different powers for a fixed time (40 W, 60 W, 80 W/60 seconds). Effects of plasma treatment were assessed using scanning electron microscopy, atomic force microscopy and water contact angle analysis. Human umbilical vein endothelial cell (HUVEC) proliferation and morphology were characterised using immunostaining, live/dead staining, and Coomassie blue staining. RESULTS Successful embossing of the micro- and nanostructures was confirmed. Oxygen plasma treatment of the different samples showed that increasing power significantly increased the hydrophilicity of the samples (p < .0001). Improved HUVEC adhesion was seen on plasma modified compared with untreated samples (p < .0001). Coomassie blue staining showed that after 5 days, cells started to form monolayers and live/dead staining showed the cells were viable. Immunostaining showed that HUVECs expressed nitric oxide synthase on all topographies with focal adhesions appearing more pronounced on nanopit surfaces, showing retention of morphology and function. CONCLUSION These encouraging results indicate a future important role for plasma treatment and nanotopography in the development of endothelialised vascular grafts.
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Affiliation(s)
- D S T Chong
- Department of Vascular Surgery, Royal Free London NHS Foundation Trust, UK; Division of Surgery and Interventional Science, UCL, UK
| | - L A Turner
- Centre for Cell Engineering, University of Glasgow, UK
| | - N Gadegaard
- Division of Biomedical Engineering, University of Glasgow, UK
| | - A M Seifalian
- Division of Surgery and Interventional Science, UCL, UK
| | - M J Dalby
- Centre for Cell Engineering, University of Glasgow, UK
| | - G Hamilton
- Department of Vascular Surgery, Royal Free London NHS Foundation Trust, UK; Division of Surgery and Interventional Science, UCL, UK.
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Bergmeister H, Seyidova N, Schreiber C, Strobl M, Grasl C, Walter I, Messner B, Baudis S, Fröhlich S, Marchetti-Deschmann M, Griesser M, di Franco M, Krssak M, Liska R, Schima H. Biodegradable, thermoplastic polyurethane grafts for small diameter vascular replacements. Acta Biomater 2015; 11:104-13. [PMID: 25218664 DOI: 10.1016/j.actbio.2014.09.003] [Citation(s) in RCA: 93] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Revised: 08/01/2014] [Accepted: 09/03/2014] [Indexed: 11/19/2022]
Abstract
Biodegradable vascular grafts with sufficient in vivo performance would be more advantageous than permanent non-degradable prostheses. These constructs would be continuously replaced by host tissue, leading to an endogenous functional implant which would adapt to the need of the patient and exhibit only limited risk of microbiological graft contamination. Adequate biomechanical strength and a wall structure which promotes rapid host remodeling are prerequisites for biodegradable approaches. Current approaches often reveal limited tensile strength and therefore require thicker or reinforced graft walls. In this study we investigated the in vitro and in vivo biocompatibility of thin host-vessel-matched grafts (n=34) formed from hard-block biodegradable thermoplastic polyurethane (TPU). Expanded polytetrafluoroethylene (ePTFE) conduits (n=34) served as control grafts. Grafts were analyzed by various techniques after retrieval at different time points (1 week; 1, 6, 12 months). TPU grafts showed significantly increased endothelial cell proliferation in vitro (P<0.001). Population by host cells increased significantly in the TPU conduits within 1 month of implantation (P=0.01). After long-term implantation, TPU implants showed 100% patency (ePTFE: 93%) with no signs of aneurysmal dilatation. Substantial remodeling of the degradable grafts was observed but varied between subjects. Intimal hyperplasia was limited to ePTFE conduits (29%). Thin-walled TPU grafts offer a new and desirable form of biodegradable vascular implant. Degradable grafts showed equivalent long-term performance characteristics compared to the clinically used, non-degradable material with improvements in intimal hyperplasia and ingrowth of host cells.
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Affiliation(s)
- Helga Bergmeister
- Division of Biomedical Research, Medical University of Vienna, Austria; Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria.
| | - Nargiz Seyidova
- Division of Biomedical Research, Medical University of Vienna, Austria; Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
| | - Catharina Schreiber
- Division of Biomedical Research, Medical University of Vienna, Austria; Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
| | - Magdalena Strobl
- Division of Biomedical Research, Medical University of Vienna, Austria; Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
| | - Christian Grasl
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria; Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
| | - Ingrid Walter
- Department of Pathobiology, University of Veterinary Medicine, Vienna, Austria
| | - Barbara Messner
- Surgical Research Laboratories - Cardiac Surgery, Department of Surgery, Medical University of Vienna, Austria
| | - Stefan Baudis
- Institute of Applied Synthetic Chemistry, Vienna University of Technology, Vienna, Austria
| | - Sophie Fröhlich
- Institute of Chemical Technologies and Analytics, Vienna University of Technology, Vienna, Austria
| | | | - Markus Griesser
- Institute of Applied Synthetic Chemistry, Vienna University of Technology, Vienna, Austria
| | - Matt di Franco
- Computational Image Analysis and Radiology Lab, Department of Radiology, Medical University of Vienna, Austria
| | - Martin Krssak
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Vienna, Austria; Centre of Excellence, High Field MR, Department of Radiology, Medical University of Vienna, Austria
| | - Robert Liska
- Institute of Applied Synthetic Chemistry, Vienna University of Technology, Vienna, Austria
| | - Heinrich Schima
- Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Austria; Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
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Gerrah R, Sunstrom Pa-C RE, Hohimer AR. Pretreatment of synthetic vascular grafts with heparin before implantation, a simple technique to reduce the risk of thrombosis. Vascular 2014; 23:513-8. [PMID: 25406265 DOI: 10.1177/1708538114560455] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Thrombosis of synthetic grafts commonly used in cardiovascular surgery is a major complication. We examined whether pretreatment of the graft with heparin reduces the risk of early thrombosis. A circuit was assembled to compare two pairs of shunts simultaneously in the same animal. The study shunts were pretreated with heparin. After 2 hours of circulation, clot formation was evaluated by image analysis techniques. The pretreated grafts had fewer blood clots adhered to the surface by direct visual inspection. The image analysis showed 5 vs. 39 clots, 0.01% vs. 1.8% clotted area, and 62 vs. 5630 clot pixel area between the treated and non-treated grafts respectively, p < 0.05. Pretreatment of the synthetic graft with heparin prior to implantation reduces the risk of early clot formation. This simple practice might be helpful to prevent initial thrombosis of the graft and later occlusion.
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Affiliation(s)
- Rabin Gerrah
- Division of Cardiothoracic Surgery, Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | | | - Alan R Hohimer
- Division of Maternal/Fetal Medicine, Oregon Health and Science University, Portland, OR, USA
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