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Weekes A, Davern JW, Pinto N, Jenkins J, Li Z, Meinert C, Klein TJ. Enhancing compliance and extracellular matrix properties of tissue-engineered vascular grafts through pulsatile bioreactor culture. BIOMATERIALS ADVANCES 2025; 175:214346. [PMID: 40378643 DOI: 10.1016/j.bioadv.2025.214346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 02/06/2025] [Accepted: 05/11/2025] [Indexed: 05/19/2025]
Abstract
Biofabrication techniques represent a promising avenue for the production of small diameter vascular grafts. However, while current tissue-engineered vascular grafts (TEVGs) fulfil certain functional requirements of native blood vessels, most exhibit very poor mechanical compliance, directly reducing patency in vivo. Here, highly compliant TEVGs were cultured in a dynamic pulsatile bioreactor which ensured enhanced compliance, using biomimetic melt electrowritten (MEW) tubular scaffolds as substrates for tissue growth. Through 6-week in vitro culture, we investigated differences in extracellular matrix (ECM) production and mechanical performance of TEVGs cultured with placental mesenchymal stem cells (MSCs) and smooth muscle cells (SMCs) in static and dynamic conditions. Pulsatile stimulation successfully maintained the high compliance (12.4 ± 0.8 % per 100 mmHg) of our biomimetic scaffolds, substantially greater than existing small diameter grafts. Dynamic TEVGs demonstrated physiologically relevant burst pressure (1125 ± 212 mmHg) and suture pull-out force (3.0 ± 0.4 N), while also accumulating greater ECM components than static TEVGs. To assess off-the-shelf suitability, grafts were decellularized and lyophilised to produce d-TEVGs, which exhibited negligible loss of mechanics or ECM integrity. Finally, rehydrated d-TEVGs were seeded with endothelial cells in vitro, with an intimal endothelial lining forming after 7 days. These findings demonstrate the production of TEVGs with specifically engineered mechanical compliance which has been maintained by dynamic in vitro culture, supporting continued work toward biofabrication of the next generation of vascular grafts.
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Affiliation(s)
- Angus Weekes
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, Australia; School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD, Australia; Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, Australia.
| | - Jordan W Davern
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, Australia; School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD, Australia.
| | - Nigel Pinto
- Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, Australia; Department of Vascular Surgery, The Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
| | - Jason Jenkins
- Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, Australia; Department of Vascular Surgery, The Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
| | - Zhiyong Li
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, Australia; School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD, Australia.
| | - Christoph Meinert
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, Australia; Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, Australia.
| | - Travis J Klein
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, Australia; School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD, Australia.
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Isella B, Sallustio F, Acosta S, Andre D, Jockenhövel S, Fernández-Colino A, Rodriguez-Cabello JC, Vaughan TJ, Kopp A. A new approach for small-diameter vascular grafts using combined dip-coating of silk fibroin and elastin-like recombinamers. BIOMATERIALS ADVANCES 2025; 174:214312. [PMID: 40215941 DOI: 10.1016/j.bioadv.2025.214312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 04/04/2025] [Accepted: 04/07/2025] [Indexed: 05/07/2025]
Abstract
Compliance mismatch and suboptimal hemocompatibility prevent the use of the traditional materials used for vascular prostheses or degradable synthetic polymers as small-diameter vessel bypass grafts. Here, we show the combination of silk fibroin and elastin-like recombinamers in a dip-coating multilayer setup to achieve smooth small-diameter vascular grafts with ultrathin wall thickness. We found in both FTIR and mechanical characterization that the novel material combination was successful through the double crosslinked interpenetrated network formed by elastin-like recombinamers and silk fibroin. This enabled the graft to have mechanical compliance that followed physiological behaviour, differently from the synthetic materials traditionally used in clinics. The mechanical behaviour of these grafts also achieved burst pressure (745.44 ± 102.92 mmHg) and suture retention strength (0.86 ± 0.13 N) required for clinical application. The structure proved to have low platelet adhesion in the thrombogenicity assessment (3.79 ± 3.26 % of platelet area coverage), which is essential for successful outcomes in physiological conditions. Our results demonstrate the successful combination of the two materials in a technology platform that can be adjusted in both diameter and wall thickness and possesses suitable properties as a small-diameter vascular graft. We anticipate these results to be the starting point for more in vitro and in vivo tests possibly transitioning into clinical application.
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Affiliation(s)
- Benedetta Isella
- Biomechanics Research Centre (BioMEC), Biomedical Engineering, School of Engineering, College of Science and Engineering, University of Galway, Galway, Ireland; Fibrothelium GmbH, Philipsstraße 8, 52068 Aachen, Germany
| | - Federica Sallustio
- Department of Biohybrid & Medical Textiles (BioTex), AME-Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany; Bioforge Lab, University of Valladolid, CIBER-BBN, Valladolid, Spain
| | - Sergio Acosta
- Department of Biohybrid & Medical Textiles (BioTex), AME-Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany; Bioforge Lab, University of Valladolid, CIBER-BBN, Valladolid, Spain
| | - Dominic Andre
- Department of Biohybrid & Medical Textiles (BioTex), AME-Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany
| | - Stefan Jockenhövel
- Department of Biohybrid & Medical Textiles (BioTex), AME-Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany
| | - Alicia Fernández-Colino
- Department of Biohybrid & Medical Textiles (BioTex), AME-Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany
| | | | - Ted J Vaughan
- Biomechanics Research Centre (BioMEC), Biomedical Engineering, School of Engineering, College of Science and Engineering, University of Galway, Galway, Ireland.
| | - Alexander Kopp
- Fibrothelium GmbH, Philipsstraße 8, 52068 Aachen, Germany
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Imeidopf G, Khaimov D, John S, Merna N. Optimization and Standardization of Plant-Derived Vascular Scaffolds. Int J Mol Sci 2025; 26:2752. [PMID: 40141394 PMCID: PMC11942841 DOI: 10.3390/ijms26062752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/05/2025] [Accepted: 03/17/2025] [Indexed: 03/28/2025] Open
Abstract
Vascular graft failure rates remain unacceptably high due to thrombosis and poor integration, necessitating innovative solutions. This study optimized plant-derived extracellular matrix scaffolds as a scalable and biocompatible alternative to synthetic grafts and autologous vessels. We refined decellularization protocols to achieve >95% DNA removal while preserving mechanical properties comparable to native vessels, significantly enhancing endothelial cell seeding. Leatherleaf viburnum leaves were decellularized using sodium dodecyl sulfate-based and Trypsin/Tergitol-based treatments, achieved via clearing in bleach and Triton X-100 for 6 to 72 h. To assess the environmental influence on scaffold performance, leaves from multiple collection sites were processed using sodium dodecyl sulfate-based protocols. Scaffold performance was evaluated through tensile testing and histological analysis to assess structural integrity, while DNA quantification and endothelial cell recellularization measured biological compatibility. Sodium dodecyl sulfate-treated scaffolds with shorter clearing durations demonstrated the highest DNA removal (≥95%) while preserving mechanical properties, significantly outperforming Trypsin/Tergitol treatments. Longer clearing times reduced fiber diameter by 60%, compromising scaffold strength. Shorter clearing times preserved extracellular matrix integrity and significantly improved endothelial cell seeding efficiency. Larger leaves supported significantly higher endothelial cell densities than smaller leaves, highlighting the need for standardized material sources. Permeability tests demonstrated minimal leakage at 120 mmHg and structural stability under dynamic flow conditions, suggesting their suitability for vascular applications. These findings establish a reliable framework for optimizing plant-derived grafts, improving their reproducibility and performance for tissue engineering applications.
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Affiliation(s)
- Gianna Imeidopf
- Fred DeMatteis School of Engineering and Applied Science, Hofstra University, Hempstead, NY 11549, USA; (G.I.); (D.K.); (S.J.)
| | - Dara Khaimov
- Fred DeMatteis School of Engineering and Applied Science, Hofstra University, Hempstead, NY 11549, USA; (G.I.); (D.K.); (S.J.)
| | - Sashane John
- Fred DeMatteis School of Engineering and Applied Science, Hofstra University, Hempstead, NY 11549, USA; (G.I.); (D.K.); (S.J.)
- Cardiothoracic Surgery, Northwell Health, New York, NY 10022, USA
| | - Nick Merna
- Fred DeMatteis School of Engineering and Applied Science, Hofstra University, Hempstead, NY 11549, USA; (G.I.); (D.K.); (S.J.)
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Nguyen TC, Nguyen TL, Nguyen XH, Bui KC, Pham TA, Do LD, Tran NT, Nguyen TL, Hoang NTM, Do XH. Fresh Human Umbilical Cord Arteries as a Potential Source for Small-Diameter Vascular Grafts. ACS Biomater Sci Eng 2024; 10:7120-7131. [PMID: 39378361 DOI: 10.1021/acsbiomaterials.4c01414] [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: 10/10/2024]
Abstract
The demand for small-diameter vascular grafts has been globally increased but still lacks optimal solutions in this category. This study evaluated the feasibility of utilizing human pretreated fresh and nondecellularized umbilical cord arteries (hUCAs) as vascular grafts without needing any immunosuppression process. A mixed lymphocyte reaction assay revealed that hUCAs did not induce lymphocyte proliferation or cytokine production. To assess the in vivo inflammatory response, hUCAs were buried in fatty tissue under the skin of the abdominal wall in the left and right iliac fossas of rats. The average sizes of the implanted hUCAs remained consistent at 30 days post implantation. To evaluate xenogeneic transplantation, hUCAs were grafted to the abdominal aorta below the kidney of Wister rats. Remarkably, all rats exhibited positive revascularization and perfusion, maintaining blood pressure values of around 110/70 mmHg. Doppler ultrasound consistently indicated good circulation, with the three separate echogenic layers corresponding to the three arterial wall layers throughout the assessment period. Grafted rats exhibited normal motor behavior, accompanied by positive responses to thermal and pain stimulation. Blood biochemical values and whole blood cell counts showed no significant differences between pre and post-transplantation. Histological analysis of the grafts revealed no calcification or thrombosis, and a mild chronic inflammatory response was presented. In conclusion, hUCAs maintained their structural and functional properties after transplantation in rats without immunosuppression. This highlights their potential as a source for allogeneic, readily accessible, small-diameter vascular grafts.
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Affiliation(s)
- Trung-Chuc Nguyen
- Department of Practical and Experimental Surgery, Vietnam Military Medical University, 160 Phung Hung Street, Phuc La, Ha Dong, Hanoi 10000, Vietnam
| | - Toan Linh Nguyen
- Department of Pathophysiology, Vietnam Military Medical University, 160 Phung Hung Street, Phuc La, Ha Dong, Hanoi 10000, Vietnam
| | - Xuan-Hung Nguyen
- Vinmec Hi-Tech Center, Vinmec Healthcare System, 458 Minh Khai Street, Hanoi 10000, Vietnam
- College of Health Sciences, VinUniversity, Hanoi 10000, Vietnam
| | - Khac-Cuong Bui
- Department of Pathophysiology, Vietnam Military Medical University, 160 Phung Hung Street, Phuc La, Ha Dong, Hanoi 10000, Vietnam
| | - Tuan-Anh Pham
- Faculty of Biology, VNU University of Science, 334 Nguyen Trai Street, Thanh Xuan, Hanoi 10000, Vietnam
| | - Linh Dieu Do
- Faculty of Biology, VNU University of Science, 334 Nguyen Trai Street, Thanh Xuan, Hanoi 10000, Vietnam
| | - Nghia Trung Tran
- Faculty of Biology, VNU University of Science, 334 Nguyen Trai Street, Thanh Xuan, Hanoi 10000, Vietnam
| | - Thanh-Liem Nguyen
- Vinmec Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, 458 Minh Khai Street, Hanoi 10000, Vietnam
| | - Nhung Thi My Hoang
- Faculty of Biology, VNU University of Science, 334 Nguyen Trai Street, Thanh Xuan, Hanoi 10000, Vietnam
| | - Xuan-Hai Do
- Department of Practical and Experimental Surgery, Vietnam Military Medical University, 160 Phung Hung Street, Phuc La, Ha Dong, Hanoi 10000, Vietnam
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Xia Y, Rao Z, Wu S, Huang J, Zhou H, Li H, Zheng H, Guo D, Quan D, Ou JS, Bai Y, Liu Y. Polyzwitterion-grafted decellularized bovine intercostal arteries as new substitutes of small-diameter arteries for vascular regeneration. Regen Biomater 2024; 11:rbae098. [PMID: 39224131 PMCID: PMC11368410 DOI: 10.1093/rb/rbae098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 06/23/2024] [Accepted: 07/08/2024] [Indexed: 09/04/2024] Open
Abstract
Coronary artery bypass grafting is acknowledged as a major clinical approach for treatment of severe coronary artery atherosclerotic heart disease. This procedure typically requires autologous small-diameter vascular grafts. However, the limited availability of the donor vessels and associated trauma during tissue harvest underscore the necessity for artificial arterial alternatives. Herein, decellularized bovine intercostal arteries were successfully fabricated with lengths ranging from 15 to 30 cm, which also closely match the inner diameters of human coronary arteries. These decellularized arterial grafts exhibited great promise following poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) grafting from the inner surface. Such surface modification endowed the decellularized arteries with superior mechanical strength, enhanced anticoagulant properties and improved biocompatibility, compared to the decellularized bovine intercostal arteries alone, or even those decellularized grafts modified with both heparin and vascular endothelial growth factor. After replacement of the carotid arteries in rabbits, all surface-modified vascular grafts have shown good patency within 30 days post-implantation. Notably, strong signal was observed after α-SMA immunofluorescence staining on the PMPC-grafted vessels, indicating significant potential for regenerating the vascular smooth muscle layer and thereby restoring full structures of the artery. Consequently, the decellularized bovine intercostal arteries surface modified by PMPC can emerge as a potent candidate for small-diameter artificial blood vessels, and have shown great promise to serve as viable substitutes of arterial autografts.
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Affiliation(s)
- Yuan Xia
- Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Zilong Rao
- Guangdong Engineering Technology Research Centre for Functional Biomaterials, Key Laboratory for Polymeric Composite & Functional Materials of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510006, China
| | - Simin Wu
- Guangdong Engineering Technology Research Centre for Functional Biomaterials, Key Laboratory for Polymeric Composite & Functional Materials of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510006, China
| | - Jiayao Huang
- Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
| | - Haiyun Zhou
- Department of Cardiac Surgery, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510160, China
| | - Hanzhao Li
- Department of Cardiac Surgery, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510160, China
| | - Hui Zheng
- Department of Cardiac Surgery, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510160, China
| | - Daxin Guo
- Department of Cardiac Surgery, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510160, China
| | - Daping Quan
- Guangdong Engineering Technology Research Centre for Functional Biomaterials, Key Laboratory for Polymeric Composite & Functional Materials of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510006, China
| | - Jing-Song Ou
- Division of Cardiac Surgery, Cardiovascular Diseases Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
- National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Engineering Technology Centre for Diagnosis and Treatment of Vascular Diseases, Guangzhou 510080, China
- Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
| | - Ying Bai
- Guangdong Engineering Technology Research Centre for Functional Biomaterials, Key Laboratory for Polymeric Composite & Functional Materials of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510006, China
| | - Yunqi Liu
- Department of Cardiac Surgery, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510160, China
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Arsyad A, Lembang GKR, Linda SL, Djabir YY, Dobson GP. Low Calcium-High Magnesium Krebs-Henseleit Solution Combined with Adenosine and Lidocaine Improved Rat Aortic Function and Structure Following Cold Preservation. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1284. [PMID: 39202566 PMCID: PMC11356418 DOI: 10.3390/medicina60081284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 07/30/2024] [Accepted: 08/06/2024] [Indexed: 09/03/2024]
Abstract
Background and objectives: The main problem of vascular preservation is the maintenance of vessel graft quality and function following extended storage. Conventional preservation solutions such as histidine-tryptophan-ketoglutarate (HTK) solution, Phosphate-Buffer Solution (PBS), or sodium chloride 0.9% has been shown to be inadequate in preserving vascular physiological function after 3 days of cold storage. This study aimed to evaluate whether adenosine and lidocaine (AL) in a modified Krebs-Henseleit (KH) solution can preserve the function and histological structure of rat aortic rings after 6 days. Materials and Methods: Thirty-five aortic rings from male Wistar rats (200-300 g) were harvested and immediately immersed in one of the assigned cold preservation solutions: standard KH, modified KH (mod KH) with lower calcium (Ca2+) and higher magnesium content (Mg2+) with or without adenosine and lidocaine (mod KH-AL), and modified KH with AL, insulin, and melatonin (Mod KH-ALMI). The contraction and relaxation function of the aortic rings were examined using an isometric force transducer after 6 days of cold preservation. Hematoxylin and eosin staining were used to analyze the rings' histological structure. Results: Vascular contraction and relaxation functions were severely affected after a 6-day cold storage period in standard KH. Modifying the KH solution by reducing the Ca2+ and increasing the Mg2+ levels greatly recovered the vessel functions. The addition of AL or ALMI to the modified KH did not further recover vascular contractility. However, only the addition of AL to the modified KH increased the ACh-induced relaxation at 6 days when compared to the conventional KH, suggesting that endothelium preservation is improved. From histological analysis, it was found that the addition of AL but not ALMI further improved the endothelial lining and the structure of the elastic membrane layers of the preserved vessels after 6 days of cold preservation. Conclusions: The addition of AL to low calcium-high magnesium KH solution significantly enhanced endothelial preservation and improved endothelial-induced relaxation of preserved vessels after 6 days of cold storage.
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Affiliation(s)
- Aryadi Arsyad
- Department of Physiology, Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia
| | - Geni K. R. Lembang
- Clinical Pharmacy Laboratory, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia; (G.K.R.L.); (S.L.L.); (Y.Y.D.)
| | - Sesilia L. Linda
- Clinical Pharmacy Laboratory, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia; (G.K.R.L.); (S.L.L.); (Y.Y.D.)
| | - Yulia Y. Djabir
- Clinical Pharmacy Laboratory, Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Indonesia; (G.K.R.L.); (S.L.L.); (Y.Y.D.)
| | - Geoffrey P. Dobson
- Heart, Trauma and Sepsis Research Laboratory, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia;
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Wolfe JT, Chen V, Chen Y, Tefft BJ. Identification of a subpopulation of highly adherent endothelial cells for seeding synthetic vascular grafts. J Thorac Cardiovasc Surg 2024:S0022-5223(24)00550-6. [PMID: 38972570 PMCID: PMC11700231 DOI: 10.1016/j.jtcvs.2024.06.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 06/07/2024] [Accepted: 06/27/2024] [Indexed: 07/09/2024]
Abstract
OBJECTIVE There is an unmet clinical need for alternatives to autologous vessel grafts. Small-diameter (<6 mm) synthetic vascular grafts are not suitable because of unacceptable patency rates. This mainly occurs due to the lack of an endothelial cell (EC) monolayer to prevent platelet activation, thrombosis, and intimal hyperplasia. There are no reliable methods to endothelialize small-diameter grafts because most seeded ECs are lost due to exposure to fluid shear stress after implantation. The goal of this work is to determine if EC loss is a random process or if it is possible to predict which cells are more likely to remain adherent. METHODS In initial studies, we sorted ECs using fluid shear stress and identified a subpopulation of ECs that are more likely to resist detachment. We use RNA sequencing to examine gene expression of adherent ECs compared with the whole population. Using fluorescence activated cell sorting, we sorted ECs based on the expression level of a candidate marker and studied their retention in small-diameter vascular grafts in vitro. RESULTS Transcriptomic analysis revealed that fibronectin leucine rich transmembrane protein 2 (FLRT2), encoding protein FLRT2, is downregulated in the ECs that are more likely to resist detachment. When seeded onto vascular grafts and exposed to shear stress, ECs expressing low levels of FLRT2 exhibit 59.2% ± 7.4% retention compared with 24.5% ± 6.1% retention for the remainder of the EC population. CONCLUSIONS For the first time, we show EC detachment is not an entirely random process. This provides validation for the concept that we can seed small-diameter vascular grafts only with highly adherent ECs to maintain a stable endothelium and improve graft patency rates.
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Affiliation(s)
- Jayne T Wolfe
- Joint Department of Biomedical Engineering, Medical College of Wisconsin and Marquette University, Milwaukee, Wis
| | - Vaya Chen
- Versiti Blood Research Institute, Milwaukee, Wis
| | - Yiliang Chen
- Versiti Blood Research Institute, Milwaukee, Wis; Department of Medicine, Medical College of Wisconsin, Milwaukee, Wis; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wis
| | - Brandon J Tefft
- Joint Department of Biomedical Engineering, Medical College of Wisconsin and Marquette University, Milwaukee, Wis; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wis.
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Bartolf-Kopp M, Jungst T. The Past, Present, and Future of Tubular Melt Electrowritten Constructs to Mimic Small Diameter Blood Vessels - A Stable Process? Adv Healthc Mater 2024; 13:e2400426. [PMID: 38607966 DOI: 10.1002/adhm.202400426] [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: 02/03/2024] [Revised: 03/20/2024] [Indexed: 04/14/2024]
Abstract
Melt Electrowriting (MEW) is a continuously growing manufacturing platform. Its advantage is the consistent production of micro- to nanometer fibers, that stack intricately, forming complex geometrical shapes. MEW allows tuning of the mechanical properties of constructs via the geometry of deposited fibers. Due to this, MEW can create complex mechanics only seen in multi-material compounds and serve as guiding structures for cellular alignment. The advantage of MEW is also shown in combination with other biotechnological manufacturing methods to create multilayered constructs that increase mechanical approximation to native tissues, biocompatibility, and cellular response. These features make MEW constructs a perfect candidate for small-diameter vascular graft structures. Recently, studies have presented fascinating results in this regard, but is this truly the direction that tubular MEW will follow or are there also other options on the horizon? This perspective will explore the origins and developments of tubular MEW and present its growing importance in the field of artificial small-diameter vascular grafts with mechanical modulation and improved biomimicry and the impact of it in convergence with other manufacturing methods and how future technologies like AI may influence its progress.
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Affiliation(s)
- Michael Bartolf-Kopp
- Department for Functional Materials in Medicine and Dentistry, Institute of Biofabrication and Functional Materials, University of Würzburg and KeyLab Polymers for Medicine of the Bavarian Polymer Institute (BPI), Würzburg, Germany
| | - Tomasz Jungst
- Department for Functional Materials in Medicine and Dentistry, Institute of Biofabrication and Functional Materials, University of Würzburg and KeyLab Polymers for Medicine of the Bavarian Polymer Institute (BPI), Würzburg, Germany
- Department of Orthopedics, Regenerative Medicine Center Utrecht, University Medical Center Utrecht, Utrecht, Netherlands
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9
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Rosellini E, Giordano C, Guidi L, Cascone MG. Biomimetic Approaches in Scaffold-Based Blood Vessel Tissue Engineering. Biomimetics (Basel) 2024; 9:377. [PMID: 39056818 PMCID: PMC11274842 DOI: 10.3390/biomimetics9070377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 06/15/2024] [Accepted: 06/19/2024] [Indexed: 07/28/2024] Open
Abstract
Cardiovascular diseases remain a leading cause of mortality globally, with atherosclerosis representing a significant pathological means, often leading to myocardial infarction. Coronary artery bypass surgery, a common procedure used to treat coronary artery disease, presents challenges due to the limited autologous tissue availability or the shortcomings of synthetic grafts. Consequently, there is a growing interest in tissue engineering approaches to develop vascular substitutes. This review offers an updated picture of the state of the art in vascular tissue engineering, emphasising the design of scaffolds and dynamic culture conditions following a biomimetic approach. By emulating native vessel properties and, in particular, by mimicking the three-layer structure of the vascular wall, tissue-engineered grafts can improve long-term patency and clinical outcomes. Furthermore, ongoing research focuses on enhancing biomimicry through innovative scaffold materials, surface functionalisation strategies, and the use of bioreactors mimicking the physiological microenvironment. Through a multidisciplinary lens, this review provides insight into the latest advancements and future directions of vascular tissue engineering, with particular reference to employing biomimicry to create systems capable of reproducing the structure-function relationships present in the arterial wall. Despite the existence of a gap between benchtop innovation and clinical translation, it appears that the biomimetic technologies developed to date demonstrate promising results in preventing vascular occlusion due to blood clotting under laboratory conditions and in preclinical studies. Therefore, a multifaceted biomimetic approach could represent a winning strategy to ensure the translation of vascular tissue engineering into clinical practice.
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Affiliation(s)
- Elisabetta Rosellini
- Department of Civil and Industrial Engineering, University of Pisa, Largo Lucio Lazzarino 1, 56122 Pisa, Italy; (C.G.); (L.G.)
| | | | | | - Maria Grazia Cascone
- Department of Civil and Industrial Engineering, University of Pisa, Largo Lucio Lazzarino 1, 56122 Pisa, Italy; (C.G.); (L.G.)
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10
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Hernandez-Sanchez D, Comtois-Bona M, Muñoz M, Ruel M, Suuronen EJ, Alarcon EI. Manufacturing and validation of small-diameter vascular grafts: A mini review. iScience 2024; 27:109845. [PMID: 38799581 PMCID: PMC11126982 DOI: 10.1016/j.isci.2024.109845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/29/2024] Open
Abstract
The field of small-diameter vascular grafts remains a challenge for biomaterials scientists. While decades of research have brought us much closer to developing biomimetic materials for regenerating tissues and organs, the physiological challenges involved in manufacturing small conduits that can transport blood while not inducing an immune response or promoting blood clots continue to limit progress in this area. In this short review, we present some of the most recent methods and advancements made by researchers working in the field of small-diameter vascular grafts. We also discuss some of the most critical aspects biomaterials scientists should consider when developing lab-made small-diameter vascular grafts.
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Affiliation(s)
- Deyanira Hernandez-Sanchez
- BioEngineering and Therapeutic Solutions (BEaTS) Research, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
| | - Maxime Comtois-Bona
- BioEngineering and Therapeutic Solutions (BEaTS) Research, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
| | - Marcelo Muñoz
- BioEngineering and Therapeutic Solutions (BEaTS) Research, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
| | - Marc Ruel
- BioEngineering and Therapeutic Solutions (BEaTS) Research, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
- Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
- Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, 451 Smyth Road, Ottawa ON K1H8M5, Canada
| | - Erik J. Suuronen
- BioEngineering and Therapeutic Solutions (BEaTS) Research, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
- Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, 451 Smyth Road, Ottawa ON K1H8M5, Canada
| | - Emilio I. Alarcon
- BioEngineering and Therapeutic Solutions (BEaTS) Research, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y4W7, Canada
- Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H8M5, Canada
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11
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Weekes A, Wasielewska JM, Pinto N, Jenkins J, Patel J, Li Z, Klein TJ, Meinert C. Harnessing the Regenerative Potential of Fetal Mesenchymal Stem Cells and Endothelial Colony-Forming Cells in the Biofabrication of Tissue-Engineered Vascular Grafts (TEVGs). J Tissue Eng Regen Med 2024; 2024:8707377. [PMID: 40225752 PMCID: PMC11919237 DOI: 10.1155/2024/8707377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 02/08/2024] [Indexed: 04/15/2025]
Abstract
Tissue engineering is a promising approach for the production of small-diameter vascular grafts; however, there are limited data directly comparing the suitability of applicable cell types for vessel biofabrication. Here, we investigated the potential of adult smooth muscle cells (SMCs), placental mesenchymal stem cells (MSCs), placental endothelial colony-forming cells (ECFCs), and a combination of MSCs and ECFCs on highly porous biocompatible poly(ɛ-caprolactone) (PCL) scaffolds produced via melt electrowriting (MEW) for the biofabrication of tissue-engineered vascular grafts (TEVGs). Cellular attachment, proliferation, and deposition of essential extracellular matrix (ECM) components were analysed in vitro over four weeks. TEVGs cultured with MSCs accumulated the highest levels of collagenous components within a dense ECM, while SMCs and the coculture were more sparsely populated, ascertained via histological and immunofluorescence imaging, and biochemical assessment. Scanning electron microscopy (SEM) enabled visualisation of morphological differences in cell attachment and growth, with MSCs and SMCs infiltrating and covering scaffolds completely within the 28-day culture period. Coverage and matrix deposition by ECFCs was limited. However, ECFCs lined the ECM formed by MSCs in coculture, visualised via immunostaining. Thus, of cells investigated, placental MSCs were identified as the preferred cell source for the fabrication of tissue-engineered constructs, exhibiting extensive population of porous polymer scaffolds and production of ECM components; with the inclusion of ECFCs for luminal endothelialisation, an encouraging outcome warranting further consideration in future studies. In combination, these findings represent a substantial step toward the development of the next generation of small-diameter vascular grafts in the management of cardiovascular disease.
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Affiliation(s)
- Angus Weekes
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, Australia
- School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD, Australia
- Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, Australia
| | - Joanna M. Wasielewska
- Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, Australia
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Nigel Pinto
- Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, Australia
- Department of Vascular Surgery, The Royal Brisbane and Women's Hospital, Herston, QLD, Australia
| | - Jason Jenkins
- Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, Australia
- Department of Vascular Surgery, The Royal Brisbane and Women's Hospital, Herston, QLD, Australia
| | - Jatin Patel
- School of Biomedical Sciences, Faculty of Health, Queensland University of Technology (QUT), Woolloongabba, QLD, Australia
| | - Zhiyong Li
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, Australia
- School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD, Australia
| | - Travis J. Klein
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, Australia
- School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD, Australia
| | - Christoph Meinert
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, Australia
- Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, Australia
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12
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Ma F, Huang X, Wang Y. Fabrication of a Triple-Layer Bionic Vascular Scaffold via Hybrid Electrospinning. J Funct Biomater 2024; 15:140. [PMID: 38921514 PMCID: PMC11204414 DOI: 10.3390/jfb15060140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Revised: 05/13/2024] [Accepted: 05/21/2024] [Indexed: 06/27/2024] Open
Abstract
Tissue engineering aims to develop bionic scaffolds as alternatives to autologous vascular grafts due to their limited availability. This study introduces a novel wet-electrospinning fabrication technique to create small-diameter, uniformly aligned tubular scaffolds. By combining this innovative method with conventional electrospinning, a bionic tri-layer scaffold that mimics the zonal structure of vascular tissues is produced. The inner and outer layers consist of PCL/Gelatin and PCL/PLGA fibers, respectively, while the middle layer is crafted using PCL through Wet Vertical Magnetic Rod Electrospinning (WVMRE). The scaffold's morphology is analyzed using Scanning Electron Microscopy (SEM) to confirm its bionic structure. The mechanical properties, degradation profile, wettability, and biocompatibility of the scaffold are also characterized. To enhance hemocompatibility, the scaffold is crosslinked with heparin. The results demonstrate sufficient mechanical properties, good wettability of the inner layer, proper degradability of the inner and middle layers, and overall good biocompatibility. In conclusion, this study successfully develops a small-diameter tri-layer tubular scaffold that meets the required specifications.
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Affiliation(s)
- Feier Ma
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
- Institute of Orthopaedic & Musculoskeletal Science, Division of Surgery and Interventional Science, University College London, The Royal National Orthopaedic Hospital, Stanmore, London HA7 4LP, UK
| | - Xiaojing Huang
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Yan Wang
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
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13
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Zumbardo-Bacelis GA, Peponi L, Vargas-Coronado RF, Rodríguez-Velázquez E, Alatorre-Meda M, Chevallier P, Copes F, Mantovani D, Abraham GA, Cauich-Rodríguez JV. A Comparison of Three-Layer and Single-Layer Small Vascular Grafts Manufactured via the Roto-Evaporation Method. Polymers (Basel) 2024; 16:1314. [PMID: 38794507 PMCID: PMC11125268 DOI: 10.3390/polym16101314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 04/18/2024] [Accepted: 05/02/2024] [Indexed: 05/26/2024] Open
Abstract
This study used the roto-evaporation technique to engineer a 6 mm three-layer polyurethane vascular graft (TVG) that mimics the architecture of human coronary artery native vessels. Two segmented polyurethanes were synthesized using lysine (SPUUK) and ascorbic acid (SPUAA), and the resulting materials were used to create the intima and adventitia layers, respectively. In contrast, the media layer of the TVG was composed of a commercially available polyurethane, Pearlbond 703 EXP. For comparison purposes, single-layer vascular grafts (SVGs) from individual polyurethanes and a polyurethane blend (MVG) were made and tested similarly and evaluated according to the ISO 7198 standard. The TVG exhibited the highest circumferential tensile strength and longitudinal forces compared to single-layer vascular grafts of lower thicknesses made from the same polyurethanes. The TVG also showed higher suture and burst strength values than native vessels. The TVG withstood up to 2087 ± 139 mmHg and exhibited a compliance of 0.15 ± 0.1%/100 mmHg, while SPUUK SVGs showed a compliance of 5.21 ± 1.29%/100 mmHg, akin to coronary arteries but superior to the saphenous vein. An indirect cytocompatibility test using the MDA-MB-231 cell line showed 90 to 100% viability for all polyurethanes, surpassing the minimum 70% threshold needed for biomaterials deemed cytocompatibility. Despite the non-cytotoxic nature of the polyurethane extracts when grown directly on the surface, they displayed poor fibroblast adhesion, except for SPUUK. All vascular grafts showed hemolysis values under the permissible limit of 5% and longer coagulation times.
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Affiliation(s)
- Gualberto Antonio Zumbardo-Bacelis
- Unidad de Materiales, Centro de Investigación Científica de Yucatán, Calle 43 #130 x 32 y 34, Colonia Chuburná de Hidalgo, Mérida C.P. 97205, Mexico; (G.A.Z.-B.); (R.F.V.-C.)
- Department of Chemical Engineering, Laval University, Quebec, QC G1V 0A6, Canada
| | - Laura Peponi
- Instituto de Ciencia y Tecnología de Polímeros (ICTP-CSIC), C/Juan de la Cierva 3, 28006 Madrid, Spain
| | - Rossana Faride Vargas-Coronado
- Unidad de Materiales, Centro de Investigación Científica de Yucatán, Calle 43 #130 x 32 y 34, Colonia Chuburná de Hidalgo, Mérida C.P. 97205, Mexico; (G.A.Z.-B.); (R.F.V.-C.)
| | - Eustolia Rodríguez-Velázquez
- Facultad de Odontología, Universidad Autónoma de Baja California, Tijuana 22390, Mexico;
- Centro de Graduados e Investigación en Química-Grupo de Biomateriales y Nanomedicina, Tecnológico Nacional de México, Instituto Tecnológico de Tijuana, Tijuana 22510, Mexico
| | - Manuel Alatorre-Meda
- Centro de Graduados e Investigación en Química-Grupo de Biomateriales y Nanomedicina, CONAHCYT-Tecnológico Nacional de México, Instituto Tecnológico de Tijuana, Tijuana 22510, Mexico;
| | - Pascale Chevallier
- Laboratory for Biomaterials and Bioengineering (CRC-I), Department of Min-Met-Materials Engineering & CHU de Quebec Research Center, Laval University, Quebec, QC G1V0A6, Canada; (P.C.)
| | - Francesco Copes
- Laboratory for Biomaterials and Bioengineering (CRC-I), Department of Min-Met-Materials Engineering & CHU de Quebec Research Center, Laval University, Quebec, QC G1V0A6, Canada; (P.C.)
| | - Diego Mantovani
- Laboratory for Biomaterials and Bioengineering (CRC-I), Department of Min-Met-Materials Engineering & CHU de Quebec Research Center, Laval University, Quebec, QC G1V0A6, Canada; (P.C.)
| | - Gustavo A. Abraham
- Research Institute for Materials Science and Technology, INTEMA (UNMdP-CONICET). Av. Colón 10850, Mar del Plata B7606BWV, Argentina
| | - Juan Valerio Cauich-Rodríguez
- Unidad de Materiales, Centro de Investigación Científica de Yucatán, Calle 43 #130 x 32 y 34, Colonia Chuburná de Hidalgo, Mérida C.P. 97205, Mexico; (G.A.Z.-B.); (R.F.V.-C.)
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14
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Goldberg LA, Zomer HD, McFetridge C, McFetridge PS. Silica nanoparticles enhance the cyto- and hemocompatibility of a multilayered extracellular matrix scaffold for vascular tissue regeneration. Biotechnol Lett 2024; 46:249-261. [PMID: 38279044 DOI: 10.1007/s10529-023-03459-8] [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: 04/17/2023] [Revised: 11/04/2023] [Accepted: 12/14/2023] [Indexed: 01/28/2024]
Abstract
PURPOSE The limited availability of autologous vessels for vascular bypass surgeries is a major roadblock to treating severe cardiovascular diseases. Based on this clinical priority, our group has developed a novel engineered vascular graft by rolling human amniotic membranes into multilayered extracellular matrixes (ECM). When treated with silica nanoparticles (SiNP), these rolled scaffolds showed a significant improvement in their structural and mechanical properties, matching those from gold standard autologous grafts. However, it remained to be determined how cells respond to SiNP-treated materials. As a first step toward understanding the biocompatibility of SiNP-dosed biomaterials, we aimed to assess how endothelial cells and blood components interact with SiNP-treated ECM scaffolds. METHODS To test this, we used established in vitro assays to study SiNP and SiNP-treated scaffolds' cyto and hemocompatibility. RESULTS Our results showed that SiNP effects on cells were concentration-dependent with no adverse effects observed up to 10 μg/ml of SiNP, with higher concentrations inducing cytotoxic and hemolytic responses. The SiNP also enhanced the scaffold's hydrophobicity state, a feature known to inhibit platelet and immune cell adhesion. Accordingly, SiNP-treated scaffolds were also shown to support endothelial cell growth while preventing platelet and leukocyte adhesion. CONCLUSION Our findings suggest that the addition of SiNP to human amniotic membrane extracellular matrixes improves the cyto- and hemocompatibility of rolled scaffolds and highlights this strategy as a robust mechanism to stabilize layered collagen scaffolds for vascular tissue regeneration.
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Affiliation(s)
- Leslie A Goldberg
- J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Biomedical Sciences Building JG-56, 1275 Center Drive, Gainesville, FL, 32611-6131, USA
| | - Helena D Zomer
- Department of Physiological Sciences, University of Florida, Gainesville, FL, USA
| | - Calum McFetridge
- J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Biomedical Sciences Building JG-56, 1275 Center Drive, Gainesville, FL, 32611-6131, USA
| | - Peter S McFetridge
- J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Biomedical Sciences Building JG-56, 1275 Center Drive, Gainesville, FL, 32611-6131, USA.
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15
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Chen E, Turng LS. A Double-Expanded Polytetrafluoroethylene Fabrication Method for Increased Mechanical Compliance in Tubular Vascular Graft Applications. POLYM ENG SCI 2024; 64:1756-1769. [PMID: 39184016 PMCID: PMC11343504 DOI: 10.1002/pen.26652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Accepted: 01/21/2024] [Indexed: 08/27/2024]
Abstract
A novel manufacturing technique has been developed to enhance the compliance of expanded polytetrafluoroethylene (ePTFE) for vascular graft applications. This new method involves modifying the existing processing procedures by introducing an additional expansion step while using a lower temperature during the first expansion stage. The new process results in the production of highly compliant ePTFE grafts without the need for supplementary additives or inherent material alterations. Tensile testing in both the longitudinal and circumferential directions as well as cyclical tensile testing were conducted to characterize the mechanical properties of double-expanded ePTFE grafts prepared using varying expansion ratios. The double-expanded ePTFE grafts consistently outperformed the prevailing, single-expanded counterparts in both tensile stress tests and cyclical assessments of its elastic compliance. Notably, the double-expanded ePTFE samples exhibited the desirable, biomimetic "toe-region" and an elastic strain capacity of up to 50%, comparable to native vascular materials. Scanning electron microscopy (SEM) imaging was used to examine the morphological characteristics of the wavy fibers within the double-expanded PTFE samples, which contributed to the enhanced compliance that is needed for vascular graft applications.
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Affiliation(s)
- Edward Chen
- Department of Mechanical Engineering, University of Wisconsin–Madison, Madison, WI 53706, USA
- Wisconsin Institute for Discovery, University of Wisconsin–Madison, Madison, WI 53715, USA
| | - Lih-Sheng Turng
- Department of Mechanical Engineering, University of Wisconsin–Madison, Madison, WI 53706, USA
- Wisconsin Institute for Discovery, University of Wisconsin–Madison, Madison, WI 53715, USA
- Department of Mechanical Engineering, Chang Gung University, Tao-Yuan 33302, Taiwan
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16
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Asakura T, Shimokawatoko H, Nakazawa Y. Characterization and promotion of endothelialization of Bombyx mori silk fibroin functionalized with REDV peptide. Int J Biol Macromol 2024; 261:129746. [PMID: 38302025 DOI: 10.1016/j.ijbiomac.2024.129746] [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: 10/23/2023] [Revised: 01/22/2024] [Accepted: 01/23/2024] [Indexed: 02/03/2024]
Abstract
In the development of small-diameter vascular grafts, it is crucial to achieve early-stage endothelialization to prevent thrombus formation and intimal hyperplasia. Silk fibroin (SF) from Bombyx mori is commonly used for such grafts. However, there is a need to expedite endothelialization post-implantation. In this study, we functionalized SF with Arg-Glu-Asp-Val (REDV) (SF + REDV) using cyanuric chloride to enhance endothelialization. The immobilization of REDV onto SF was confirmed and the amount of immobilized REDV could be calculated by 1H NMR. Furthermore, the conformational changes in Tyr, Ser, and Ala residues in [3-13C]Tyr- and [3-13C]Ser-SF due to REDV immobilization were monitored using 13C solid-state NMR. The REDV immobilized onto the SF film was found to be exposed on the film's surface, as confirmed by biotin-avidin system. Cell culture experiments, including adhesiveness, proliferation, and extensibility, were conducted using normal human umbilical vein endothelial cells (HUVEC) and normal human aortic smooth muscle cells (HAoSMC) on both SF and SF + REDV films to evaluate the impact of REDV on endothelialization. The results indicated a trend towards promoting HUVEC proliferation while inhibiting HAoSMC proliferation. Therefore, these findings suggest that SF + REDV may be more suitable than SF alone for coating small-diameter SF knitted tubes made of SF threads.
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Affiliation(s)
- Tetsuo Asakura
- Department of Biotechnology, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo 184-8588, Japan.
| | - Haruka Shimokawatoko
- Department of Biotechnology, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo 184-8588, Japan
| | - Yasumoto Nakazawa
- Department of Biotechnology, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo 184-8588, Japan
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17
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Ozdemir S, Oztemur J, Sezgin H, Yalcin-Enis I. Optimization of Electrospun Bilayer Vascular Grafts through Assessment of the Mechanical Properties of Monolayers. ACS Biomater Sci Eng 2024; 10:960-974. [PMID: 38196384 DOI: 10.1021/acsbiomaterials.3c01161] [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: 01/11/2024]
Abstract
Small-diameter vascular grafts must be obtained with the most appropriate materials and design selection to harmoniously display a variety of features, including adequate tensile strength, compliance, burst strength, biocompatibility, and biodegradability against challenging physiological and hemodynamic conditions. In this study, monolayer vascular grafts with randomly distributed or radially oriented fibers are produced using neat, blended, and copolymer forms of polycaprolactone (PCL) and poly(lactic acid) (PLA) via the electrospinning technique. The blending ratio is varied by increasing 10 in the range of 50-100%. Bilayer graft designs are realized by determining the layers with a random fiber distribution for the inner layer and radial fiber orientation for the outer layer. SEM analysis, wall thickness and fiber diameter measurements, tensile strength, elongation, burst strength, and compliance tests are done for both mono- and bilayer scaffolds. The findings revealed that the scaffolds made of neat PCL show more flexibility than the neat PLA samples, which possess higher tensile strength values than neat PCL scaffolds. Also, in blended samples, the tensile strength values do not show a significant improvement, whereas the elongation values are enhanced in tubular samples, depending on the blending ratio. Also, neat poly(l-lactide-co-caprolactone) (PLCL) samples have both higher elongation and strength values than neat and blended scaffolds, with some exceptions. The blended specimens comprising a combination of PCL and PLA, with blending ratios of 80/20 and 70/30, exhibited the most elevated burst pressures. Conversely, the PLCL scaffolds demonstrated superior compliance levels. These findings suggest that the blending approach and fiber orientation offer enhanced burst strength, while copolymer utilization in PLCL scaffolds without fiber alignment enhances their compliance properties. Thus, it is evident that using a copolymer instead of blending PCL and PLA and combining the PLCL layer with PCL and PLA monolayers in bilayer vascular graft design is promising in terms of mechanical and biological properties.
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Affiliation(s)
- Suzan Ozdemir
- Textile Engineering Department, Istanbul Technical University, Istanbul 34437, Turkey
| | - Janset Oztemur
- Textile Engineering Department, Istanbul Technical University, Istanbul 34437, Turkey
| | - Hande Sezgin
- Textile Engineering Department, Istanbul Technical University, Istanbul 34437, Turkey
| | - Ipek Yalcin-Enis
- Textile Engineering Department, Istanbul Technical University, Istanbul 34437, Turkey
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18
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Carrabba M, Fagnano M, Ghorbel MT. Development of a Novel Hierarchically Biofabricated Blood Vessel Mimic Decorated with Three Vascular Cell Populations for the Reconstruction of Small-Diameter Arteries. ADVANCED FUNCTIONAL MATERIALS 2024; 34:adfm.202300621. [PMID: 39257639 PMCID: PMC7616429 DOI: 10.1002/adfm.202300621] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Indexed: 09/12/2024]
Abstract
The availability of grafts to replace small-diameter arteries remains an unmet clinical need. Here, the validated methodology is reported for a novel hybrid tissue-engineered vascular graft that aims to match the natural structure of small-size arteries. The blood vessel mimic (BVM) comprises an internal conduit of co-electrospun gelatin and polycaprolactone (PCL) nanofibers (corresponding to the tunica intima of an artery), reinforced by an additional layer of PCL aligned fibers (the internal elastic membrane). Endothelial cells are deposited onto the luminal surface using a rotative bioreactor. A bioprinting system extrudes two concentric cell-laden hydrogel layers containing respectively vascular smooth muscle cells and pericytes to create the tunica media and adventitia. The semi-automated cellularization process reduces the production and maturation time to 6 days. After the evaluation of mechanical properties, cellular viability, hemocompatibility, and suturability, the BVM is successfully implanted in the left pulmonary artery of swine. Here, the BVM showed good hemostatic properties, capability to withstand blood pressure, and patency at 5 weeks post-implantation. These promising data open a new avenue to developing an artery-like product for reconstructing small-diameter blood vessels.
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Affiliation(s)
- Michele Carrabba
- Bristol Heart Institute, School of Translational Health Sciences, Bristol Medical School, University of Bristol, BristolBS2 8HW, UK
| | - Marco Fagnano
- Bristol Heart Institute, School of Translational Health Sciences, Bristol Medical School, University of Bristol, BristolBS2 8HW, UK
| | - Mohamed T Ghorbel
- Bristol Heart Institute, School of Translational Health Sciences, Bristol Medical School, University of Bristol, BristolBS2 8HW, UK
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19
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Wang N, Wang H, Weng D, Wang Y, Yu L, Wang F, Zhang T, Liu J, He Z. Nanomaterials for small diameter vascular grafts: overview and outlook. NANOSCALE ADVANCES 2023; 5:6751-6767. [PMID: 38059025 PMCID: PMC10696638 DOI: 10.1039/d3na00666b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 11/05/2023] [Indexed: 12/08/2023]
Abstract
Small-diameter vascular grafts (SDVGs) cannot meet current clinical demands owing to their suboptimal long-term patency rate. Various materials have been employed to address this issue, including nanomaterials (NMs), which have demonstrated exceptional capabilities and promising application potentials. In this review, the utilization of NMs in different forms, including nanoparticles, nanofibers, and nanofilms, in the SDVG field is discussed, and future perspectives for the development of NM-loading SDVGs are highlighted. It is expected that this review will provide helpful information to scholars in the innovative interdiscipline of cardiovascular disease treatment and NM.
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Affiliation(s)
- Nuoxin Wang
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
- The Clinical Stem Cell Research Institute, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
- Collaborative Innovation Center of Chinese Ministry of Education, Zunyi Medical University Zunyi 563003 Guizhou China
- The First Clinical Institute, Zunyi Medical University Zunyi 563003 Guizhou China
| | - Haoyuan Wang
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
- Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Zunyi Medical University Zunyi 563006 Guizhou China
- The Second Clinical Institute, Zunyi Medical University Zunyi 563003 Guizhou China
| | - Dong Weng
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
- The First Clinical Institute, Zunyi Medical University Zunyi 563003 Guizhou China
| | - Yanyang Wang
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
- The First Clinical Institute, Zunyi Medical University Zunyi 563003 Guizhou China
| | - Limei Yu
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
- The Clinical Stem Cell Research Institute, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
- Collaborative Innovation Center of Chinese Ministry of Education, Zunyi Medical University Zunyi 563003 Guizhou China
| | - Feng Wang
- Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Zunyi Medical University Zunyi 563006 Guizhou China
- The Second Clinical Institute, Zunyi Medical University Zunyi 563003 Guizhou China
- Department of Cardiovascular Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang 550004 Guizhou China
| | - Tao Zhang
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
- The Clinical Stem Cell Research Institute, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
- Collaborative Innovation Center of Chinese Ministry of Education, Zunyi Medical University Zunyi 563003 Guizhou China
| | - Juan Liu
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
- The Clinical Stem Cell Research Institute, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
- Collaborative Innovation Center of Chinese Ministry of Education, Zunyi Medical University Zunyi 563003 Guizhou China
| | - Zhixu He
- Key Laboratory of Cell Engineering of Guizhou Province, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
- The Clinical Stem Cell Research Institute, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
- Collaborative Innovation Center of Chinese Ministry of Education, Zunyi Medical University Zunyi 563003 Guizhou China
- The First Clinical Institute, Zunyi Medical University Zunyi 563003 Guizhou China
- Department of Pediatrics, Affiliated Hospital of Zunyi Medical University Zunyi 563003 Guizhou China
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Li Z, Giarto J, Zhang J, Kulkarni N, Mahalingam E, Klipstine W, Turng LS. Anti-thrombotic poly(AAm-co-NaAMPS)-xanthan hydrogel-expanded polytetrafluoroethylene (ePTFE) vascular grafts with enhanced endothelialization and hemocompatibility properties. BIOMATERIALS ADVANCES 2023; 154:213625. [PMID: 37722163 PMCID: PMC10841274 DOI: 10.1016/j.bioadv.2023.213625] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 08/23/2023] [Accepted: 09/12/2023] [Indexed: 09/20/2023]
Abstract
Cardiovascular diseases (CVDs) are the leading cause of death among all non-communicable diseases globally. Although expanded polytetrafluoroethylene (ePTFE) has been widely used for larger-diameter vascular graft transplantation, the persistent thrombus formation and intimal hyperplasia of small-diameter vascular grafts (SDVGs) made of ePTFE to treat severe CVDs remain the biggest challenges due to lack of biocompatibility and endothelium. In this study, bi-layered poly(acrylamide-co-2-Acrylamido-2-methyl-1-propanesulfonic acid sodium)-xanthan hydrogel-ePTFE (poly(AAm-co-NaAMPS)-xanthan hydrogel-ePTFE) vascular grafts capable of promoting endothelialization and prohibiting thrombosis were synthesized and fabricated. While the external ePTFE layer of the vascular grafts provided the mechanical stability, the inner hydrogel layer offered much-needed cytocompatibility, hemocompatibility, and endothelialization functions. The interface morphology between the inner hydrogel layer and the outer ePTFE layer was observed by scanning electron microscope (SEM), which revealed that the hydrogel was well attached to the porous ePTFE through mechanical interlocking. Among all the hydrogel compositions tested with cell culture using human umbilical vein endothelial cells (HUVECs), the hydrogel with the molar ratio of 40:60 (NaAMPS/AAm) composition (i.e., Hydrogel 40:60) exhibited the best endothelialization function, as it produced the largest endothelialization area that was three times more than of that of plain ePTFE on day 14, maintained the highest average cell viability, and had the best cell morphology. Hydrogel 40:60 also showed excellent hemocompatibility, prolonged activated partial thromboplastin time (aPTT), and good mechanical properties. Overall, bi-layered poly(AAm-co-NaAMPS)-xanthan hydrogel-ePTFE vascular grafts with the Hydrogel 40:60 composition could potentially solve the critical challenge of thrombus formation in vascular graft transplantation applications.
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Affiliation(s)
- Zhutong Li
- Department of Mechanical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA
| | - Joshua Giarto
- Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA
| | - Jue Zhang
- Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53715, USA
| | - Neha Kulkarni
- Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA
| | - Esha Mahalingam
- Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA; College of Letters and Science, University of Wisconsin-Madison, Madison, WI, 53706, USA
| | - Will Klipstine
- Department of Mechanical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA
| | - Lih-Sheng Turng
- Department of Mechanical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA; Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA; Department of Mechanical Engineering, Chang Gung University, Tao-Yuan 33302, Taiwan.
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21
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Rohringer S, Grasl C, Ehrmann K, Hager P, Hahn C, Specht SJ, Walter I, Schneider KH, Zopf LM, Baudis S, Liska R, Schima H, Podesser BK, Bergmeister H. Biodegradable, Self-Reinforcing Vascular Grafts for In Situ Tissue Engineering Approaches. Adv Healthc Mater 2023; 12:e2300520. [PMID: 37173073 PMCID: PMC11468867 DOI: 10.1002/adhm.202300520] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 04/21/2023] [Indexed: 05/15/2023]
Abstract
Clinically available small-diameter synthetic vascular grafts (SDVGs) have unsatisfactory patency rates due to impaired graft healing. Therefore, autologous implants are still the gold standard for small vessel replacement. Bioresorbable SDVGs may be an alternative, but many polymers have inadequate biomechanical properties that lead to graft failure. To overcome these limitations, a new biodegradable SDVG is developed to ensure safe use until adequate new tissue is formed. SDVGs are electrospun using a polymer blend composed of thermoplastic polyurethane (TPU) and a new self-reinforcing TP(U-urea) (TPUU). Biocompatibility is tested in vitro by cell seeding and hemocompatibility tests. In vivo performance is evaluated in rats over a period for up to six months. Autologous rat aortic implants serve as a control group. Scanning electron microscopy, micro-computed tomography (µCT), histology, and gene expression analyses are applied. TPU/TPUU grafts show significant improvement of biomechanical properties after water incubation and exhibit excellent cyto- and hemocompatibility. All grafts remain patent, and biomechanical properties are sufficient despite wall thinning. No inflammation, aneurysms, intimal hyperplasia, or thrombus formation are observed. Evaluation of graft healing shows similar gene expression profiles of TPU/TPUU and autologous conduits. These new biodegradable, self-reinforcing SDVGs may be promising candidates for clinical use in the future.
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Affiliation(s)
- Sabrina Rohringer
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
| | - Christian Grasl
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
- Center for Medical Physics and Biomedical EngineeringMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
| | - Katharina Ehrmann
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Institute of Applied Synthetic ChemistryTechnical University of ViennaGetreidemarkt 9/163Vienna1060Austria
| | - Pia Hager
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
| | - Clemens Hahn
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
| | - Sophie J. Specht
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
| | - Ingrid Walter
- Department of PathobiologyUniversity of Veterinary MedicineVeterinaerplatz 1Vienna1210Austria
| | - Karl H. Schneider
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
| | - Lydia M. Zopf
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Ludwig Boltzmann Institute for TraumatologyDonaueschingenstraße 13Vienna1200Austria
| | - Stefan Baudis
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Institute of Applied Synthetic ChemistryTechnical University of ViennaGetreidemarkt 9/163Vienna1060Austria
| | - Robert Liska
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Institute of Applied Synthetic ChemistryTechnical University of ViennaGetreidemarkt 9/163Vienna1060Austria
| | - Heinrich Schima
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
- Center for Medical Physics and Biomedical EngineeringMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
| | - Bruno K. Podesser
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
| | - Helga Bergmeister
- Center for Biomedical Research and Translational SurgeryMedical University of ViennaWaehringer Gürtel 18‐20Vienna1090Austria
- Austrian Cluster for Tissue RegenerationDonaueschingenstraße 13Vienna1200Austria
- Ludwig Boltzmann Institute for Cardiovascular ResearchWaehringer Gürtel 18‐20Vienna1090Austria
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22
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Skepastianos G, Mallis P, Kostopoulos E, Michalopoulos E, Skepastianos V, Palazi C, Pannuto L, Tsourouflis G. Efficient Decellularization of the Full-Thickness Rat-Derived Abdominal Wall to Produce Acellular Biologic Scaffolds for Tissue Reconstruction: Promising Evidence Acquired from In Vitro Results. Bioengineering (Basel) 2023; 10:913. [PMID: 37627798 PMCID: PMC10451677 DOI: 10.3390/bioengineering10080913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 07/26/2023] [Accepted: 07/30/2023] [Indexed: 08/27/2023] Open
Abstract
BACKGROUND Functional restoration of abdominal wall defects represents one of the fundamental challenges of reconstructive surgery. Synthetic grafts or crosslinked animal-derived biological grafts are characterized by significant adverse reactions, which are mostly observed after their implantation. The aim of this study was to evaluate the efficacy of the decellularization protocol to produce a completely acellular full-thickness abdominal wall scaffold. METHODS Full-thickness abdominal wall samples were harvested from Wistar rats and submitted to a three-cycle decellularization process. Histological, biochemical, and DNA quantification analyses were applied to evaluate the effect of the decellularization protocol. Mechanical testing and immunogenicity assessment were also performed. RESULTS Histological, biochemical, and DNA analysis results showed efficient decellularization of the abdominal wall samples after the third cycle. Decellularized abdominal wall scaffolds were characterized by good biochemical and mechanical properties. CONCLUSION The data presented herein confirm the effective production of a rat-derived full-thickness abdominal wall scaffold. Expanding this approach will allow the exploitation of the capacity of the proposed decellularization protocol in producing acellular abdominal wall scaffolds from larger animal models or human cadaveric donors. In this way, the utility of biological scaffolds with preserved in vivo remodeling properties may be one step closer to its application in clinical studies.
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Affiliation(s)
- George Skepastianos
- Plastic Surgery Department, EANP Metaxa, National Hospital of Athens, 51 Botatsi Street, 185 37 Pireus, Greece; (G.S.); (E.K.); (V.S.); (C.P.)
- Center of Experimental Surgery, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece
| | - Panagiotis Mallis
- Hellenic Cord Blood Bank, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece;
| | - Epameinondas Kostopoulos
- Plastic Surgery Department, EANP Metaxa, National Hospital of Athens, 51 Botatsi Street, 185 37 Pireus, Greece; (G.S.); (E.K.); (V.S.); (C.P.)
| | - Efstathios Michalopoulos
- Hellenic Cord Blood Bank, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece;
| | - Vasileios Skepastianos
- Plastic Surgery Department, EANP Metaxa, National Hospital of Athens, 51 Botatsi Street, 185 37 Pireus, Greece; (G.S.); (E.K.); (V.S.); (C.P.)
| | - Chrysoula Palazi
- Plastic Surgery Department, EANP Metaxa, National Hospital of Athens, 51 Botatsi Street, 185 37 Pireus, Greece; (G.S.); (E.K.); (V.S.); (C.P.)
| | - Lucia Pannuto
- Queen Victoria Hospital NHS Foundation Trust, East Grinstead RH19 3DZ, UK;
| | - Gerasimos Tsourouflis
- Second Department of Propedeutic Surgery, Medical School, University of Athens, 115 27 Athens, Greece;
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23
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Cheng C, Li H, Liu J, Wu L, Fang Z, Xu G. MCP-1-Loaded Poly(l-lactide- co-caprolactone) Fibrous Films Modulate Macrophage Polarization toward an Anti-inflammatory Phenotype and Improve Angiogenesis. ACS Biomater Sci Eng 2023. [PMID: 37367696 DOI: 10.1021/acsbiomaterials.3c00476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/28/2023]
Abstract
Tissue engineering approaches such as the electrospinning technique can fabricate nanofibrous scaffolds which are widely used for small-diameter vascular grafting. However, foreign body reaction (FBR) and lack of endothelial coverage are still the main cause of graft failure after the implantation of nanofibrous scaffolds. Macrophage-targeting therapeutic strategies have the potential to address these issues. Here, we fabricate a monocyte chemotactic protein-1 (MCP-1)-loaded coaxial fibrous film with poly(l-lactide-co-ε-caprolactone) (PLCL/MCP-1). The PLCL/MCP-1 fibrous film can polarize macrophages toward anti-inflammatory M2 macrophages through the sustained release of MCP-1. Meanwhile, these specific functional polarization macrophages can mitigate FBR and promote angiogenesis during the remodeling of implanted fibrous films. These studies indicate that MCP-1-loaded PLCL fibers have a higher potential to modulate macrophage polarity, which provides a new strategy for small-diameter vascular graft designing.
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Affiliation(s)
- Can Cheng
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P. R. China
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P. R. China
| | - Heng Li
- Department of Comprehensive Surgery, Anhui Provincial Cancer Hospital, West District of The First Affiliated Hospital of USTC, Hefei, Anhui 230001, P. R. China
| | - Jingwen Liu
- Anhui Provincial Hospital Health Management Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P. R. China
| | - Liang Wu
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P. R. China
| | - Zhengdong Fang
- Department of Vascular Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P. R. China
| | - Geliang Xu
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P. R. China
- Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P. R. China
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24
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Li MX, Wei QQ, Mo HL, Ren Y, Zhang W, Lu HJ, Joung YK. Challenges and advances in materials and fabrication technologies of small-diameter vascular grafts. Biomater Res 2023; 27:58. [PMID: 37291675 PMCID: PMC10251629 DOI: 10.1186/s40824-023-00399-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 05/21/2023] [Indexed: 06/10/2023] Open
Abstract
The arterial occlusive disease is one of the leading causes of cardiovascular diseases, often requiring revascularization. Lack of suitable small-diameter vascular grafts (SDVGs), infection, thrombosis, and intimal hyperplasia associated with synthetic vascular grafts lead to a low success rate of SDVGs (< 6 mm) transplantation in the clinical treatment of cardiovascular diseases. The development of fabrication technology along with vascular tissue engineering and regenerative medicine technology allows biological tissue-engineered vascular grafts to become living grafts, which can integrate, remodel, and repair the host vessels as well as respond to the surrounding mechanical and biochemical stimuli. Hence, they potentially alleviate the shortage of existing vascular grafts. This paper evaluates the current advanced fabrication technologies for SDVGs, including electrospinning, molding, 3D printing, decellularization, and so on. Various characteristics of synthetic polymers and surface modification methods are also introduced. In addition, it also provides interdisciplinary insights into the future of small-diameter prostheses and discusses vital factors and perspectives for developing such prostheses in clinical applications. We propose that the performance of SDVGs can be improved by integrating various technologies in the near future.
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Affiliation(s)
- Mei-Xian Li
- National and Local Joint Engineering Research Center of Technical Fiber Composites for Safety and Protection, Nantong University, Nantong, 226019, China
- School of Textile and Clothing, Nantong University, Nantong, 226019, China
- Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
| | - Qian-Qi Wei
- Department of Infectious Diseases, General Hospital of Tibet Military Command, Xizang, China
| | - Hui-Lin Mo
- School of Textile and Clothing, Nantong University, Nantong, 226019, China
| | - Yu Ren
- National and Local Joint Engineering Research Center of Technical Fiber Composites for Safety and Protection, Nantong University, Nantong, 226019, China
- School of Textile and Clothing, Nantong University, Nantong, 226019, China
| | - Wei Zhang
- National and Local Joint Engineering Research Center of Technical Fiber Composites for Safety and Protection, Nantong University, Nantong, 226019, China.
- School of Textile and Clothing, Nantong University, Nantong, 226019, China.
| | - Huan-Jun Lu
- Institute of Special Environmental Medicine, Nantong University, Nantong, 226019, China.
| | - Yoon Ki Joung
- Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea.
- Division of Bio-Medical Science and Technology, University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon, 34113, Republic of Korea.
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25
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Elfawy LA, Ng CY, Amirrah IN, Mazlan Z, Wen APY, Fadilah NIM, Maarof M, Lokanathan Y, Fauzi MB. Sustainable Approach of Functional Biomaterials-Tissue Engineering for Skin Burn Treatment: A Comprehensive Review. Pharmaceuticals (Basel) 2023; 16:ph16050701. [PMID: 37242483 DOI: 10.3390/ph16050701] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/21/2023] [Accepted: 04/25/2023] [Indexed: 05/28/2023] Open
Abstract
Burns are a widespread global public health traumatic injury affecting many people worldwide. Non-fatal burn injuries are a leading cause of morbidity, resulting in prolonged hospitalization, disfigurement, and disability, often with resulting stigma and rejection. The treatment of burns is aimed at controlling pain, removing dead tissue, preventing infection, reducing scarring risk, and tissue regeneration. Traditional burn wound treatment methods include the use of synthetic materials such as petroleum-based ointments and plastic films. However, these materials can be associated with negative environmental impacts and may not be biocompatible with the human body. Tissue engineering has emerged as a promising approach to treating burns, and sustainable biomaterials have been developed as an alternative treatment option. Green biomaterials such as collagen, cellulose, chitosan, and others are biocompatible, biodegradable, environment-friendly, and cost-effective, which reduces the environmental impact of their production and disposal. They are effective in promoting wound healing and reducing the risk of infection and have other benefits such as reducing inflammation and promoting angiogenesis. This comprehensive review focuses on the use of multifunctional green biomaterials that have the potential to revolutionize the way we treat skin burns, promoting faster and more efficient healing while minimizing scarring and tissue damage.
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Affiliation(s)
- Loai A Elfawy
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Chiew Yong Ng
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Ibrahim N Amirrah
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Zawani Mazlan
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Adzim Poh Yuen Wen
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
- Department of Surgery, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Nur Izzah Md Fadilah
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Manira Maarof
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Yogeswaran Lokanathan
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Mh Busra Fauzi
- Centre for Tissue Engineering and Regenerative Medicine, Faculty of Medicine, University Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
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Goldman J, Liu SQ, Tefft BJ. Anti-Inflammatory and Anti-Thrombogenic Properties of Arterial Elastic Laminae. Bioengineering (Basel) 2023; 10:bioengineering10040424. [PMID: 37106611 PMCID: PMC10135563 DOI: 10.3390/bioengineering10040424] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 03/07/2023] [Accepted: 03/16/2023] [Indexed: 03/30/2023] Open
Abstract
Elastic laminae, an elastin-based, layered extracellular matrix structure in the media of arteries, can inhibit leukocyte adhesion and vascular smooth muscle cell proliferation and migration, exhibiting anti-inflammatory and anti-thrombogenic properties. These properties prevent inflammatory and thrombogenic activities in the arterial media, constituting a mechanism for the maintenance of the structural integrity of the arterial wall in vascular disorders. The biological basis for these properties is the elastin-induced activation of inhibitory signaling pathways, involving the inhibitory cell receptor signal regulatory protein α (SIRPα) and Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1). The activation of these molecules causes deactivation of cell adhesion- and proliferation-regulatory signaling mechanisms. Given such anti-inflammatory and anti-thrombogenic properties, elastic laminae and elastin-based materials have potential for use in vascular reconstruction.
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27
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Avci-Adali M, Grözinger G, Cabane V, Schreve M, Wendel HP. Improving Bioactive Characteristics of Small Diameter Polytetrafluoroethylene Stent Grafts by Electrospinning: A Comparative Hemocompatibility Study. Bioengineering (Basel) 2023; 10:bioengineering10040411. [PMID: 37106598 PMCID: PMC10135465 DOI: 10.3390/bioengineering10040411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 03/11/2023] [Accepted: 03/21/2023] [Indexed: 03/29/2023] Open
Abstract
Polytetrafluoroethylene (PTFE) is a commonly used biomaterial for the manufacturing of vascular grafts and several strategies, such as coatings, have been explored to improve the hemocompatibility of small-diameter prostheses. In this study, the hemocompatibility properties of novel stent grafts covered with electrospun PTFE (LimFlow Gen-1 and LimFlow Gen-2) were compared with uncoated and heparin-coated PTFE grafts (Gore Viabahn®) using fresh human blood in a Chandler closed-loop system. After 60 min of incubation, the blood samples were examined hematologically and activation of coagulation, platelets, and the complement system were analyzed. In addition, the adsorbed fibrinogen on the stent grafts was measured and the thrombogenicity was assessed by SEM. Significantly lower adsorption of fibrinogen was measured on the surface of heparin-coated Viabahn than on the surface of the uncoated Viabahn. Furthermore, LimFlow Gen-1 stent grafts showed lower fibrinogen adsorption than the uncoated Viabahn®, and the LimFlow Gen-2 stent grafts showed comparable fibrinogen adsorption as the heparin-coated Viabahn®. SEM analysis revealed no sign of thrombus formation on any of the stent surfaces. LimFlow Gen-2 stent grafts covered with electrospun PTFE exhibited bioactive characteristics and revealed improved hemocompatibility in terms of reduced adhesion of fibrinogen, activation of platelets, and coagulation (assessed by β-TG and TAT levels) similar to heparin-coated ePTFE prostheses. Thus, this study demonstrated improved hemocompatibility of electrospun PTFE. The next step is to conduct in vivo studies to confirm whether electrospinning-induced changes to the PTFE surface can reduce the risk of thrombus formation and provide clinical benefits.
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Affiliation(s)
- Meltem Avci-Adali
- Department of Thoracic and Cardiovascular Surgery, University Hospital Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany
- Correspondence: ; Tel.: +49-7071-2986605; Fax: +49-7071-295369
| | - Gerd Grözinger
- Department of Diagnostic and Interventional Radiology, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen, Germany
| | | | - Michiel Schreve
- LimFlow SA, 15 Rue Traversière, 75012 Paris, France
- Department of Surgery, Northwest Clinics, 1815 JD Alkmaar, The Netherlands
| | - Hans Peter Wendel
- Department of Thoracic and Cardiovascular Surgery, University Hospital Tuebingen, Calwerstraße 7/1, 72076 Tuebingen, Germany
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Adhami M, Martin NK, Maguire C, Courtenay AJ, Donnelly RF, Domínguez-Robles J, Larrañeta E. Drug loaded implantable devices to treat cardiovascular disease. Expert Opin Drug Deliv 2023; 20:507-522. [PMID: 36924328 DOI: 10.1080/17425247.2023.2190580] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
INTRODUCTION It is widely acknowledged that cardiovascular diseases (CVDs) continue to be the leading cause of death globally. Furthermore, CVDs are the leading cause of diminished quality of life for patients, frequently as a result of their progressive deterioration. Medical implants that release drugs into the body are active implants that do more than just provide mechanical support; they also have a therapeutic role. Primarily, this is achieved through the controlled release of active pharmaceutical ingredients (API) at the implementation site. AREAS COVERED In this review, the authors discuss drug-eluting stents, drug-eluting vascular grafts, and drug-eluting cardiac patches with the aim of providing a broad overview of the three most common types of cardiac implant. EXPERT OPINION Drug eluting implants are an ideal alternative to traditional drug delivery because they allow for accurate drug release, local drug delivery to the target tissue, and minimise the adverse side effects associated with systemic administration. Despite the fact that there are still challenges that need to be addressed, the ever-evolving new technologies are making the fabrication of drug eluting implants a rewarding therapeutic endeavour with the possibility for even greater advances.
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Affiliation(s)
| | | | | | - Aaron J Courtenay
- School of Pharmacy and Pharmaceutical Sciences, Ulster University, UK
| | | | - Juan Domínguez-Robles
- School of Pharmacy, Queen's University Belfast, UK.,Department of Pharmacy and Pharmaceutical Technology, University of Seville, Seville, Spain
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29
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Infection of Vascular Prostheses: A Comprehensive Review. PROSTHESIS 2023. [DOI: 10.3390/prosthesis5010012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Vascular graft or endograft infection (VGEI) is a complex disease that complicates vascular-surgery and endovascular-surgery procedures and determines high morbidity and mortality. This review article provides the most updated general evidence on the pathogenesis, prevention, diagnosis, and treatment of VGEI. Several microorganisms are involved in VGEI development, but the most frequent one, responsible for over 75% of infections, is Staphylococcus aureus. Specific clinical, surgical, radiologic, and laboratory criteria are pivotal for the diagnosis of VGEI. Surgery and antimicrobial therapy are cornerstones in treatment for most patients with VGEI. For patients unfit for surgery, alternative treatment is available to improve the clinical course of VGEI.
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Ratner B. Vascular Grafts: Technology Success/Technology Failure. BME FRONTIERS 2023; 4:0003. [PMID: 37849668 PMCID: PMC10521696 DOI: 10.34133/bmef.0003] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 11/15/2022] [Indexed: 10/19/2023] Open
Abstract
Vascular prostheses (grafts) are widely used for hemodialysis blood access, trauma repair, aneurism repair, and cardiovascular reconstruction. However, smaller-diameter (≤4 mm) grafts that would be valuable for many reconstructions have not been achieved to date, although hundreds of papers on small-diameter vascular grafts have been published. This perspective article presents a hypothesis that may open new research avenues for the development of small-diameter vascular grafts. A historical review of the vascular graft literature and specific types of vascular grafts is presented focusing on observations important to the hypothesis to be presented. Considerations in critically reviewing the vascular graft literature are discussed. The hypothesis that perhaps the "biocompatible biomaterials" comprising our vascular grafts-biomaterials that generate dense, nonvascularized collagenous capsules upon implantation-may not be all that biocompatible is presented. Examples of materials that heal with tissue reconstruction and vascularity, in contrast to the fibrotic encapsulation, are offered. Such prohealing materials may lead the way to a new generation of vascular grafts suitable for small-diameter reconstructions.
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Affiliation(s)
- Buddy Ratner
- Center for Dialysis Innovation (CDI), Departments of Bioengineering and Chemical Engineering, University of Washington, Seattle, WA 98195, USA
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de Silva L, Bernal PN, Rosenberg A, Malda J, Levato R, Gawlitta D. Biofabricating the vascular tree in engineered bone tissue. Acta Biomater 2023; 156:250-268. [PMID: 36041651 DOI: 10.1016/j.actbio.2022.08.051] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 08/22/2022] [Accepted: 08/23/2022] [Indexed: 01/18/2023]
Abstract
The development of tissue engineering strategies for treatment of large bone defects has become increasingly relevant, given the growing demand for bone substitutes. Native bone is composed of a dense vascular network necessary for the regulation of bone development, regeneration and homeostasis. A major obstacle in fabricating living, clinically relevant-sized bone mimics (1-10 cm3) is the limited supply of nutrients, including oxygen to the core of the construct. Therefore, strategies to support vascularization are pivotal for the development of tissue engineered bone constructs. Creating a functional bone construct integrated with a vascular network, capable of delivering the necessary nutrients for optimal tissue development is imperative for translation into the clinics. The vascular system is composed of a complex network that runs throughout the body in a tree-like hierarchical branching fashion. A significant challenge for tissue engineering approaches lies in mimicking the intricate, multi-scale structures consisting of larger vessels (macro-vessels) which interconnect with multiple sprouting vessels (microvessels) in a closed network. The advent of biofabrication has enabled complex, out of plane channels to be generated and has laid the groundwork for the creation of multi-scale vasculature in recent years. This review highlights the key state-of-the-art achievements for the development of vascular networks of varying scales in the field of biofabrication with a particular focus for its application in developing a functional tissue engineered bone construct. STATEMENT OF SIGNIFICANCE: There is a growing need for bone substitutes to overcome the limited supply of patient-derived bone. Bone tissue engineering aims to overcome this by combining stem cells with scaffolds to restore missing bone. The current bottleneck in upscaling is the lack of an integrated vascular network, required for the delivery of nutrients to cells. 3D bioprinting techniques has enabled the creation of complex hollow structures of varying dimensions that resemble native blood vessels. The convergence of multiple materials, cell types and fabrication approaches, opens the possibility of developing clinically-relevant sized vascularized bone constructs. This review provides an up-to-date insight of the technologies currently available for the generation of complex vascular networks, with a focus on their application in bone tissue engineering.
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Affiliation(s)
- Leanne de Silva
- Department of Oral and Maxillofacial Surgery & Special Dental Care, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 GA, the Netherlands; Regenerative Medicine Center Utrecht, Utrecht, 3584 CT, the Netherlands.
| | - Paulina N Bernal
- Regenerative Medicine Center Utrecht, Utrecht, 3584 CT, the Netherlands; Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 GA, the Netherlands
| | - Ajw Rosenberg
- Department of Oral and Maxillofacial Surgery & Special Dental Care, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 GA, the Netherlands
| | - Jos Malda
- Regenerative Medicine Center Utrecht, Utrecht, 3584 CT, the Netherlands; Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 GA, the Netherlands; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CT, the Netherlands
| | - Riccardo Levato
- Regenerative Medicine Center Utrecht, Utrecht, 3584 CT, the Netherlands; Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 GA, the Netherlands; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CT, the Netherlands
| | - Debby Gawlitta
- Department of Oral and Maxillofacial Surgery & Special Dental Care, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 GA, the Netherlands; Regenerative Medicine Center Utrecht, Utrecht, 3584 CT, the Netherlands
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Li Y, Zhou Y, Qiao W, Shi J, Qiu X, Dong N. Application of decellularized vascular matrix in small-diameter vascular grafts. Front Bioeng Biotechnol 2023; 10:1081233. [PMID: 36686240 PMCID: PMC9852870 DOI: 10.3389/fbioe.2022.1081233] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 12/13/2022] [Indexed: 01/09/2023] Open
Abstract
Coronary artery bypass grafting (CABG) remains the most common procedure used in cardiovascular surgery for the treatment of severe coronary atherosclerotic heart disease. In coronary artery bypass grafting, small-diameter vascular grafts can potentially replace the vessels of the patient. The complete retention of the extracellular matrix, superior biocompatibility, and non-immunogenicity of the decellularized vascular matrix are unique advantages of small-diameter tissue-engineered vascular grafts. However, after vascular implantation, the decellularized vascular matrix is also subject to thrombosis and neoplastic endothelial hyperplasia, the two major problems that hinder its clinical application. The keys to improving the long-term patency of the decellularized matrix as vascular grafts include facilitating early endothelialization and avoiding intravascular thrombosis. This review article sequentially introduces six aspects of the decellularized vascular matrix as follows: design criteria of vascular grafts, components of the decellularized vascular matrix, the changing sources of the decellularized vascular matrix, the advantages and shortcomings of decellularization technologies, modification methods and the commercialization progress as well as the application prospects in small-diameter vascular grafts.
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Affiliation(s)
| | | | | | | | - Xuefeng Qiu
- *Correspondence: Xuefeng Qiu, ; Nianguo Dong,
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Shakeel A, Corridon PR. Mitigating challenges and expanding the future of vascular tissue engineering-are we there yet? Front Physiol 2023; 13:1079421. [PMID: 36685187 PMCID: PMC9846051 DOI: 10.3389/fphys.2022.1079421] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 12/14/2022] [Indexed: 01/06/2023] Open
Affiliation(s)
- Adeeba Shakeel
- Department of Immunology and Physiology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates
| | - Peter R. Corridon
- Department of Immunology and Physiology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates
- Biomedical Engineering, Healthcare Engineering Innovation Center, Khalifa University, Abu Dhabi, United Arab Emirates
- Center for Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates
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Sellahewa SG, Li JY, Xiao Q. Updated Perspectives on Direct Vascular Cellular Reprogramming and Their Potential Applications in Tissue Engineered Vascular Grafts. J Funct Biomater 2022; 14:21. [PMID: 36662068 PMCID: PMC9866165 DOI: 10.3390/jfb14010021] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 12/25/2022] [Accepted: 12/27/2022] [Indexed: 01/03/2023] Open
Abstract
Cardiovascular disease is a globally prevalent disease with far-reaching medical and socio-economic consequences. Although improvements in treatment pathways and revascularisation therapies have slowed disease progression, contemporary management fails to modulate the underlying atherosclerotic process and sustainably replace damaged arterial tissue. Direct cellular reprogramming is a rapidly evolving and innovative tissue regenerative approach that holds promise to restore functional vasculature and restore blood perfusion. The approach utilises cell plasticity to directly convert somatic cells to another cell fate without a pluripotent stage. In this narrative literature review, we comprehensively analyse and compare direct reprogramming protocols to generate endothelial cells, vascular smooth muscle cells and vascular progenitors. Specifically, we carefully examine the reprogramming factors, their molecular mechanisms, conversion efficacies and therapeutic benefits for each induced vascular cell. Attention is given to the application of these novel approaches with tissue engineered vascular grafts as a therapeutic and disease-modelling platform for cardiovascular diseases. We conclude with a discussion on the ethics of direct reprogramming, its current challenges, and future perspectives.
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Affiliation(s)
- Saneth Gavishka Sellahewa
- William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK
| | - Jojo Yijiao Li
- William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK
| | - Qingzhong Xiao
- William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK
- Key Laboratory of Cardiovascular Diseases, School of Basic Medical Sciences, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
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Mallis P. Design and Fabrication of Artificial Stem Cell Microenvironments. Bioengineering (Basel) 2022; 9:756. [PMID: 36550962 PMCID: PMC9774650 DOI: 10.3390/bioengineering9120756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 11/30/2022] [Indexed: 12/12/2022] Open
Abstract
Major key features of stem cells' functions are self-renewal and their capacity for differentiation, allowing for maintain a proper stem cell reservoir as well as producing lineage-committed cells [...].
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Affiliation(s)
- Panagiotis Mallis
- Hellenic Cord Blood Bank, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece; or
- Immunology Department & National Tissue Typing Center, General Hospital of Athens “Gennimatas”, 154 Mesogeion Ave., 115 27 Athens, Greece
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Tardalkar KR, Marsale TB, Bhamare NC, Kshersagar JR, Patil JK, Adnaik A, Joshi MG. Heparin coated decellularized xenogeneic small diameter vascular conduit for vascular repair with early luminal reendothelialization. Cell Tissue Bank 2022; 24:449-469. [DOI: 10.1007/s10561-022-10046-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 10/23/2022] [Indexed: 11/09/2022]
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Chen X, Han S, Wu W, Wu Z, Yuan Y, Wu J, Liu C. Harnessing 4D Printing Bioscaffolds for Advanced Orthopedics. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2106824. [PMID: 35060321 DOI: 10.1002/smll.202106824] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 12/15/2021] [Indexed: 05/13/2023]
Abstract
The development of programmable functional biomaterials makes 4D printing add a new dimension, time (t), based on 3D structures (x, y, z), therefore, 4D printed constructs could transform their morphology or function over time in response to environmental stimuli. Nowadays, highly efficient bone defect repair remains challenging in clinics. Combining programmable biomaterials, living cells, and bioactive factors, 4D bioprinting provides greater potential for constructing dynamic, personalized, and precise bone tissue engineering scaffolds by complex structure formation and functional maturation. Therefore, 4D bioprinting has been regarded as the next generation of bone repair technology. This review focuses on 4D printing and its advantages in orthopedics. The applications of different smart biomaterials and 4D printing strategies are briefly introduced. Furthermore, one summarizes the recent advancements of 4D printing in bone tissue engineering, uncovering the addressed and unaddressed medical requirements. In addition, current challenges and future perspectives are further discussed, which will offer more inspiration about the clinical transformation of this emerging 4D bioprinting technology in bone regeneration.
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Affiliation(s)
- Xi Chen
- Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Engineering Research Center for Biomaterials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China
| | - Shuyan Han
- Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou, 510006, China
| | - Weihui Wu
- Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Engineering Research Center for Biomaterials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China
| | - Zihan Wu
- Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Engineering Research Center for Biomaterials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China
| | - Yuan Yuan
- Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Engineering Research Center for Biomaterials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China
| | - Jun Wu
- Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou, 510006, China
| | - Changsheng Liu
- Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Engineering Research Center for Biomaterials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China
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Cell Adhesion Strength Indicates the Antithrombogenicity of Poly(2-Methoxyethyl Acrylate) (PMEA): Potential Candidate for Artificial Small-Diameter Blood Vessel. SURFACES 2022. [DOI: 10.3390/surfaces5030027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Poly (2-methoxyethyl acrylate) (PMEA) is a US FDA-approved biocompatible polymer, although there is insufficient work on human umbilical vein endothelial cells (HUVECs) and platelet interaction analysis on PMEA-analogous polymers. In this study, we extensively investigated HUVEC–polymer and platelet–polymer interaction behavior by measuring the adhesion strength using single-cell force spectroscopy. Furthermore, the hydration layer of the polymer interface was observed using frequency-modulation atomic force microscopy. We found that endothelial cells can attach and spread on the PMEA surface with strong adhesion strength compared to other analogous polymers. We found that the hydration layers on the PMEA-analogous polymers were closely related to their weak platelet adhesion behavior. Based on our results, it can be concluded that PMEA is a promising candidate for the construction of artificial small-diameter blood vessels owing to the presence of IW and a hydration layer on the interface.
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Hemocompatibility Evaluation of Thai Bombyx mori Silk Fibroin and Its Improvement with Low Molecular Weight Heparin Immobilization. Polymers (Basel) 2022; 14:polym14142943. [PMID: 35890719 PMCID: PMC9319666 DOI: 10.3390/polym14142943] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/15/2022] [Accepted: 07/18/2022] [Indexed: 02/04/2023] Open
Abstract
Bombyx mori silk fibroin (SF), from Nangnoi Srisaket 1 Thai strain, has shown potential for various biomedical applications such as wound dressing, a vascular patch, bone substitutes, and controlled release systems. The hemocompatibility of this SF is one of the important characteristics that have impacts on such applications. In this study, the hemocompatibility of Thai SF was investigated and its improvement by low molecular weight heparin (LMWH) immobilization was demonstrated. Endothelial cell proliferation on the SF and LMWH immobilized SF (Hep/SF) samples with or without fibroblast growth factor-2 (FGF-2) was also evaluated. According to hemocompatibility evaluation, Thai SF did not accelerate clotting time, excess stimulate complement and leukocyte activation, and was considered a non-hemolysis material compared to the negative control PTFE sheet. Platelet adhesion of SF film was comparable to that of the PTFE sheet. For hemocompatibility enhancement, LMWH was immobilized successfully and could improve the surface hydrophilicity of SF films. The Hep/SF films demonstrated prolonged clotting time and slightly lower complement and leukocyte activation. However, the Hep/SF films could not suppress platelet adhesion. The Hep/SF films demonstrated endothelial cell proliferation enhancement, particularly with FGF-2 addition. This study provides fundamental information for the further development of Thai SF as a hemocompatible biomaterial.
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Sembiring YE, Ledyastatin RA, Nurrahmah A, Sulistyaningsih NK, Sinatra JAR, Puruhito I, Suroto H. Comparative Assessment of Various Concentration and Exposure Time of Sodium Dodecyl Sulfate as Decellularization Agents for Small-Vessels Vascular Tissue Engineering. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.9396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Finding the optimum vascular grafts (VG) to replace damaged blood arteries in cardiac surgery is still a work in progress. To be employed, a tissue-engineered VG (TEVG) must have the appropriate biological and mechanical qualities. Decellularized arteries may be a better TEVG than synthetic grafts because of their natural three-dimensional architecture.
AIM: The goal of this study was to compare different concentrations and times of sodium dodecyl sulfate (SDS) to decellularize tissue to find the best decellularized VG.
METHODS: In all decellularized scaffolds, which are 1% SDS-2 weeks group, hematoxylin and eosin and Masson’s trichrome staining exhibited looser collagen networks and fewer nuclei.
RESULTS: The orientation of collagen fibers was identical to native vascular scaffolds. Collagen I deposition was seen in the immunohistochemistry assay. A tensile strength test revealed that the decellularized scaffold (0.5% SDS for 4 weeks and 0.5% SDS for 2 weeks) had exceeded the native arteries’ maximal strength. In comparison to 1% SDS in 4 weeks treated groups, scanning electron microscopy following decellularization revealed no endothelial cells on the inner side of 1% SDS in 2 weeks group with minimum extracellular matrix damage. The endothelial cells remained marginally visible on the inner side of all 0.5% SDS treated groups. The 3-(4,5-dimethylthiazol-2yl)2,5-diphenyltetrazolium bromide test was used to determine the cytotoxicity of the decellularized scaffolds.
CONCLUSION: This study reveals that exposing a bovine mesenteric artery to 1% SDS for 2 weeks is an excellent procedure for extracting the most acellular VG, potentially serving as a biological scaffold for TEVGs.
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Fegan KL, Green NC, Britton MM, Iqbal AJ, Thomas-Seale LEJ. Design and Simulation of the Biomechanics of Multi-Layered Composite Poly(Vinyl Alcohol) Coronary Artery Grafts. Front Cardiovasc Med 2022; 9:883179. [PMID: 35833186 PMCID: PMC9272978 DOI: 10.3389/fcvm.2022.883179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 06/01/2022] [Indexed: 11/25/2022] Open
Abstract
Coronary artery disease is among the primary causes of death worldwide. While synthetic grafts allow replacement of diseased tissue, mismatched mechanical properties between graft and native tissue remains a major cause of graft failure. Multi-layered grafts could overcome these mechanical incompatibilities by mimicking the structural heterogeneity of the artery wall. However, the layer-specific biomechanics of synthetic grafts under physiological conditions and their impact on endothelial function is often overlooked and/or poorly understood. In this study, the transmural biomechanics of four synthetic graft designs were simulated under physiological pressure, relative to the coronary artery wall, using finite element analysis. Using poly(vinyl alcohol) (PVA)/gelatin cryogel as the representative biomaterial, the following conclusions are drawn: (I) the maximum circumferential stress occurs at the luminal surface of both the grafts and the artery; (II) circumferential stress varies discontinuously across the media and adventitia, and is influenced by the stiffness of the adventitia; (III) unlike native tissue, PVA/gelatin does not exhibit strain stiffening below diastolic pressure; and (IV) for both PVA/gelatin and native tissue, the magnitude of stress and strain distribution is heavily dependent on the constitutive models used to model material hyperelasticity. While these results build on the current literature surrounding PVA-based arterial grafts, the proposed method has exciting potential toward the wider design of multi-layer scaffolds. Such finite element analyses could help guide the future validation of multi-layered grafts for the treatment of coronary artery disease.
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Affiliation(s)
- Katie L. Fegan
- Physical Sciences for Health Centre for Doctoral Training, University of Birmingham, Birmingham, United Kingdom
- Department of Mechanical Engineering, University of Birmingham, Birmingham, United Kingdom
| | - Naomi C. Green
- Department of Mechanical Engineering, University of Birmingham, Birmingham, United Kingdom
| | - Melanie M. Britton
- School of Chemistry, College of Engineering and Physical Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Asif J. Iqbal
- Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
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Poly(2-Methoxyethyl Acrylate) (PMEA)-Coated Anti-Platelet Adhesive Surfaces to Mimic Native Blood Vessels through HUVECs Attachment, Migration, and Monolayer Formation. COATINGS 2022. [DOI: 10.3390/coatings12060869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Confluent monolayers of human umbilical vein endothelial cells (HUVECs) on a poly(2-methoxyethyl acrylate) (PMEA) antithrombogenic surface play a major role in mimicking the inner surface of native blood vessels. In this study, we extensively investigated the behavior of cell–polymer and cell–cell interactions by measuring adhesion strength using single-cell force spectroscopy. In addition, the attachment and migration of HUVECs on PMEA-analogous substrates were detected, and the migration rate was estimated. Moreover, the bilateral migration of HUVECs between two adjacent surfaces was observed. Furthermore, the outer surface of HUVEC was examined using frequency-modulation atomic force microscopy (FM-AFM). Hydration was found to be an indication of a healthy glycocalyx layer. The results were compared with the hydration states of individual PMEA-analogous polymers to understand the adhesion mechanism between the cells and substrates in the interface region. HUVECs could attach and spread on the PMEA surface with stronger adhesion strength than self-adhesion strength, and migration occurred over the surface of analogue polymers. We confirmed that platelets could not adhere to HUVEC monolayers cultured on the PMEA surface. FM-AFM images revealed a hydration layer on the HUVEC surfaces, indicating the presence of components of the glycocalyx layer in the presence of intermediate water. Our findings show that PMEA can mimic original blood vessels through an antithrombogenic HUVEC monolayer and is thus suitable for the construction of artificial small-diameter blood vessels.
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Fayon A, Helle D, Francius G, Vincourt JB, Regnault V, Dumas D, Menu P, El Omar R. Characterization of an Innovative Biomaterial Derived From Human Wharton’s Jelly as a New Promising Coating for Tissue Engineering Applications. Front Bioeng Biotechnol 2022; 10:884069. [PMID: 35769101 PMCID: PMC9234273 DOI: 10.3389/fbioe.2022.884069] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 05/18/2022] [Indexed: 11/16/2022] Open
Abstract
The extracellular matrix (ECM) offers the opportunity to create a biomaterial consisting of a microenvironment with interesting biological and biophysical properties for improving and regulating cell functions. Animal-derived ECM are the most widely used as an alternative to human tissues that are of very limited availability. However, incomplete decellularization of these tissues presents a high risk of immune rejection and disease transmission. In this study, we present an innovative method to extract human ECM derived from the Wharton’s jelly (WJ-ECMaa) of umbilical cords as a novel biomaterial to be used in tissue engineering. WJ-ECMaa was very efficiently decellularized, suggesting its possible use in allogeneic conditions. Characterization of its content allowed the identification of type I collagen as its main component. Various other matrix proteins, playing an important role in cell adhesion and proliferation, were also detected. WJ-ECMaa applied as a surface coating was analyzed by fluorescent labeling and atomic force microscopy. The results revealed a particular arrangement of collagen fibers not previously described in the literature. This biomaterial also presented better cytocompatibility compared to the conventional collagen coating. Moreover, it showed adequate hemocompatibility, allowing its use as a surface with direct contact with blood. Application of WJ-ECMaa as a coating of the luminal surface of umbilical arteries for a use in vascular tissue engineering, has improved significantly the cellularization of this surface by allowing a full and homogeneous cell coverage. Taking these results together, our novel extraction method of human ECM offers a very promising biomaterial with many potential applications in tissue engineering such as the one presented direct in vascular tissue engineering. Further characterization of the composition and functionality will help explore the ways it can be used in tissue engineering applications, especially as a scaffold or a surface coating.
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Affiliation(s)
- Adrien Fayon
- Université de Lorraine, CNRS, IMoPA, Nancy, France
| | | | - Gregory Francius
- CNRS, Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l’Environnement, Université de Lorraine, Nancy, France
| | - Jean-Baptiste Vincourt
- Université de Lorraine, CNRS, IMoPA, Nancy, France
- Université de Lorraine, CNRS, INSERM, IBSLor (UMS2008/US40), Nancy, France
| | | | | | - Patrick Menu
- Université de Lorraine, CNRS, IMoPA, Nancy, France
- *Correspondence: Patrick Menu,
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Matveeva VG, Senokosova EA, Sevostianova VV, Khanova MY, Glushkova TV, Akentieva TN, Antonova LV, Barbarash LS. Advantages of Fibrin Polymerization Method without the Use of Exogenous Thrombin for Vascular Tissue Engineering Applications. Biomedicines 2022; 10:biomedicines10040789. [PMID: 35453539 PMCID: PMC9026760 DOI: 10.3390/biomedicines10040789] [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: 02/15/2022] [Revised: 03/16/2022] [Accepted: 03/25/2022] [Indexed: 01/01/2023] Open
Abstract
Fibrin is widely used in vascular tissue engineering. Typically, fibrin polymerization is initiated by adding exogenous thrombin. In this study, we proposed a protocol for the preparation of completely autologous fibrin without the use of endogenous thrombin and compared the properties of the prepared fibrin matrix with that obtained by the traditional method. Fibrinogen was obtained by ethanol precipitation followed by fibrin polymerization by adding either exogenous thrombin and calcium chloride (ExThr), or only calcium chloride (EnThr). We examined the structure, mechanical properties, thrombogenicity, degradation rate and cytocompatibility of fibrin matrices. Factor XIII (FXIII) quantitative assay was performed by ELISA, and FXIII activity was assessed by SDS-PAGE detection of γ-γ cross-links. The results show that network structure of EnThr fibrin was characterized by thinner fibers. The EnThr fibrin matrices had higher strength, stiffness and resistance to proteolytic degradation compared to ExThr fibrin. EnThr fibrin matrices exhibited less thrombogenicity in vitro than ExThr, and retained high cytocompatibility. Thus, the proposed approach has several advantages over the traditional method, namely the fabrication of a completely autologous coating material that has better mechanical properties, higher resistance to proteolysis and lower thrombogenicity.
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Jiao Y, Zhang Y, Xiao Y, Xing Y, Cai Z, Wang C, Zhou Z, Feng Z, Gu Y. The crescendo pulse frequency of shear stress stimulates the endothelialization of bone marrow mesenchymal stem cells on the luminal surface of decellularized scaffold in the bioreactor. Bioengineered 2022; 13:7925-7938. [PMID: 35358008 PMCID: PMC9278976 DOI: 10.1080/21655979.2022.2039502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
A completely confluent endothelial cell (EC) monolayer is required to maintain proper vascular function in small diameter tissue-engineered vascular graft (TEVG). However, the most effective method for EC attachment to the luminal surface and formation of an entire endothelium layer that works in vitro remains a complicated challenge that requires urgent resolution. Although pulsatile flow has been shown to be better suited for the generation of functional endothelium, the optimal frequency setting is unknown. Several pulsatile flow frequencies were used to implant rat bone mesenchymal stem cells (MSC) into the lumen of decellularized porcine carotid arteries. The endothelium's integrity and cell activity were investigated in order to determine the best pulse frequency settings. The results showed that MSC were maximally preserved and exhibited maximal morphological changes with improved endothelialization performance in response to increased pulse stimulation frequency. Increased pulse frequency stimulation stimulates the expression of mechanoreceptor markers, cytoskeleton reorganization in the direction of blood flow, denser skeletal proteins fibronectin, and stronger intercellular connections when compared to constant pulse frequency stimulation. MSC eventually develops an intact endothelial layer with anti-thrombotic properties on the inner wall of the decellularized tubular lumen. Conclusion: The decellularized vessels retain the three-dimensional structure of the vasculature, have a surface topography suitable for MSC growth, and have good mechanical properties. By increasing the frequency of pulsed stimulation, MSC endothelialize the lumen of the decellularized vasculature. It is expected to have anti-thrombotic and anti-neointimal hyperplasia properties after implantation, ultimately improving the patency of TEVG.
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Affiliation(s)
- Yuhao Jiao
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yuanguo Zhang
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yonghao Xiao
- School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, China
| | - Yuehao Xing
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Zhiwen Cai
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Cong Wang
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Zhengtong Zhou
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Zengguo Feng
- School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, China
| | - Yongquan Gu
- Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
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Bacakova L, Novotna K, Hadraba D, Musilkova J, Slepicka P, Beran M. Influence of Biomimetically Mineralized Collagen Scaffolds on Bone Cell Proliferation and Immune Activation. Polymers (Basel) 2022; 14:polym14030602. [PMID: 35160591 PMCID: PMC8838484 DOI: 10.3390/polym14030602] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/30/2022] [Accepted: 02/01/2022] [Indexed: 12/21/2022] Open
Abstract
Collagen, as the main component of connective tissue, is frequently used in various tissue engineering applications. In this study, porous sponge-like collagen scaffolds were prepared by freeze-drying and were then mineralized in a simulated body fluid. The mechanical stability was similar in both types of scaffolds, but the mineralized scaffolds (MCS) contained significantly more calcium, magnesium and phosphorus than the unmineralized scaffolds (UCS). Although the MCS contained a lower percentage (~32.5%) of pores suitable for cell ingrowth (113–357 μm in diameter) than the UCS (~70%), the number of human-osteoblast-like MG-63 cells on days 1, 3 and 7 after seeding was higher on MCS than on UCS, and the cells penetrated deeper into the MCS. The cell growth in extracts prepared by eluting the scaffolds for 7 days in a cell culture medium was also markedly higher in the MCS extracts, as indicated by real-time monitoring in the sensory xCELLigence system for 7 days. From this point of view, MCS are more promising for bone tissue engineering than UCS. However, MCS evoked a more pronounced inflammatory response than UCS, as indicated by the production of tumor necrosis factor-alpha (TNF-α) in macrophage-like RAW 264.7 cells in cultures on these scaffolds.
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Affiliation(s)
- Lucie Bacakova
- Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.N.); (D.H.); (J.M.)
- Correspondence: ; Tel.: +420-2-9644-3743
| | - Katarina Novotna
- Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.N.); (D.H.); (J.M.)
| | - Daniel Hadraba
- Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.N.); (D.H.); (J.M.)
| | - Jana Musilkova
- Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic; (K.N.); (D.H.); (J.M.)
| | - Petr Slepicka
- Department of Solid State Engineering, Faculty of Chemical Technology, University of Chemistry and Technology, Technicka 5, 166 28 Prague 6, Czech Republic;
| | - Milos Beran
- Food Research Institute Prague, Radiova 7, 102 31 Prague 10, Czech Republic;
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Weekes A, Bartnikowski N, Pinto N, Jenkins J, Meinert C, Klein TJ. Biofabrication of small diameter tissue-engineered vascular grafts. Acta Biomater 2022; 138:92-111. [PMID: 34781026 DOI: 10.1016/j.actbio.2021.11.012] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/21/2021] [Accepted: 11/09/2021] [Indexed: 12/12/2022]
Abstract
Current clinical treatment strategies for the bypassing of small diameter (<6 mm) blood vessels in the management of cardiovascular disease frequently fail due to a lack of suitable autologous grafts, as well as infection, thrombosis, and intimal hyperplasia associated with synthetic grafts. The rapid advancement of 3D printing and regenerative medicine technologies enabling the manufacture of biological, tissue-engineered vascular grafts (TEVGs) with the ability to integrate, remodel, and repair in vivo, promises a paradigm shift in cardiovascular disease management. This review comprehensively covers current state-of-the-art biofabrication technologies for the development of biomimetic TEVGs. Various scaffold based additive manufacturing methods used in vascular tissue engineering, including 3D printing, bioprinting, electrospinning and melt electrowriting, are discussed and assessed against the biomechanical and functional requirements of human vasculature, while the efficacy of decellularization protocols currently applied to engineered and native vessels are evaluated. Further, we provide interdisciplinary insight into the outlook of regenerative medicine for the development of vascular grafts, exploring key considerations and perspectives for the successful clinical integration of evolving technologies. It is expected that continued advancements in microscale additive manufacturing, biofabrication, tissue engineering and decellularization will culminate in the development of clinically viable, off-the-shelf TEVGs for small diameter applications in the near future. STATEMENT OF SIGNIFICANCE: Current clinical strategies for the management of cardiovascular disease using small diameter vessel bypassing procedures are inadequate, with up to 75% of synthetic grafts failing within 3 years of implantation. It is this critically important clinical problem that researchers in the field of vascular tissue engineering and regenerative medicine aim to alleviate using biofabrication methods combining additive manufacturing, biomaterials science and advanced cellular biology. While many approaches facilitate the development of bioengineered constructs which mimic the structure and function of native blood vessels, several challenges must still be overcome for clinical translation of the next generation of tissue-engineered vascular grafts.
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Affiliation(s)
- Angus Weekes
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, 4059, Australia; School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD, 4059, Australia; Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, 4006, Australia.
| | - Nicole Bartnikowski
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, 4059, Australia; School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD, 4059, Australia; Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD, 4035, Australia.
| | - Nigel Pinto
- Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, 4006, Australia; Department of Vascular Surgery, The Royal Brisbane and Women's Hospital, Herston, QLD, 4006, Australia.
| | - Jason Jenkins
- Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, 4006, Australia; Department of Vascular Surgery, The Royal Brisbane and Women's Hospital, Herston, QLD, 4006, Australia.
| | - Christoph Meinert
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, 4059, Australia; School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD, 4059, Australia; Herston Biofabrication Institute, Metro North Hospital and Health Services, Herston, QLD, 4006, Australia.
| | - Travis J Klein
- Centre for Biomedical Technologies, Queensland University of Technology (QUT), Brisbane, QLD, 4059, Australia; School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology (QUT), Brisbane, QLD, 4059, Australia.
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Mallis P, Michalopoulos E, Stavropoulos-Giokas C. Modern Approaches in Cardiovascular Disease Therapeutics: From Molecular Genetics to Tissue Engineering. Bioengineering (Basel) 2021; 8:174. [PMID: 34821740 PMCID: PMC8614975 DOI: 10.3390/bioengineering8110174] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 11/03/2021] [Indexed: 02/07/2023] Open
Abstract
Cardiovascular disease (CVD) currently represents one of the leading causes of death worldwide. It is estimated that more than 17.9 million people die each year due to CVD manifestations. Often, occlusion or stenosis of the vascular network occurs, either in large- or small-diameter blood vessels. Moreover, the obstruction of small vessels such as the coronary arteries may be related to more pronounced events, which can be life-threatening. The gold standard procedure utilizes the transplantation of secondary vessels or the use of synthetic vascular grafts. However, significant adverse reactions have accompanied the use of the above grafts. Therefore, modern therapeutic strategies must be evaluated for better disease administration. In the context of alternative therapies, advanced tissue-engineering approaches including the decellularization procedure and the 3D additive bioprinting methods, have been proposed. In this way the availability of bioengineered vascular grafts will be increased, covering the great demand that exists globally. In this Special Issue of Bioengineering, we tried to highlight the modern approaches which are focused on CVD therapeutics. This issue includes articles related to the efficient development of vascular grafts, 3D printing approaches and suitable atherosclerosis models.
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Affiliation(s)
- Panagiotis Mallis
- Hellenic Cord Blood Bank, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece; (E.M.); (C.S.-G.)
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Yousefi-Ahmadipour A, Asadi F, Pirsadeghi A, Nazeri N, Vahidi R, Abazari MF, Afgar A, Mirzaei-Parsa MJ. Current Status of Stem Cell Therapy and Nanofibrous Scaffolds in Cardiovascular Tissue Engineering. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2021. [DOI: 10.1007/s40883-021-00230-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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50
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Xu ZY, Huang JJ, Liu Y, Zhao Y, Wu XW, Ren JA. Current knowledge on the multiform reconstitution of intestinal stem cell niche. World J Stem Cells 2021; 13:1564-1579. [PMID: 34786158 PMCID: PMC8567451 DOI: 10.4252/wjsc.v13.i10.1564] [Citation(s) in RCA: 1] [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: 07/06/2021] [Revised: 08/02/2021] [Accepted: 09/17/2021] [Indexed: 02/06/2023] Open
Abstract
The development of “mini-guts” organoid originates from the identification of Lgr5+ intestinal stem cells (ISCs) and circumambient signalings within their specific niche at the crypt bottom. These in vitro self-renewing “mini-guts”, also named enteroids or colonoids, undergo perpetual proliferation and regulated differentiation, which results in a high-performance, self-assembling and physiological organoid platform in diverse areas of intestinal research and therapy. The triumphant reconstitution of ISC niche in vitro also relies on Matrigel, a heterogeneous sarcoma extract. Despite the promising prospect of organoids research, their expanding applications are hampered by the canonical culture pattern, which reveals limitations such as inaccessible lumen, confine scale, batch to batch variation and low reproducibility. The tumor-origin of Matrigel also raises biosafety concerns in clinical treatment. However, the convergence of breakthroughs in cellular biology and bioengineering contribute to multiform reconstitution of the ISC niche. Herein, we review the recent advances in the microfabrication of intestinal organoids on hydrogel systems.
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Affiliation(s)
- Zi-Yan Xu
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Jin-Jian Huang
- Medical School, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ye Liu
- Medical School, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Yun Zhao
- Department of General Surgery, BenQ Medical Center, Nanjing 210019, Jiangsu Province, China
| | - Xiu-Wen Wu
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Jian-An Ren
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
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