Tissue engineering vascular grafts a fortiori: looking back and going forward

Natasha, G; Tan, Aaron; Gundogan, Buket; Farhatnia, Yasmin; Nayyer, Leila; Mahdibeiraghdar, Sara; Rajadas, Jayakumar; Coppi, Paolo De; Davies, Alun H.; Seifalian, Alexander M.

doi:10.1517/14712598.2015.980234

Cited by 40 publications

(31 citation statements)

References 96 publications

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“…A utologous blood vessels for arterial bypassing remain the gold standard treatment for small-caliber (<4 mm) arterial diseases despite their limited source-ability and related morbidity at the donor site, 1 providing a strong impetus for R&D on tissue-engineered vascular grafts (TEVGs). Several TEVG strategies have been therefore suggested in recent years, utilizing either cell sheet-based self-assembly techniques 2 or biodegradable synthetic/natural scaffold-guided tissue engineering approaches 1 with the aim of generating viable substitutes for autologous small-caliber grafting.…”

Section: Introductionmentioning

confidence: 99%

“…Several TEVG strategies have been therefore suggested in recent years, utilizing either cell sheet-based self-assembly techniques 2 or biodegradable synthetic/natural scaffold-guided tissue engineering approaches 1 with the aim of generating viable substitutes for autologous small-caliber grafting. Both approaches displayed some promising results in vitro , in vivo , and even in several case studies and ongoing clinical trials; however, neither has of yet been translated into wide clinical applications.…”

Section: Introductionmentioning

confidence: 99%

“…Both approaches displayed some promising results in vitro , in vivo , and even in several case studies and ongoing clinical trials; however, neither has of yet been translated into wide clinical applications. 1,3,4 For instance, despite the great promise of cell sheet-based self-assembly techniques, their production process is labor-intensive, requires costly bioreactor work, and involves long in vitro manipulation periods (typically >12 weeks). 1,3 …”

Section: Introductionmentioning

confidence: 99%

“…1,3,4 These scaffolds may represent a compromise between traditional in vitro and more advanced in situ tissue engineering, in that they can not only be preconditioned in a bioreactor in vitro but also be intrinsically bioactive in vivo in recruiting an adequate host cell regenerative response following implantation. 6 Major issues of concern, though, relate to their ability to maintain graft patency, flexibility, and contractility following implantation.…”

Section: Introductionmentioning

confidence: 99%

“…1,9 Two major cell types reside within the natural blood vessel: endothelial cells (ECs) on the luminal side and smooth muscle cells (SMCs) in the vascular wall. Endothelialization—the process of graft lumen coating with a semipermeable and thromboresistant EC barrier—masks the ECM collagen thromboactive moieties and is thereby hypothesized to inhibit graft failure by preventing coagulation, increasing patency rates, and improving overall graft function.…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Autologous Reendothelialization of Small-Caliber Arterial Extracellular Matrix: A Preclinical Large Animal Study

Dahan

Sarig

Bronshtein

et al. 2017

Tissue Engineering Part A

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Effective cellularization is a key approach to prevent small-caliber (<4 mm) tissue-engineered vascular graft (TEVG) failure and maintain patency and contractility following implantation. To achieve this goal, however, improved biomimicking designs and/or relatively long production times (typically several months) are required. We previously reported on porcine carotid artery decellularization yielding biomechanically stable and cell supportive small-caliber (3–4 mm diameter, 5 cm long) arterial extracellular matrix (scaECM) vascular grafts. In this study, we aimed to study the scaECM graft patency in vivo and possibly improve that patency by graft pre-endothelialization with the recipient porcine autologous cells using our previously reported custom-designed dynamic perfusion bioreactor system. Decellularized scaECM vascular grafts were histologically characterized, their immunoreactivity studied in vitro, and their biocompatibility profile evaluated as a xenograft subcutaneous implantation in a mouse model. To study the scaECM cell support and remodeling ability, pig autologous endothelial and smooth muscle cells (SMCs) were seeded and dynamically cultivated within the scaECM lumen and externa/media, respectively. Finally, endothelialized-only scaECMs—hypothesized as a prerequisite for maintaining graft patency and controlling intimal hyperplasia—were transplanted as an interposition carotid artery graft in a porcine model. Graft patency was evaluated through angiography online and endpoint pathological assessment for up to 6 weeks. Our results demonstrate the scaECM-TEVG biocompatibility preserving a structurally and mechanically stable vascular wall not just following decellularization and recellularization but also after implantation. Using our dynamic perfusion bioreactor, we successfully demonstrated the ability of this TEVG to support in vitro recellularization and remodeling by primary autologous endothelial and SMCs, which were seeded on the lumen and the externa/media layers, respectively. Following transplantation, dynamically endothelialized scaECM-TEVGs remained patent for 6 weeks in a pig carotid interposition bypass model. When compared with nonrevitalized control grafts, reendothelialized grafts provided excellent antithrombogenic activity, inhibited intimal hyperplasia formation, and encouraged media wall infiltration and reorganization with recruited host SMCs. We thus demonstrate that readily available decellularized scaECM can be promptly revitalized with autologous cells in a 3-week period before implantation, indicating applicability as a future platform for vascular reconstructive procedures.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dynamic Autologous Reendothelialization of Small-Caliber Arterial Extracellular Matrix: A Preclinical Large Animal Study

Dahan

Sarig

Bronshtein

et al. 2017

Tissue Engineering Part A

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Cell Seeding on UV‐C‐Treated 3D Polymeric Templates Allows for Cost‐Effective Production of Small‐Caliber Tissue‐Engineered Blood Vessels

Galbraith

Roy

Bourget

et al. 2018

Biotechnology Journal

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There is a strong clinical need to develop small‐caliber tissue‐engineered blood vessels for arterial bypass surgeries. Such substitutes can be engineered using the self‐assembly approach in which cells produce their own extracellular matrix (ECM), creating a robust vessel without exogenous material. However, this approach is currently limited to the production of flat sheets that need to be further rolled into the final desired tubular shape. In this study, human fibroblasts and smooth muscle cells were seeded directly on UV‐C‐treated cylindrical polyethylene terephthalate glycol‐modified (PETG) mandrels of 4.8 mm diameter. UV‐C treatment induced surface modification, confirmed by Fourier‐transform infrared spectroscopy (FTIR) analysis, was necessary to ensure proper cellular attachment and optimized ECM secretion/assembly. This novel approach generated solid tubular conduits with high level of cohesion between concentric cellular layers and enhanced cell‐driven circumferential alignment that can be manipulated after 21 days of culture. This simple and cost‐effective mandrel‐seeded approach also allowed for endothelialization of the construct and the production of perfusable trilayered tissue‐engineered blood vessels with a closed lumen. This study lays the foundation for a broad field of possible applications enabling custom‐made reconstructed tissues of specialized shapes using a surface treated 3D structure as a template for tissue engineering.

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Determining the optimal protocol for preparing an acellular scaffold of tissue engineered small‐diameter blood vessels

Pan

et al. 2017

J Biomed Mater Res

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Although detergent-based decellularization protocols have been widely used to obtain a natural extracellular matrix (ECM) scaffold in tissue engineering, some key challenges still exist. To achieve an optimum natural decellularized scaffold for the construction of tissue-engineered small-diameter blood vessels (TEBV), porcine carotid arteries (PCAs) were decellularized by combining sodium dodecyl sulfate (SDS), sodium deoxycholate (SDC) and Triton X-100 (Triton) in different concentrations. Tissue samples were processed and their histological, biochemical and biomechanical characteristics were investigated. Results showed that only two methods 0.5% (SDS + SDC) and 1% (SDS + SDC) could completely remove of the cellular contents and preserve the native ECM architecture. Furthermore, 1% (SDS + SDC) based methods acquire preferable porosity and suitable mechanical strength. Residual Triton in the ECM scaffold holds intensive cytotoxity. In conclusion, 1%(SDS + SDC) based method can obtain a superior PCAs scaffold for the construction of TEBV. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 619-631, 2018.

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Tissue engineering vascular grafts a fortiori: looking back and going forward

Abstract: TEVG holds great promise with advances in nanotechnology, coupled with important refinements in tissue engineering and decellularisation techniques. This will undoubtedly be an important milestone for cardiovascular medicine when it is eventually translated to clinical use.

Cited by 40 publications

References 96 publications

Dynamic Autologous Reendothelialization of Small-Caliber Arterial Extracellular Matrix: A Preclinical Large Animal Study

Dynamic Autologous Reendothelialization of Small-Caliber Arterial Extracellular Matrix: A Preclinical Large Animal Study

Cell Seeding on UV‐C‐Treated 3D Polymeric Templates Allows for Cost‐Effective Production of Small‐Caliber Tissue‐Engineered Blood Vessels

Determining the optimal protocol for preparing an acellular scaffold of tissue engineered small‐diameter blood vessels

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