Vascular tissue engineering: The next generation

Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, 10 Amistad Street, Amistad Building Room 301, New Haven, CT 06520, USA.
Trends in Molecular Medicine (Impact Factor: 9.45). 06/2012; 18(7):394-404. DOI: 10.1016/j.molmed.2012.04.013
Source: PubMed

ABSTRACT It is the ultimate goal of tissue engineering: an autologous tissue engineered vascular graft (TEVG) that is immunologically compatible, nonthrombogenic, and can grow and remodel. Currently, native vessels are the preferred vascular conduit for procedures such as coronary artery bypass (CABG) or peripheral bypass surgery. However, in many cases these are damaged, have already been harvested, or are simply unusable. The use of synthetic conduits is severely limited in smaller diameter vessels due to increased incidence of thrombosis, infection, and graft failure. Current research has therefore energetically pursued the development of a TEVG that can incorporate into a patient's circulatory system, mimic the vasoreactivity and biomechanics of the native vasculature, and maintain long-term patency.

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    • "Furthermore, the seeded cells may lead to the homing of circulating monocytes [29] that, in turn, release the monocyte chemotactic protein-1, stimulating the regeneration of the blood vessel [38]. Although it has not been verified whether the seeded ECs were present on the implanted grafts, we can suppose that the initial endothelial coverage could be transient and progressively replaced by the host cells [39]. At both time points, the external diameter of the explanted grafts was similar to the one of host aorta (Figures 3(c) and 3(d)). "
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    ABSTRACT: To overcome the issues connected to the use of autologous vascular grafts and artificial materials for reconstruction of small diameter (<6 mm) blood vessels, this study aimed to develop acellular matrix- (AM-) based vascular grafts. Rat iliac arteries were decellularized by a detergent-enzymatic treatment, whereas endothelial cells (ECs) were obtained through enzymatic digestion of rat skin followed by immunomagnetic separation of CD31-positive cells. Sixteen female Lewis rats (8 weeks old) received only AM or previously in vitro reendothelialized AM as abdominal aorta interposition grafts (about 1 cm). The detergent-enzymatic treatment completely removed the cellular part of vessels and both MHC class I and class II antigens. One month after surgery, the luminal surface of implanted AMs was partially covered by ECs and several platelets adhered in the areas lacking cell coverage. Intimal hyperplasia, already detected after 1 month, increased at 3 months. On the contrary, all grafts composed by AM and ECs were completely covered at 1 month and their structure was similar to that of native vessels at 3 months. Taken together, our findings show that prostheses composed of AM preseeded with ECs could be a promising approach for the replacement of blood vessels.
    BioMed Research International 07/2014; 2014:685426. DOI:10.1155/2014/685426 · 3.17 Impact Factor
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    • "ECs, however, have limited capacity for regeneration and exhaust their renewal after approximately 70 cell cycles, leading to the hypothesis that endothelialization of vascular grafts occurs via one of four mechanisms: (i) by seeding ECs, (ii) via EC migration from adjacent native vessel, (iii) through deposition of circulating endothelial progenitor cells onto the luminal surface, or (iv) via ingrowth of capillaries through porous grafts [62]. Since Herring proposed a method of seeding ECs onto the luminal surface of synthetic conduits back in 1978 [63] [64], many studies have attempted to improve clinical rates of patency by optimizing EC attachment. Parallel to this, in scaffold-based blood vessel engineering, bioreactors and pulsatile flow systems, designed by many scientists, have been found to progress the mechanical property of the engineered blood vessels by augmenting the deposition and remodeling of extracellular matrix as well as the maturation and differentiation of self-assembled microtissues [65] [66] [67] [68] "
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    ABSTRACT: With the high occurrence of cardiovascular disease and increasing numbers of patients requiring vascular access, there is a significant need for small-diameter (<6 mm inner diameter) vascular graft that can provide long-term patency. Despite the technological improvements, restenosis and graft thrombosis continue to hamper the success of the implants. Vascular tissue engineering is a new field that has undergone enormous growth over the last decade and has proposed valid solutions for blood vessels repair. The goal of vascular tissue engineering is to produce neovessels and neoorgan tissue from autologous cells using a biodegradable polymer as a scaffold. The most important advantage of tissue-engineered implants is that these tissues can grow, remodel, rebuild, and respond to injury. This review describes the development of polymeric materials over the years and current tissue engineering strategies for the improvement of vascular conduits.
    International Journal of Polymer Science 01/2014; 2014. DOI:10.1155/2014/689390 · 1.20 Impact Factor
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    ABSTRACT: Tissue-engineered vascular autografts (TEVAs) were made by seeding 4-6 x 10(6) of mixed cells obtained from femoral veins of mongrel dogs onto tube-shaped biodegradable polymer scaffolds composed of a polyglycolid acid (PGA) nonwoven fabric sheet and a copolymer of L-lactide and caprolactone (n = 4). After 7 days, the inferior vena cavas (IVCs) of the same dogs were replaced with TEVAs. After 3, 4, 5, and 6 months, angiographies were performed, and the dogs were sacrificed. The implanted TEVAs were examined both grossly and immunohistologically. The implanted TEVAs showed no evidence of stenosis or dilatation. No thrombus was found inside the TEVAs, even without any anticoagulation therapy. Remnants of the polymer scaffolds were not observed in all specimens, and the overall gross appearance similar to that of native IVCs. Immunohistological staining revealed the presence of factor VIII positive nucleated cells at the luminal surface of the TEVAs. In addition, lesions were observed where alpha-smooth muscle actin and desmin positive cells existed. Implanted TEVAs contained a sufficient amount of extracellular matrix, and showed neither occlusion nor aneurysmal formation. In addition, endothelial cells were found to line the luminal surface of each TEVA. These results strongly suggest that "ideal" venous grafts with antithrombogenicity can be produced.
    Tissue Engineering 09/2001; 7(4):429-39. DOI:10.1089/10763270152436481 · 4.25 Impact Factor
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