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
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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- "Another important aspect is the biodegradation of scaffold materials, which should ideally occur in parallel with tissue regeneration . In this regard, naturally occurring polymers have multiple advantages over the synthetic materials currently used in tissue engineering, as they are able to provide extracellular environment and a scaffold structure similar to the ECM of native tissues    . Alginate, a non-toxic polysaccharide easily obtainable from many species of the brown algae , is one of the biomaterials of choice for various tissue engineering and additive manufacturing applications, because of its ability to form hydrogel  which provides an aqueous environment necessary for sustainable cell growth. "
ABSTRACT: Developing matrices biocompatible with vascular cells is one of the most challenging tasks in tissue engineering. Here, we compared the growth of vascular cells on different hydrogels as potential materials for bioplotting of vascular tissue. Formulations containing alginate solution (Alg, 2%, w/v) blended with protein solutions (silk fibroin, gelatin, keratin, or elastin) at 1% w/v were prepared. Human umbilical vein endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts were cultivated on hydrogels for 7 days. Cell number and morphology was visualised using fluorescent staining at day 3 and 7. Cell metabolic activity was analysed using WST assay. Compared to pure Alg, Alg/keratin, Alg/gelatin and Alg/silk fibroin provided superb surfaces for ECs, supporting their attachment, growth, spreading and metabolic activity. SMCs showed best colonization and growth on Alg/silk fibroin and Alg/keratin hydrogels, whereas on elastin-containing hydrogels, cell clustering was observed. Fibroblasts growth was enhanced on Alg/elastin, and strongly improved on silk fibroin- and keratin-containing hydrogels. In contrast to the previous studies with alginate dialdehyde-gelatin crosslinked gels, Alg/gelatin blend hydrogels provided a less favourable scaffold for fibroblasts. Taken together, the most promising results were obtained with silk fibroin- and keratin-containing hydrogels, which supported the growth of all types of vascular cells. This article is protected by copyright. All rights reserved.Journal of Biomedical Materials Research Part A 10/2015; DOI:10.1002/jbm.a.35590 · 3.37 Impact Factor
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- "The ideal graft would combine the advantages of both, synthetic and autologous grafts and overcome their respective disadvantages . Over recent years, a number of different approaches have been described which have applied various biological or alloplastic scaffold materials with varying levels of efficacy  . Here, biocompatibility and immediate availability have emerged in particular as crucial factors for clinical use . "
ABSTRACT: The generation of tissue-engineered blood vessel substitutes remains an ongoing challenge for cardiovascular tissue engineering. Full biocompatibility and immediate availability have emerged as central issues for clinical use. To address these issues, we developed a technique that allows the generation of highly stable tubular fibrin segments. The process is based on the compaction of fibrin in a custom-made high-speed rotation mould. In an automated process, fibrin is precipitated from plasma by means of the Vivostat(®) system. Following application to the rotating mould, the fibrin was compacted by centrifugal force and excess fluid was pressed out. This compaction results in increasing cross-links between the fibrin fibrils and a corresponding significant increase of biomechanical stability up to a burst strength of 230 mm of mercury. The moulding process allows for a simultaneous seeding procedure. In a first in vivo evaluation in a sheep model, segments of the carotid artery were replaced by tissue-engineered vascular grafts, generated immediately prior to implantation (n=6). Following subjection to the body's remodelling mechanisms, the segments showed a high structural similarity to a native artery after explantation at 6 months. Thus, this technique may represent a powerful tool for the generation of biomechanically stable vascular grafts immediately prior to implantation.Acta biomaterialia 10/2015; DOI:10.1016/j.actbio.2015.10.012 · 6.03 Impact Factor
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- "Furthermore, the seeded cells may lead to the homing of circulating monocytes  that, in turn, release the monocyte chemotactic protein-1, stimulating the regeneration of the blood vessel . 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 . 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)). "
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 · 1.58 Impact Factor
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