Glycosaminoglycan entrapment by fibrin in engineered heart valve tissues

Alfonso, Abraham; Rath, Sasmita; Rafiee, Parvin; Hernandez-Espino, Mario; Din, Mahreen; George, Florence; Ramaswamy, Sharan

doi:10.1016/j.actbio.2013.06.009

Cited by 11 publications

(9 citation statements)

References 45 publications

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“…The relevance of GAG preservation in decellularized cardiovascular implants is controversially discussed (Converse et al , ). GAG, hydrophilic polymers of disaccharide units, are a main component of the spongiosa layer of heart valves, with hyaluronan representing 50–60% of the whole GAG content in semilunar valves (Alfonso et al , ). Due to their hydrophilicity, GAG induce water storage in the spongiosa that supports shock absorbance during valve movement (Rabkin‐Aikawa et al , ).…”

Section: Discussionmentioning

confidence: 99%

Improvement of the in vivo cellular repopulation of decellularized cardiovascular tissues by a detergent-free, non-proteolytic, actin-disassembling regimen

Assmann

Struß

Schiffer

et al. 2017

J Tissue Eng Regen Med

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Low immunogenicity and high repopulation capacity are crucial determinants for the functional and structural performance of acellular cardiovascular implants. The present study evaluates a detergent-free, non-proteolytic, actin-disassembling regimen (BIO) for decellularization of heart valve and vessel grafts, particularly focusing on their bio-functionality. Rat aortic conduits (rAoC; n = 89) and porcine aortic valve samples (n = 106) are decellularized using detergents (group DET) or the BIO regimen. BIO decellularization results in effective elimination of cellular proteins and significantly improves removal of DNA as compared with group DET, while the extracellular matrix (ECM) structure as well as mechanical properties are preserved. The architecture of rAoC in group BIO allows for improved bio-functionalization with fibronectin (FN) in a standardized rat implantation model: BIO treatment significantly increases speed and amount of autologous medial cellular repopulation in vivo (p < 0.001) and decreases the formation of hyperplastic intima (p < 0.001) as compared with FN-coated DET-decellularized grafts. Moreover, there are no signs of infiltration with inflammatory cells. The present biological, detergent-free, non-proteolytic regimen balances effective decellularization and ECM preservation in cardiovascular grafts, and provides optimized bio-functionality. Additionally, this study implies that the actin-disassembling regimen may be a promising approach for bioengineering of acellular scaffolds from other muscular tissues, as for example myocardium or intestine. Copyright © 2017 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

Improvement of the in vivo cellular repopulation of decellularized cardiovascular tissues by a detergent-free, non-proteolytic, actin-disassembling regimen

Assmann

Struß

Schiffer

et al. 2017

J Tissue Eng Regen Med

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“…Fibrin promotes ECM synthesis in the cells that it houses while also retaining deposited ECM due to the gel-like nature of the biomaterial. Fibrin, collagen and GAGs together have proven to be a suitable environment for both cardiovascular (Flanagan et al 2006;van Vlimmeren et al 2013;Alfonso et al 2013;Neidert & Tranquillo 2006) and cartilage applications (Eyrich et al 2007;Deponti et al 2014). GAGs such as chondroitin sulphate and hyaluronic acid are found abundantly in the cardiac cushion, from which valvulogenesis occurs, and studies have shown that the signalling molecules contained within these GAGs, regulate further heart valve development (Armstrong & Bischoff 2004;Person et al 2005;Eckert et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Incorporation of fibrin into a collagen–glycosaminoglycan matrix results in a scaffold with improved mechanical properties and enhanced capacity to resist cell-mediated contraction

et al. 2015

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Fibrin is a versatile scaffold for tissue engineering applications, but its weak mechanical properties leave it susceptible to cell-mediated contraction, meaning the dimensions of the fibrin construct will change over time. We have reinforced fibrin with a collagen glycosaminoglycan matrix and characterised the mechanical properties and bioactivity of the reinforced fibrin (FCG). This is the first scaffold manufactured from all naturally derived materials that resists cell-mediated contraction. In fact, over 7 days, the FCG scaffold fully resisted cell-mediated contraction of vascular smooth muscle cells. This FCG scaffold has many potential applications where natural scaffold materials can encourage regeneration.

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“…75 Recently, Alfonso et al demonstrated that fibrin in the flex-flow culture of engineered heart valve tissues could promote collagen production of adult human periodontal ligament cells and enhance retention of GAGs within the developing ECM. 76 The major problem for the biological protein based TEHV is that leaflets significantly contract because the imposed stress on the leaflets cannot counteract the stress generated by the leaflets, leading to pronounced insufficiency and loss of coaptation. 77 …”

Section: Tissue Engineered Heart Valvesmentioning

confidence: 99%

Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions

Cheung

Duan

Butcher

2015

Expert Opinion on Biological Therapy

149

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Introduction Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. Areas covered This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally-derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Expert opinion While much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells.

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Glycosaminoglycan entrapment by fibrin in engineered heart valve tissues

Cited by 11 publications

References 45 publications

Improvement of the in vivo cellular repopulation of decellularized cardiovascular tissues by a detergent-free, non-proteolytic, actin-disassembling regimen

Improvement of the in vivo cellular repopulation of decellularized cardiovascular tissues by a detergent-free, non-proteolytic, actin-disassembling regimen

Incorporation of fibrin into a collagen–glycosaminoglycan matrix results in a scaffold with improved mechanical properties and enhanced capacity to resist cell-mediated contraction

Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions

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