Progress in developing a living human tissue-engineered tri-leaflet heart valve assembled from tissue produced by the self-assembly approach

Dubé, Jean; Bourget, Jean-Michel; Gauvin, Robert; Lafrance, Hugues; Roberge, Claude; Auger, François A.; Germain, Lucie

doi:10.1016/j.actbio.2014.04.033

Cited by 30 publications

(22 citation statements)

References 80 publications

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“…The fact that cells reside in their specific ECM within a complex in vivo milieu elicits the necessity to further illustrate the impacts of ECMs produced by various cell sources on overall cell fates [714]. More exciting than expected, a cohesive cell-formed sheet can be layered into 3D tissues or organs with physiological mechanical strength [715,716]; this concept has been demonstrated to be feasible in clinical sittings [717]. In addition, there is a wealth of evidence that cell-formed ECM products can be applied to enhance the large-scale expansion of highly functional adult human MSCs [718] or to decorate the surfaces of synthetic polymers and manufactured metals on which subsequent cell adhesion is regulated by adsorbed ECM proteins [96,184,719,720].…”

Section: Future Directions and Outlookmentioning

confidence: 99%

Advancing biomaterials of human origin for tissue engineering

Chen

Liu

2016

Progress in Polymer Science

920

513

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Biomaterials have played an increasingly prominent role in the success of biomedical devices and in the development of tissue engineering, which seeks to unlock the regenerative potential innate to human tissues/organs in a state of deterioration and to restore or reestablish normal bodily function. Advances in our understanding of regenerative biomaterials and their roles in new tissue formation can potentially open a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multi-component construction of native extracellular matrices (ECMs) for cell accommodation, the synthetic biomaterials produced today routinely incorporate biologically active components to define an artificial in vivo milieu with complex and dynamic interactions that foster and regulate stem cells, similar to the events occurring in a natural cellular microenvironment. The range and degree of biomaterial sophistication have also dramatically increased as more knowledge has accumulated through materials science, matrix biology and tissue engineering. However, achieving clinical translation and commercial success requires regenerative biomaterials to be not only efficacious and safe but also cost-effective and convenient for use and production. Utilizing biomaterials of human origin as building blocks for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural tissue with regard to its physical and chemical properties for the orchestration of wound healing and tissue regeneration. In addition to directly using tissue transfers and transplants for repair, new applications of human-derived biomaterials are now focusing on the use of naturally occurring biomacromolecules, decellularized ECM scaffolds and autologous preparations rich in growth factors/non-expanded stem cells to either target acceleration/magnification of the body's own repair capacity or use nature's paradigms to create new tissues for restoration. In particular, there is increasing interest in separating ECMs into simplified functional domains and/or biopolymeric assemblies so that these components/constituents can be discretely exploited and manipulated for the production of bioscaffolds and new biomimetic biomaterials. Here, following an overview of tissue auto-/allo-transplantation, we discuss the recent trends and advances as well as the challenges and future directions in the evolution and application of human-derived biomaterials for reconstructive surgery and tissue engineering. In particular, we focus on an exploration of the structural, mechanical, biochemical and biological information present in native human tissue for bioengineering applications and to provide inspiration for the design of future biomaterials.

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Section: Future Directions and Outlookmentioning

confidence: 99%

Advancing biomaterials of human origin for tissue engineering

Chen

Liu

2016

Progress in Polymer Science

920

513

View full text Add to dashboard Cite

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“…Similarly, Dubé et al constructed TEHV using self-assembled fibroblast sheets, taking 7 weeks for the sheet to yield the thick construct which were cut and assembled together on a Edwards Lifesciences ® stent, based on techniques used for commercially available replacement valves (Figure 2C) . 124 The valve had similar ultimate tensile strength measurements comparable to native porcine leaflets, but the elastic modulus was at least an order of magnitude lower. This technique generates TEHV containing cells embedded in their own extracellular matrix and has the potential to provide enough strength to support physiological stress.…”

Section: Tissue Engineered Heart Valvesmentioning

confidence: 86%

“…123,124 Although they fabricated homogeneous TEHVs, the technique has tremendous potential to recapitulate the heterogeneous ECM structure of the native aortic leaflets by superimposing self-assembled sheets with different compositions with potentially higher accuracy than many other techniques. The newest process takes approximately 12 weeks, which may not be clinically feasible, but it has the potential to be scaled-up industrially to decrease construction time and make “off-the-shelf” products.…”

Section: Expert Opinionmentioning

confidence: 99%

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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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“…In one study, Flanagan et al molded a fibrin-based scaffold into a valve shape, seeded the construct with autologous cells, conditioned in a bioreactor for 28 days, and implanted into sheep for 3 months [81]. More recently, Dubé et al constructed TEHV using self-assembled fibroblast sheets, taking only 7 weeks for the sheet to assemble and yielded promising results [86]. However, the leaflets lost coaptation due to tissue contraction.…”

Section: Molded Polymer Scaffoldsmentioning

confidence: 99%