The future of heart valve replacement: recent developments and translational challenges for heart valve tissue engineering: The future of heart valve replacement

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Abstract

<p class="first" id="d14578494e107">Heart valve replacement is often the only solution for patients suffering from valvular heart disease. However, currently available valve replacements require either life-long anticoagulation or are associated with valve degeneration and calcification. Moreover, they are suboptimal for young patients, because they do not adapt to the somatic growth. Tissue-engineering has been proposed as a promising approach to fulfil the urgent need for heart valve replacements with regenerative and growth capacity. This review will start with an overview on the currently available valve substitutes and the techniques for heart valve replacement. The main focus will be on the evolution of and different approaches for heart valve tissue engineering, namely the in vitro, in vivo and in situ approaches. More specifically, several heart valve tissue-engineering studies will be discussed with regard to their shortcomings or successes and their possible suitability for novel minimally invasive implantation techniques. As in situ heart valve tissue engineering based on cell-free functionalized starter materials is considered to be a promising approach for clinical translation, this review will also analyse the techniques used to tune the inflammatory response and cell recruitment upon implantation in order to stir a favourable outcome: controlling the blood-material interface, regulating the cytokine release, and influencing cell adhesion and differentiation. In the last section, the authors provide their opinion about the future developments and the challenges towards clinical translation and adaptation of heart valve tissue engineering for valve replacement. Copyright © 2016 John Wiley & Sons, Ltd. </p>

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Kate E. Armstrong, JOYCE BISCHOFF (2004)

During the past decade, single gene disruption in mice and large-scale mutagenesis screens in zebrafish have elucidated many fundamental genetic pathways that govern early heart patterning and differentiation. Specifically, a number of genes have been revealed serendipitously to play important and selective roles in cardiac valve development. These initially surprising results have now converged on a finite number of signaling pathways that regulate endothelial proliferation and differentiation in developing and postnatal heart valves. This review highlights the roles of the most well-established ligands and signaling pathways, including VEGF, NFATc1, Notch, Wnt/beta-catenin, BMP/TGF-beta, ErbB, and NF1/Ras. Based on the interactions among and relative timing of these pathways, a signaling network model for heart valve development is proposed.

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Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling.

Brooks Udelsman, W. Saltzman, Tamar L Mirensky … (2010)

Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are the earliest tissue-engineered vascular grafts (TEVGs) to be used clinically. These TEVGs transform into living blood vessels in vivo, with an endothelial cell (EC) lining invested by smooth muscle cells (SMCs); however, the process by which this occurs is unclear. To test if the seeded BMCs differentiate into the mature vascular cells of the neovessel, we implanted an immunodeficient mouse recipient with human BMC (hBMC)-seeded scaffolds. As in humans, TEVGs implanted in a mouse host as venous interposition grafts gradually transformed into living blood vessels over a 6-month time course. Seeded hBMCs, however, were no longer detectable within a few days of implantation. Instead, scaffolds were initially repopulated by mouse monocytes and subsequently repopulated by mouse SMCs and ECs. Seeded BMCs secreted significant amounts of monocyte chemoattractant protein-1 and increased early monocyte recruitment. These findings suggest TEVGs transform into functional neovessels via an inflammatory process of vascular remodeling.

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Acellular vascular tissues: natural biomaterials for tissue repair and tissue engineering.

Christine Schmidt, Jennie M. Baier (2000)

Various research groups around the world are actively investigating cardiovascular prostheses of biological origin. This review article discusses the need for such bioprosthetics and the potential role for natural tissues in cardiovascular applications such as cardiac valves and vascular grafts. Upon implantation, unmodified natural materials are subject to chemical and enzymatic degradation, seriously decreasing the life of the prosthesis. Therefore, methods such as glutaraldehyde and polyepoxide crosslinking treatments and dye-mediated photooxidation have been developed to stabilize the tissue while attempting to maintain its natural mechanical properties. Also, residual cellular components in a bioprosthetic material have been associated with undesired effects, such as calcification and immunological recognition, and thus have been the motivation for various decellularization processes. The effects of these stabilization and decellularization treatments on mechanical, biological and chemical properties of treated tissues have been investigated, specifically with regard to calcification, immunogenicity, and cytotoxicity concerns. Despite significant advances in the area of cardiovascular prostheses, there has yet to be developed a completely biocompatible, long-lasting implant. However, with the recent advent of tissue engineering, the possibility of applying selective cell seeding to naturally derived bioprosthetics moves us closer to a living tissue replacement.