Bioreactors for heart valve tissue engineering: a review

Abstract

Bioreactors have great potential in the successful development of tissue-engineered heart valve replacements, both at the research stage and in commercial platforms. Their ability to mimick the chemical and physiological conditions of the body has allowed researchers to study in vitro cellular responses, and this has helped in the fabrication of better and more efficient tissues in vivo. Use of different bioreactors, such as, rotating, dynamic flexure, cyclic stretch and pulsatile bioreactors, in tissue engineering of heart valves has been widely investigated. However, this research is still at its early stage, and many critical issues need to be resolved to make tissue engineered heart valves sufficiently reliable for clinical applications. In the following article, after a brief introduction to the structure and role of heart valves, the efforts of tissue engineers in designing heart valves using different bioreactors is described.

Tissue Engineering Heart Valves – a Review of More than Two Decades into Preclinical and Clinical Testing for Obtaining the Next Generation of Heart Valve Substitutes

“…In order to anticipate and to evaluate the behavior of TEHV, considerable attention is given to biomechanics using dedicated bioreactors and functioning models in laboratories [62][63][64] , but the imminent challenges to overcome are their in vivo translation.…”

Flow and deformation due to periodic loading in a soft porous material

“…2005; Haj, Hampson & Gogniat 2009; Gauvin et al. 2011; Amrollahi & Tayebi 2015; Peroglio et al. 2018).…”

“…The former scenario has attracted great interest recently as a potential driver of transport in brain tissue (Franceschini et al 2006;Kedarasetti, Drew & Costanzo 2020;Bojarskaite et al 2023) and the latter is important for load-bearing and transport in cartilage (Riches et al 2002;Mauck, Hung & Ateshian 2003;Ferguson, Ito & Pyrak-Nolte 2004;Sengers, Oomens & Baaijens 2004;Schmidt et al 2010;Zhang 2011;Di Domenico, Wang & Bonassar 2017;Cacheux et al 2023) and bone (Piekarski & Munro 1977;Zhang & Cowin 1994;Manfredini et al 1999;Nguyen, Lemaire & Naili 2010;Witt et al 2014). Periodic loads are also commonly applied in regenerative medicine to improve cell differentiation in scaffolds via mechanotransduction (Kim et al 1999;Butler, Goldstein & Guilak 2000;Mauck et al 2000;Grenier et al 2005;Haj, Hampson & Gogniat 2009;Gauvin et al 2011;Amrollahi & Tayebi 2015;Peroglio et al 2018). Soils and sediments experience periodic loading due to seismicity (Genna & Cividini 1989;Li, Borja & Regueiro 2004;Popescu et al 2006;Bonazzi, Jha & de Barros 2021), vehicle traffic (Hu, Zhu & Cheng 2011;Ni et al 2015;Ni & Geng 2022) and ocean waves and tides (Madsen 1978;Yamamoto et al 1978;Karim, Nogami & Wang 2002;Cheng 2016;Trefry et al 2019).…”

Cardiac Valve Bioreactor for Physiological Conditioning and Hydrodynamic Performance Assessment

“…Often, cells are seeded onto a scaffold and conditioned in a bioreactor prior to implantation. 2,10 Ideally, the cells would be autologous and obtained from blood, bone marrow, adipose tissue, skin, or myocardium either directly or via stem or progenitor cell populations. 16 Scaffolds being investigated include decellularized allogenic and xenogenic valves, biological polymers, and synthetic polymers.…”

“…15 Cell-seeded scaffolds may be conditioned in a bioreactor to develop and strengthen the tissue valve prior to implantation. 2,10 Appropriate biomechanical and biochemical stimulation may induce the cells to proliferate, migrate, differentiate, and remodel the scaffold into a suitable extracellular matrix (ECM). Over time, a mature tissue with appropriate composition, biological properties, mechanical properties, and function may develop.…”