title: Biomechanical conditioning of tissue engineered heart valves: Too much of a good thing?
abstract: Surgical replacement of dysfunctional valves is the primary option for the treatment of valvular disease and congenital defects. Existing mechanical and bioprosthetic replacement valves are far from ideal, requiring concomitant anticoagulation therapy or having limited durability, thus necessitating further surgical intervention. Heart valve tissue engineering (HVTE) is a promising alternative to existing replacement options, with the potential to synthesize mechanically robust tissue capable of growth, repair, and remodeling. The clinical realization of a bioengineered valve relies on the appropriate combination of cells, biomaterials, and/or bioreactor conditioning. Biomechanical conditioning of valves in vitro promotes differentiation of progenitor cells to tissue-synthesizing myofibroblasts and prepares the construct to withstand the complex hemodynamic environment of the native valve. While this is a crucial step in most HVTE strategies, it also may contribute to fibrosis, the primary limitation of engineered valves, through sustained myofibrogenesis. In this review, we examine the progress of HVTE and the role of mechanical conditioning in the synthesis of mechanically robust tissue, and suggest approaches to achieve myofibroblast quiescence and prevent fibrosis.
authors.affiliation: The Ted Rogers Centre for Heart Research, 661 University Avenue, 14th Floor, Toronto, ON M5G 1M1, Canada; Institute of Biomaterials & Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada.
authors.forename: Shouka
authors.initials: S
authors.lastname: Parvin Nejad
authors.affiliation: The Ted Rogers Centre for Heart Research, 661 University Avenue, 14th Floor, Toronto, ON M5G 1M1, Canada; Institute of Biomaterials & Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Blaser
authors.affiliation: The Ted Rogers Centre for Heart Research, 661 University Avenue, 14th Floor, Toronto, ON M5G 1M1, Canada; Institute of Biomaterials & Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada; Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, ON M5G 1G6, Canada.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Santerre
authors.affiliation: The Ted Rogers Centre for Heart Research, 661 University Avenue, 14th Floor, Toronto, ON M5G 1M1, Canada; Institute of Biomaterials & Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada; Division of Cardiovascular Surgery, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Caldarone
authors.affiliation: The Ted Rogers Centre for Heart Research, 661 University Avenue, 14th Floor, Toronto, ON M5G 1M1, Canada; Institute of Biomaterials & Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada; Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, ON M5G 1G6, Canada; Department of Mechanical & Industrial Engineering, University of Toronto, 5 King's College Road, Toronto, ON M5S 3G8, Canada. Electronic address: c.simmons@utoronto.ca.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Simmons
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001705:Bioprosthesis; D019149:Bioreactors; D002454:Cell Differentiation; D005109:Extracellular Matrix / Q000737:chemistry; D006350:Heart Valve Prosthesis; D006351:Heart Valves / Q000033:anatomy & histology / Q000166:cytology / Q000502:physiology*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D058628:Myofibroblasts / Q000166:cytology; D057139:Nanofibers / Q000737:chemistry; D016062:Porosity; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D020100:Hydrogels
keywords: Bioreactors; Fibrosis; Heart valves; Mechanical conditioning; Mechanobiology; Mesenchymal stem cells; Tissue engineering; Valvular interstitial cells