title: How to make a heart valve: from embryonic development to bioengineering of living valve substitutes.
abstract: Cardiac valve disease is a significant cause of ill health and death worldwide, and valve replacement remains one of the most common cardiac interventions in high-income economies. Despite major advances in surgical treatment, long-term therapy remains inadequate because none of the current valve substitutes have the potential for remodeling, regeneration, and growth of native structures. Valve development is coordinated by a complex interplay of signaling pathways and environmental cues that cause disease when perturbed. Cardiac valves develop from endocardial cushions that become populated by valve precursor mesenchyme formed by an epithelial-mesenchymal transition (EMT). The mesenchymal precursors, subsequently, undergo directed growth, characterized by cellular compartmentalization and layering of a structured extracellular matrix (ECM). Knowledge gained from research into the development of cardiac valves is driving exploration into valve biomechanics and tissue engineering directed at creating novel valve substitutes endowed with native form and function.
authors.affiliation: Program of Cardiovascular Developmental Biology, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
authors.forename: Donal
authors.initials: D
authors.lastname: MacGrogan
authors.affiliation: Program of Cardiovascular Developmental Biology, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Luxán
authors.affiliation: Biomedical Engineering/Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
authors.forename: Anita
authors.initials: A
authors.lastname: Driessen-Mol
authors.affiliation: Biomedical Engineering/Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
authors.forename: Carlijn
authors.initials: C
authors.lastname: Bouten
authors.affiliation: Biomedical Engineering/Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Baaijens
authors.affiliation: Program of Cardiovascular Developmental Biology, Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: de la Pompa
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000502:physiology; D006350:Heart Valve Prosthesis; D006351:Heart Valves / Q000033:anatomy & histology / Q000166:cytology / Q000196:embryology*; D006801:Humans; D009024:Morphogenesis / Q000502:physiology; D023822:Tissue Engineering; D054457:Tissue Scaffolds