Which Biological Properties of Heart Valves Are Relevant to Tissue Engineering?

Abstract

Over the last 20 years, the designs of tissue engineered heart valves have evolved considerably. An initial focus on replicating the mechanical and structural features of semilunar valves has expanded to endeavors to mimic the biological behavior of heart valve cells as well. Studies on the biology of heart valves have shown that the function and durability of native valves is underpinned by complex interactions between the valve cells, the extracellular matrix, and the mechanical environment in which heart valves function. The ability of valve interstitial cells to synthesize extracellular matrix proteins and remodeling enzymes and the protective mediators released by endothelial cells are key factors in the homeostasis of valve function. The extracellular matrix provides the mechanical strength and flexibility required for the valve to function, as well as communicating with the cells that are bound within. There are a number of regulatory mechanisms that influence valve function, which include neuronal mechanisms and the tight regulation of growth and angiogenic factors. Together, studies into valve biology have provided a blueprint for what a tissue engineered valve would need to be capable of, in order to truly match the function of the native valve. This review addresses the biological functions of heart valve cells, in addition to the influence of the cells' environment on this behavior and examines how well these functions are addressed within the current strategies for tissue engineering heart valves in vitro, in vivo, and in situ.

Biofabrication in Congenital Cardiac Surgery: A Plea from the Operating Theatre, Promise from Science

“…The monocusp leaflet, however, typically becomes immobile independent of the prosthetic material (e.g., 0.1 mm ePTFE or autologous pericardium is used) on long-term [ 85 ]. There are currently various tissue-engineering attempts to develop viable implants focusing on rheological properties, structural and viability aspects [ 86 , 87 , 88 , 89 ].…”

Biology and Biomechanics of the Heart Valve Extracellular Matrix

“…Unfortunately, the preliminary results of these trials have demonstrated some significant valve-related complications that have prevented their widespread use, most notably leaflet retraction which leads to regurgitation. Currently available TEHV can broadly be separated into two categories, based on the scaffold used to create the TEHV [ 153 ]. Synthetic scaffolds are typically fabricated from man-made synthetic polymers including a variety of biomaterials such as polyglycolic acid, polycaprolactone, and 4-hydroxybuterate.…”

Biodegradable synthetic polymeric composite scaffold‐based tissue engineered heart valve with minimally invasive transcatheter implantation

“…The integrity of the entire matrix during the lifetime of the valve relied on matrix proteins and remodeling enzymes provided by the valve interstitial cells. And the formation of a continuous endothelium that mediated hemostasis and inflammation was promoted by the adhesion of valve endothelial cells to the basement membrane laminins 49 . Therefore, the TEHV scaffold should have a suitable degradation rate to support the cells to produce enough extracellular matrix and maintain the normal physiological function of the valve before that.…”

“…First of all, the blood‐contacting surfaces of the TEHV scaffold must be smooth enough with a low friction coefficient to prevent thrombosis, coagulation, or calcification 53 . Moreover, we can adopt some strategies such as the seeding of endothelial cells onto the surface of scaffolds, the attraction of circulating endothelial progenitor cells onto implanted valves, incorporation of anticalcification agents into the scaffold material and so on 49 …”