Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions

Abstract

Introduction Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. Areas covered This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally-derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Expert opinion While much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells.

Calcification of Biomaterials and Diseased States

“…Stenosis can be described as a stiffening of the leaflets, leading to improper opening and closing of the valves. Regurgitation occurs when blood flows back through the valve indicating inadequate valve closure [8]. Almost 2.5% of the U.S. population is affected by VHDs.…”

“…The specific mechanisms leading to VHD are not fully known, meaning it is unclear how important genetics, cellular characteristics, and microenvironmental characteristics are in this disease. However, in light of recent evidence, it is believed that alterations in developmental morphogenesis signaling pathways could play a role in VHD [8]. One affected pathway is that of Notch1.…”

“…As mentioned before, there is not a specific mechanism that leads to VHD, so further understanding of the various processes involved will improve treatment strategies that include tissue engineering and drug-coated biomaterials [8]. Some studies have reported that tissue engineering scaffolds have similar uniaxial mechanical properties but need more investigation with biaxial mechanical properties that are more related to soft tissue.…”

Heart Valve Replacements with Regenerative Capacity

“…Moreover, the material can be tuned to ensure sufficient mechanical properties at the time of implantation and controlled scaffold degradation while endogenous tissue is formed over time. The large variety of possible materials and scaffold fabrication methods suitable for the development of polymeric valve replacements have been reviewed elsewhere [14][15][16].…”

Complete Static Repopulation of Decellularized Porcine Tissues for Heart Valve Engineering: An in vitro Study

“…Decellularization is the process used in biomedical engineering to remove all cells and cellular components from a tissue while retaining the ECM structure and proteins and providing a biomechanically sufficient scaffold that allows efficient reseeding [Cheung et al, 2015]. Complete decellularization of tissues remains crucial to minimize or avoid an adverse immunologic response to foreign cellular antigens, which can trigger the calcification process and evoke an adverse immune response after implantation [Courtman et al, 1994].…”