In addition to biocompatibility, an ideal scaffold for the regeneration of valvular tissue should also replicate the natural heart valve extracellular matrix (ECM) in terms of biomechanical properties and structural stability. In our previous paper, we demonstrated the development of collagen type I and hyaluronic acid (HA)-based scaffolds with interlaced microstructure. Such hybrid scaffolds were found to be compatible with cardiosphere-derived cells (CDCs) to potentially regenerate the diseased aortic heart valve. This paper focused on the quantification of the effect of crosslinking density on the mechanical properties under dry and wet conditions as well as degradation resistance. Elastic moduli increased with increasing crosslinking densities, in the dry and wet state, for parent networks, whereas those of interlaced scaffolds were higher than either network alone. Compressive and storage moduli ranged from 35 ± 5 to 95 ± 5 kPa and 16 ± 2 kPa to 113 ± 6 kPa, respectively, in the dry state. Storage moduli, in the dry state, matched and exceeded those of human aortic valve leaflets (HAVL). Similarly, degradation resistance increased with increasing the crosslinking densities for collagen-only and HA-only scaffolds. Interlaced scaffolds showed partial degradation in the presence of either collagenase or hyaluronidase as compared to when exposed to both enzymes together. These results agree with our previous findings that interlaced scaffolds were composed of independent collagen and HA networks without crosslinking between them. Thus, collagen/HA interlaced scaffolds have the potential to fill in the niche for designing an ideal tissue engineered heart valve (TEHV).

Currently, custom made heart implants suffer from critical imperfections in terms of mechanical incompatibility and uncontrolled degradation rate, which leads to premature in vivo failure. Interpenetrating polymer networks (IPNs) are a success story in drug delivery and regenerative medicine where they offer fascinating morphologies and tailored properties like controlled degradation rate. This review will critically discuss the current state of the art with respect to the two most important biopolymers found in heart valve, i.e. collagen and hyaluronic acid formulated IPNs as tissue engineered heart valve (TEHV). Comparison of the existing experimental approaches and recent technical challenges will be demonstrated. Finally, multifaceted proposals for improvements in design and performance of TEHVs will be presented as a route map for future research.