Fabrication of a Matrigel-collagen Semi-interpenetrating Scaffold for Use in Dynamic Valve Interstitial Cell Culture

The study of heart valve homeostatic and disease mechanisms are often limited by the challenges in simulating the in vivo milieu, where valve cells are surrounded by the extracellular matrix in a three-dimensional (3D) environment and experience multiple dynamic mechanical forces. Type I collagen is typically the most common 3D matrix used to culture valve cells in vitro. Unfortunately, this material has poor mechanical behavior due to an inherent propensity to compact significantly, unlike native valve leaflets. We hypothesized that incorporation of matrigel, which contains other heart valve-relevant matrix components such as type IV collagen and sulfated proteoglycans, to type I collagen would provide an appropriate physiological milieu for in vitro valve interstitial cell culture. Different semi-interpenetrating mixtures of collagen type I and matrigel were prepared and a thorough characterization of their physical, mechanical and biocompatibility properties was performed. We observed that the matrigel-collagen hydrogel was porous and degradable with tunable swelling behavior. Incorporation of matrigel not only enhanced the mechanical behavior of the composite hydrogel but also presented the cultured valve interstitial cells with a more enriched extracellular matrix network for in vitro culture. We showed that cells cultured in the composite hydrogel had comparable viability, proliferation and cell phenotype as compared with those in a collagen only gel. Importantly, the composite hydrogel was also amenable to in vitro cyclic stretching culture for 48 h. Overall, we report here the potential use of the matrigel-collagen hydrogel as a three dimensional scaffold for the dynamic mechanical culture of valve interstitial cells in vitro.