Designing scaffolds for valvular interstitial cells

Valvular interstitial cells (VICs) were isolated from porcine aortic heart valves and cultured in vitro on a variety of natural and synthetic surfaces to identify suitable scaffolds for tissue engineering a heart valve. VICs possess many properties that make them attractive for use in the construction of a tissue engineered valve; however, the surfaces to which VICs will adhere and spread are very limited. For example, VICs adhere and spread on collagen and laminin-coated surfaces, but display greatly altered morphology and do not, proliferate. Interestingly, fibronectin was one adhesion protein that facilitated VIC adhesion and proliferation. Yet, VICs did not spread on surfaces modified with RGD, a ubiquitous cell-adhesive peptide, nor to EILDV, a fibronectin-specific peptide sequence. Hyaluronic acid (HA), a highly elastic polysaccharide, was modified to form photopolymerizable hydrogels. VICs were found to spread and proliferate on these gels, forming a confluent monolayer on the gels within four days. Because HA alone experiences rapid enzymatic degradation, it was also combined with photopolymerizable poly(ethylene glycol) (PEG) to form gels with better mechanical properties and extended degradation times. These HA-PEG hydrogels possess desirable macroscopic properties while simultaneously providing a suitable cellular environment for VICs to form a tissue engineered heart valve.