Anisotropic Fiber-Reinforced Glycosaminoglycan Hydrogels For Heart Valve Tissue Engineering

This study investigates polymer fiber-reinforced protein-polysaccharide-based hydrogels for heart valve tissue engineering applications. Polycaprolactone and gelatin (3:1) blends were jet-spun to fabricate aligned fibers that possessed fiber diameters in the range found in the native heart valve. These fibers were embedded in methacrylated hydrogels made from gelatin, sodium hyaluronate, and chondroitin sulfate to create fiber-reinforced hydrogel composites (HCs). The fiber-reinforced gelatin glycosaminoglycan (GAG)-based HC possessed interconnected porous structures and porosity higher than fiber-only conditions. These fiber-reinforced HCs exhibited compressive modulus and biaxial mechanical behavior comparable to that of native porcine aortic valves. The fiber-reinforced HCs were able to swell higher and degraded less than the hydrogels. Elution studies revealed that less than 20% of incorporated gelatin methacrylate and GAGs were released over 2 weeks, with a steady-state release after the first day. When cultured with porcine valve interstitial cells (VICs), the fiber-reinforced composites were able to maintain higher cell viability compared with fiber-only samples. Quiescent VICs expressed alpha smooth muscle actin and calponin showing an activated phenotype, along with a few cells expressing the proliferation marker Ki67 and negative expression for RUNX2, an osteogenic marker. Our study demonstrated that compared with the hydrogels and fibers alone, combining both components can yield durable, reinforced composites that mimic heart valve mechanical behavior, while maintaining high cell viability and expressing positive activation as well as proliferation markers.Impact statement Current technologies in the field of heart valve tissue engineering focus on either fibrous scaffolds or soft hydrogel constructs. In this study, we report the fabrication of fiber-reinforced hydrogels by combining aligned fibers and hydrogels to create composite scaffolds that closely mimic the structure and mechanical properties of the native valve. We believe that future studies involving aligned elastomeric polymer-reinforced hydrogels would lead to engineering better valve replacements.