Polymer Fiber-reinforced GAG Based Hydrogel Scaffolds for Heart Valve Tissue Engineering

Objective: An ideal scaffold for TE valve replacement requires native features such as the anisotropic collagen architecture and its surrounding GAG matrix. In this study, we propose to fabricate a fiber-hydrogel composite scaffold to design a TE valve template with fine control over its multilayered architecture. Methods: 8% (wt/v) polycaprolactone and gelatin (PCL-gel 3:1 ratio) fibers with fiber diameters ranging between 0.3-0.6 μm were fabricated via centrifugal jet spinning. Gelatin, HA, and CS were cross-linked with methacrylic anhydride to create GelMA, HAMA, and CSMA respectively. PCL-gel fiber was placed on 200 μL of the pre-polymer solution and exposed to UV light (365 nm) at 2.6 mW/cm2 for 15 mins to create a ~500 μm thick composite (Figure 1). We performed scanning electron microscopy (SEM) to study the surface and cross-sectional morphology of the composites. We also tested the linear modulus, ultimate tensile strength, and percent elongation of the composites. Scaffolds were seeded with porcine valve interstitial cells (pVICs) and studied for cell attachment and viability. Fiber-only scaffold and native porcine aortic valve served as controls. Results: We were able to fabricate fibers using 8% PCL-gel with diameters ranging between 0.4-0.5 μm with high alignment. SEM analysis of fibrous scaffolds cultured with pVICs revealed that the cells attached to the scaffolds preferential to the fiber direction. Our scaffolds exhibited a linear modulus (~100 MPa) close to that of native valves, and an ultimate tensile strength ranging between 10-13 MPa, which was slightly higher than the native valve. They also had a percent elongation of ~20-25%, which matched the magnitudes of stretch experienced by native aortic valves. Conclusions: We demonstrate the ability to fabricate fiber-hydrogel composites that closely mimic the architecture and mechanical properties of the native aortic valve. Future studies on swelling, enzymatic degradation, cell proliferation, and inflammatory responses are ongoing. KEYWORD: ICTEHV-O-12 The authors do not declare any conflict of interest.