Hydrogel-polyurethane fiber composites with enhanced microarchitectural control for heart valve replacement.

Polymeric heart valves offer the potential to overcome the limited durability of tissue based bioprosthetic valves and the need for anticoagulant therapy of mechanical valve replacement options. However, developing a single-phase material with requisite biological properties and target mechanical properties remains a challenge. In this study, a composite heart valve material was developed where an electrospun mesh provides tunable mechanical properties and a hydrogel coating confers an antifouling surface for thromboresistance. Key biological responses were evaluated in comparison to glutaraldehyde-fixed pericardium. Platelet and bacterial attachment were reduced by 38% and 98%, respectively, as compared to pericardium that demonstrated the antifouling nature of the hydrogel coating. There was also a notable reduction (59%) in the calcification of the composite material as compared to pericardium. A custom 3D-printed hydrogel coating setup was developed to make valve composites for device-level hemodynamic testing. Regurgitation fraction (9.6 ± 1.8%) and effective orifice area (1.52 ± 0.34 cm2 ) met ISO 5840-2:2021 requirements. Additionally, the mean pressure gradient was comparable to current clinical bioprosthetic heart valves demonstrating preliminary efficacy. Although the hemodynamic properties are promising, it is anticipated that the random microarchitecture will result in suboptimal strain fields and peak stresses that may accelerate leaflet fatigue and degeneration. Previous computational work has demonstrated that bioinspired fiber microarchitectures can improve strain homogeneity of valve materials toward improving durability. To this end, we developed advanced electrospinning methodologies to achieve polyurethane fiber microarchitectures that mimic or exceed the physiological ranges of alignment, tortuosity, and curvilinearity present in the native valve. Control of fiber alignment from a random fiber orientation at a normalized orientation index (NOI) 14.2 ± 6.9% to highly aligned fibers at a NOI of 85.1 ± 1.4%. was achieved through increasing mandrel rotational velocity. Fiber tortuosity and curvilinearity in the range of native valve features were introduced through a post-spinning annealing process and fiber collection on a conical mandrel geometry, respectively. Overall, these studies demonstrate the potential of hydrogel-polyurethane fiber composite as a heart valve material. Future studies will utilize the developed advanced electrospinning methodologies in combination with model-directed fabrication toward optimizing durability as a function of fiber microarchitecture.

Interpenetrating network design of bioactive hydrogel coatings with enhanced damage resistance.

Bioactive hydrogel coatings offer a promising route to introduce sustained thromboresistance to cardiovascular devices without compromising bulk mechanical properties. Poly(ethylene glycol)-based hydrogels provide antifouling properties to limit acute thromobosis and incorporation of adhesive ligands can be used to promote endothelialization. However, conventional PEG-based hydrogels at stiffnesses that promote cell attachment can be brittle and prone to damage in a surgical setting, limiting their utility in clinical applications. In this work, we developed a durable hydrogel coating using interpenetrating networks of polyether urethane diacrylamide (PEUDAm) and poly(N-acryloyl glycinamide) (pNAGA). First, diffusion-mediated redox initiation of PEUDAm was used to coat electrospun polyurethane fiber meshes with coating thickness controlled by the immersion time. The second network of pNAGA was then introduced to enhance damage resistance of the hydrogel coating. The durability, thromboresistance, and bioactivity of the resulting multilayer grafts were then assessed. The IPN hydrogel coatings displayed resistance to surgically-associated damage mechanisms and retained the anti-fouling nature of PEG-based hydrogels as indicated by reduced protein adsorption and platelet attachment. Moreover, incorporation of functionalized collagen into the IPN hydrogel coating conferred bioactivity that supported endothelial cell adhesion. Overall, this conformable and durable hydrogel coating provides an improved approach for cardiovascular device fabrication with targeted biological activity.