Speaker
Description
"Bioinspired polymer processing, with focus on improved control over biomaterial structure-function, is a research strategy that can play a critical role in facilitating the translation of a biomedical device. In this work, we utilize the specific example of tissue engineered heart valves to demonstrate this notion.
Valvular heart disease is currently treated with mechanical valves, which benefit from longevity, but are burdened by chronic anticoagulation therapy, or with bioprosthetic valves, which have reduced thromboembolic risk, but limited durability. Tissue engineered heart valves (TEHV) have been proposed to resolve these issues by implanting scaffolds designed to be replaced by endogenous tissue growth, leaving autologous, functional leaflets. This approach would putatively eliminate the need for anticoagulation and avoid calcification. Human heart valve tissue structure-function is still inadequately characterized and, despite the progress in scaffold fabrication strategies and encouraging results in large animal models, control over engineered valve structure-function remains at best partial. Moreover, while the notion of bioinspired control of structure and function is recognized as a promising strategy to enhance TEHV performance, the approach and its potential impact remain relatively unexplored in vivo.
We face these challenges by introducing double component deposition (DCD), a polymer electrodeposition technique that employs multi-phase electrodes to dictate valve macro and microstructure and resultant function. Engineered valve in vitro characterization included: leaflet thickness, biaxial and bending properties, and quantitative structural analysis of scanning electron micrographs. Results demonstrated the capacity of the DCD method to simultaneously control scaffold macro-scale morphology, mechanics, and microstructure while producing fully assembled multi-leaflet valves composed of microscopic fibers. The efficacy of this technology was further assessed in vivo in an acute (24 hrs) porcine model with the evaluation of three different devices: stented pulmonary valve (n=5), stentless tricuspid valve (n=5), and stentless mitral valve (n=2). Processing variables for these scaffolds were set to duplicate native heart valve tissue structural properties.
More recently, bioinspired DCD processed scaffolds have been implanted in an ovine model of pulmonary valve replacement with time point 1 (n=4) and 3 months (n=4,). Two groups were compared: scaffold with physiological leaflet thickness (120 µm) and scaffolds with over physiological leaflet thickness (240 µm). Explants at 1 month have shown a substantially higher extracellular matrix (ECM) production for the physiological thickness group. While these results suggest a more favorable tissue remodeling outcome for the physiological group and support the biomimetic approach, the mechanism for these preliminary observations remains unknown and re-iterate the urgent need for in-vitro platform able to elucidate the complex ECM process of ECM formation in vivo."
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