Design optimization of a cardiovascular stent with application to a balloon expandable prosthetic heart valve.

A cardiovascular stent design optimization method is proposed with application to a pediatric balloon-expandable prosthetic heart valve. The prosthetic valved conduit may be expanded to a larger permanent diameter in vivo via subsequent transcatheter balloon dilation procedures. While multiple expandable prosthetic heart valves are currently at different stages of development, this work is focused on one particular design in which a stent is situated inside of an expandable polymeric valved conduit. Since the valve and conduit must be joined with a robust manufacturing technique, a polymeric glue layer is inserted between the two, which results in radial retraction of the valved region after expansion. Design of an appropriate stent is proposed to counteract this phenomenon and maintain the desired permanent diameter throughout the device after a single non-compliant balloon dilation procedure. The finite element method is used to compute performance metrics related to the permanent expansion diameter and required radial force. Additionally, failure due not only to high cycle fatigue but also due to ductile fracture is incorporated into the design study through the use of an existing ductile fracture criterion for metals. Surrogate models are constructed with the results of the high fidelity simulations and are subsequently used to numerically obtain a set of Pareto-optimal stent designs. Finally, a single design is identified by optimizing a normalized aggregate objective function with equal weighting of all design objectives.

Engineering edgeless human skin with enhanced biomechanical properties.

Despite the advancements in skin bioengineering, 3D skin constructs are still produced as flat tissues with open edges, disregarding the fully enclosed geometry of human skin. Therefore, they do not effectively cover anatomically complex body sites, e.g., hands. Here, we challenge the prevailing paradigm by engineering the skin as a fully enclosed 3D tissue that can be shaped after a body part and seamlessly transplanted as a biological clothing. Our wearable edgeless skin constructs (WESCs) show enhanced dermal extracellular matrix (ECM) deposition and mechanical properties compared to conventional constructs. WESCs display region-specific cell/ECM alignment, as well as physiologic anisotropic mechanical properties. WESCs replace the skin in full-thickness wounds of challenging body sites (e.g., mouse hindlimbs) with minimal suturing and shorter surgery time. This study provides a compelling technology that may substantially improve wound care and suggests that the recapitulation of the tissue macroanatomy can lead to enhanced biological function.

In Vitro Proof of Concept of a First-Generation Growth-Accommodating Heart Valved Conduit for Pediatric Use.

Currently available heart valve prostheses have no growth potential, requiring children with heart valve diseases to endure multiple valve replacement surgeries with compounding risks. This study demonstrates the in vitro proof of concept of a biostable polymeric trileaflet valved conduit designed for surgical implantation and subsequent expansion via transcatheter balloon dilation to accommodate the growth of pediatric patients and delay or avoid repeated open-heart surgeries. The valved conduit is formed via dip molding using a polydimethylsiloxane-based polyurethane, a biocompatible material shown here to be capable of permanent stretching under mechanical loading. The valve leaflets are designed with an increased coaptation area to preserve valve competence at expanded diameters. Four 22 mm diameter valved conduits are tested in vitro for hydrodynamics, balloon dilated to new permanent diameters of 23.26 ± 0.38 mm, and then tested again. Upon further dilation, two valved conduits sustain leaflet tears, while the two surviving devices reach final diameters of 24.38 ± 0.19 mm. After each successful dilation, the valved conduits show increased effective orifice areas and decreased transvalvular pressure differentials while maintaining low regurgitation. These results demonstrate concept feasibility and motivate further development of a polymeric balloon-expandable device to replace valves in children and avoid reoperations.