Patient-specific multi-scale design optimization of transcatheter aortic valve stents.

BACKGROUND AND OBJECTIVE: Transcatheter aortic valve implantation (TAVI) has become the standard treatment for a wide range of patients with aortic stenosis. Although some of the TAVI post-operative complications are addressed in newer designs, other complications and lack of long-term and durability data on the performance of these prostheses are limiting this procedure from becoming the standard for heart valve replacements. The design optimization of these devices with the finite element and optimization techniques can help increase their performance quality and reduce the risk of malfunctioning. Most performance metrics of these prostheses are morphology-dependent, and the design and the selection of the device before implantation should be planned for each individual patient. METHODS: In this study, a patient-specific aortic root geometry was utilized for the crimping and implantation simulation of 50 stent samples. The results of simulations were then evaluated and used for developing regression models. The strut width and thickness, the number of cells and patterns, the size of stent cells, and the diameter profile of the stent were optimized with two sets of optimization processes. The objective functions included the maximum crimping strain, radial strength, anchorage area, and the eccentricity of the stent. RESULTS: The optimization process was successful in finding optimal models with up to 40% decrease in the maximum crimping strain, 261% increase in the radial strength, 67% reduction in the eccentricity, and about an eightfold increase in the anchorage area compared to the reference device. CONCLUSIONS: The stents with larger distal diameters perform better in the selected objective functions. They provide better anchorage in the aortic root resulting in a smaller gap between the device and the surrounding tissue and smaller contact pressure. This framework can be used in designing patient-specific stents and improving the performance of these devices and the outcome of the implantation process.

The nuclear import of the transcription factor MyoD is reduced in mesenchymal stem cells grown in a 3D micro-engineered niche.

Smart biomaterials are increasingly being used to control stem cell fate in vitro by the recapitulation of the native niche microenvironment. By integrating experimental measurements with numerical models, we show that in mesenchymal stem cells grown inside a 3D synthetic niche both nuclear transport of a myogenic factor and the passive nuclear diffusion of a smaller inert protein are reduced. Our results also suggest that cell morphology modulates nuclear proteins import through a partition of the nuclear envelope surface, which is a thin but extremely permeable annular portion in cells cultured on 2D substrates. Therefore, our results support the hypothesis that in stem cell differentiation, the nuclear import of gene-regulating transcription factors is controlled by a strain-dependent nuclear envelope permeability, probably related to the reorganization of stretch-activated nuclear pore complexes.

The impact of calcification patterns in transcatheter aortic valve performance: a fluid-structure interaction analysis.

Transcatheter aortic valve replacement (TAVR) strongly depends on the calcification patterns, which may lead to a malapposition of the stented valve and complication onsets in terms of structure kinematics and paravalvular leakage (PVL). From one anatomical-resembling model of the aortic root, six configurations with different calcific deposits were built. TAVR fluid-structure interaction simulations predicted different outcomes for the different calcifications patterns in terms of the final valve configuration in the implantation site and the PVL estimations. In particular models with deposits along the cups coaptation resulted in mild PVL, while those with deposits along the attachment line in moderate PVL.