Browsing by Author "Little, Stephen H."

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    Development of 3D Printed Mitral Valve Constructs for Transcatheter Device Modeling of Tissue and Device Deformation
    (Springer Nature, 2022) Vukicevic, Marija; Mehta, Shail Maharshi; Grande-Allen, K. Jane; Little, Stephen H.; Bioengineering
    Transcatheter mitral valve repair (TMVR) therapies offer a minimally invasive alternative to surgical mitral valve (MV) repair for patients with prohibitive surgical risks. Pre-procedural planning and associated medical device modeling is primarily performed in silico, which does not account for the physical interactions between the implanted TMVR device and surrounding tissue and may result in poor outcomes. We developed 3D printed tissue mimics for modeling TMVR therapies. Structural properties of the mitral annuli, leaflets, and chordae were replicated from multi-material blends. Uniaxial tensile testing was performed on the resulting composites and their mechanical properties were compared to those of their target native components. Mimics of the MV annulus printed in homogeneous strips approximated the tangent moduli of the native mitral annulus at 2% and 6% strain. Mimics of the valve leaflets printed in layers of different stiffnesses approximated the force–strain and stress–strain behavior of native MV leaflets. Finally, mimics of the chordae printed as reinforced cylinders approximated the force–strain and stress–strain behavior of native chordae. We demonstrated that multi-material 3D printing is a viable approach to the development of tissue phantoms, and that printed patient-specific geometries can approximate the local deformation force which may act upon devices used for TMVR therapies.
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    Regurgitation Hemodynamics Alone Cause Mitral Valve Remodeling Characteristic of Clinical Disease States In Vitro
    (Springer, 2016) Connell, Patrick S.; Azimuddin, Anam F.; Kim, Seulgi E.; Ramirez, Fernando; Jackson, Matthew S.; Little, Stephen H.; Grande-Allen, K. Jane; Bioengineering
    Mitral valve regurgitation is a challenging clinical condition that is frequent, highly varied, and poorly understood. While the causes of mitral regurgitation are multifactorial, how the hemodynamics of regurgitation impact valve tissue remodeling is an understudied phenomenon. We employed a pseudo-physiological flow loop capable of long-term organ culture to investigate the early progression of remodeling in living mitral valves placed in conditions resembling mitral valve prolapse (MVP) and functional mitral regurgitation (FMR). Valve geometry was altered to mimic the hemodynamics of controls (no changes from native geometry), MVP (5ﾠmm displacement of papillary muscles towards the annulus), and FMR (5ﾠmm apical, 5ﾠmm lateral papillary muscle displacement, 65% larger annular area). Flow measurements ensured moderate regurgitant fraction for regurgitation groups. After 1-week culture, valve tissues underwent mechanical and compositional analysis. MVP conditioned tissues were less stiff, weaker, and had elevated collagen III and glycosaminoglycans. FMR conditioned tissues were stiffer, more brittle, less extensible, and had more collagen synthesis, remodeling, and crosslinking related enzymes and proteoglycans, including decorin, matrix metalloproteinase-1, and lysyl oxidase. These models replicate clinical findings of MVP (myxomatous remodeling) and FMR (fibrotic remodeling), indicating that valve cells remodel extracellular matrix in response to altered mechanical homeostasis resulting from disease hemodynamics.