title: Relative Effects of Fluid Oscillations and Nutrient Transport in the In Vitro Growth of Valvular Tissues.
abstract: Engineered valvular tissues are cultured dynamically, and involve specimen movement. We previously demonstrated that oscillatory shear stresses (OSS) under combined steady flow and specimen cyclic flexure (flex-flow) promote tissue formation. However, localized efficiency of specimen mass transport is also important in the context of cell viability within the growing tissues. Here, we investigated the delivery of two essential species for cell survival, glucose and oxygen, to 3-dimensional (3D) engineered valvular tissues. We applied a convective-diffusive model to characterize glucose and oxygen mass transport with and without valve-like specimen flexural movement. We found the mass transport effects for glucose and oxygen to be negligible for scaffold porosities typically present during in vitro experiments and non-essential unless the porosity was unusually low (<40%). For more typical scaffold porosities (75%) however, we found negligible variation in the specimen mass fraction of glucose and oxygen in both non-moving and moving constructs (p > 0.05). Based on this result, we conducted an experiment using bone marrow stem cell (BMSC)-seeded scaffolds under Pulsatile flow-alone states to permit OSS without any specimen movement. BMSC-seeded specimen collagen from the pulsatile flow and flex-flow environments were subsequently found to be comparable (p > 0.05) and exhibited some gene expression similarities. We conclude that a critical magnitude of fluid-induced, OSS created by either pulsatile flow or flex-flow conditions, particularly when the oscillations are physiologically-relevant, is the direct, principal stimulus that promotes engineered valvular tissues and its phenotype, whereas mass transport benefits derived from specimen movement are minimal.
authors: Tissue Engineering, Mechanics, Imaging, and Materials Laboratory, Department of Biomedical Engineering, College of Engineering and Computing, Florida International University, 10555 W. Flagler Street, EC 2612, Miami, FL, 33174, USA.
authors: Manuel
authors: M
authors: Salinas
authors: Tissue Engineering, Mechanics, Imaging, and Materials Laboratory, Department of Biomedical Engineering, College of Engineering and Computing, Florida International University, 10555 W. Flagler Street, EC 2612, Miami, FL, 33174, USA.
authors: Sasmita
authors: S
authors: Rath
authors: Tissue Engineering, Mechanics, Imaging, and Materials Laboratory, Department of Biomedical Engineering, College of Engineering and Computing, Florida International University, 10555 W. Flagler Street, EC 2612, Miami, FL, 33174, USA.
authors: Ana
authors: A
authors: Villegas
authors: Department of Aerospace Engineering and Mechanics, The University of Alabama, Tuscaloosa, AL, USA.
authors: Vinu
authors: V
authors: Unnikrishnan
authors: Tissue Engineering, Mechanics, Imaging, and Materials Laboratory, Department of Biomedical Engineering, College of Engineering and Computing, Florida International University, 10555 W. Flagler Street, EC 2612, Miami, FL, 33174, USA. sramaswa@fiu.edu.
authors: Sharan
authors: S
authors: Ramaswamy
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D019149:Bioreactors; D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D006351:Heart Valves / Q000737:chemistry / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D057446:Hydrodynamics; D010100:Oxygen / Q000378:metabolism; D016062:Porosity; D012756:Sheep; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D015415:Biomarkers; D003094:Collagen; D005947:Glucose; D010100:Oxygen
keywords: Computational fluid dynamics; Glucose and oxygen; Heart valve tissue engineering; Mass transport; Oscillatory shear stresses; Porosity