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.
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The authors acknowledge funds received from the department of Biomedical Engineering at Florida International University to carry out this research work. Funding for M.S. by NIH/NIGMS R25 GM061347 is gratefully acknowledged.
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The authors have no conflict of interests.
Statement of Human and Animal Studies
No Human and Animal Studies were involved in this study.
Associate Editor Ajit P. Yoganathan oversaw the review of this article.
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Salinas, M., Rath, S., Villegas, A. et al. Relative Effects of Fluid Oscillations and Nutrient Transport in the In Vitro Growth of Valvular Tissues. Cardiovasc Eng Tech 7, 170–181 (2016). https://doi.org/10.1007/s13239-016-0258-x
- Heart valve tissue engineering
- Computational fluid dynamics
- Mass transport
- Glucose and oxygen
- Oscillatory shear stresses