Insights into interstitial flow,shear stress,and mass transport effects on ECM heterogeneity in bioreactor-cultivated engineered cartilage hydrogels |
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Authors: | Tony Chen Mark Buckley Itai Cohen Lawrence Bonassar Hani A Awad |
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Institution: | (1) Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA;(2) Department of Biomedical Engineering, The Center for Musculoskeletal Research, University of Rochester Medical Center, Box 665, 601 Elmwood Avenue, Rochester, NY 14642, USA;(3) Department of Physics, Cornell University, Ithaca, NY, USA;(4) Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA; |
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Abstract: | Interstitial flow in articular cartilage is secondary to compressive and shear deformations during joint motion and has been
linked with the well-characterized heterogeneity in structure and composition of its extracellular matrix. In this study,
we investigated the effects of introducing gradients of interstitial flow on the evolution of compositional heterogeneity
in engineered cartilage. Using a parallel-plate bioreactor, we observed that Poiseuille flow stimulation of chondrocyte-seeded
agarose hydrogels led to an increase in glycosaminoglycan and type II collagen deposition in the surface region of the hydrogel
exposed to flow. Experimental measurements of the interstitial flow fields based on the fluorescence recovery after photobleaching
technique suggested that the observed heterogeneity in composition is associated with gradients in interstitial flow in a
boundary layer at the hydrogel surface. Interestingly, the interstitial flow velocity profiles were nonlinearly influenced
by flow rate, which upon closer examination led us to the original observation that the apparent hydrogel permeability decreased
exponentially with increased interfacial shear stress. We also observed that interstitial flow enhances convective mass transport
irrespective of molecular size within the boundary layer near the hydrogel surface and that the convective contribution to
transport diminishes with depth in association with interstitial flow gradients. The implications of the nonlinearly inverse
relationship between the interfacial shear stress and the interstitial flux and permeability and its consequences for convective
transport are important for tissue engineering, since porous scaffolds comprise networks of Poiseuille channels (pores) through
which interstitial flow must navigate under mechanical stimulation or direct perfusion. |
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