Effect of Dynamic Loading on the Transport of Solutes into Agarose Hydrogels

Abstract

In functional tissue engineering, the application of dynamic loading has been shown to improve the mechanical properties of chondrocyte-seeded agarose hydrogels relative to unloaded free swelling controls. The goal of this study is to determine the effect of dynamic loading on the transport of nutrients in tissue-engineered constructs. To eliminate confounding effects, such as nutrient consumption in cell-laden disks, this study examines the response of solute transport due to loading using a model system of acellular agarose disks and dextran in phosphate-buffered saline (3 and 70 kDa). An examination of the passive diffusion response of dextran in agarose confirms the applicability of Fick's law of diffusion in describing the behavior of dextran. Under static loading, the application of compressive strain decreased the total interstitial volume available for the 70 kDa dextran, compared to free swelling. Dynamic loading significantly enhanced the rate of solute uptake into agarose disks, relative to static loading. Moreover, the steady-state concentration under dynamic loading was found to be significantly greater than under static loading, for larger-molecular-mass dextran (70 kDa). This experimental finding confirms recent theoretical predictions that mechanical pumping of a porous tissue may actively transport solutes into the disk against their concentration gradient. The results of this study support the hypothesis that the application of dynamic loading in the presence of growth factors of large molecular weight may result in both a mechanically and chemically stimulating environment for tissue growth.