Validation of theoretical framework explaining active solute uptake in dynamically loaded porous media

Abstract

Solute transport in biological tissues is a fundamental process necessary for cell metabolism. In connective soft tissues, such as articular cartilage, cells are embedded within a dense extracellular matrix that hinders the transport of solutes. However, according to a recent theoretical study (Mauck et al., 2003, J. Biomech. Eng. 125, 602-614), the convective motion of a dynamically loaded porous solid matrix can also impart momentum to solutes, pumping them into the tissue and giving rise to concentrations which exceed those achived under passive diffusion alone. In this study, the theoretical predictions of this model are verified against experimental measurements. The mechanical and transport properties of an agarose-dextran model system were characterized from independent measurements and substituted into the theory to predict solute uptake or desorption under dynamic mechanical loading for various agarose concentrations and dextran molecular weights, as well as different boundary and initial conditions. In every tested case, agreement was observed between experiments and theoretical predictions as assessed by coefficients of determination ranging from R 2 =0.61 to 0.95. These results provide strong support for the hypothesis that dynamic loading of a deformable porous tissue can produce active transport of solutes via a pumping mechanisms mediated by momentum exchange between the solute and solid matrix.

Agarose Hydrogel Characterization for Regenerative Medicine Applications: Focus on Engineering Cartilage

“…Dynamic compressive loading, a biomimetic approach, has been shown to enhance the active transport of large solutes in agarose gels [22][23][24], improving solute diffusion by ∼50% compared with statically loaded gels [22]. These results have been validated using techniques such as fluorescent molecule absorption/desorption and fluorescent recovery after photobleaching (FRAP) and have been shown to agree with solute modeling [23], Fickian diffusion theory [22], and mixture theory [24,25]. Under these applied cyclic strains, large chemical factors, such as IGF-1 (8 kDa) or TGF-β1 (25 kDa), can easily diffuse into an agarose scaffold.…”

Flow-Induced Deformation of Poroelastic Tissues and Gels: A New Perspective on Equilibrium Pressure-Flow-Thickness Relations

“…(11) while making use of Eq. (12) shows that ij/ = dfi^l -4>f) at z = d regardless of the strain distribution. That is, the 1^ coordinate of a given material point within the solid network of the tissue remains constant as deformations occur.…”

“…(5)] should provide k = Q for total dehydration when e = (^y [Eq. (12)]. This does not occur and as a result the present treatment is not appropriate for very high strains.…”

“…It is a basic feature of poroelastic mechanics and soft material behavior which appears in many contexts. Examples include physiological fiows through arterial wall [1], infusion of tumors [2] or nervous tissue [3] for drug delivery, selfcompression of collagen gels [4], flows through engineered tissue constructs in mechanostimulatory bioreactors [5], and direct measurements of hydraulic permeability (materials testing) of cartilage [6][7][8][9], intervertebral disk [10,11], agarose [12], and other gels [13].…”

“…Direct measurement is typically of interest for material characterization under low strains or for multiaxial flows, or as an altemative to indirect methods such as creep and stress relaxation [14]. It involves placing a pressure drop across a specimen and measuring fiow rate [6][7][8][9]12,15], or imposing a fiow rate and measuring pressure [1,5,11,13]. Mean permeability is then estimated using a macroscale implementation of Darcy's law.…”