MACROSCOPIC AND MICROSCOPIC FLUID TRANSPORT IN LIVING TISSUES - APPLICATION TO SOLID TUMORS

Transvascular and interstitial fluid movements are involved in many im portant biological processes such as convective macromolecular transpo rt and contribute to the mechanical behavior of tissue. Although intim ately coupled, there is a tendency in the literature to regard these t wo fluid-transport mechanisms separately; if the interaction is consid ered, the description is usually confined to the local level (e.g., tr ansvascular or interstitial perivascular). A general framework present ed here combines transvascular and interstitial fluid movement with th e mechanics of soft tissue and integrates macro- and microscopic views of the phenomena. On the macroscopic level interstitial fluid transpo rt is described by adapting the field equations of the poroelastic the ory using average field variables defined on a scale of several blood vessel diameters (approximate to 1 mm), while transvascular transport is described by a generalized Starling's law. As an example, the model equations have been specialized for a spherical solid tumor and an an alytical solution is presented for the transient redistribution of int erstitial fluid following a rapid change in vascular pressure or flow. The model describes the overall average profiles of the interstitial fluid pressure and velocity, as well as the dilatation, displacement a nd stress of the solid matrix. Moreover on a smaller length scale the model can describe the local fluid movement (perivascular) using the a verage field variables as boundary conditions. The basic theory provid es new insight into understanding the fluid transport in biological ti ssues and a valuable tool for determining relevant fluid-transport par ameters. Implications for improving drug delivery to solid tumors are also discussed.