Modeling Fluorescence Recovery After Photobleaching in Loaded Bone: Potential Applications in Measuring Fluid and Solute Transport in the Osteocytic Lacunar-Canalicular System

Abstract

Solute transport through the bone lacunar-canalicular system is essential for osteocyte viability and function, and it can be measured using fluorescence recovery after photobleaching (FRAP). The mathematical model developed here aims to analyze solute transport during FRAP in mechanically loaded bone. Combining both whole bone-level poroelasticity and cellular-level solute transport, we found that load-induced solute transport during FRAP is characterized by an exponential recovery rate, which is determined by the dimensionless Strouhal (St) number that characterizes the oscillation effects over the mean flows, and that significant transport occurs only for St values below a threshold, when the solute stroke displacement exceeds the distance between the source and sink (the canalicular length). This threshold mechanism explains the general flow behaviors such as increasing transport with increasing magnitude and decreasing frequency. Mechanical loading is predicted to enhance transport of all tracers relative to diffusion, with the greatest enhancement for medium-sized tracers and less enhancement for small and large tracers. This study provides guidelines for future FRAP experiments, based on which the model can be used to quantify bone permeability, solute-matrix interaction, and flow velocities. These studies should provide insights into bone adaptation and metabolism, and help to treat various bone diseases and conditions.