Dynamic loading of immature epiphyseal cartilage pumps nutrients out of vascular canals

Abstract

The potential influence of mechanical loading on transvascular transport in vascularized soft tissues has not been explored extensively. This experimental investigation introduced and explored the hypothesis that dynamic mechanical loading can pump solutes out of blood vessels and into the surrounding tissue, leading to faster uptake and higher solute concentrations than could otherwise be achieved under unloaded conditions. Immature epiphyseal cartilage was used as a model tissue system, with fluorescein (332 Da), dextran (3, 10 and 70 kDa) and transferrin (80 kDa) as model solutes. Cartilage disks were either dynamically loaded (±10% compression over a 10% static offset strain, at 0.2 Hz) or maintained unloaded in solution for up to 20 hours. Results demonstrated statistically significant solute uptake in dynamically loaded (DL) explants relative to passive diffusion (PD) controls for all solutes except unbound fluorescein, as evidenced by the DL:PD concentration ratios after 20 hours (1.0 ± 0.2, 2.4 ± 1.1, 6.1 ± 3.3, 9.0 ± 4.0, and 5.5±1.6 for fluorescein, 3, 10, and 70 kDa dextran, and transferrin). Significant uptake enhancements were also observed within the first 30 seconds of loading. Termination of dynamic loading produced dissipation of enhanced solute uptake back to PD control values. Confocal images confirmed that solute uptake occurred from cartilage canals into their surrounding extracellular matrix. The incidence of this loading-induced transvascular solute pumping mechanism may significantly alter our understanding of the interaction of mechanical loading and tissue metabolism.

Toward Engineering a Biological Joint Replacement

“…4). These findings in engineered cartilage are consistent with the observation that dynamic loading produces enhanced uptake of solutes into agarose and cartilage, 72,73 considerably greater than under passive diffusion. However, other mechanotransduction pathways may also be at work when constructs are being loaded dynamically.…”

“…Thus, loading provides an active solute pumping mechanism because the solid matrix of the immature cartilage can impart momentum to the solute at the tissue-bath interface, pulling it into the tissue. 72,73 Similarly, short-term dynamic loading of engineered cartilage constructs (i.e., for less than three hours) has demonstrated improved nutrient diffusion. 33,34,74 Loading of anatomical size patellar constructs doubled the concentration of large molecules (70 kDa) in the constructs compared with constructs under free-swelling conditions (control; Fig.…”

Finite Element Implementation of Mechanochemical Phenomena in Neutral Deformable Porous Media Under Finite Deformation

“…Mauck et al [38] performed a finite difference analysis which demonstrated that, for certain combinations of material properties, dynamic deformational loading of a cylindrical disk of a porous tissue or gel may pump solute from the external bath into the disk to achieve concentrations in excess of the value in the bath. This theoretical prediction was verified in subsequent experimental studies that examined dextran and transferrin uptake in agarose and cartilage disks [39, 60], further validated with a direct comparison of experiments and theory [40]. …”

Dynamic mechanical compression of devitalized articular cartilage does not activate latent TGF-β

“…Devitalized cartilage explants (Ø4.3 mm, n=84 from 3 joints) were subjected to a continuous dynamic (cyclic) loading regimen (DL) with a custom-made mechanical actuator as described previously (Albro et al, 2011). Explants were subjected to a low physiologic strain regimen (±2%) or high regimen (±7.5%), both superposed over a 10% static strain offset at 0.5 Hz.…”