title: 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 h. 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 h (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 30s 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.
authors.affiliation: Department of Mechanical Engineering, Columbia University, 500 West 120th Street, 220 SW Mudd Mail Code 4703, New York, NY 10027, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Albro
authors.forename: Rajan E
authors.initials: RE
authors.lastname: Banerjee
authors.forename: Roland
authors.initials: R
authors.lastname: Li
authors.forename: Sevan R
authors.initials: SR
authors.lastname: Oungoulian
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Amaya P
authors.initials: AP
authors.lastname: del Palomar
authors.forename: Clark T
authors.initials: CT
authors.lastname: Hung
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Ateshian
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001706:Biopsy; D001808:Blood Vessels / Q000502:physiology*; D002356:Cartilage / Q000737:chemistry; D002417:Cattle; D003911:Dextrans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism; D019793:Fluorescein / Q000494:pharmacology; D006132:Growth Plate / Q000502:physiology*; D018613:Microscopy, Confocal / Q000379:methods; D012996:Solutions / Q000378:metabolism; D013314:Stress, Mechanical; D013997:Time Factors; D014168:Transferrin / Q000737:chemistry
chemical_list: D003911:Dextrans; D012996:Solutions; D014168:Transferrin; D019793:Fluorescein