Distributing a fixed amount of cyclic loading to tendon explants over longer periods induces greater cellular and mechanical responses

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Abstract
Tendon overuse injuries are a major source of clinical concern. Cyclic loading causes material damage and induces biochemical responses in tendon. The purpose of this study was to examine the biochemical and biomechanical tendon response after applying cyclical loading over varying durations. Avian flexor digitorum profundus tendons were loaded (3 or 12 MPa) to a fixed number of cycles across either 1 or 12 days in vitro. The tendon response evaluations included biomechanical data gathered during loading and subsequent failure testing. Evaluations also included cellular viability, cell death, and proteoglycan, collagen, collagenase, and prostaglandin E2 (PGE2) content measurements obtained from tissue specimens and media samples. Significant strains (up to 2%) accumulated during loading. Loading to 12 MPa significantly reduced maximum stress (33% and 27%) and energy density (42% and 50%) when applied across 1 or 12 days, respectively. Loading to 3 MPa also caused a 40% reduction in energy density, but only when applied across 12 days. Cell death and collagenase activity increased significantly with increasing magnitude and duration. However, no differences occurred in cell viability or collagen content. Glycosaminoglycan content increased 50% with load magnitude, while PGE2 production increased 2.5-fold with loading magnitude and 11-fold with increased duration. Mechanical fatigue-induced mechanical property changes were exhibited by the tendons in response to increased loading magnitude across just 1 day. However, when the same loading was applied over a longer period, most outcomes were magnified substantially, relative to the short duration regimens. This is presumably due to the increased response time for the complex cellular response to loading. A key contributor may be the inflammatory mediator, PGE2, which exhibited large magnitude and duration dependent increases to cyclic loading. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1078–1086, 2007