Andrew D Allen1, Alex M Bassil1, David J Berkoff1, Mohammed Al Maliki1, Reid W Draeger1, Paul S Weinhold1,2. 1. Department of Orthopaedics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. 2. Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina and North Carolina State University, Raleigh, NC, USA.
Abstract
BACKGROUND: Tetracycline antibiotics inhibit matrix metalloproteinases and pro-inflammatory cytokines implicated in the pathogenesis of tendinopathy, while microsphere formulations allow sustained release of drug contents. The purpose of this study was to evaluate the ability of a local minocycline microsphere injection to restore normal tendon properties in a rat model of collagenase-induced patellar tendinopathy. METHODS: A total of 22 rats were randomly assigned to the control (n = 11) or minocycline (n = 11) group and received bilateral patellar tendon injections of collagenase. After 7 days, the minocycline group received the minocycline microsphere treatment and the control group received phosphate buffered solution. Pain was assessed via activity monitors and Von Frey filament testing. At 4 weeks post-collagenase injections, animals were euthanized. RESULTS: Cage crossings significantly decreased among all rats 2-3 days following each injection period, however, tactile allodynia measures did not reflect this injury response. Biomechanical properties, interleukin-1 beta levels, and glycosaminoglycan content did not differ between groups. While not statistically significant, levels of leukotriene B4 were lower in the minocycline group compared to controls (p = 0.061), suggesting a trend. CONCLUSIONS: Our study further characterizes the collagenase model of tendinopathy by demonstrating no evidence of central sensitization with collagenase-induced injury. We found no adverse effect of intratendinous injections of minocycline-loaded poly-lactic-co-glycolic acid microspheres, although no therapeutic effect was observed. Future studies involving a more substantial tendon injury with a greater inflammatory component may be necessary to more thoroughly evaluate the effects of minocycline on tendon pathology.
BACKGROUND: Tetracycline antibiotics inhibit matrix metalloproteinases and pro-inflammatory cytokines implicated in the pathogenesis of tendinopathy, while microsphere formulations allow sustained release of drug contents. The purpose of this study was to evaluate the ability of a local minocycline microsphere injection to restore normal tendon properties in a rat model of collagenase-induced patellar tendinopathy. METHODS: A total of 22 rats were randomly assigned to the control (n = 11) or minocycline (n = 11) group and received bilateral patellar tendon injections of collagenase. After 7 days, the minocycline group received the minocycline microsphere treatment and the control group received phosphate buffered solution. Pain was assessed via activity monitors and Von Frey filament testing. At 4 weeks post-collagenase injections, animals were euthanized. RESULTS: Cage crossings significantly decreased among all rats 2-3 days following each injection period, however, tactile allodynia measures did not reflect this injury response. Biomechanical properties, interleukin-1 beta levels, and glycosaminoglycan content did not differ between groups. While not statistically significant, levels of leukotriene B4 were lower in the minocycline group compared to controls (p = 0.061), suggesting a trend. CONCLUSIONS: Our study further characterizes the collagenase model of tendinopathy by demonstrating no evidence of central sensitization with collagenase-induced injury. We found no adverse effect of intratendinous injections of minocycline-loaded poly-lactic-co-glycolic acid microspheres, although no therapeutic effect was observed. Future studies involving a more substantial tendon injury with a greater inflammatory component may be necessary to more thoroughly evaluate the effects of minocycline on tendon pathology.
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