4.5 Article

Dose-response effect of an intra-tendon application of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in a rat Achilles tendinopathy model

Journal

JOURNAL OF ORTHOPAEDIC RESEARCH
Volume 31, Issue 3, Pages 413-420

Publisher

WILEY
DOI: 10.1002/jor.22222

Keywords

platelet-derived growth factor-BB; tendinopathy; biomechanics; proliferation

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Funding

  1. BioMimetic Therapeutics, Inc

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The purpose of this study was to assess whether intra-tendon delivery of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) would improve Achilles tendon repair in a rat collagenase-induced tendinopathy model. Seven days following collagenase induction of tendinopathy, one of four intra-tendinous treatments was administered: (i) Vehicle control (sodium acetate buffer), (ii) 1.02 mu g rhPDGF-BB, (iii) 10.2 mu g rhPDGF-BB, or (iv) 102?mu g rhPDGF-BB. Treated tendons were assessed for histopathological (e.g., proliferation, tendon thickness, collagen fiber density/orientation) and biomechanical (e.g., maximum load-to-failure and stiffness) outcomes. By 7 days post-treatment, there was a significant increase in cell proliferation with the 10.2 and 102 mu g rhPDGF-BB-treated groups (p?=?0.049 and 0.015, respectively) and in thickness at the tendon midsubstance in the 10.2 mu g of rhPDGF-BB group (p?=?0.005), compared to controls. All groups had equivalent outcomes by Day 21. There was a dose-dependent effect on the maximum load-to-failure, with no significant difference in the 1.02 and 102 mu g rhPDGF-BB doses but the 10.2 mu g rhPDGF-BB group had a significant increase in load-to-failure at 7 (p?=?0.003) and 21 days (p?=?0.019) compared to controls. The rhPDGF-BB treatment resulted in a dose-dependent, transient increase in cell proliferation and sustained improvement in biomechanical properties in a rat Achilles tendinopathy model, demonstrating the potential of rhPDGF-BB treatment in a tendinopathy application. Consequently, in this model, data suggest that rhPDGF-BB treatment is an effective therapy and thus, may be an option for clinical applications to treat tendinopathy. (C) 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 413420, 2013

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