Dose–response effect of an intra‐tendon application of recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) in a rat Achilles tendinopathy model
Identifieur interne : 001B78 ( Istex/Corpus ); précédent : 001B77; suivant : 001B79Dose–response effect of an intra‐tendon application of recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) in a rat Achilles tendinopathy model
Auteurs : Vivek Shah ; Alison Bendele ; Joshua S. Dines ; Hans K. Kestler ; Jeffrey O. Hollinger ; Nadeen O. Chahine ; Christopher K. HeeSource :
- Journal of Orthopaedic Research [ 0736-0266 ] ; 2013-03.
English descriptors
- KwdEn :
- Achilles, Achilles tendinopathy model, Achilles tendon, Achilles tendon injury, Achilles tendon repair, Baseline, Biochemical activity, Biomechanical, Biomechanical properties, Biomechanical strength, Biomimetic therapeutics, Calcaneal insertion, Cell number, Cell proliferation, Cellular proliferation, Cochrane database syst, Collagen, Collagen fiber orientation, Collagen fibrils, Collagen synthesis, Collagenase, Collagenase treatment, Contralateral, Contralateral controls, Corticosteroid, Corticosteroid injections, Days posttreatment, Exor tendons, Growth factor, Growth factors, Hand surg, Healing response, Histopathology, Histopathology scores, Institutional funds, Lateral, Lateral elbow pain, Lateral epicondylitis, Local tissue concentrations, Material biomechanical properties, Material properties, Mechanical properties, Mechanical strength, Microscopic tendon thickness, Ocular micrometer, Orthop, Orthopaedic, Orthopaedic research march, Orthopaedic research society, Proliferation, Proliferative phase, Sodium acetate buffer, Stiffness, Stiffness values, Structural repair, Study design, Study support, Surg, Systematic review, Tendinopathy, Tendinopathy model, Tendon, Tendon healing, Tendon injury, Tendon midsubstance, Tendon repair, Tendon thickness, Treatment group, Treatment options, Vascularization, Vehicle control, Vehicle control group, Vehicle controls, Washout period, Wiley periodicals.
- Teeft :
- Achilles, Achilles tendinopathy model, Achilles tendon, Achilles tendon injury, Achilles tendon repair, Baseline, Biochemical activity, Biomechanical, Biomechanical properties, Biomechanical strength, Biomimetic therapeutics, Calcaneal insertion, Cell number, Cell proliferation, Cellular proliferation, Cochrane database syst, Collagen, Collagen fiber orientation, Collagen fibrils, Collagen synthesis, Collagenase, Collagenase treatment, Contralateral, Contralateral controls, Corticosteroid, Corticosteroid injections, Days posttreatment, Exor tendons, Growth factor, Growth factors, Hand surg, Healing response, Histopathology, Histopathology scores, Institutional funds, Lateral, Lateral elbow pain, Lateral epicondylitis, Local tissue concentrations, Material biomechanical properties, Material properties, Mechanical properties, Mechanical strength, Microscopic tendon thickness, Ocular micrometer, Orthop, Orthopaedic, Orthopaedic research march, Orthopaedic research society, Proliferation, Proliferative phase, Sodium acetate buffer, Stiffness, Stiffness values, Structural repair, Study design, Study support, Surg, Systematic review, Tendinopathy, Tendinopathy model, Tendon, Tendon healing, Tendon injury, Tendon midsubstance, Tendon repair, Tendon thickness, Treatment group, Treatment options, Vascularization, Vehicle control, Vehicle control group, Vehicle controls, Washout period, Wiley periodicals.
Abstract
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 µg rhPDGF‐BB, (iii) 10.2 µg rhPDGF‐BB, or (iv) 102 µg 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 µg rhPDGF‐BB‐treated groups (p = 0.049 and 0.015, respectively) and in thickness at the tendon midsubstance in the 10.2 µg 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 µg rhPDGF‐BB doses but the 10.2 µg 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. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 413–420, 2013
Url:
DOI: 10.1002/jor.22222
Links to Exploration step
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<term>Achilles tendon repair</term>
<term>Baseline</term>
<term>Biochemical activity</term>
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<term>Growth factors</term>
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<term>Histopathology</term>
<term>Histopathology scores</term>
<term>Institutional funds</term>
<term>Lateral</term>
<term>Lateral elbow pain</term>
<term>Lateral epicondylitis</term>
<term>Local tissue concentrations</term>
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<term>Orthopaedic research society</term>
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<front><div type="abstract" xml:lang="en">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 µg rhPDGF‐BB, (iii) 10.2 µg rhPDGF‐BB, or (iv) 102 µg 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 µg rhPDGF‐BB‐treated groups (p = 0.049 and 0.015, respectively) and in thickness at the tendon midsubstance in the 10.2 µg 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 µg rhPDGF‐BB doses but the 10.2 µg 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. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 413–420, 2013</div>
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<p>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 µg rhPDGF‐BB, (iii) 10.2 µg rhPDGF‐BB, or (iv) 102 µg 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 µg rhPDGF‐BB‐treated groups (<hi rend="italic">p</hi>
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<p>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 µg rhPDGF‐BB, (iii) 10.2 µg rhPDGF‐BB, or (iv) 102 µg 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 µg rhPDGF‐BB‐treated groups (<i>p</i>
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<name type="personal"><namePart type="given">Christopher K.</namePart>
<namePart type="family">Hee</namePart>
<affiliation>Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee</affiliation>
<affiliation>E-mail: chee@biomimetics.com</affiliation>
<affiliation>Correspondence address: Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee. T: 615‐236‐4949; F: 615‐236‐4864</affiliation>
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<dateIssued encoding="w3cdtf">2013-03</dateIssued>
<dateCaptured encoding="w3cdtf">2012-03-29</dateCaptured>
<dateValid encoding="w3cdtf">2012-08-07</dateValid>
<copyrightDate encoding="w3cdtf">2013</copyrightDate>
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<abstract lang="en">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 µg rhPDGF‐BB, (iii) 10.2 µg rhPDGF‐BB, or (iv) 102 µg 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 µg rhPDGF‐BB‐treated groups (p = 0.049 and 0.015, respectively) and in thickness at the tendon midsubstance in the 10.2 µg 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 µg rhPDGF‐BB doses but the 10.2 µg 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. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 413–420, 2013</abstract>
<note type="funding">BioMimetic Therapeutics, Inc.</note>
<subject lang="en"><genre>keywords</genre>
<topic>platelet‐derived growth factor‐BB</topic>
<topic>tendinopathy</topic>
<topic>biomechanics</topic>
<topic>proliferation</topic>
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<relatedItem type="host"><titleInfo><title>Journal of Orthopaedic Research</title>
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<titleInfo type="abbreviated"><title>J. Orthop. Res.</title>
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<topic>Research Article</topic>
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<identifier type="ISSN">0736-0266</identifier>
<identifier type="eISSN">1554-527X</identifier>
<identifier type="DOI">10.1002/(ISSN)1554-527X</identifier>
<identifier type="PublisherID">JOR</identifier>
<part><date>2013</date>
<detail type="volume"><caption>vol.</caption>
<number>31</number>
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<detail type="issue"><caption>no.</caption>
<number>3</number>
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<extent unit="pages"><start>413</start>
<end>420</end>
<total>8</total>
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<identifier type="DOI">10.1002/jor.22222</identifier>
<identifier type="ArticleID">JOR22222</identifier>
<accessCondition type="use and reproduction" contentType="copyright">Copyright © 2012 Orthopaedic Research Society</accessCondition>
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