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
ISTEX:77574D10E0D2B4058B28922DF663F0DDE9C11C8ELe document en format XML
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Dines</name><affiliation><mods:affiliation>Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, New York</mods:affiliation></affiliation></author><author><name sortKey="Kestler, Hans K" sort="Kestler, Hans K" uniqKey="Kestler H" first="Hans K." last="Kestler">Hans K. Kestler</name><affiliation><mods:affiliation>Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee</mods:affiliation></affiliation></author><author><name sortKey="Hollinger, Jeffrey O" sort="Hollinger, Jeffrey O" uniqKey="Hollinger J" first="Jeffrey O." last="Hollinger">Jeffrey O. Hollinger</name><affiliation><mods:affiliation>Departments of Biomedical Engineering and Biological Sciences, Bone Tissue Engineering Center, Carnegie Mellon University, Pittsburgh, Pennsylvania</mods:affiliation></affiliation></author><author><name sortKey="Chahine, Nadeen O" sort="Chahine, Nadeen O" uniqKey="Chahine N" first="Nadeen O." last="Chahine">Nadeen O. Chahine</name><affiliation><mods:affiliation>Biomechanics & Bioengineering Research Laboratory, Feinstein Institute for Medical Research, North Shore Long Island Jewish Health System, Manhasset, New York</mods:affiliation></affiliation></author><author><name sortKey="Hee, Christopher K" sort="Hee, Christopher K" uniqKey="Hee C" first="Christopher K." last="Hee">Christopher K. Hee</name><affiliation><mods:affiliation>Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: chee@biomimetics.com</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence address: Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee. T: 615‐236‐4949; F: 615‐236‐4864</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Orthopaedic Research</title><title level="j" type="alt">JOURNAL OF ORTHOPAEDIC RESEARCH</title><idno type="ISSN">0736-0266</idno><idno type="eISSN">1554-527X</idno><imprint><biblScope unit="vol">31</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="413">413</biblScope><biblScope unit="page" to="420">420</biblScope><biblScope unit="page-count">8</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2013-03">2013-03</date></imprint><idno type="ISSN">0736-0266</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0736-0266</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Achilles</term><term>Achilles tendinopathy model</term><term>Achilles tendon</term><term>Achilles tendon injury</term><term>Achilles tendon repair</term><term>Baseline</term><term>Biochemical activity</term><term>Biomechanical</term><term>Biomechanical properties</term><term>Biomechanical strength</term><term>Biomimetic therapeutics</term><term>Calcaneal insertion</term><term>Cell number</term><term>Cell proliferation</term><term>Cellular proliferation</term><term>Cochrane database syst</term><term>Collagen</term><term>Collagen fiber orientation</term><term>Collagen fibrils</term><term>Collagen synthesis</term><term>Collagenase</term><term>Collagenase treatment</term><term>Contralateral</term><term>Contralateral controls</term><term>Corticosteroid</term><term>Corticosteroid injections</term><term>Days posttreatment</term><term>Exor tendons</term><term>Growth factor</term><term>Growth factors</term><term>Hand surg</term><term>Healing response</term><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><term>Material biomechanical properties</term><term>Material properties</term><term>Mechanical properties</term><term>Mechanical strength</term><term>Microscopic tendon thickness</term><term>Ocular micrometer</term><term>Orthop</term><term>Orthopaedic</term><term>Orthopaedic research march</term><term>Orthopaedic research society</term><term>Proliferation</term><term>Proliferative phase</term><term>Sodium acetate buffer</term><term>Stiffness</term><term>Stiffness values</term><term>Structural repair</term><term>Study design</term><term>Study support</term><term>Surg</term><term>Systematic review</term><term>Tendinopathy</term><term>Tendinopathy model</term><term>Tendon</term><term>Tendon healing</term><term>Tendon injury</term><term>Tendon midsubstance</term><term>Tendon repair</term><term>Tendon thickness</term><term>Treatment group</term><term>Treatment options</term><term>Vascularization</term><term>Vehicle control</term><term>Vehicle control group</term><term>Vehicle controls</term><term>Washout period</term><term>Wiley periodicals</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Achilles</term><term>Achilles tendinopathy model</term><term>Achilles tendon</term><term>Achilles tendon injury</term><term>Achilles tendon repair</term><term>Baseline</term><term>Biochemical activity</term><term>Biomechanical</term><term>Biomechanical properties</term><term>Biomechanical strength</term><term>Biomimetic therapeutics</term><term>Calcaneal insertion</term><term>Cell number</term><term>Cell proliferation</term><term>Cellular proliferation</term><term>Cochrane database syst</term><term>Collagen</term><term>Collagen fiber orientation</term><term>Collagen fibrils</term><term>Collagen synthesis</term><term>Collagenase</term><term>Collagenase treatment</term><term>Contralateral</term><term>Contralateral controls</term><term>Corticosteroid</term><term>Corticosteroid injections</term><term>Days posttreatment</term><term>Exor tendons</term><term>Growth factor</term><term>Growth factors</term><term>Hand surg</term><term>Healing response</term><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><term>Material biomechanical properties</term><term>Material properties</term><term>Mechanical properties</term><term>Mechanical strength</term><term>Microscopic tendon thickness</term><term>Ocular micrometer</term><term>Orthop</term><term>Orthopaedic</term><term>Orthopaedic research march</term><term>Orthopaedic research society</term><term>Proliferation</term><term>Proliferative phase</term><term>Sodium acetate buffer</term><term>Stiffness</term><term>Stiffness values</term><term>Structural repair</term><term>Study design</term><term>Study support</term><term>Surg</term><term>Systematic review</term><term>Tendinopathy</term><term>Tendinopathy model</term><term>Tendon</term><term>Tendon healing</term><term>Tendon injury</term><term>Tendon midsubstance</term><term>Tendon repair</term><term>Tendon thickness</term><term>Treatment group</term><term>Treatment options</term><term>Vascularization</term><term>Vehicle control</term><term>Vehicle control group</term><term>Vehicle controls</term><term>Washout period</term><term>Wiley periodicals</term></keywords></textClass></profileDesc></teiHeader><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></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>tendon</json:string><json:string>tendinopathy</json:string><json:string>biomechanical</json:string><json:string>orthopaedic</json:string><json:string>vehicle control</json:string><json:string>collagenase</json:string><json:string>contralateral</json:string><json:string>contralateral controls</json:string><json:string>orthopaedic research march</json:string><json:string>orthop</json:string><json:string>tendinopathy model</json:string><json:string>vascularization</json:string><json:string>surg</json:string><json:string>corticosteroid</json:string><json:string>histopathology</json:string><json:string>baseline</json:string><json:string>achilles</json:string><json:string>vehicle control group</json:string><json:string>vehicle controls</json:string><json:string>cell proliferation</json:string><json:string>tendon healing</json:string><json:string>tendon thickness</json:string><json:string>corticosteroid injections</json:string><json:string>stiffness</json:string><json:string>collagen</json:string><json:string>hand surg</json:string><json:string>biomechanical strength</json:string><json:string>lateral epicondylitis</json:string><json:string>mechanical properties</json:string><json:string>collagen fibrils</json:string><json:string>biomechanical properties</json:string><json:string>lateral</json:string><json:string>histopathology scores</json:string><json:string>tendon midsubstance</json:string><json:string>achilles tendinopathy model</json:string><json:string>tendon repair</json:string><json:string>achilles tendon</json:string><json:string>cochrane database syst</json:string><json:string>growth factors</json:string><json:string>systematic review</json:string><json:string>calcaneal insertion</json:string><json:string>lateral elbow pain</json:string><json:string>growth factor</json:string><json:string>biomimetic therapeutics</json:string><json:string>proliferation</json:string><json:string>proliferative phase</json:string><json:string>microscopic tendon thickness</json:string><json:string>collagen fiber orientation</json:string><json:string>ocular micrometer</json:string><json:string>days posttreatment</json:string><json:string>sodium acetate buffer</json:string><json:string>collagenase treatment</json:string><json:string>material biomechanical properties</json:string><json:string>achilles tendon repair</json:string><json:string>treatment group</json:string><json:string>stiffness values</json:string><json:string>cellular proliferation</json:string><json:string>study support</json:string><json:string>washout period</json:string><json:string>cell number</json:string><json:string>biochemical activity</json:string><json:string>material properties</json:string><json:string>local tissue concentrations</json:string><json:string>study design</json:string><json:string>institutional funds</json:string><json:string>collagen synthesis</json:string><json:string>mechanical strength</json:string><json:string>tendon injury</json:string><json:string>structural repair</json:string><json:string>treatment options</json:string><json:string>healing response</json:string><json:string>wiley periodicals</json:string><json:string>exor tendons</json:string><json:string>orthopaedic research society</json:string><json:string>achilles tendon injury</json:string></teeft></keywords><author><json:item><name>Vivek Shah</name><affiliations><json:string>Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee</json:string></affiliations></json:item><json:item><name>Alison Bendele</name><affiliations><json:string>Bolder BioPATH, Inc., Boulder, Colorado</json:string></affiliations></json:item><json:item><name>Joshua S. Dines</name><affiliations><json:string>Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, New York</json:string></affiliations></json:item><json:item><name>Hans K. Kestler</name><affiliations><json:string>Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee</json:string></affiliations></json:item><json:item><name>Jeffrey O. Hollinger</name><affiliations><json:string>Departments of Biomedical Engineering and Biological Sciences, Bone Tissue Engineering Center, Carnegie Mellon University, Pittsburgh, Pennsylvania</json:string></affiliations></json:item><json:item><name>Nadeen O. Chahine</name><affiliations><json:string>Biomechanics & Bioengineering Research Laboratory, Feinstein Institute for Medical Research, North Shore Long Island Jewish Health System, Manhasset, New York</json:string></affiliations></json:item><json:item><name>Christopher K. Hee</name><affiliations><json:string>Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee</json:string><json:string>E-mail: chee@biomimetics.com</json:string><json:string>Correspondence address: Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee. T: 615‐236‐4949; F: 615‐236‐4864</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>platelet‐derived growth factor‐BB</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>tendinopathy</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>biomechanics</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>proliferation</value></json:item></subject><articleId><json:string>JOR22222</json:string></articleId><arkIstex>ark:/67375/WNG-SQPCPGL9-L</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><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</abstract><qualityIndicators><refBibsNative>true</refBibsNative><abstractWordCount>244</abstractWordCount><abstractCharCount>1805</abstractCharCount><keywordCount>4</keywordCount><score>9.575</score><pdfWordCount>4647</pdfWordCount><pdfCharCount>30549</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>8</pdfPageCount><pdfPageSize>594 x 792 pts</pdfPageSize></qualityIndicators><title>Dose–response effect of an intra‐tendon application of recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) in a rat Achilles tendinopathy model</title><pmid><json:string>22933269</json:string></pmid><genre><json:string>article</json:string></genre><host><title>Journal of Orthopaedic Research</title><language><json:string>unknown</json:string></language><doi><json:string>10.1002/(ISSN)1554-527X</json:string></doi><issn><json:string>0736-0266</json:string></issn><eissn><json:string>1554-527X</json:string></eissn><publisherId><json:string>JOR</json:string></publisherId><volume>31</volume><issue>3</issue><pages><first>413</first><last>420</last><total>8</total></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Research Article</value></json:item></subject></host><namedEntities><unitex><date><json:string>2013</json:string></date><geogName></geogName><orgName><json:string>Wiley Periodicals, Inc.</json:string><json:string>Bioengineering Research Laboratory, Feinstein Institute for Medical Research, North Shore Long Island Jewish Health System, Manhasset, New York Received</json:string><json:string>Hospital for Special Surgery, New York, New York</json:string><json:string>Bone Tissue Engineering Center</json:string><json:string>Orthopaedic Research Society</json:string><json:string>Bolder BioPATH, Inc., Boulder</json:string><json:string>BioMimetic Therapeutics, Inc</json:string><json:string>Bolder BioPATH, Inc</json:string><json:string>BioMimetic Therapeutics, Inc.</json:string><json:string>ORTHOPAEDIC RESEARCH MARCH</json:string><json:string>Carnegie Mellon University, Pittsburgh</json:string><json:string>Wiley Periodicals, Inc</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Jeffrey O. Hollinger</json:string><json:string>Mike Bendele</json:string><json:string>Brian Omura</json:string><json:string>SEM Thickness</json:string><json:string>C.K. Hee</json:string><json:string>Scott Boswell</json:string><json:string>H.K. Kestler</json:string><json:string>Luis A. Solchaga</json:string><json:string>Joshua S. Dines</json:string><json:string>Jack Ratliff</json:string><json:string>J.S. Dines</json:string><json:string>Christopher K. Hee</json:string><json:string>V. Shah</json:string><json:string>Dean J. Aguiar</json:string><json:string>N.O. Chahine</json:string><json:string>A. Bendele</json:string><json:string>Committee</json:string><json:string>Yanchun Liu</json:string><json:string>J.O. Hollinger</json:string><json:string>Hans K. Kestler</json:string><json:string>O. Chahine</json:string></persName><placeName></placeName><ref_url></ref_url><ref_bibl><json:string>[1]</json:string><json:string>Model 5566</json:string><json:string>[2]</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/WNG-SQPCPGL9-L</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - orthopedics</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - clinical medicine</json:string><json:string>3 - orthopedics</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Orthopedics and Sports Medicine</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string><json:string>4 - nephrologie. maladies des voies urinaires</json:string></inist></categories><publicationDate>2013</publicationDate><copyrightDate>2013</copyrightDate><doi><json:string>10.1002/jor.22222</json:string></doi><id>77574D10E0D2B4058B28922DF663F0DDE9C11C8E</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/77574D10E0D2B4058B28922DF663F0DDE9C11C8E/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/77574D10E0D2B4058B28922DF663F0DDE9C11C8E/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/77574D10E0D2B4058B28922DF663F0DDE9C11C8E/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Dose–response effect of an intra‐tendon application of recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) in a rat Achilles tendinopathy model</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><licence>Copyright © 2012 Orthopaedic Research Society</licence></availability><date type="published" when="2013-03"></date></publicationStmt><notesStmt><note type="content-type" subtype="article" source="article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</note><note type="publication-type" subtype="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="article"><analytic><title level="a" type="main" xml:lang="en">Dose–response effect of an intra‐tendon application of recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) in a rat Achilles tendinopathy model</title><title level="a" type="short" xml:lang="en">rhPDGF‐BB IN A TENDINOPATHY MODEL</title><author xml:id="author-0000"><persName><forename type="first">Vivek</forename><surname>Shah</surname></persName><affiliation>Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee<address><country key="US"></country></address></affiliation></author><author xml:id="author-0001"><persName><forename type="first">Alison</forename><surname>Bendele</surname></persName><affiliation>Bolder BioPATH, Inc., Boulder, Colorado<address><country key="US"></country></address></affiliation></author><author xml:id="author-0002"><persName><forename type="first">Joshua S.</forename><surname>Dines</surname></persName><affiliation>Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, New York<address><country key="US"></country></address></affiliation></author><author xml:id="author-0003"><persName><forename type="first">Hans K.</forename><surname>Kestler</surname></persName><affiliation>Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee<address><country key="US"></country></address></affiliation></author><author xml:id="author-0004"><persName><forename type="first">Jeffrey O.</forename><surname>Hollinger</surname></persName><affiliation>Departments of Biomedical Engineering and Biological Sciences, Bone Tissue Engineering Center, Carnegie Mellon University, Pittsburgh, Pennsylvania<address><country key="US"></country></address></affiliation></author><author xml:id="author-0005"><persName><forename type="first">Nadeen O.</forename><surname>Chahine</surname></persName><affiliation>Biomechanics & Bioengineering Research Laboratory, Feinstein Institute for Medical Research, North Shore Long Island Jewish Health System, Manhasset, New York<address><country key="US"></country></address></affiliation></author><author xml:id="author-0006" role="corresp"><persName><forename type="first">Christopher K.</forename><surname>Hee</surname></persName><email>chee@biomimetics.com</email><affiliation>Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee<address><country key="US"></country></address></affiliation><affiliation>Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee. T: 615‐236‐4949; F: 615‐236‐4864</affiliation></author><idno type="istex">77574D10E0D2B4058B28922DF663F0DDE9C11C8E</idno><idno type="ark">ark:/67375/WNG-SQPCPGL9-L</idno><idno type="DOI">10.1002/jor.22222</idno><idno type="unit">JOR22222</idno><idno type="toTypesetVersion">file:JOR.JOR22222.pdf</idno></analytic><monogr><title level="j" type="main">Journal of Orthopaedic Research</title><title level="j" type="alt">JOURNAL OF ORTHOPAEDIC RESEARCH</title><idno type="pISSN">0736-0266</idno><idno type="eISSN">1554-527X</idno><idno type="book-DOI">10.1002/(ISSN)1554-527X</idno><idno type="book-part-DOI">10.1002/jor.v31.3</idno><idno type="product">JOR</idno><imprint><biblScope unit="vol">31</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="413">413</biblScope><biblScope unit="page" to="420">420</biblScope><biblScope unit="page-count">8</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2013-03"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><abstract xml:lang="en" style="main"><head>Abstract</head><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> = 0.049 and 0.015, respectively) and in thickness at the tendon midsubstance in the 10.2 µg of rhPDGF‐BB group (<hi rend="italic">p</hi> = 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 (<hi rend="italic">p</hi> = 0.003) and 21 days (<hi rend="italic">p</hi> = 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. 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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> = 0.049 and 0.015, respectively) and in thickness at the tendon midsubstance in the 10.2 µg of rhPDGF‐BB group (<i>p</i> = 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 (<i>p</i> = 0.003) and 21 days (<i>p</i> = 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</p></abstract></abstractGroup></contentMeta></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Dose–response effect of an intra‐tendon application of recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) in a rat Achilles tendinopathy model</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>rhPDGF‐BB IN A TENDINOPATHY MODEL</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Dose–response effect of an intra‐tendon application of recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) in a rat Achilles tendinopathy model</title></titleInfo><name type="personal"><namePart type="given">Vivek</namePart><namePart type="family">Shah</namePart><affiliation>Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alison</namePart><namePart type="family">Bendele</namePart><affiliation>Bolder BioPATH, Inc., Boulder, Colorado</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Joshua S.</namePart><namePart type="family">Dines</namePart><affiliation>Sports Medicine and Shoulder Service, Hospital for Special Surgery, New York, New York</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Hans K.</namePart><namePart type="family">Kestler</namePart><affiliation>Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jeffrey O.</namePart><namePart type="family">Hollinger</namePart><affiliation>Departments of Biomedical Engineering and Biological Sciences, Bone Tissue Engineering Center, Carnegie Mellon University, Pittsburgh, Pennsylvania</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nadeen O.</namePart><namePart type="family">Chahine</namePart><affiliation>Biomechanics & Bioengineering Research Laboratory, Feinstein Institute for Medical Research, North Shore Long Island Jewish Health System, Manhasset, New York</affiliation><role><roleTerm type="text">author</roleTerm></role></name><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><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-6N5SZHKN-D">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><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></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><extent unit="figures">3</extent><extent unit="tables">5</extent><extent unit="references">37</extent><extent unit="words">5758</extent></physicalDescription><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></subject><relatedItem type="host"><titleInfo><title>Journal of Orthopaedic Research</title></titleInfo><titleInfo type="abbreviated"><title>J. Orthop. Res.</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><subject><genre>article-category</genre><topic>Research Article</topic></subject><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></detail><detail type="issue"><caption>no.</caption><number>3</number></detail><extent unit="pages"><start>413</start><end>420</end><total>8</total></extent></part></relatedItem><identifier type="istex">77574D10E0D2B4058B28922DF663F0DDE9C11C8E</identifier><identifier type="ark">ark:/67375/WNG-SQPCPGL9-L</identifier><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><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-L0C46X92-X">wiley</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/77574D10E0D2B4058B28922DF663F0DDE9C11C8E/metadata/json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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