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.
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.
authors.affiliation: Sports Medicine, BioMimetic Therapeutics, Inc., 389 Nichol Mill Lane, Franklin, Tennessee, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Shah
authors.forename: Alison
authors.initials: A
authors.lastname: Bendele
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Dines
authors.forename: Hans K
authors.initials: HK
authors.lastname: Kestler
authors.forename: Jeffrey O
authors.initials: JO
authors.lastname: Hollinger
authors.forename: Nadeen O
authors.initials: NO
authors.lastname: Chahine
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Hee
mesh_terms: D000125:Achilles Tendon / Q000293:injuries* / Q000502:physiology; D000818:Animals; D000077214:Becaplermin; D001696:Biomechanical Phenomena / Q000187:drug effects / Q000502:physiology; D002111:Calcaneus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013708:Tendon Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D016896:Treatment Outcome; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin