title: PDGF-BB released in tendon repair using a novel delivery system promotes cell proliferation and collagen remodeling.
abstract: The purpose of this study was to promote fibroblast proliferation and collagen remodeling in flexor tendon repair through sustained delivery of platelet derived growth factor (PDGF-BB). The release kinetics of PDGF-BB from a novel fibrin matrix delivery system was initially evaluated in vitro. After the in vivo degradation rate of the fibrin matrix was determined using fluorescently tagged fibrin, PDGF-BB was delivered to the site of flexor tendon repair in vivo in a canine model. The effect of PDGF-BB on intrasynovial tendon healing was studied using histology-based assays (cell density, proliferation, and type I collagen expression) and by measuring total DNA levels and reducible collagen crosslink levels. The fibrin matrix delivery system provided sustained release of PDGF-BB in vitro at a rate modulated by the ratio of heparin to growth factor. In vivo, the fibrin matrix remained at the repair site for more than 10 days. Delivery of PDGF-BB led to a qualitative increase in cell density, cell proliferation, and type I collagen mRNA expression. PDGF-BB also led to statistically significant increases in total DNA (20% increase at 7 days, 18% increase at 14 days) and reducible collagen crosslinks (30% increase at 7 days). Sustained delivery of growth factors may be achieved using a novel fibrin-based delivery system. PDGF-BB delivery increased cell proliferation and matrix remodeling and thus may accelerate flexor tendon healing.
authors.affiliation: Department of Orthopaedics, Washington University, St. Louis, Missouri 63110, USA. ThomopoulosS@wustl.edu
authors.forename: Stavros
authors.initials: S
authors.lastname: Thomopoulos
authors.forename: Melissa
authors.initials: M
authors.lastname: Zaegel
authors.forename: Rosalina
authors.initials: R
authors.lastname: Das
authors.forename: Fredrick L
authors.initials: FL
authors.lastname: Harwood
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Silva
authors.forename: David
authors.initials: D
authors.lastname: Amiel
authors.forename: Shelly
authors.initials: S
authors.lastname: Sakiyama-Elbert
authors.forename: Richard H
authors.initials: RH
authors.lastname: Gelberman
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage*; D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D003131:Combined Modality Therapy; D004151:Dipeptides / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage*; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins / Q000008:administration & dosage*; D013537:Sutures; D013708:Tendon Injuries / Q000188:drug therapy / Q000601:surgery; D013710:Tendons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D043925:Angiogenesis Inducing Agents; D004151:Dipeptides; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; C007428:5,5'-dihydroxylysylnorleucine; D000077214:Becaplermin; D003094:Collagen