title: Bone morphogenetic protein but not transforming growth factor-beta enhances bone formation in canine diaphyseal nonunions implanted with a biodegradable composite polymer.
abstract: BACKGROUND
  The purpose of the present study was to create an effective bone-graft substitute for the treatment of a diaphyseal nonunion.
  
  
  METHODS
  A standardized nonunion was established in the midportion of the radial diaphysis in thirty mongrel dogs by creating a three-millimeter segmental bone defect (at least 2 percent of the total length of the bone). The nonunion was treated with implantation of a carrier comprised of poly(DL-lactic acid) and polyglycolic acid copolymer (50:50 polylactic acid-polyglycolic acid [PLG50]) containing canine purified bone morphogenetic protein (BMP) or recombinant human transforming growth factor-beta (TGF-beta1), or both, or the carrier without BMP or TGF-beta1. Five groups, consisting of six dogs each, were treated with implantation of the carrier alone, implantation of the carrier with fifteen milligrams of BMP, implantation of the carrier with 1.5 milligrams of BMP, implantation of the carrier with fifteen milligrams of BMP and ten nanograms of TGF-beta1, or implantation of the carrier with ten nanograms of TGF-beta1. At twelve weeks after implantation, the radii were examined radiographically and the sites of nonunion were examined histomorphometrically.
  
  
  RESULTS
  We found that implantation of the polylactic acid-polyglycolic acid carrier alone or in combination with ten nanograms of TGF-beta1 failed to induce significant radiographic or histomorphometric evidence of healing at the site of the nonunion. The radii treated with the carrier enriched with either 1.5 or fifteen milligrams of BMP showed significantly increased periosteal and endosteal bone formation on histomorphometric (p < 0.05) and radiographic (p < 0.02) analysis.
  
  
  CONCLUSIONS
  Bone formation in a persistent osseous defect that is similar to an ununited diaphyseal fracture is increased when species-specific BMP incorporated into a polylactic acid-polyglycolic acid carrier is implanted at the site of the nonunion. TGF-beta1 at a dose of ten nanograms per implant did not induce a similar degree of bone formation or potentiate the effect of BMP in this model.
  
  
  CONCLUSIONS
  The biodegradable implant containing BMP that was used in the present study to treat diaphyseal nonunion is an effective bone-graft substitute.
authors.affiliation: Department of Orthopaedics, The University of Texas Health Science Center at San Antonio, 78284-7774, USA. heckman@uthscsa.edu
authors.forename: J D
authors.initials: JD
authors.lastname: Heckman
authors.forename: W
authors.initials: W
authors.lastname: Ehler
authors.forename: B P
authors.initials: BP
authors.lastname: Brooks
authors.forename: T B
authors.initials: TB
authors.lastname: Aufdemorte
authors.forename: C H
authors.initials: CH
authors.lastname: Lohmann
authors.forename: T
authors.initials: T
authors.lastname: Morgan
authors.forename: B D
authors.initials: BD
authors.lastname: Boyan
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D001861:Bone Regeneration / Q000187:drug effects; D018786:Bone Substitutes; D018483:Diaphyses / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D004285:Dogs; D004343:Drug Implants; D004359:Drug Therapy, Combination; D017102:Fracture Healing / Q000187:drug effects*; D019344:Lactic Acid; D010012:Osteogenesis / Q000187:drug effects*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011859:Radiography; D011885:Radius Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
chemical_list: D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D004343:Drug Implants; D011108:Polymers; D016212:Transforming Growth Factor beta; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid