title: Ectopic bone formation after implantation of a slow release system of polylactic acid and rhBMP-2.
abstract: OBJECTIVE
  The present study was conducted to test the hypothesis that preshaped polylactic acid (PLA) implants loaded with recombinant human bone morphogenic protein 2 (rhBMP-2) can induce bone formation in a rat ectopic model.
  
  
  METHODS
  Two groups of porous cylindrical poly-DL-lactic acid implants of 8-mm diameter were produced by gas foaming with CO(2), incorporating 48 and 96 microg rhBMP-2, respectively, into each implant. Blank PLA implants were used as controls. The release of BMPs and the induction of alkaline phosphatase were assessed in vitro. Osteoinduction in vivo was tested by insertion of 15 implants from each group into the gluteal muscles of Wistar rats. Five implants from each group were retrieved after 6, 13 and 26 weeks and assessed using flat panel volume detector computed tomography and light microscopy.
  
  
  RESULTS
  Both groups of implants showed increased release of rhBMP-2 during the first 24-48 h, with a slightly higher amount being released from the implants with 48 microg. Release during subsequent intervals was <100 ng/72 h in the low-concentration group and >100 ng in the group with 96 microg rhBMP-2. Implants with 95 microg rhBMP-2 exhibited bone formation in vivo on the outside of the implants across the observation period of 26 weeks with invasion of bone into the pores, whereas implants with 48 microg rhBMP-2 failed to induce the formation of bone tissue. No bone formation was found in the control implants.
  
  
  CONCLUSIONS
  The results suggest that release rates of rhBMP-2 for ectopic bone induction have to be >100 ng/72 h to maintain the osteoinductive activity of the tested porous PLA implants. This slow release system may have impact on alveolar bone augmentation procedures when used as individually preformed osteoinductive implants.
authors.affiliation: Department of Oral and Maxillofacial Surgery, George-Augusta-University, Göttingen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Gruber
authors.forename: H A
authors.initials: HA
authors.lastname: Weich
authors.forename: C
authors.initials: C
authors.lastname: Dullin
authors.forename: H
authors.initials: H
authors.lastname: Schliephake
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002081:Buttocks; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006801:Humans; D019344:Lactic Acid; D008297:Male; D009999:Ossification, Heterotopic; D010012:Osteogenesis / Q000187:drug effects*; D011091:Polyesters; D011108:Polymers; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D019344:Lactic Acid; C033616:poly(lactide)