Long-term evaluation of recombinant human bone morphogenetic protein-2 induced bone formation with a biologic and synthetic delivery system.
The efficacy of microspheres made of polylactic acid polyglycolic acid copolymer mixed with blood clot as a delivery system for recombinant human bone morphogenetic protein-2 (rhBMP-2) was evaluated and the long term behaviour of rhBMP-2 in rats was studied. Twenty micro grams of rhBMP-2 in 200 microliter carrier (blood coagulum and polylactic acid polyglycolic acid porous microspheres) were implanted subcutaneously over both sides of the chest muscles in 40 5-week-old male Long Evans rats. The control group were implanted with carrier alone. Specimens were retrieved after 3 days and weekly for 9 weeks. Outcome was measured by signs of bone formation on low power radiographs, and signs of bony growth on histological examination. There were no signs of foreign body or inflammatory reactions to the carrier in either group. In the experimental group signs of bone formation had started to appear by the end of the first week, and there was a gradual increase in both radio-opacity and size during the observation period. Histologically the bony growth was beginning to mature by 4 weeks and was fully mature by 7-9 weeks. In contrast there was no sign of cartilage or bone formation in the control group and the carrier had resorbed by 4-6 weeks. It is concluded that rhBMP-2 implanted in a carrier consisting of blood clot and porous microspheres made of polylactic acid polyglycolic acid induces rapid proliferation of mesenchymal cells that lead to formation of cartilage and bone by 7 days which had matured by 9 weeks. rhBMP-2 in this carrier may be useful clinically because of its capacity to induce early formation of bone.
First Department of Oral and Maxillofacial Surgery, Niigata University School of Dentistry, Japan.
C
C
Alpaslan
K
K
Irie
K
K
Takahashi
N
N
Ohashi
H
H
Sakai
T
T
Nakajima
H
H
Ozawa
D000818:Animals; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D016503:Drug Delivery Systems; D005069:Evaluation Studies as Topic; D006801:Humans; D019344:Lactic Acid; D008297:Male; D008863:Microspheres; D010012:Osteogenesis / Q000187:drug effects*; D010369:Pectoralis Muscles; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011108:Polymers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid