Ectopic bone formation in mice associated with a lactic acid/dioxanone/ethylene glycol copolymer-tricalcium phosphate composite with added recombinant human bone morphogenetic protein-2.
A new putty-like material with bone-inducing capacity was made by combining a block copolymer of poly d,l-lactic acid with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) and beta-tricalcium phosphate (beta-TCP) powder with added recombinant human bone morphogenetic protein-2 (rhBMP-2). To optimize the material's efficacy for bone formation, we formulated the optimal composition ratio of the respective constituent that gives the greatest osteoinductive efficacy in a mouse model of ectopic bone formation. In this series of studies, we investigated the size of ectopic bone mass induced 3 and 6 weeks after implantation of the materials composed of 30 mg of PLA-DX-PEG with 2 microg of rhBMP-2 and 0, 15, 30, or 60 mg of beta-TCP powder. An additional experiment was designed to investigate how content ratios of beta-TCP powder in 30 mg-putty implants (0%, 16.7%, 33.3%, 50%, 66.7%, 83.3%, or 100%) for a fixed dose (5 microg) of the rhBMP-2 altered the size of the induced ossicle. The results from the first experiment indicated that the bone yields were linearly dependent on the amount of additional beta-TCP powder. In the second experiment, the largest ossicles induced by 5 microg of rhBMP-2 were obtained when the polymer/beta-TCP ratio was 1/2 in mice. The data provide important insights into the fabrication of implants that provide efficacious delivery of rhBMP-2. The new putty-like material may be valuable for repairing or regenerating bone in a clinical setting.
Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. minori@msic.med.osaka-cu.ac.jp
Minori
M
Kato
Takashi
T
Namikawa
Hidetomi
H
Terai
Masatoshi
M
Hoshino
Shimpei
S
Miyamoto
Kunio
K
Takaoka
D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000737:chemistry* / Q000235:genetics; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D007773:Lactates / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D051379:Mice; D008813:Mice, Inbred ICR; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000737:chemistry* / Q000235:genetics
C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007773:Lactates; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C432470:polylactic acid-dioxanone-polyethylene glycol block copolymer; D011092:Polyethylene Glycols