New synthetic absorbable polymers as BMP carriers: plastic properties of poly-D,L-lactic acid-polyethylene glycol block copolymers.
Bone morphogenetic proteins (BMPs) are biologically active molecules capable of eliciting new bone formation. In combination with biomaterials, these proteins can be used in a clinical setting as bone-graft substitutes to promote bone repair. To find new synthetic absorbable polymers with plastic nature that can be used as BMP-carrier materials, six types of poly-D,L-lactic acid-polyethylene glycol block copolymer (PLA-PEG) with various molecular weights of PLA and PEG were synthesized. These were PLA6, 500-PEG3,000 (P-1), PLA11,500-PEG3,000 (P-2), PLA17,500-PEG3,000 (P-3), PLA6,500-PEG1,000 (P-4), PLA15,000-PEG8,000 (P-5), and PLA8, 500-PEG1,000 (P-6). Fifty milligrams of these polymers was mixed with 0 microg (control) or 5, 10, or 20 microg of recombinant human BMP-2 (rhBMP-2). These pellets were implanted into the dorsal muscle pouches of 144 mice (six pellets consisting of the same polymer and dose of rhBMP-2 for a specific group). Three weeks after surgery, the pellets were harvested and examined by radiographic and histological methods. All P-1 pellets with 10 or 20 microg of rhBMP-2 showed bone formation with hematopoietic marrow and bony trabeculae, as did one third of those with 5 microg of rhBMP-2. The incidence of new bone formation with P-2 pellets or that of P-5 pellets was lower than that of P-1 pellets. No bone was formed in any other type of pellet. These results indicated that the PLA6, 500-PEG3,000 polymer with plastic properties was found to work well as a BMP carrier.
Saito
N
N
Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 Japan.
Okada
T
T
Toba
S
S
Miyamoto
S
S
Takaoka
K
K
D000042:Absorption; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D018786:Bone Substitutes / Q000008:administration & dosage*; D004337:Drug Carriers; D006801:Humans; D066298:In Vitro Techniques; D007773:Lactates / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D051379:Mice; D008970:Molecular Weight; D016348:Osseointegration; D011092:Polyethylene Glycols / Q000737:chemistry*; D019736:Prostheses and Implants; D011994:Recombinant Proteins / Q000008:administration & dosage; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; D001672:Biocompatible Materials; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D004337:Drug Carriers; D007773:Lactates; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C088513:poly(lactic acid-ethylene glycol); C499469:recombinant human bone morphogenetic protein-2; D011092:Polyethylene Glycols