Experimental studies on bone induction using low-molecular-weight poly (DL-lactide-co-glycolide) as a carrier for recombinant human bone morphogenetic protein-2.
An appropriate carrier acting as a slow delivery vehicle for the BMPs is required for maximal clinical effectiveness of these bone-inductive proteins. The purpose of this study was to evaluate a low-molecular-weight PLGA copolymer as a synthetic, biodegradable carrier for rhBMP-2 implantation in vivo. Two, 10, or 50 microg of recombinant human BMP-2 were mixed with 10 mg of a poly (DL-lactide-co-glycolide) (PLGA) 50:50 copolymer and implanted into the calf muscles of Wistar rats. Soft X-ray analysis and histologic examination indicated that new bone formation occurred at all rhBMP-2-implanted sites within 3 weeks after implantation. Correlation of rhBMP-2 concentration with the amount of bone induction was confirmed by specific alkaline phosphatase activity and calcium content assay. In vitro analysis indicated that 78.5% of the PLGA copolymer was degraded to smaller molecular weight material after 14 days in PBS solution. It is suggested that rhBMP-2 was released in an active form at the implant site during the degradation of the copolymer, resulting in the induction of new bone formation. Thus this low-molecular-weight PLGA copolymer material represents a promising delivery vehicle for BMPs, and possibly other growth factors, around dental and orthopedic implants.
Bessho
K
K
Kyoto University, Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, 54 Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Carnes
D L
DL
Cavin
R
R
Ong
J L
JL
D000042:Absorption; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D004337:Drug Carriers; D006801:Humans; D008970:Molecular Weight; D018482:Muscle, Skeletal / Q000166:cytology / Q000000981:diagnostic imaging / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D011098:Polyglactin 910 / Q000737:chemistry*; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; 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; D004337:Drug Carriers; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D011098:Polyglactin 910