Abstract
A new type of degradable biomaterial with bone-inducing capacity was made by combining porous beta-tricalcium phosphate (beta-TCP) with a delivery system for recombinant human bone morphogenetic protein-2 (rhBMP-2). The BMP delivery system consisted of a block copolymer composed of poly-D,L-lactic acid with random insertion of p-dioxanone and polyethylene glycol (PLA-DX-PEG), a known biocompatible and biodegradable material. The efficacy of this biomaterial in terms of its bone-inducing capacity was examined by ectopic bone formation in the dorsal muscles of the mouse. In the beta-TCP implants coated with the PLA-DX-PEG polymer containing more than 0.0025% (w/w) of rhBMP-2, new ectopic bone tissues with marrow were consistently found on the surface of implants. The radiographic density of beta-TCP was diminished in a time-dependent manner. On histological examination, numerous multinucleated osteoclasts with positive tartrate-resistant acid-phosphatase (TRAP) staining were noted on the surface of the beta-TCP. These experimental results indicate that beta-TCP implants coated with synthetic rhBMP-2 delivery system might provide effective artificial bone-graft substitutes with osteoinductive capacity and biodegradable properties. In addition, this type of biomaterial may require less rhBMP-2 to induce significant new bone mass.
Copyright 2004 Wiley Periodicals, Inc.
MeSH terms
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Absorbable Implants*
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Acid Phosphatase / metabolism
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Animals
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins / chemistry
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Bone Morphogenetic Proteins / genetics
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Bone Morphogenetic Proteins / metabolism
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Bone Regeneration / physiology*
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Bone and Bones / cytology
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Bone and Bones / diagnostic imaging
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Bone and Bones / pathology
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Calcium Phosphates / chemistry*
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Calcium Phosphates / metabolism*
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Coated Materials, Biocompatible / chemistry*
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Coated Materials, Biocompatible / metabolism
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Dioxanes / chemistry
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Drug Delivery Systems
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Humans
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Isoenzymes / metabolism
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Lactic Acid / chemistry
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Male
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Mice
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Mice, Inbred Strains
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Microscopy, Electron, Scanning
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Polyesters
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Polyethylene Glycols / chemistry
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Polymers / chemistry
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Radiography
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Surface Properties
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Tartrate-Resistant Acid Phosphatase
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Time Factors
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Transforming Growth Factor beta / chemistry
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism
Substances
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BMP2 protein, human
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Bmp2 protein, mouse
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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Calcium Phosphates
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Coated Materials, Biocompatible
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Dioxanes
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Isoenzymes
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Polyesters
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Polymers
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Recombinant Proteins
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Transforming Growth Factor beta
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beta-tricalcium phosphate
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recombinant human bone morphogenetic protein-2
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Lactic Acid
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Polyethylene Glycols
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poly(lactide)
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Acid Phosphatase
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Acp5 protein, mouse
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Tartrate-Resistant Acid Phosphatase
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4-dioxanone