Bone inductive properties of rhBMP-2 loaded porous calcium phosphate cement implants in cranial defects in rabbits.
In this study, the osteoinductive properties of porous calcium phosphate (Ca-P) cement loaded with bone morphogenetic protein 2 (rhBMP-2) were evaluated and compared with rhBMP-2 loaded absorbable collagen sponge (ACS). Discs with a diameter of 8mm were loaded with a buffer solution with or without 10 microg rhBMP-2 and inserted in 8mm full thickness cranial defects in rabbits for 2 and 10 weeks of implantation. Histological analysis revealed excellent osteoconductive properties of the Ca-P material. It maintained its shape and stability during the implantation time better than the ACS but showed no degradation like the ACS. Quantification of the Ca-P cement implants showed that bone formation was increased significantly by administration of rhBMP-2 (10 weeks pore fill: 53.0+/-5.4%), and also reached a reasonable amount without rhBMP-2 (43.1+/-10.4%). Remarkably, callus-like bone formation outside the implant was observed frequently in the 2 weeks rhBMP-2 loaded Ca-P cement implants, suggesting a correlation with the presence of growth factor in the surrounding tissue. However, an additional in vitro assay revealed an accumulative release of no more than 9.7+/-0.9% after 4 weeks. We conclude that: (1). Porous Ca-P cement is an appropriate candidate scaffold material for bone engineering. (2). Bone formation can be enhanced by lyophilization of rhBMP-2 on the cement. (3). Degradation of porous Ca-P cement is species-, implantation site- and implant dimension-specific.
Ruhé
P Quinten
PQ
University Medical Center, Department of Biomaterials, PO Box 9101, THK 117, 6500 HB, Nijmegen, Netherlands.
Kroese-Deutman
Henriette C
HC
Wolke
Joop G C
JG
Spauwen
Paul H M
PH
Jansen
John A
JA
D000818:Animals; D001843:Bone Cements / Q000627:therapeutic use*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D018786:Bone Substitutes / Q000627:therapeutic use*; D002130:Calcium Phosphates / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D020007:Implants, Experimental; D008422:Materials Testing; D010012:Osteogenesis / Q000187:drug effects*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D012887:Skull Fractures / Q000473:pathology* / Q000628:therapy*; D016212:Transforming Growth Factor beta; D016896:Treatment Outcome
D001843:Bone Cements; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D002130:Calcium Phosphates; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C020243:calcium phosphate