Delivery Mode and Efficacy of BMP-2 in Association with Implants

Bone healing may be improved in implant patients by the administration of osteogenic agents, such as bone morphogenetic protein 2 (BMP-2). But the efficacy of BMP-2 depends upon its mode of application. We hypothesized that BMP-2 is capable of a higher osteogenic efficacy when delivered physiologically, viz., when incorporated into a calcium-phosphate carrier that mimics mineralized bone matrix, than when administered via simple pharmacological modes, such as by adsorption onto a carrier surface. Using an ectopic rat model, we compared the osteoinductive efficacies of calcium-phosphate implant-coatings bearing either incorporated, adsorbed, or incorporated and adsorbed BMP-2. When adsorbed directly onto the naked implant surface, BMP-2 was not osteogenic. When adsorbed onto a calcium-phosphate coating, it was osteoinductive, but not highly efficacious. When BMP-2 was incorporated into calcium-phosphate coatings, it was a potent bone-inducer, whose efficacy was compromised, not potentiated, by the additional deposition of an adsorbed pool.

[1]  A G Mikos,et al.  Controlled release of rhBMP-2 loaded poly(dl-lactic-co-glycolic acid)/calcium phosphate cement composites in vivo. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[2]  E. Hunziker,et al.  BMP-2 liberated from biomimetic implant coatings induces and sustains direct ossification in an ectopic rat model. , 2005, Bone.

[3]  J. Jansen,et al.  Ectopic bone formation in rats: the importance of the carrier. , 2005, Biomaterials.

[4]  Pierre Layrolle,et al.  Bone morphogenetic protein 2 incorporated into biomimetic coatings retains its biological activity. , 2004, Tissue engineering.

[5]  E. Hunziker,et al.  Biomimetic Coatings vs. Collagen Sponges as a Carrier for BMP-2: A Comparison of the Osteogenic Responses Triggered In Vivo Using an Ectopic Rat Model , 2003 .

[6]  E. Hunziker,et al.  Introduction of Ectopic Bone Formation by BMP-2 Incorporated Biomimetically into Calcium Phosphate Coatings of Titanium-Alloy Implants , 2002 .

[7]  C. V. van Blitterswijk,et al.  Biomimetic coprecipitation of calcium phosphate and bovine serum albumin on titanium alloy. , 2001, Journal of biomedical materials research.

[8]  A. Reddi,et al.  Morphogenesis and tissue engineering of bone and cartilage: inductive signals, stem cells, and biomimetic biomaterials. , 2000, Tissue engineering.

[9]  C. V. van Blitterswijk,et al.  Biomimetic calcium phosphate coatings on Ti6AI4V: a crystal growth study of octacalcium phosphate and inhibition by Mg2+ and HCO3-. , 1999, Bone.

[10]  J. Wozney,et al.  Characterization of rhBMP-2 pharmacokinetics implanted with biomaterial carriers in the rat ectopic model. , 1999, Journal of biomedical materials research.

[11]  G. Karsenty,et al.  Cbfa1 as a regulator of osteoblast differentiation and function. , 1999, Bone.

[12]  D. Brunette,et al.  The effects of the surface topography of micromachined titanium substrata on cell behavior in vitro and in vivo. , 1999, Journal of biomechanical engineering.

[13]  D Buser,et al.  Bone response to unloaded and loaded titanium implants with a sandblasted and acid-etched surface: a histometric study in the canine mandible. , 1998, Journal of biomedical materials research.

[14]  L. Cruz-Orive,et al.  Comparison of the rate of phagocytosis of orthorhombic cyclosporine A (CsA) and latex particles by alveolar macrophages from hamsters , 1997, Cellular and Molecular Life Sciences CMLS.

[15]  I. Ono,et al.  Efficacy of hydroxyapatite ceramic as a carrier for recombinant human bone morphogenetic protein. , 1995, The Journal of craniofacial surgery.

[16]  M. Habal,et al.  Bone Grafts and Bone Substitutes , 1994 .

[17]  D Buser,et al.  Influence of surface characteristics on bone integration of titanium implants. A histomorphometric study in miniature pigs. , 1991, Journal of biomedical materials research.

[18]  T Kitsugi,et al.  Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W. , 1990, Journal of biomedical materials research.

[19]  K. deGroot Hydroxylapatite coated implants. , 1989 .

[20]  H J Gundersen,et al.  The efficiency of systematic sampling in stereology and its prediction * , 1987, Journal of microscopy.

[21]  L M Cruz-Orive,et al.  Estimation of surface area from vertical sections , 1986, Journal of microscopy.

[22]  P. Layrolle,et al.  Biomimetic Calcium Phosphate Coatings on Ti6Al4V: A Crystal Growth Study of Octacalcium Phosphate and , 1999 .

[23]  Meffert Rm Do implant surfaces make a difference , 1997 .

[24]  J. Hollinger,et al.  Poly(alpha-hydroxy acids): carriers for bone morphogenetic proteins. , 1996, Biomaterials.

[25]  K. Leong,et al.  Poly(α-hydroxy acids). Carriers for bone morphogenetic proteins , 1996 .

[26]  P. Patka,et al.  Long-term in vivo study of plasma-sprayed coatings on titanium alloys of tetracalcium phosphate, hydroxyapatite and alpha-tricalcium phosphate. , 1994, Biomaterials.

[27]  P. Patka,et al.  Long-term in vivo study of plasma-sprayed coatings on titanium alloys of tetracalcium phosphate, hydroxyapatite and α-tricalcium phosphate , 1994 .

[28]  高木 克公,et al.  牛骨のBone Morphogenetic Protein (BMP) による実験的ラット頭蓋骨欠損部の修復 , 1983 .