Hostname: page-component-7bb8b95d7b-l4ctd Total loading time: 0 Render date: 2024-10-04T04:21:52.432Z Has data issue: false hasContentIssue false

α-BSM™: A Calcium Phosphate Delivery Vehicle

Published online by Cambridge University Press:  15 February 2011

D. Knaack
Affiliation:
ETEX Corporation, University Park at MIT, 350 Massachusetts Avenue, Cambridge, MA 02139, Tel (617) 577-7270, Fax (617) 577-7170
D.D. Lee
Affiliation:
ETEX Corporation, University Park at MIT, 350 Massachusetts Avenue, Cambridge, MA 02139, Tel (617) 577-7270, Fax (617) 577-7170
Get access

Abstract

α-BSM™ is an injectable endothermically setting calcium phosphate bone substitute. α-BSM™ has been shown to be effective in promoting the healing of surgically created critical size defects and restoring bone biomechanical strength in several animal models. It has received regulatory clearance for orthopedic indications in both Canada and Europe and for dental and craniofacial indications in the United States.

α-BSM™ is distinguished as a bone substitute by its prolonged working time at room temperature, and rapid hardening at body temperature. These properties, as well as its compatibility with a variety of aqueous hydrating agents, make α-BSM™ an attractive vehicle for the in situ delivery of therapeutic agents. In vitro studies have shown that antibiotics, such as gentamicin, can be stably incorporated into α-BSM™ prior to and during hardening, and that delivery kinetics can be controlled with the appropriate formulation and preparative procedures. The setting reaction is also compatible with biologically active proteins. rhBMP-2 has been incorporated into α-BSM™ and was demonstrated to be effective in stimulating ectopic bone formation in soft tissue and accelerating the restoration of a differentiated phenotype in a rabbit osteotomy model.

Type
Research Article
Copyright
Copyright © Materials Research Society 1999

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Urist, M.R.: Experimental Delivery Systems for Bone Morphogenetic Protein. In Wise, D.L. (ed), et al. Encyclopedic Handbook of Biomaterials and Bioengineering. Part A-Materials. New York, Marcel Dekker 10931133, 1995.Google Scholar
2. Robinson, J.R., in Controlled Drug Delivery, edited by Park, K. (American Chemical Society, Washington D.C., 1997), pp. 17.Google Scholar
3. Hanes, J., Chiba, M., and Langer, R., in Vaccine Design: The Subunit and Adjuvant Approach, edited by Powell, M.F. and Newman, M.J. (Plenum Press, New York, 1995) pp. 389412.Google Scholar
4. Hnatyszyn, H.J., Kossovsky, N., Gelman, A., and Sponsler, E.: Drug Delivery Systems for the Future. PDA Journal of Pharmaceutical Science & Technology 48:247254, 1994.Google Scholar
5. Lasserre, A. and Bajpai, P.K.: Ceramic Drug-Delivery Devices. Critical Reviews in Therapeutic Drug Carrier Systems 15:156, 1998.Google Scholar
6. Toth, J. and Lynch, K.: Mechanical and Biological Characterization of Calcium Phospatesfor Use as Biomaterials. In Wise, D.L. (ed), et al. Encyclopedic Handbook of Biomaterials and Bioengineering. Part A-Material. New York, Marcel Dekker 14651499, 1995 Google Scholar
7. Hollinger, J.O., Battisone, G.C.: Biodegradable Bone Repair Materials. Synthetic Polymers and Ceramics, Clin Orthop 207:290305, 1986.Google Scholar
8. Jarcho, M.: Calcium Phosphate Ceramics as Hard Tissue Prosthetics. Clin Orthop Rel Res 157:259278, 1981.Google Scholar
9. Ongpipattanakul, B., Nguyen, T., Zioncheck, T.F., Wong, R., Osaka, G., DeGuzman, L., Lee, W.P., and Beck, L.S.: Development of Tricalcium Phosphate/Amylopectin Paste Combined With Recombinant Human Transforming Growth Factor Beta 1 as a Bone Defect Filler. J Biomed Mater Res 36:295305, 1997.Google Scholar
10. Guicheux, J., Gauthier, O., Aguado, E., Pilet, P., Couillaud, S., Jegou, D., Daculsi, G., and Heymann, D.: Human Growth Hormone Locally Released in Bone Sites by Calcium-Phosphate Biomaterial Stimulates Ceramic Bone Substitution Without Systemic Effects: A Rabbit Study. J Bone Miner Res 13:739748, 1998.Google Scholar
11. Koempel, J.A., Part, B.S., O'Grady, K., Wozney, J., and Toriumi, D.M.: The Effect of Recombinant Human Bone Morphogenetic Protein-2 on the Integration of Porous Hydroxyapatite Implants with Bone. J Biomed Mater Res 41: 15, 1998.Google Scholar
12. Ijiri, S., Nakamura, T., Fujisawa, Y., Hazama, M., and Komatsudani, S.: Ectopic Bone Induction in Porous Apatite-Wollastonite-Containing Glass Ceramic Combined with Bone Morphogenetic Protein. J Biomed Mater Res 35:421432, 1997.Google Scholar
13. Kuboki, Y., Takita, H., Kobayashi, D., Tsuruga, E., Inoue, M., Murata, M., Nagai, N., Dohi, Y., and Ohgushi, H.: BMP-Induced Osteogenesis on the Surface of Hydroxyapatite with Geometrically Feasible and Nonfeasible Structures: Topology of Osteogenesis. J Biomed Mater Res 39:190199, 1998.Google Scholar
14. Radin, S., Campbell, J.T., Ducheyne, P., and Cuckler, J.M.: Calcium Phosphate Ceramic Coatings as Carriers of Vancomycin. Biomaterials 18:777782, 1997.Google Scholar
15. Bohner, M., Lemaitre, J., Van Landuyt, P., Zambelli, P., Merkle, H.P., and Gander, B.: Gentamicin-Loaded Hydraulic Calcium Phosphate Bone Cement as Antibiotic Delivery System. J Pharm Sciences 86:565572, 1997.Google Scholar
16. Relyveld, E. and Chermann, JC: Humoral Response in Rabbits Immunized with Calcium Phosphate Adjuvanted HIV-1 gp160 Antigen. Biomed & Pharmacother 48:7983, 1994.Google Scholar
17. Relyveld, E.H.: Preparation and Use of Calcium Phosphate Adsorbed Vaccines. Develop. Biol. Standard 65:131136, 1986.Google Scholar
18. Itokazu, M., Sugiyama, T., Ohno, T., Wada, E., and Katagiri, Y.: Development of Porous Apatite Ceramic for Local Delivery of Chemotherapeutic Agents. J Biomed Mater Res 39: 536538, 1998.Google Scholar
19. Sciadini, M.F., Dawson, J.M., and Johnson, K.D.: Evaluation of Bovine-Derived Bone Protein with a Natural Coral Carrier as a Bone-Graft Substitute in a Canine Segmental Defect Model. J Orthop Res 15:844857, 1997.Google Scholar
20. Knaack, D, Goad, MEP, Aiolova, M, Rey, C., Tofighi, A, Chakravarthy, P, Lee, DD: A fully resorbable calcium phosphate bone substitute. J Biomed Mater Res (Appl Biomater) 43:399409, 1998.Google Scholar
21. Constanz, BR, Ison, IC, Fulmer, MT et al. : Skeletal repair by in situ formation of the mineral phase of bone. Science 267:17961799, 1995.Google Scholar
22. Brown, WE, Chow, LC: A new calcium phosphate setting cement. J Dent Res 62:672, 1983.Google Scholar
23. Driessens, FCM, Planell, JA, Gil, FJ: Calcium Phosphate Bone Cements. In Wise, DL (ed), et al. Encyclopedic Handbook of Biomaterials and Bioengineering. Part B - Applications. New York, Marcel Dekker 855877, 1995.Google Scholar
24. Wippermann, B, Schratt, HE, Donow, C, den Boer, FC: Vergleich von Alpha-BSM und Hydroxylapatitkeramikermik-Granulat (HA) in einem Tibiasegmentdefekt des Schafes, Abstract band der 61, Jahrestgung der Deutschen Gesellschaft fhr Unfallchirurgie e. V., 1922, Nov 1997.Google Scholar
25. Knaack, D, Goad, MEP, Aiolova, M et al. : Novel fully resorbable calcium phosphate bone substitute. J Bone Miner Res Suppl 1 12:202, 1997.Google Scholar
26. Knaack, D, Goad, MEP, Aiolova, M et al. : A fully resorbable calcium phosphate bone substitute. In Hollinger, JO (ed). Proceedings of the Portland Bone Symposium, 692708, 1997.Google Scholar
27. Goad, MEP, Aiolova, M, Tofighi, A, Jacobs, M, Lee, DD: Resorbable apatitic bone substitute material, Alpha BSM, is associated with rapid bone regrowth in defects of rabbit tibias. J Bone Miner Res Suppl 1 12:518, 1997.Google Scholar
28. Knaack, D, Aiolova, M, Tofighi, A, Catalano, A, Rey, C, Neis, B, Lee, DD: α-BSM™: A Resorbable Apatitic Calcium Phosphate Bone Substitute. Proceedings-of the 11th International Symposium on Ceramics in Medicine; New York, NY, USA. World Scientific Publishing Co., 357361, 1998.Google Scholar
29. Zegzula, HD, Buck, DC, Brekke, J, Wozney, JM, Hollinger, JO: Bone formation with use of rhBMP-2 (Recombinant Human Bone Morphogenetic Proteon-2). J Bone Joint Surg 79A:17791780, 1997.Google Scholar
30. United States Pharmacopeial Convention, Inc.: Antibiotics c Microbial Assays. In The United States Pharmacopeia, USP 23/NF 18. Rockville MD, 16901696, 1995.Google Scholar