The Effect of Si-Doping on the Release of Antibiotic from Hydroxyapatite Coatings

Abstract

Herein, we show that incorporation of ions during biomimetic coating deposition may be utilized to tailor the drug loading capacity of hydroxyapatite (HA) coatings. Pure biomimetic HA (HA-B) and Si-doped equivalents (SiHA-B) where deposited by a biomimetic process onto titanium dioxide covered titanium substrates. The antibiotic Cephalothin was incorporated into the coatings by adsorptive loading and the release was studied in-vitro. SiHA-B coatings exhibited superior drug incorporation capacity compared to pure HA-B coatings, resulting in a drug release profile dominated by an initial 10 min burst effect while a more prolonged 10 hour release was observed from HA-B coatings. The results emphasize the possibility to impact the drug release kinetics from implant coatings by selective doping elements and the use of thin, biomimetic HA-coatings as drug delivery vehicles. Functionalizing metal implants with SiHA-B coatings presents an interesting strategy towards creating synergetic effects through ion- and antibiotic release and, hence, contributing both towards preventing post-surgical infections while at the same time enhancing the bone-bonding ability.

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M. Lilja, C. Lindahl, W. Xia, H. Engqvist and M. Strømme, "The Effect of Si-Doping on the Release of Antibiotic from Hydroxyapatite Coatings," Journal of Biomaterials and Nanobiotechnology, Vol. 4 No. 3, 2013, pp. 237-241. doi: 10.4236/jbnb.2013.43029.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] K. Degroot, R. Geesink, C. Klein and P. Serekain, “Plasma Sprayed Coatings of Hydroxyapatite,” Journal of Biomedical Materials Research, Vol. 21, No. 12, 1992, pp. 1375-1381.
[2] W. Jaffe and D. Scott, “Total Hip Arthroplasty with Hydroxyapatite-Coated Prosthesis,” Journal of Bone and Joint Surgery, Vol. 78, No. 12, 1996, pp. 1918-1934.
[3] J. H. Shepherd, D. V. Shepherd and S. M. Best, “Substituted Hydroxyapatites for Bone Repair,” Journal of Materials Science—Materials in Medicine, Vol. 23, No. 10, 2012, pp. 2335-2347.
[4] M. Vallet-Regi and D. Arcos, “Silicon Substituted Hydroxyapatites. A Method to Upgrade Calcium Phosphate Based Implants,” Materials Chemistry, Vol. 15, 2005, pp. 1509-1516.
[5] A. Oliveira, R. Reis and P. Li, “Strontium-Substituted Apatite Coating Grown on Ti6Al4V Substrate through Biomimetic Synthesis,” Journal of Biomedical Materials Research B, Vol. 83, No. 1, 2007, pp. 258-265.
[6] S. Cazalbou, C. Combes and C. Rey, “Biomimetic Approach for Strontium Containing Ca-P Bioceramics with Enhanced Biological Activity,” Key Engineering Materials, Vol. 92, No. 13, 2001, pp. 192-195.
[7] P. Ritger and N. Peppas, “A Simple Equation for Description of Solute Release I. Fickian and Non-Fickian Release from Non-Swellable Devices in the Form of Slabs, Spheres, Cylinders or Discs,” Journal of Control Release, Vol. 5, No. 1, 1987, pp. 23-36.
[8] N. Peppas, “Analysis of Fickian and Non-Fickian Drug Release from Polymers, “Pharmaceutica Acta Helvetiae, Vol. 60, No. 4, 1985, pp. 110-111.
[9] E. Zhang and C. Zou, “Porous Titanium and Silicon-Substituted Hydroxyapatite Biomodification Prepared by a Biomimetic Process: Characterization and in Vivo Evaluation,” Acta Biomaterialia, Vol. 5, No. 5, 2009, pp. 1732-1741.
[10] K. Schantz and D. B. Milne, “Growth-Promoting Effects of Silicon in Rats,” Nature, Vol. 239, No. 5371, 1972, pp. 333-334.
[11] K. A. Hing, P. A. Revell, N. Smith and T. Buckland, “Effect of Silicon Level on Rate, Quality and Progression of Bone Healing within Silicate-Substituted Porous Hydroxyapatite Scaffolds,” Biomaterials, Vol. 27, No. 29, 2006; pp. 5014-5026.
[12] M. Stigter, J. Bezemer, K. de Groot and P. Layrolle, “Incorporation of Different Antibiotics into Carbonated Hydroxyapatite Coatings on Titanium Implants, Release and Antibiotic Efficacy,” Journal of Control Release, Vol. 99, No. 1, 2004, pp. 127-137.
[13] S. Piskounova, J. Forsgren, U. Brohede, H. Engqvist and M. Str?mme, “In Vitro Characterization of Bioactive Titanium Dioxide/Hydroxyapatite Surfaces Functionalized with BMP-2,” Journal of Biomedical Materials Research B, Vol. 91B, No. 2, 2009, pp. 780-787.
[14] J. Forsgren, U. Brohede, H. Engqvist and M. Str?mme, “Co-Loading of Bisphosphonates and Antibiotics to a Biomimetic Hydroxyapatite Coating,” Biotechnological Letters, Vol. 33, No. 6, 2011, pp. 1265-1268.
[15] M. Lilja, J. S?rensen, U. Brohede, M. ?strand, J. Arnoldi, P. Procter, H. Steckel and M. Str?mme, “Drug Loading and Release of Tobramycin from Hydroxyapatite Coated Fixation Pins,” Journal of Materials Science—Materials in Medicine, 2013, in press. doi:10.1007/s10856-013-4979-1
[16] M. Stigter, K. de Groot and P. Layrolle, “Incorporation of Tobramycin into Biomimetic Hydroxyapatite Coating on Titanium,” Biomaterials, Vol. 23, No. 20, 2002, pp. 4143-4153.
[17] U. Brohede, J. Forsgren, S. Roos, A. Mihranyan, H. Engqvist and M. Str?mme, “Multifunctional Implant Coatings Providing Possibilities for Fast Antibiotics Loading with Subsequent Slow Release,” Journal of Materials Science —Materials in Medicine, Vol. 20, No. 9, 2009, pp. 18591867.
[18] J. ?berg, U. Brohede, A. Mihranyan, M. Str?mme and H. Engqvist, “Bisphosphonate Incorporation in Surgical Implant Coatings by Fast Loading and Co-Precipitation at Low Drug Concentrations,” Journal of Materials Science —Materials in Medicine, Vol. 20, No. 10, 2009, pp. 2053-2061.
[19] J. Forsgren, U. Brohede, S. Piskounova, A. Mihranyan, S. Larsson, M. Str?mme and H. Engqvist, “In Vivo Evaluation of Functionalized Biomimetic Hydroxyapatite for Local Delivery of Active Agents,” Biomater Nanobiotech, Vol. 2, No. 2, 2011, pp. 149-154.
[20] A. Mihranyan, J. Forsgren, M. Str?mme and H. Engqvist, “Assessing Surface Area Evolution during Biomimetic Growth of Hydroxyapatite Coatings,” Langmuir, Vol. 25, No. 3, 2009, pp. 1292-1295.
[21] T. Kokubo, H. Kushitani, S. Sakka, T. Kitsugi and T. Yamamuro, “Solutions Able to Reproduce in Vivo SurfaceStructure Changes in Bioactive Glass-Ceramic A-W,” Journal of Biomedical Materials Research, Vol. 4, No. 6, 1990, pp. 721-734.
[22] S. Kuroda, A. S. Virdi, P. Li, K. E. Healy and D. R. Sumner, “A Low Temperature Biomimetic Calcium Phosphate Surface Enhances Early Implant Fixation in a Rat Model,” Journal of Biomedical Materials Research, Vol. 70A, No. 1, 2004, pp. 66-73.
[23] B. C. Yang, M. Uchidab, H. M. Kimc, X. Zhanga and T. Kokubo, “Preparation of Bioactive Titanium Metal via Anodic Oxidation Treatment,” Biomaterials, Vol. 25, No. 6, 2004, pp. 1003-1010.
[24] W. Zhou, X. Zhong, X. Wu, L. Yaun, Q. Shu, Y. Xia and K. Ostrikov, “Plasma-Controlled Nanocrystallinity and Phase Composition of TiO2: A Smart Way to Enhance Biomimetic Response,” Journal of Biomedical Materials Research, Vol. 81A, No. 2, 2007, pp. 453-464.
[25] U. Brohede, S. Zhao, F. Lindberg A. Mihranyan, J. Forsgren, M. Str?mme and H. Engqvist, “A Novel Graded Bioactive High Adhesion Implant Coating,” Applied Surface Science, Vol. 225, No. 17, 2009, pp. 7723-7728.
[26] M. Lilja, A. Genvad, M. ?strand, M. Str?mme and H. Engqvist, “Influence of Microstructure and Chemical Composition of Sputter Deposited TiO2 Thin Films on in Vitro Bioactivity,” Journal of Materials Science—Materials in Medicine, Vol. 22, No. 12, 2011, pp. 2727-2734.
[27] A. Lebugle, A. Rodrigues, P. Bonnevialle, J. J. Voigt, P. Canal and F. Rodriguez, “Study of Implantable Calcium Phosphate Systems for the Slow Release of Metho-Trexate,” Biomaterials, Vol. 23, No. 16, 2002, pp. 3517-3522.
[28] A. E. Burgos, J. C. Belchior and R. D. Sinisterra, “Controlled Release of Rhodium (II) Carboxylates and Their Association Complexes with Cyclodextrins from HydroxyApatite Matrix,” Biomaterials, Vol. 23, No. 12, 2002, pp. 2519-2526.
[29] I. Gibson, S. Best and W. Bonfield, “Chemical Characterization of Silicon-Substituted Hydroxyapatite,” Journal of Biomedical Materials Research, Vol. 44, No. 4, 1996, pp. 422-428.
[30] M. Lilja, K. Welch, M. ?strand, H. Engqvist and M. Str?mme, “Effect of Deposition Parameters on the Photocatalytic Activity and Bioactivity of TiO2 Thin Films Deposited by Vacuum Arc on Ti-6Al-4V Substrates,” Journal of Biomedical Materials Research B, Vol. 100, No. 4, 2012, pp. 1078-1085.
[31] W. Xia, C. Lindahl, C. Persson, P. Thomsen, J. Lausmaa and H. Engqvist, “Changes of Surface Composition and Morphology after Incorporation of Ions into Biomimetic Apatite Coatings,” Journal of Biomaterials and Nanobiotechnology, Vol. 1, No. 1, 2010, pp. 7-16.
[32] C. Lindahl, W. Xia, J. Lausmaa, P. Borchardt and H. Engqvist, “Strontium and Silicon Co-Doped Apatite Coating: Preparation and Function as Vehicles for Ion Delivery,” Journal of Biomaterials and Nanobiotechnology, Vol. 3, No. 3, 2012, pp. 335-341.
[33] C. M. Botelho, M. A. Lopes, I. R. Gibson, S. M. Best and J. D. Santos, “Structural Analysis of Si-Substituted Hydroxyapatite: Zeta Potential and X-Ray Photoelectron Spectroscopy,” Journal of Materials Science—Materials in Medicine, Vol. 13, No. 12, 2002, pp. 1123-1127.
[34] W. H. Streng, “Microionization Constants of Commercial Cephalosporins,” Journal of Pharmaceutical Sciences, Vol. 67, No. 5, 1978, pp. 666-669.
[35] B. Palazzo, M. Iafisco, M. Laforgia, N. Margiotta, G. Natile, C. L. Bianchi, D. Walsh, S. Mann and N. Roveri, “Biomimetic Hydroxyapatite-Drug Nanocrystals as Potential Bone Substitutes with Antitumor Drug Delivery Properties,” Advanced Functional Materials, Vol. 17, No. 13, 2007, pp. 2180-2188.
[36] T. Leventouri, C. E. Bunaciu and V. Perdikatsis, “Neutron Powder Diffraction Studies of Silicon-Substituted Hydroxyapatite,” Biomaterials, Vol. 24, No. 23, 2003, pp. 4205-4211.
[37] C. Lindahl, W. Xia, J. Lausmaa and H. Engqvist, “Incorporation of Active Ions into Calcium Phosphate Coatings, Their Release Behavior and Mechanism,” Biomedical Materials, Vol. 7, No. 4, 2012, Article ID: 045018.
[38] G. D. Venkatasubbu, S. Ramasamy, V. Ramakrishnan and J. Kumar, “Nanocrystallinehydroxyapatite and Zinc-Doped Hydroxyapatite as Carrier Material for Controlled Delivery of Ciprofloxacin,” Biotech, Vol. 1, No. 3, 2011, pp. 173-186.
[39] Y. Liu, P. Layrolle, J. de Bruijn, C. van Blitterswijk and K. de Groot, “Biomimetic Coprecipitation of Calcium Phosphate and Bovine Serum Albumin on Titanium Alloy,” Journal of Biomedical Materials Research, Vol. 57, No. 3, 2001, pp. 327-335.

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