Impact of Biomechanical Forces on Antibiotics Release Kinetics from Hydroxyapatite Coated Surgical Fixation Pins

Mirjam Lilja, Jan H. Sörensen, Torben C. Sörensen, Maria Åstrand, Philip Procter, Hartwig Steckel, Maria Strømme

Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Kiel, Germany;.
Division for Nanotechnology and Functional Materials, Department of Engineering Sciences, The ?ngstr?m Laboratory, Uppsala University, Uppsala, Sweden;.
Sandvik Coromant AB, Stockholm, Sweden;.
Stryker Trauma AG, Selzach, Switzerland;.
Stryker Trauma GmbH, Sch?nkirchen, Germany;.

DOI: 10.4236/jbnb.2013.44043                

Abstract

This work investigates the impact of biomechanical wear and abrasion on the antibiotic release profiles of hydroxyapatite (HA) coated fixation pins during their insertion into synthetic bone. Stainless steel fixation pins are coated with crystalline TiO₂ by cathodic arc evaporation forming the bioactive layer for biomimetic deposition of Tobramycin containing HA. Tobramycin is either introduced by co-precipitation during HA formation or by adsorption-loading after HA deposition. The samples containing antibiotics are inserted into bone mimicking polyethylene foam after which the drug release is monitored using high performance liquid chromatography. This analysis shows that HA coating wear and delamination significantly decrease the amount of drug released during initial burst, but only marginally influence the sustained release period. Spalled coating fragments are found to remain within the synthetic bone material structure. The presence of HA within this structure supports the assumption that the local release of Tobramycin is not only expected to eliminate bacteria growth directly at the pin interface but as well at some distance from the implant. Furthermore, no negative effect of gamma sterilization could be observed on the drug release profile. Overall, the observed results demonstrate the feasibility of a multifunctional implant coating that is simultaneously able to locally deliver clinically relevant doses of antibiotics and an HA coating capable of promoting osteoconduction. This is a potentially promising step toward orthopaedic devices that combine good fixation with the ability to treat and prevent post-surgical infections.

Keywords

Hydroxyapatite; Fixation Pin; Tobramycin; Coating Wear; Drug Release; Gamma Sterilization

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	J. Schalamon, T. Petnehazy, H. Ainoedhofer, E. B. Zwick, G. Singer and M. E. Hoellwarth, “Pin Tract Infection with External Fixation of Pediatric Fractures,” Journal of Pediatric Surgery, Vol. 42, No. 9, 2007, pp. 1584-1587. http://dx.doi.org/10.1016/j.jpedsurg.2007.04.022
[2]	T. Miclau, A. Remiger, S. Tepic and R. Lindsey, “Mechanical Comparison of the Dynamic Compression Plate, Limited Contact-Dynamic Compression Plate, and Point Contact Fixator,” Journal of Orthopaedic Trauma, Vol. 9, No. 1, 1995, pp. 17-22. http://dx.doi.org/10.1097/00005131-199502000-00003
[3]	J. Mahan, D. Seligson, S. L. Henry, P. Hynes and J. Dobbins, “Factors in Pin Tract Infections,” Orthopedics, Vol. 14, No. 3, 1991, pp. 305-308.
[4]	G. Pizá, V. L. Caja, M. A. Gonzalez-Viejo and A. Navarro, “Hydroxyapatite-Coated External-Fixation Pins: The Effect on Pin Loosening and Pin-Track Infection in Leg Lengthening for Short Stature,” Journal of Bone & Joint Surgery, Vol. 86B, No. 6, 2004, pp. 892-897. http://dx.doi.org/10.1302/0301-620X.86B6.13875
[5]	H. G. Ahlborg and P. O. Josefsson, “Pin-Tract Complications in External Fixation of Fractures of Distal Radius,” Acta Orthopaedica Scandinavica, Vol. 70, No. 2, 1999, pp. 116-118. http://dx.doi.org/10.3109/17453679909011246
[6]	A. Moroni, L. Orienti, S. Stea and M. Visentin, “Improvement of the Bone Pin Interface with Hydroxyapatite Coating: An in Vivo Long Term Experimental Study,” Journal of Orthopaedic Trauma, Vol. 10, No. 2, 1996, pp. 236-242. http://dx.doi.org/10.1097/00005131-199605000-00003
[7]	Y. C. Tsui, C. Doyle and T. W. Clyne, “Plasma Sprayed Hydroxyapatite Coatings on Titanium Substrates. Part 1: Mechanical Properties and Residual Stress Levels,” Biomaterials, Vol. 19, No. 22, 1998, pp. 2015-2029. http://dx.doi.org/10.1016/S0142-9612(98)00103-3
[8]	C. C. Berndt, G. N. Haddad, A. J. D. Farmer and K. A. Gross, “Thermal Spraying for Bioceramic Applications,” Materials Science Forum, Vol. 14, No. 3, 1990, pp. 161-173.
[9]	A. Moroni, F. Vannini, M. Mosca and S. Giannini, “State of the Art Review: Techniques to Avoid Pin Loosening and Infection in External Fixation,” Journal of Orthopaedic Trauma, Vol. 16, No. 3, 2002, pp. 189-195. http://dx.doi.org/10.1097/00005131-200203000-00009
[10]	R. Placzek, M. Ruffer, G. Deuretzbacher, E. Heijens and A. L. Meiss, “The Fixation Strength of HydroxyapatiteCoated Schanz Screws and Standard Stainless Steel Schanz Screws in Lower Extremity Lengthening: A Comparison Based on a New Torque Value Index: The Fixation Index,” Archives of Orthopaedic and Trauma Surgery, Vol. 126, No. 6, 2006, pp. 369-373. http://dx.doi.org/10.1007/s00402-006-0142-5
[11]	A. Pommer, G. Muhr and A. David, “HydroxyapatiteCoated Schanz Pins in External Fixators Used for Distraction Osteogenesis: A Randomized, Controlled Trial,” Journal of Bone and Joint Surgery, Vol. 84A, No. 7, 2002, pp. 1162-1166.
[12]	M. J. Raschke and G. Schmidmaier, “Biological Coating of Implants in Trauma and Orthopedic Surgery,” Unfallchirurg, Vol. 107, No. 8, 2004, pp. 653-663.
[13]	S. Piskounova, J. Forsgren, U. Brohede, H. Engqvist and M. Strømme, “In Vitro Characterization of Bioactive Titanium Dioxide/Hydroxyapatite Surfaces Functionalized with BMP-2,” Journal of Biomedical Materials Research Part B, Vol. 91B, No. 2, 2009, pp. 780-787. http://dx.doi.org/10.1002/jbm.b.31456
[14]	J. Forsgren, U. Brohede, H. Engqvist and M. Strømme, “Co-Loading of Bisphosphonates and Antibiotics to a Biomimetic Hydroxyapatite Coating,” Biotechnology Letters, Vol. 33, No. 6, 2011, pp. 1265-1268. http://dx.doi.org/10.1007/s10529-011-0542-7
[15]	M. Lilja, J. Sorensen, U. Brohede, M. Astrand, J. Arnoldi, P. Procter, H. Steckel and M. Strømme, “Drug Loading and Release of Tobramycin from Hydroxyapatite Coated Fixation Pins,” Journal of Materials Science: Materials in Medicine, Vol. 24, No. 9, 2013, pp. 2265-2274. http://dx.doi.org/10.1007/s10856-013-4979-1
[16]	U. Brohede, J. Forsgren, S. Roos, A. Mihranyan, H. Engqvist and M. Strømme, “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. 1859-1867. http://dx.doi.org/10.1007/s10856-009-3749-6
[17]	J. Forsgren, U. Brohede, S. Piskounova, A. Mihranyan, S. Larsson, M. Strømme and H. Engqvist, “In Vivo Evaluation of Functionalized Biomimetic Hydroxyapatite for Local Delivery of Active Agents,” Journal of Biomaterials and Nanobiotechnology, Vol. 2, No. 2, 2011, pp. 149-154. http://dx.doi.org/10.4236/jbnb.2011.22019
[18]	M. Lilja, J. Forsgren, K. Welch, M. Astrand, H. Engqvist and M. Strømme, “Photocatalytic and Antimicrobial Properties of Surgical Implant Coatings of Titanium Dioxide Deposited though Cathodic Arc Evaporation,” Biotechnology Letters, Vol. 34, No. 12, 2012, pp. 2299-2305. http://dx.doi.org/10.1007/s10529-012-1040-2
[19]	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. http://dx.doi.org/10.4236/jbnb.2013.43029
[20]	J. Aberg, U. Brohede, A. Mihranyan, M. Strømme 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. http://dx.doi.org/10.1007/s10856-009-3771-8
[21]	L. Sun, C. C. Berndt, K. A. Gross and A. Kucuk, “Material Fundamentals and Clinical Performance of Plasma-Sprayed Hydroxyapatite Coatings: A Review,” Journal of Biomedical Materials Research, Vol. 58, No. 5, 2001, pp. 570-592. http://dx.doi.org/10.1002/jbm.1056
[22]	H. W. Debissen, W. Kalk, H. M. de Nieuport, J. C. Maltha and A van deHooff, “Mandibular Bone Response to Plasma Sprayed Coatings of Hydroxyapatite,” International Journal of Prosthodontics, Vol. 3, No. 1, 1990, pp. 53-58.
[23]	A. David, J. Eitenmueller, G. Muhr, A. Pommer, H. F. Baer, P. A. W. Ostermann and T. A. Schildhauer, “Mechanical and Histological Evaluation of Hydroxyapatite-Coated, Titanium-Coated and Grit Blasted Surfaces under Weight-Bearing Conditions,” Archives of Orthopaedic and Trauma Surgery, Vol. 114, No. 2, 1995, pp. 112-118. http://dx.doi.org/10.1007/BF00422838
[24]	R. J. Friedman, J. Black, K. A. Gustke, W. M. Braunohler, W.D. Guyer and C. Savory, “Four to Six Year Results of Hydroxyapatite Total Hip Arthroplasty,” 20th Annual Meeting of The Society of Biomaterials, 1994, p. 37.
[25]	H. Kurzweg, R. B. Heimann, T. Troczynski and M. L. Wayman, “Development of Plasma-Sprayed Bioceramics Coatings with Bond Coats Based on Titania and Zirconia,” Biomaterials, Vol. 19, No. 16, 1998, pp. 1507-1511. http://dx.doi.org/10.1016/S0142-9612(98)00067-2
[26]	W. N Capello and T. W. Bauer, “Hydroxyapatite in Orthopedic Surgery,” In: H. U. Cameron, Ed., Bone Implant Interface, C.V. Mosby, St. Louis, 1994, pp. 191-202.
[27]	T. W. Bauer, “Hydroxyapatite: Coating Controversies,” Orthopedics, Vol. 18, No. 9, 1995, pp. 885-888.
[28]	J. Sorensen, M. Lilja, T. Sorensen, M. Astrand, P. Procter, M. Strømme and H. Steckel, “Co-Precipitation of Tobramycin into Hydroxyapatite Coatings,” unpublished.
[29]	K. A. Gross and M. Babovic, “Influence of Abrasion on the Surface Characteristics of Thermally Sprayed Hydroxyapatite Coatings,” Biomaterials, Vol. 23, No. 24, 2002, pp. 4731-4737. http://dx.doi.org/10.1016/S0142-9612(02)00222-3
[30]	M. Lilja, K. Welch, M. Astrand, H. Engqvist and M. Strømme, “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 Part B, Vol. 100, No. 4, 2012, pp. 1078-1085. http://dx.doi.org/10.1002/jbm.b.32674
[31]	A. Mihranyan, J. Forsgren, M. Strømme and H. Engqvist, “Assessing Surface Area Evolution during Biomimetic Growth of Hydroxyapatite Coatings,” Langmuir, Vol. 25, No. 3, 2009, pp. 1292-1295. http://dx.doi.org/10.1021/la803520k
[32]	J. Sorensen, M. Lilja, T. Sorensen, M. Astrand, P. Procter, M. Strømme and H. Steckel, “Biomechanical and Antbacterial Properties of Hydroxyapatite Coated Fixation Pins,” unpublished.
[33]	“HPLC Detection of Gentamicin Sulphate,” In: British Pharmacopoeia, London, England, 1999, pp. 695-697.
[34]	H. Fabre, M. Sekkat, M. D. Blanchin and B. Mandrou, “Determination of Aminoglycosides in Pharmaceutical Formulations-II. High-Performance Liquid Chromatography,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 7, No. 12, 1989, pp. 1711-1718. http://dx.doi.org/10.1016/0731-7085(89)80185-2
[35]	M. D’Arrigo, G. Ginestra, G. Mandalari and P. M. Furneri, “Synergism and Postantibiotic Effect of Tobramycin and Melaleuca alternifolia (teatree) Oil against Staphylococcus aureus and Escherichia coli,” Phytomedicine, Vol. 17, No. 5, 2010, pp. 317-322. http://dx.doi.org/10.1016/j.phymed.2009.07.008
[36]	S. Ban, S. Maruno, N. Arimoto, A. Harada and J. Hasegawa, “Effect of Electrochemically Deposited Apatite Coating on Bonding of Bone to the HA-G-Ti Composite and Titanium,” Journal of Biomedical Materials Research, Vol. 36, No. 1, 1997, pp. 9-15. http://dx.doi.org/10.1002/(SICI)1097-4636(199707)36:1<9::AID-JBM2>3.0.CO;2-P
[37]	J. H. Lee, H. S. Ryu, K. S. Hong, D. S. Lee, K. B. S. Chang and C. K. Lee, “Biomechanical and Histomorphometric Study on the Bone-Screw Interface of Bioactive Ceramic-Coated Titanium Screws,” Biomaterials, Vol. 26, No. 16, 2005, pp. 3249-3257. http://dx.doi.org/10.1016/j.biomaterials.2004.08.033
[38]	U. Brohede, S. Zhao, F. Lindberg A. Mihranyan, J. Forsgren, M. Strømme and H. Engqvist, “A Novel Graded Bioactive High Adhesion Implant Coating,” Applied Surface Science, Vol. 225, No. 17, 2009, pp. 7723-7728. http://dx.doi.org/10.1016/j.apsusc.2009.04.149
[39]	A. Kuhn, T. McIff, J. Cordey, F. W. Baumgart and B. A. Rahn, “Bone Deformation by Thread-Cutting and ThreadForming Cortex Screws,” Injury, Vol. 26, No. 1, 1995, pp. 12-20. http://dx.doi.org/10.1016/0020-1383(95)90117-5
[40]	A. W. Kwok, J. A. Finkelstein, T. Woodside, T. C. Hearn and R. W. Hu, “Insertional Torque and Pull-Out Strengths of Conical and Cylindrical Pedicle Screws in Cadaveric Bone,” Spine, Vol. 21, No. 1, 1996, pp. 2429-2434. http://dx.doi.org/10.1097/00007632-199611010-00004
[41]	A. F. Tencer and K. D. Johnson, “Biomechanics in Orthopedic Trauma,” In: Bone Fracture and Fixation, M. Dunitz, Ltd, London, 1994, pp. 118-157.
[42]	M. Capper, C. Soutis and O. O. A. Onit, “Comparison of the Stresses Generated at the Pin-Bone Interface by Standard and Conical External Fixator Pins,” Biomaterials, Vol. 15, No. 6, pp. 471-473. http://dx.doi.org/10.1016/0142-9612(94)90227-5
[43]	A. Koistinen, S. S. Santavirta, H. Kroger and R. Lappalainen, “Effect of Bone Mineral Density and Amorphous Diamond Coatings on Insertion Torque of Bone Screws,” Biomaterials, Vol. 26, No. 28, 2005, pp. 5687-5694. http://dx.doi.org/10.1016/j.biomaterials.2005.02.003
[44]	S. M. T. Chan, C. P. Neu, K. Komvopoulos and A. H. Redd, “The Role of Lubricant Entrapment at Biological Interfaces: Reduction of Friction and Adhesion in Articular Cartilage,” Journal of Biomechanics, Vol. 44, No. 11, 2011, pp. 2015-2020. http://dx.doi.org/10.1016/j.jbiomech.2011.04.015