Biomimetic Hydroxyapatite Coated Titanium Screws Demonstrate Rapid Implant Stabilization and Safe Removal In-Vivo
Author(s)
Jan Henrik Sörensen1,
Lutz Dürselen2,
Ken Welch3,
Torben Christian Sörensen4,
Philip Procter5,
Håkan Engqvist6,
Maria Strømme3,
Anita Ignatius2,
Hartwig Steckel1*
Affiliation(s)
1 Department of Pharmaceutics and Biopharmaceutics, Christian-Albrechts University, Kiel, Germany. 2 Institute of Orthopaedic Research and Biomechanics, Centre of Musculoskeletal Research, Ulm, Germany. 3 Division for Nanotechnology and Functional Materials, The Ångström Laboratory, Uppsala University, Uppsala, Sweden. 4 Stryker Trauma GmbH, Schönkirchen, Germany. 5 Stryker Trauma AG, Selzach, Switzerland. 6 Division for Applied Materials Sciences, The Ångström Laboratory, Uppsala University, Uppsala, Sweden.
1 Department of Pharmaceutics and Biopharmaceutics, Christian-Albrechts University, Kiel, Germany. 2 Institute of Orthopaedic Research and Biomechanics, Centre of Musculoskeletal Research, Ulm, Germany. 3 Division for Nanotechnology and Functional Materials, The Ångström Laboratory, Uppsala University, Uppsala, Sweden. 4 Stryker Trauma GmbH, Schönkirchen, Germany. 5 Stryker Trauma AG, Selzach, Switzerland. 6 Division for Applied Materials Sciences, The Ångström Laboratory, Uppsala University, Uppsala, Sweden.
ABSTRACT
The early fixation of bone screws after surgical implantation still remains a challenge in the field of traumatology. Whilst hydroxyapatite (HA) coatings are known to enhance the fixation of implants; their removal at a later time-point may be problematic. An HA coating has been developed to demonstrate that both implant fixation and safe removal are feasible in the same design. Accordingly the aim of this study was to compare the In-Vivo performance of thin biomimetic HA coated titanium screws to uncoated counterparts used as control after bilateral implantation in the femoral condyle of 36 New Zealand White Rabbits. The screws were analysed macroscopically, by histology, micro-CT and biomechanically at both two and six weeks post-implantation. The HA coated screws demonstrated excellent biocompatibility. At two weeks the HA coated screws demonstrated a significant increase in removal torque values as well as a strong trend towards higher pull-out forces. In addition histology confirmed a higher degree of osseointegration and direct bone to implant contact. At six weeks no difference in pull-out force and removal torque could be detected. SEM images confirmed the absence of any residual HA coating indicating a fast coating degradation In-Vivo. The low level of removal torque after full osseointegration at 6 weeks supports the feasibility of safe and easy removal of the implant. The HA coating under study appears to offer a unique characteristic of enhanced fixation with a minimal increase in removal torque after full osseointegration. This may be of value in clinical applications where it is necessary to assure both screw fixation and later removal.
The early fixation of bone screws after surgical implantation still remains a challenge in the field of traumatology. Whilst hydroxyapatite (HA) coatings are known to enhance the fixation of implants; their removal at a later time-point may be problematic. An HA coating has been developed to demonstrate that both implant fixation and safe removal are feasible in the same design. Accordingly the aim of this study was to compare the In-Vivo performance of thin biomimetic HA coated titanium screws to uncoated counterparts used as control after bilateral implantation in the femoral condyle of 36 New Zealand White Rabbits. The screws were analysed macroscopically, by histology, micro-CT and biomechanically at both two and six weeks post-implantation. The HA coated screws demonstrated excellent biocompatibility. At two weeks the HA coated screws demonstrated a significant increase in removal torque values as well as a strong trend towards higher pull-out forces. In addition histology confirmed a higher degree of osseointegration and direct bone to implant contact. At six weeks no difference in pull-out force and removal torque could be detected. SEM images confirmed the absence of any residual HA coating indicating a fast coating degradation In-Vivo. The low level of removal torque after full osseointegration at 6 weeks supports the feasibility of safe and easy removal of the implant. The HA coating under study appears to offer a unique characteristic of enhanced fixation with a minimal increase in removal torque after full osseointegration. This may be of value in clinical applications where it is necessary to assure both screw fixation and later removal.
Cite this paper
Sörensen, J. , Dürselen, L. , Welch, K. , Sörensen, T. , Procter, P. , Engqvist, H. , Strømme, M. , Ignatius, A. and Steckel, H. (2015) Biomimetic Hydroxyapatite Coated Titanium Screws Demonstrate Rapid Implant Stabilization and Safe Removal In-Vivo. Journal of Biomaterials and Nanobiotechnology, 6, 20-35. doi: 10.4236/jbnb.2015.61003.
Sörensen, J. , Dürselen, L. , Welch, K. , Sörensen, T. , Procter, P. , Engqvist, H. , Strømme, M. , Ignatius, A. and Steckel, H. (2015) Biomimetic Hydroxyapatite Coated Titanium Screws Demonstrate Rapid Implant Stabilization and Safe Removal In-Vivo. Journal of Biomaterials and Nanobiotechnology, 6, 20-35. doi: 10.4236/jbnb.2015.61003.
References
[1] Krappinger, D., Bizzotto, N., Riedmann, S., Kammerlander, C., Hengg, C. and Kralinger, F.S. (2011) Predicting Failure after Surgical Fixation of Proximal Humerus Fractures. Injury, 42, 1283-1288.
http://dx.doi.org/10.1016/j.injury.2011.01.017 [2] Adams, C.I., Robinson, C.M., Court-Brown, C.M. and McQueen, M.M. (2001) Prospective Randomized Controlled Trial of an Intramedullary Nail versus Dynamic Screw and Plate for Intertrochanteric Fractures of the Femur. Journal of Orthopaedic Trauma, 15, 394-400.
http://dx.doi.org/10.1097/00005131-200108000-00003 [3] Basler, S.E., Traxler, J., Müller, R. and van Lenthe, G.H. (2013) Peri-Implant Bone Microstructure Determines Dynamic Implant Cut-Out. Medical Engineering & Physics, 35, 1442-1449.
http://dx.doi.org/10.1016/j.medengphy.2013.03.016 [4] Windolf, M., Braunstein, V., Dutoit, C. and Schwieger, K. (2009) Is a Helical Shaped Implant a Superior Alternative to the Dynamic Hip Screw for Unstable Femoral Neck Fractures? A Biomechanical Investigation. Clinical Biomechanics, 24, 59-64. http://dx.doi.org/10.1016/j.clinbiomech.2008.07.004 [5] Fakler, J.K.M., Hogan, C., Heyde, C.E. and John, T. (2008) Current Concepts in the Treatment of Proximal Humeral Fractures. Orthopedics, 31, 42-51. http://dx.doi.org/10.3928/01477447-20080101-13 [6] Dhert, W.J., Thomsen, P., Blomgren, A.K., Esposito, M., Ericson, L.E. and Verbout, A.J. (1998) Integration of Press- Fit Implants in Cortical Bone: A Study on Interface Kinetics. Journal of Biomedical Materials Research, 41, 574-583.
http://dx.doi.org/10.1002/(SICI)1097-4636(19980915)41:4<574::AID-JBM9>3.0.CO;2-9 [7] Slaets, E., Carmeliet, G., Naert, I. and Duyck, J. (2006) Early Cellular Responses in Cortical Bone Healing around Unloaded Titanium Implants: An Animal Study. Journal of Periodontology, 77, 1015-1024.
http://dx.doi.org/10.1902/jop.2006.050196 [8] Heimann, R.B. (2013) Structure, Properties, and Biomedical Performance of Osteoconductive Bioceramic Coatings. Surface and Coatings Technology, 233, 27-38.
http://dx.doi.org/10.1016/j.surfcoat.2012.11.013 [9] Moroni, A., Caja, V.L., Egger, E.L., Trinchese, L. and Chao, E.Y. (1994) Histomorphometry of Hydroxyapatite Coated and Uncoated Porous Titanium Bone Implants. Biomaterials, 15, 926-930.
http://dx.doi.org/10.1016/0142-9612(94)90119-8 [10] Kusakabe, H., Sakamaki, T., Nihei, K., Oyama, Y., Yanagimoto, S., Ichimiya, M., et al. (2004) Osseointegration of a Hydroxyapatite-Coated Multilayered Mesh Stem. Biomaterials, 25, 2957-2969.
http://dx.doi.org/10.1016/j.biomaterials.2003.09.090 [11] Hasegawa, M., Sudo, A., Komlev, V.S., Barinov, S.M. and Uchida, A. (2004) High Release of Antibiotic from a Novel Hydroxyapatite with Bimodal Pore Size Distribution. Journal of Biomedical Materials Research, 70, 332-339.
http://dx.doi.org/10.1002/jbm.b.30047 [12] Sörensen, T.C., Arnoldi, J., Procter, P., Beimel, C., Jönsson, A., Lennerås, M., et al. (2013) Locally Enhanced Early Bone Formation of Zoledronic Acid Incorporated into a Bone Cement Plug in Vivo. Journal of Pharmacy and Pharmacology, 65, 201-212.
http://dx.doi.org/10.1111/j.2042-7158.2012.01588.x [13] Forsgren, J., Brohede, U., Piscounova, S., Mihranyan, A., Larsson, S., StrØmme, M., et al. (2011) In Vivo Evaluation of Functionalized Biomimetic Hydroxyapatite for Local Delivery of Active Agents. Journal of Biomaterials and Nanobiotechnology, 2, 149-154.
http://dx.doi.org/10.4236/jbnb.2011.22019 [14] Larsson, S. and Procter, P. (2011) Optimising Implant Anchorage (Augmentation) during Fixation of Osteoporotic Fractures: Is There a Role for Bone-Graft Substitutes? Injury, 42, S72-S76.
http://dx.doi.org/10.1016/j.injury.2011.06.019 [15] Baker, K., Anderson, M., Oehlke, S., Astashkina, A., Haikio, D., Drelich, J., et al. (2006) Growth, Characterization and Biocompatibility of Bone-Like Calcium Phosphate Layers Biomimetically Deposited on Metallic Substrata. Materials Science and Engineering: C, 26, 1351-1360. http://dx.doi.org/10.1016/j.msec.2005.08.015 [16] Allegrini, S., Rumpel, E., Kauschke, E., Fanghänel, J. and König, B. (2006) Hydroxyapatite Grafting Promotes New Bone Formation and Osseointegration of Smooth Titanium Implants. Annals of Anatomy—Anatomischer Anzeiger, 188, 143-151. http://dx.doi.org/10.1016/j.aanat.2005.08.019 [17] Alt, V., Bitschnau, A., Böhner, F., Heerich, K.E., Magesin, E., Sewing, A., et al. (2011) Effects of Gentamicin and Gentamicin-RGD Coatings on Bone Ingrowth and Biocompatibility of Cementless Joint Prostheses: An Experimental Study in Rabbits. Acta Biomaterialia, 7, 1274-1280. http://dx.doi.org/10.1016/j.actbio.2010.11.012 [18] Cao, N., Dong, J., Wang, Q., Ma, Q., Xue, C. and Li, M. (2010) An Experimental Bone Defect Healing with Hydroxyapatite Coating Plasma Sprayed on Carbon/Carbon Composite Implants. Surface and Coatings Technology, 205, 1150-1156. http://dx.doi.org/10.1016/j.surfcoat.2010.05.008 [19] Sörensen, T.C., Arnoldi, J., Procter, P., Robioneck, B. and Steckel, H. (2013) Bone Substitute Materials Delivering Zoledronic Acid: Physicochemical Characterization, Drug Load, and Release Properties. Journal of Biomaterials Applications, 27, 727-738. http://dx.doi.org/10.1177/0885328211424623 [20] Xue, W., Tao, S., Liu, X., Zheng, X. and Ding, C. (2004) In Vivo Evaluation of Plasma Sprayed Hydroxyapatite Coatings Having Different Crystallinity. Biomaterials, 25, 415-421. http://dx.doi.org/10.1016/S0142-9612(03)00545-3 [21] Zhang, H. and Darvell, B.W. (2011) Morphology and Structural Characteristics of Hydroxyapatite Whiskers: Effect of the Initial Ca Concentration, Ca/P Ratio and pH. Acta Biomaterialia, 7, 2960-2968.
http://dx.doi.org/10.1016/j.actbio.2011.03.020 [22] Wang, P., Li, C., Gong, H., Jiang, X., Wang, H. and Li, K. (2010) Effects of Synthesis Conditions on the Morphology of Hydroxyapatite Nanoparticles Produced by Wet Chemical Process. Powder Technology, 203, 315-321.
http://dx.doi.org/10.1016/j.powtec.2010.05.023 [23] Mihranyan, A., Forsgren, J., StrØmme, M. and Engqvist, H. (2009) Assessing Surface Area Evolution during Biomimetic Growth of Hydroxyapatite Coatings. Langmuir, 25, 1292-1295.
http://dx.doi.org/10.1021/la803520k [24] Brohede, U., Zhao, S., Lindberg, F., Mihranyan, A., Forsgren, J., StrØmme, M., et al. (2009) A Novel Graded Bioactive High Adhesion Implant Coating. Applied Surface Science, 255, 7723-7728.
http://dx.doi.org/10.1016/j.apsusc.2009.04.149 [25] Brohede, U., Forsgren, J., Roos, S., Mihranyan, A., Engqvist, H. and StrØmme, M. (2009) Multifunctional Implant Coatings Providing Possibilities for Fast Antibiotics Loading with Subsequent Slow Release. Journal of Materials Science: Materials in Medicine, 20, 1859-1867.
http://dx.doi.org/10.1007/s10856-009-3749-6 [26] Forsgren, J., Svahn, F., Jarmar, T. and Engqvist, H. (2007) Formation and Adhesion of Biomimetic Hydroxyapatite Deposited on Titanium Substrates. Acta Biomaterialia, 3, 980-984.
http://dx.doi.org/10.1016/j.actbio.2007.03.006 [27] Ma, J., Wang, C. and Peng, K. (2003) Electrophoretic Deposition of Porous Hydroxyapatite Scaffold. Biomaterials, 24, 3505-3510. http://dx.doi.org/10.1016/S0142-9612(03)00203-5 [28] Liu, D.M., Troczynski, T. and Tseng, W.J. (2001) Water-Based Sol-Gel Synthesis of Hydroxyapatite: Process Development. Biomaterials, 22, 1721-1730.
http://dx.doi.org/10.1016/S0142-9612(00)00332-X [29] Shapiro, S.S. and Wilk, M.B. (1965) An Analysis of Variance Test for Normality Complete Samples. Biometrika, 52, 591-611. http://dx.doi.org/10.1093/biomet/52.3-4.591 [30] Seebeck, J., Goldhahn, J., Morlock, M.M. and Schneider, E. (2005) Mechanical Behavior of Screws in Normal and Osteoporotic Bone. Osteoporosis International, 16, S107-S111.
http://dx.doi.org/10.1007/s00198-004-1777-0 [31] Moroni, A., Faldini, C., Marchetti, S., Manca, M., Consoli, V. and Giannini, S. (2001) Improvement of the Bone-Pin Interface Strength in Osteoporotic Bone with Use of Hydroxyapatite-Coated Tapered External-Fixation Pins. A Prospective, Randomized Clinical Study of Wrist Fractures. Journal of Bone and Joint Surgery (American Volume), 83, 717-721. [32] Caja, V.L. and Moroni, A. (1996) Hydroxyapatite Coated External Fixation Pins: An Experimental Study. Clinical Orthopaedics and Related Research, 325, 269-275.
http://dx.doi.org/10.1097/00003086-199604000-00033 [33] Shepperd, J.A.N. and Apthorp, H. (2005) A Contemporary Snapshot of the Use of Hydroxyapatite Coating in Orthopaedic Surgery. Journal of Bone and Joint Surgery (British Volume), 87, 1046-1049.
http://dx.doi.org/10.1302/0301-620X.87B8.16692 [34] Piza, G., Caja, V.L., Gonzalez-Viejo, M.A. and Navarro, A. (2004) Hydroxyapatite-Coated External-Fixation Pins. The Effect on Pin Loosening and Pin-Track Infection in Leg Lengthening for Short Stature. Journal of Bone and Joint Surgery (British Volume), 86, 892-897. [35] Magyar, G., Toksvig-Larsen, S. and Moroni, A. (1997) Hydroxyapatite Coating of Threaded Pins Enhances Fixation. Journal of Bone and Joint Surgery (British Volume), 79, 487-489. http://dx.doi.org/10.1302/0301-620X.79B3.7190 [36] Yang, G., He, F., Yang, X., Wang, X. and Zhao, S. (2008) Bone Responses to Titanium Implants Surface-Roughened by Sandblasted and Double Etched Treatments in a Rabbit Model. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 106, 516-524. http://dx.doi.org/10.1016/j.tripleo.2008.03.017 [37] Yang, G., He, F., Hu, J., Wang, X. and Zhao, S. (2009) Effects of Biomimetically and Electrochemically Deposited Nano-Hydroxyapatite Coatings on Osseointegration of Porous Titanium Implants. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 107, 782-789. http://dx.doi.org/10.1016/j.tripleo.2008.12.023 [38] Zhang, E. and Zou, C. (2009) Porous Titanium and Silicon-Substituted Hydroxyapatite Biomodification Prepared by a Biomimetic Process: Characterization and in Vivo Evaluation. Acta Biomaterialia, 5, 1732-1741.
http://dx.doi.org/10.1016/j.actbio.2009.01.014 [39] Eom, T., Jeon, G., Jeong, C., Kim, Y., Kim, S., Cho, I., et al. (2012) Experimental Study of Bone Response to Hydroxyapatite Coating Implants: Bone-Implant Contact and Removal Torque Test. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 114, 411-418. http://dx.doi.org/10.1016/j.oooo.2011.10.036 [40] Esposito, M., Hirsch, J.M., Lekholm, U. and Thomsen, P. (1998) Biological Factors Contributing to Failures of Osseointegrated Oral Implants. (I). Success Criteria and Epidemiology. European Journal of Oral Sciences, 106, 527-551.
http://dx.doi.org/10.1046/j.0909-8836..t01-2-.x [41] Yildirim, O., Aksakal, B., Celik, H., Vangolu, Y. and Okur, A. (2005) An Investigation of the Effects of Hydroxyapatite Coatings on the Fixation Strength of Cortical Screws. Medical Engineering & Physics, 27, 221-228.
http://dx.doi.org/10.1016/j.medengphy.2004.10.006 [42] Pieske, O., Kaltenhauser, F., Pichlmaier, L., Schramm, N., Trentzsch, H., L?ffler, T., et al. (2010) Clinical Benefit of Hydroxyapatite-Coated Pins Compared with Stainless Steel Pins in External Fixation at the Wrist: A Randomised Prospective Study. Injury, 41, 1031-1036. http://dx.doi.org/10.1016/j.injury.2010.03.030 [43] Sennerby, L., Thomsen, P. and Ericson, L. (1993) Early Tissue Response to Titanium Implants Inserted in Rabbit Cortical Bone. Journal of Materials Science: Materials in Medicine, 4, 240-250. http://dx.doi.org/10.1007/BF00122275 [44] Roshan-Ghias, A., Arnoldi, J., Procter, P. and Pioletti, D.P. (2011) In Vivo Assessment of Local Effects after Application of Bone Screws Delivering Bisphosphonates into a Compromised Cancellous Bone Site. Clinical Biomechanics, 26, 1039-1043. http://dx.doi.org/10.1016/j.clinbiomech.2011.06.004 [45] Mittal, M., Nath, S. and Prakash, S. (2011) Splat Formation and Degradation of Hydroxyapatite during Plasma Spraying Process. Advances in Materials Sciences, 11, 26-36. [46] Rigo, E., Boschi, A., Yoshimoto, M., Allegrini, S., Konig, B. and Carbonari, M. (2004) Evaluation in Vitro and in Vivo of Biomimetic Hydroxyapatite Coated on Titanium Dental Implants. Materials Science and Engineering: C, 24, 647- 651. http://dx.doi.org/10.1016/j.msec.2004.08.044 [47] Lilja, M., Sörensen, J.H., Sörensen, T.C., Åstrand, M., Procter, P., Steckel, H., et al. (2013) Impact of Biomechanical Forces on Antibiotics Release Kinetics from Hydroxyapatite Coated Surgical Fixation Pins. Journal of Biomaterials and Nanobiotechnology, 4, 343-350.
http://dx.doi.org/10.4236/jbnb.2013.44043 [48] Sörensen, J.H., Lilja, M., Sörensen, T.C., Astrand, M., Procter, P., Fuchs, S., et al. (2014) Biomechanical and Antibacterial Properties of Tobramycin Loaded Hydroxyapatite Coated Fixation Pins. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 102, 1381-1392. http://dx.doi.org/10.1002/jbm.b.33117 [49] Chan, S., Neu, C., Komvopoulos, K. and Reddi, A. (2011) The Role of Lubricant Entrapment at Biological Interfaces: Reduction of Friction and Adhesion in Articular Cartilage. Journal of Biomechanics, 44, 2015-2020.
http://dx.doi.org/10.1016/j.jbiomech.2011.04.015 [50] Peter, B., Pioletti, D.P., Laib, S., Bujoli, B., Pilet, P., Janvier, P., et al. (2005) Calcium Phosphate Drug Delivery System: Influence of Local Zoledronate Release on Bone Implant Osteointegration. Bone, 36, 52-60.
http://dx.doi.org/10.1016/j.bone.2004.10.004 [51] Wermelin, K., Suska, F., Tengvall, P., Thomsen, P. and Aspenberg, P. (2008) Stainless Steel Screws Coated with Bisphosphonates Gave Stronger Fixation and More Surrounding Bone. Histomorphometry in Rats. Bone, 42, 365-371.
http://dx.doi.org/10.1016/j.bone.2007.10.013
[1] Krappinger, D., Bizzotto, N., Riedmann, S., Kammerlander, C., Hengg, C. and Kralinger, F.S. (2011) Predicting Failure after Surgical Fixation of Proximal Humerus Fractures. Injury, 42, 1283-1288.
http://dx.doi.org/10.1016/j.injury.2011.01.017 [2] Adams, C.I., Robinson, C.M., Court-Brown, C.M. and McQueen, M.M. (2001) Prospective Randomized Controlled Trial of an Intramedullary Nail versus Dynamic Screw and Plate for Intertrochanteric Fractures of the Femur. Journal of Orthopaedic Trauma, 15, 394-400.
http://dx.doi.org/10.1097/00005131-200108000-00003 [3] Basler, S.E., Traxler, J., Müller, R. and van Lenthe, G.H. (2013) Peri-Implant Bone Microstructure Determines Dynamic Implant Cut-Out. Medical Engineering & Physics, 35, 1442-1449.
http://dx.doi.org/10.1016/j.medengphy.2013.03.016 [4] Windolf, M., Braunstein, V., Dutoit, C. and Schwieger, K. (2009) Is a Helical Shaped Implant a Superior Alternative to the Dynamic Hip Screw for Unstable Femoral Neck Fractures? A Biomechanical Investigation. Clinical Biomechanics, 24, 59-64. http://dx.doi.org/10.1016/j.clinbiomech.2008.07.004 [5] Fakler, J.K.M., Hogan, C., Heyde, C.E. and John, T. (2008) Current Concepts in the Treatment of Proximal Humeral Fractures. Orthopedics, 31, 42-51. http://dx.doi.org/10.3928/01477447-20080101-13 [6] Dhert, W.J., Thomsen, P., Blomgren, A.K., Esposito, M., Ericson, L.E. and Verbout, A.J. (1998) Integration of Press- Fit Implants in Cortical Bone: A Study on Interface Kinetics. Journal of Biomedical Materials Research, 41, 574-583.
http://dx.doi.org/10.1002/(SICI)1097-4636(19980915)41:4<574::AID-JBM9>3.0.CO;2-9 [7] Slaets, E., Carmeliet, G., Naert, I. and Duyck, J. (2006) Early Cellular Responses in Cortical Bone Healing around Unloaded Titanium Implants: An Animal Study. Journal of Periodontology, 77, 1015-1024.
http://dx.doi.org/10.1902/jop.2006.050196 [8] Heimann, R.B. (2013) Structure, Properties, and Biomedical Performance of Osteoconductive Bioceramic Coatings. Surface and Coatings Technology, 233, 27-38.
http://dx.doi.org/10.1016/j.surfcoat.2012.11.013 [9] Moroni, A., Caja, V.L., Egger, E.L., Trinchese, L. and Chao, E.Y. (1994) Histomorphometry of Hydroxyapatite Coated and Uncoated Porous Titanium Bone Implants. Biomaterials, 15, 926-930.
http://dx.doi.org/10.1016/0142-9612(94)90119-8 [10] Kusakabe, H., Sakamaki, T., Nihei, K., Oyama, Y., Yanagimoto, S., Ichimiya, M., et al. (2004) Osseointegration of a Hydroxyapatite-Coated Multilayered Mesh Stem. Biomaterials, 25, 2957-2969.
http://dx.doi.org/10.1016/j.biomaterials.2003.09.090 [11] Hasegawa, M., Sudo, A., Komlev, V.S., Barinov, S.M. and Uchida, A. (2004) High Release of Antibiotic from a Novel Hydroxyapatite with Bimodal Pore Size Distribution. Journal of Biomedical Materials Research, 70, 332-339.
http://dx.doi.org/10.1002/jbm.b.30047 [12] Sörensen, T.C., Arnoldi, J., Procter, P., Beimel, C., Jönsson, A., Lennerås, M., et al. (2013) Locally Enhanced Early Bone Formation of Zoledronic Acid Incorporated into a Bone Cement Plug in Vivo. Journal of Pharmacy and Pharmacology, 65, 201-212.
http://dx.doi.org/10.1111/j.2042-7158.2012.01588.x [13] Forsgren, J., Brohede, U., Piscounova, S., Mihranyan, A., Larsson, S., StrØmme, M., et al. (2011) In Vivo Evaluation of Functionalized Biomimetic Hydroxyapatite for Local Delivery of Active Agents. Journal of Biomaterials and Nanobiotechnology, 2, 149-154.
http://dx.doi.org/10.4236/jbnb.2011.22019 [14] Larsson, S. and Procter, P. (2011) Optimising Implant Anchorage (Augmentation) during Fixation of Osteoporotic Fractures: Is There a Role for Bone-Graft Substitutes? Injury, 42, S72-S76.
http://dx.doi.org/10.1016/j.injury.2011.06.019 [15] Baker, K., Anderson, M., Oehlke, S., Astashkina, A., Haikio, D., Drelich, J., et al. (2006) Growth, Characterization and Biocompatibility of Bone-Like Calcium Phosphate Layers Biomimetically Deposited on Metallic Substrata. Materials Science and Engineering: C, 26, 1351-1360. http://dx.doi.org/10.1016/j.msec.2005.08.015 [16] Allegrini, S., Rumpel, E., Kauschke, E., Fanghänel, J. and König, B. (2006) Hydroxyapatite Grafting Promotes New Bone Formation and Osseointegration of Smooth Titanium Implants. Annals of Anatomy—Anatomischer Anzeiger, 188, 143-151. http://dx.doi.org/10.1016/j.aanat.2005.08.019 [17] Alt, V., Bitschnau, A., Böhner, F., Heerich, K.E., Magesin, E., Sewing, A., et al. (2011) Effects of Gentamicin and Gentamicin-RGD Coatings on Bone Ingrowth and Biocompatibility of Cementless Joint Prostheses: An Experimental Study in Rabbits. Acta Biomaterialia, 7, 1274-1280. http://dx.doi.org/10.1016/j.actbio.2010.11.012 [18] Cao, N., Dong, J., Wang, Q., Ma, Q., Xue, C. and Li, M. (2010) An Experimental Bone Defect Healing with Hydroxyapatite Coating Plasma Sprayed on Carbon/Carbon Composite Implants. Surface and Coatings Technology, 205, 1150-1156. http://dx.doi.org/10.1016/j.surfcoat.2010.05.008 [19] Sörensen, T.C., Arnoldi, J., Procter, P., Robioneck, B. and Steckel, H. (2013) Bone Substitute Materials Delivering Zoledronic Acid: Physicochemical Characterization, Drug Load, and Release Properties. Journal of Biomaterials Applications, 27, 727-738. http://dx.doi.org/10.1177/0885328211424623 [20] Xue, W., Tao, S., Liu, X., Zheng, X. and Ding, C. (2004) In Vivo Evaluation of Plasma Sprayed Hydroxyapatite Coatings Having Different Crystallinity. Biomaterials, 25, 415-421. http://dx.doi.org/10.1016/S0142-9612(03)00545-3 [21] Zhang, H. and Darvell, B.W. (2011) Morphology and Structural Characteristics of Hydroxyapatite Whiskers: Effect of the Initial Ca Concentration, Ca/P Ratio and pH. Acta Biomaterialia, 7, 2960-2968.
http://dx.doi.org/10.1016/j.actbio.2011.03.020 [22] Wang, P., Li, C., Gong, H., Jiang, X., Wang, H. and Li, K. (2010) Effects of Synthesis Conditions on the Morphology of Hydroxyapatite Nanoparticles Produced by Wet Chemical Process. Powder Technology, 203, 315-321.
http://dx.doi.org/10.1016/j.powtec.2010.05.023 [23] Mihranyan, A., Forsgren, J., StrØmme, M. and Engqvist, H. (2009) Assessing Surface Area Evolution during Biomimetic Growth of Hydroxyapatite Coatings. Langmuir, 25, 1292-1295.
http://dx.doi.org/10.1021/la803520k [24] Brohede, U., Zhao, S., Lindberg, F., Mihranyan, A., Forsgren, J., StrØmme, M., et al. (2009) A Novel Graded Bioactive High Adhesion Implant Coating. Applied Surface Science, 255, 7723-7728.
http://dx.doi.org/10.1016/j.apsusc.2009.04.149 [25] Brohede, U., Forsgren, J., Roos, S., Mihranyan, A., Engqvist, H. and StrØmme, M. (2009) Multifunctional Implant Coatings Providing Possibilities for Fast Antibiotics Loading with Subsequent Slow Release. Journal of Materials Science: Materials in Medicine, 20, 1859-1867.
http://dx.doi.org/10.1007/s10856-009-3749-6 [26] Forsgren, J., Svahn, F., Jarmar, T. and Engqvist, H. (2007) Formation and Adhesion of Biomimetic Hydroxyapatite Deposited on Titanium Substrates. Acta Biomaterialia, 3, 980-984.
http://dx.doi.org/10.1016/j.actbio.2007.03.006 [27] Ma, J., Wang, C. and Peng, K. (2003) Electrophoretic Deposition of Porous Hydroxyapatite Scaffold. Biomaterials, 24, 3505-3510. http://dx.doi.org/10.1016/S0142-9612(03)00203-5 [28] Liu, D.M., Troczynski, T. and Tseng, W.J. (2001) Water-Based Sol-Gel Synthesis of Hydroxyapatite: Process Development. Biomaterials, 22, 1721-1730.
http://dx.doi.org/10.1016/S0142-9612(00)00332-X [29] Shapiro, S.S. and Wilk, M.B. (1965) An Analysis of Variance Test for Normality Complete Samples. Biometrika, 52, 591-611. http://dx.doi.org/10.1093/biomet/52.3-4.591 [30] Seebeck, J., Goldhahn, J., Morlock, M.M. and Schneider, E. (2005) Mechanical Behavior of Screws in Normal and Osteoporotic Bone. Osteoporosis International, 16, S107-S111.
http://dx.doi.org/10.1007/s00198-004-1777-0 [31] Moroni, A., Faldini, C., Marchetti, S., Manca, M., Consoli, V. and Giannini, S. (2001) Improvement of the Bone-Pin Interface Strength in Osteoporotic Bone with Use of Hydroxyapatite-Coated Tapered External-Fixation Pins. A Prospective, Randomized Clinical Study of Wrist Fractures. Journal of Bone and Joint Surgery (American Volume), 83, 717-721. [32] Caja, V.L. and Moroni, A. (1996) Hydroxyapatite Coated External Fixation Pins: An Experimental Study. Clinical Orthopaedics and Related Research, 325, 269-275.
http://dx.doi.org/10.1097/00003086-199604000-00033 [33] Shepperd, J.A.N. and Apthorp, H. (2005) A Contemporary Snapshot of the Use of Hydroxyapatite Coating in Orthopaedic Surgery. Journal of Bone and Joint Surgery (British Volume), 87, 1046-1049.
http://dx.doi.org/10.1302/0301-620X.87B8.16692 [34] Piza, G., Caja, V.L., Gonzalez-Viejo, M.A. and Navarro, A. (2004) Hydroxyapatite-Coated External-Fixation Pins. The Effect on Pin Loosening and Pin-Track Infection in Leg Lengthening for Short Stature. Journal of Bone and Joint Surgery (British Volume), 86, 892-897. [35] Magyar, G., Toksvig-Larsen, S. and Moroni, A. (1997) Hydroxyapatite Coating of Threaded Pins Enhances Fixation. Journal of Bone and Joint Surgery (British Volume), 79, 487-489. http://dx.doi.org/10.1302/0301-620X.79B3.7190 [36] Yang, G., He, F., Yang, X., Wang, X. and Zhao, S. (2008) Bone Responses to Titanium Implants Surface-Roughened by Sandblasted and Double Etched Treatments in a Rabbit Model. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 106, 516-524. http://dx.doi.org/10.1016/j.tripleo.2008.03.017 [37] Yang, G., He, F., Hu, J., Wang, X. and Zhao, S. (2009) Effects of Biomimetically and Electrochemically Deposited Nano-Hydroxyapatite Coatings on Osseointegration of Porous Titanium Implants. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 107, 782-789. http://dx.doi.org/10.1016/j.tripleo.2008.12.023 [38] Zhang, E. and Zou, C. (2009) Porous Titanium and Silicon-Substituted Hydroxyapatite Biomodification Prepared by a Biomimetic Process: Characterization and in Vivo Evaluation. Acta Biomaterialia, 5, 1732-1741.
http://dx.doi.org/10.1016/j.actbio.2009.01.014 [39] Eom, T., Jeon, G., Jeong, C., Kim, Y., Kim, S., Cho, I., et al. (2012) Experimental Study of Bone Response to Hydroxyapatite Coating Implants: Bone-Implant Contact and Removal Torque Test. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 114, 411-418. http://dx.doi.org/10.1016/j.oooo.2011.10.036 [40] Esposito, M., Hirsch, J.M., Lekholm, U. and Thomsen, P. (1998) Biological Factors Contributing to Failures of Osseointegrated Oral Implants. (I). Success Criteria and Epidemiology. European Journal of Oral Sciences, 106, 527-551.
http://dx.doi.org/10.1046/j.0909-8836..t01-2-.x [41] Yildirim, O., Aksakal, B., Celik, H., Vangolu, Y. and Okur, A. (2005) An Investigation of the Effects of Hydroxyapatite Coatings on the Fixation Strength of Cortical Screws. Medical Engineering & Physics, 27, 221-228.
http://dx.doi.org/10.1016/j.medengphy.2004.10.006 [42] Pieske, O., Kaltenhauser, F., Pichlmaier, L., Schramm, N., Trentzsch, H., L?ffler, T., et al. (2010) Clinical Benefit of Hydroxyapatite-Coated Pins Compared with Stainless Steel Pins in External Fixation at the Wrist: A Randomised Prospective Study. Injury, 41, 1031-1036. http://dx.doi.org/10.1016/j.injury.2010.03.030 [43] Sennerby, L., Thomsen, P. and Ericson, L. (1993) Early Tissue Response to Titanium Implants Inserted in Rabbit Cortical Bone. Journal of Materials Science: Materials in Medicine, 4, 240-250. http://dx.doi.org/10.1007/BF00122275 [44] Roshan-Ghias, A., Arnoldi, J., Procter, P. and Pioletti, D.P. (2011) In Vivo Assessment of Local Effects after Application of Bone Screws Delivering Bisphosphonates into a Compromised Cancellous Bone Site. Clinical Biomechanics, 26, 1039-1043. http://dx.doi.org/10.1016/j.clinbiomech.2011.06.004 [45] Mittal, M., Nath, S. and Prakash, S. (2011) Splat Formation and Degradation of Hydroxyapatite during Plasma Spraying Process. Advances in Materials Sciences, 11, 26-36. [46] Rigo, E., Boschi, A., Yoshimoto, M., Allegrini, S., Konig, B. and Carbonari, M. (2004) Evaluation in Vitro and in Vivo of Biomimetic Hydroxyapatite Coated on Titanium Dental Implants. Materials Science and Engineering: C, 24, 647- 651. http://dx.doi.org/10.1016/j.msec.2004.08.044 [47] Lilja, M., Sörensen, J.H., Sörensen, T.C., Åstrand, M., Procter, P., Steckel, H., et al. (2013) Impact of Biomechanical Forces on Antibiotics Release Kinetics from Hydroxyapatite Coated Surgical Fixation Pins. Journal of Biomaterials and Nanobiotechnology, 4, 343-350.
http://dx.doi.org/10.4236/jbnb.2013.44043 [48] Sörensen, J.H., Lilja, M., Sörensen, T.C., Astrand, M., Procter, P., Fuchs, S., et al. (2014) Biomechanical and Antibacterial Properties of Tobramycin Loaded Hydroxyapatite Coated Fixation Pins. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 102, 1381-1392. http://dx.doi.org/10.1002/jbm.b.33117 [49] Chan, S., Neu, C., Komvopoulos, K. and Reddi, A. (2011) The Role of Lubricant Entrapment at Biological Interfaces: Reduction of Friction and Adhesion in Articular Cartilage. Journal of Biomechanics, 44, 2015-2020.
http://dx.doi.org/10.1016/j.jbiomech.2011.04.015 [50] Peter, B., Pioletti, D.P., Laib, S., Bujoli, B., Pilet, P., Janvier, P., et al. (2005) Calcium Phosphate Drug Delivery System: Influence of Local Zoledronate Release on Bone Implant Osteointegration. Bone, 36, 52-60.
http://dx.doi.org/10.1016/j.bone.2004.10.004 [51] Wermelin, K., Suska, F., Tengvall, P., Thomsen, P. and Aspenberg, P. (2008) Stainless Steel Screws Coated with Bisphosphonates Gave Stronger Fixation and More Surrounding Bone. Histomorphometry in Rats. Bone, 42, 365-371.
http://dx.doi.org/10.1016/j.bone.2007.10.013