ABB  Vol.5 No.4 , March 2014
The 5 Hallmarks of Biomaterials Success: An Emphasis on Orthopaedics
Abstract: Over the past 200 years, there has been significant advancements in the fields of bioengineering and orthopaedics. Investigators, clinicians and manufactures are learning that the success of implant systems is not limited to a single factor, but a combination of variables that must work in unison to provide stability and high survivorship. Innovations continue to advance these fields and include: biomimetic alterations, three-dimensional, patient-specific reconstructions and novel coatings to mitigate aseptic loosening or other pathologies. However, implant systems continue to fail in clinical practice since they do not adhere to key fundamental principles. Therefore, this article is intended to highlight 5 hallmarks of biomaterials that should be considered during design, surgery, and post-operative rehabilitation.
Cite this paper: Williams, D. and Isaacson, B. (2014) The 5 Hallmarks of Biomaterials Success: An Emphasis on Orthopaedics. Advances in Bioscience and Biotechnology, 5, 283-293. doi: 10.4236/abb.2014.54035.

[1]   Apple, D.J. and Sims, J. (1996) Harold Ridley and the Invention of Intraocular Lens. Survey of Ophthalmology, 40, 279-292.

[2]   Agins, H.J., Alcock, N.W., Bansal, M., Salvati, E.A., Wilson, P.D., Pellicei, P.M., et al. (1988) Metallic Wear in Failed Titanium-Alloy Total Hip Replacements. The Journal of Bone & Joint Surgery, 70-A, 347-356.

[3]   Tummler, H.-P., Thull, R. and Schaldach, M. (1982) The Mechanism of Repassivation and the Concentration of Corrosion Products Shown on TIALV. Proceedings of the World Congress on Medical Physics and Biomedical Engineering, 13th International Conference on Medical and Biological Engineering, 6th International Conference on Medical Physics, Congress Centrum Hamburg, Germany, 3-11.

[4]   Bothe, R.T., Beaton, L.E. and Davenport, H.A. (1940) Reaction of Bone to Multiple Metallic Implants. Surgery, Gynecology and Obstetrics, 71, 598-602.

[5]   Leventhal, G.S. (1951) Titanium, a Metal for Surgery. Journal of Bone and Joint Surgery, 33A, 473-474.

[6]   Brånemark, P.-I. (2005) The Biologic Origin of Osseointegration. The Osseointegration Book: From Calvarium to Calcaneus. Quintessence Books, Berlin, 22.

[7]   Bloebaum, R.D., Bachus, K.N., Momberger, N.G. and Hofmann, A.A. (1994) Mineral Apposition Rates of Human Cancellous Bone at the Interface of Porous Coated Implants. Journal of Biomedical Materials Research, 28, 537-544.

[8]   Bloebaum, R.D., Willie, B.M., Mitchell, B.S. and Hofmann, A.A. (2007) Relationship between Bone Ingrowth, Mineral Apposition Rate, and Osteoblast Activity. Journal of Biomedical Materials Research, Part A, 81, 505-514.

[9]   Gore, D., Frazer, R., Kovarik, R. and Yepes, J. (2005) Vitallium. Journal of Long-Term Effects of Medical Implants, 15, 673-686.

[10]   Davis, J.R. (2006) Metallic Materials. In: Davis, J.R., Ed., Handbook of Materials for Medical Devices, ASM International, Materials Park, 31.

[11]   Gore, D.R., Frazer, R.Q., Kovarik, R.E. and Yepes, J.F. (2005) Vitallium. Journal of Long-Term Effects of Medical Implants, 15, 673-686.

[12]   Gomez, P.F. and Morcuende, J.A. (2005) Early Attempts at Hip Arthorplasty—1700s to 1950s. The Iowa Orthopaedic Journal, 25, 5-9.

[13]   Charnley, J. (1966) Letter to the Editor. The Journal of Bone and Joint Surgery, 48-A, 819.

[14]   Charnley, J. (1976) The Wear of Plastics Materials in the Hip-Joint. Plastics and Rubber, 1, 59-63.

[15]   Charnley, J., Kamangar, A. and Longfield, M.D. (1969) The Optimum Size of Prosthetic Heads in Relation to the Wear of Plastic Sockets in Total Replacement of the Hip. Medical and Biological Engineering, 7, 31-39.

[16]   Good, V.D., Clarke, I.C., Gustafson, G.A., Downs, B., Anissian, L. and Sorensen, K. (2000) Wear of Ultra-High Molecular Weight Polyethylene and Polytetrafluorethylene in a Hip Simulator. Acta Orthopaedica, 71, 365-369.

[17]   Kennedy, W.F., Roberts, C.G., Zuege, R.C. and Dicus, W.T. (1993) Use of Pulsed Electromagnetic Fields in Treatment of Loosened Cemented Hip Prostheses. A Double-Blind Trial. Clinical Orthopaedics and Related Research, 286, 198-205.

[18]   Ilfeld, B.M., Mariano, E.R., Williams, B.A., Woodard, J.N. and Macario, A. (2007) Hospitalization Costs of Total Knee Arthroplasty with a Continuous Femoral Nerve Block Provided only in the Hospital versus on an Ambulatory Basis: A Retrospective, Case-Control, Cost-Minimization Analysis. Regional Anesthesia and Pain Medicine, 32, 46-54.

[19]   Williams, D.F. (2004) Definitions in Biomaterials. Proceedings of a Consensus Conference of the European Society for Biomaterials. March 2-5, 1986. In: Ratner, B.D., Hoffman, A.S., Schoen, F.J. and Lemons, J.E., Eds., Biomaterials Science: An Introduction to Materials in Medicine, 2 Edition, Academic Press, 2.

[20]   Mardis, H.K. and Kroeger, R.M. (1988) Ureteral Stents. The Urologic Clinics of North America, 15, 471-479.

[21]   Furno, F. and Bayston, R. (2008) Antimicrobial/Antibiotic (Infection Resistance) Materials. In: Wnek, G.E. and Bowlin, G.L., Eds., Encyclopedia of Biomaterials and Biomedical Engineering, Informa Healthcare, New York, 61.

[22]   Koenig, A.L., Gambillara, V. and Grainger, D.W. (2002) Correlating Fibronectin Adsorption with Endothelial Cell Adhesion and Signaling on Polymer Substrates. Journal of Biomedical Materials Research Part A, 64, 20-37.

[23]   Thevenot, P., Hu, W. and Tang, L. (2008) Surface Chemistry Influences Implant Biocompatibility. Current Topics in Medicinal Chemistry, 8, 270-280.

[24]   Reid, G. (1999) Biofilms in Infectious Disease and on Medical Devices. International Journal of Antimicrobial Agents, 11, 223-226.

[25]   Bruder, S.P., Fink, D.J. and Caplan, A.I. (1994) Mesenchymal Stem Cells in Bone Development, Bone Repair, and Skeletal Regeneration Therapy. Journal of Cellular Biochemistry, 56, 283-294.

[26]   Nygren, H. (1996) Initial Reactions of Whole Blood with Hydrophilic and Hydrophobic Titanium Surfaces. Colloids and Surfaces B, 6, 329-333.

[27]   Eriksson, C. and Nygren, H. (2001) Polymorphonuclear Leukocytes in Coagulating Whole Blood Recognize Hydrophilic and Hydrophobic Titanium Surfaces by Different Adhesion Receptors and Show Different Patterns of Receptor Expression. Journal of Laboratory and Clinical Medicine, 137, 296-302.

[28]   Blumenfeld, T.J. and Bargar, W.L. (2006) Early Aseptic Loosening of a Modern Acetabular Component Secondary to a Change in Manufacturing. Journal of Arthroplasty, 21, 689-695.

[29]   Bloebaum, R.D., Ferguson, R.P., Neff, C.M., Gorp, C.V., Woolley, D.L. and Hofmann, A.A. (2004) Bone Viability Determination in Human Cancellous Bone from Patients Undergoing Revision Hip Arthroplasty. The Journal of Arthroplasty, 19, 745-750.

[30]   Campbell, P., Mirra, J. and Catelas, I. (2002) Histopathology of Tissues from Inter-Op Acetabular Sockets. 48th Annual Meeting of the Orthopaedic Research Society, Dallas.

[31]   Spiegelberg, S., Deluzio, K. and Muratoglu, O. (2003) Extractable Residue from Recalled Inter-Op Acetabular Shells. 49th Annual Meeting of Orthopaedic Research Society, New Orleans.

[32]   Aaron, R.K., Herr, H.M., Ciombor, D.M., Hochberg, L.R., Donoghue, J.P., Briant, C.L., et al. (2006) Horizons in Prosthesis Development for the Restoration of Limb Function. Journal of the American Academy of Orthopaedic Surgeons, 14, S198-S204.

[33]   Nygren, H. (1996) Initial Reactions of Whole Blood with Hydrophilic and Hydrophobic Titanium Surfaces. Colloids Surf B: Biointerfaces, 6, 329-333.

[34]   Jacobs, J.J. (2001) What Are the Systemic Consequences of Wear Debris Clinically? In: Wright, T.M. and Goodman, S.B., Eds., Implant Wear in Total Joint Replacement: Clinical and Biologic Issues, Material and Design Considerations, American Academy of Orthopedic Surgeons, Rosemont, 31-42.

[35]   Purdue, P., Koulouvaris, P., Nestor, B. and Sculco, T. (2006) The Central Role of Wear Debris in Periprosthetic Osteolysis. HSS Journal, 2, 102-113.

[36]   Meldrum, R.D., Wurtz, L.D., Feinberg, J.R. and Capello, W.N. (2005) Does Smoking Affect Implant Survivorship in Total Hip Arthroplasty? A Preliminary Retrospective Case Series. The Iowa Orthopaedic Journal, 25, 17-24.

[37]   Santaguida, P.L., Hawker, G.A., Hudak, P.L., Glazier, R., Mahomed, N.N., Kreder, H.J., Coyte, P.C. and Wright, J.G. (2008) Patient Characteristics Affecting the Prognosis of Total Hip and Knee Joint Arthroplasty: A Systematic Review. Canadian Journal of Surgery, 51, 428-436.

[38]   Nixon, M., Taylor, G., Sheldon, P., Iqbal, S.J. and Harper, W. (2007) Does Bone Quality Predict Loosening of Cemented Total Hip Replacements? The Journal of Bone and Joint Surgery (British volume), 89-B, 1303-1308.

[39]   Abdul Kadir, M. and Kamsah, N. (2009) The Effect of Bone Properties due to Skeletal Diseases on Stability of Cementless Hip Stems. American Journal of Applied Sciences, 6, 1988-1994.

[40]   Delforge, G. (2002) Soft Tissue Connective Repair. Musculoskeletal Trauma: Implications for Sports Injury Management, Human Kinetics, Champaign, 44.

[41]   Albrektsson, T. and Albrektsson, B. (1987) Osseointegration of Bone Implants. A Review of an Alternative Mode of Fixation. Acta Orthopaedica Scandinavica, 58, 567-577.

[42]   Eriksson, A.R. and Albrektsson, T. (1983) Temperature Threshold Levels for Heat-Induced Bone Tissue Injury: A VitalMicroscopic Study in the Rabbit. Journal of Prosthetic Dentistry, 50, 101-107.

[43]   Sela, J., Gross, U.M., Kohavi, D., Shani, J., Dean, D.D., Boyan, B.D. and Schwartz, Z. (2000) Primary Mineralization at the Surfaces of Implants. Critical Reviews in Oral Biology & Medicine, 11, 423-436.

[44]   Rafel, S.S. (1962) Temperature Changes during High-Speed Drilling on Bone. Journal of Oral Surgery, Anesthesia, and Hospital Dental Service, 20, 475-477.

[45]   Williams, D.F. (1982) Biocompatibility of Orthopedic Implants. Volume I. In: Williams, D.F., Ed., CRC Series in Biocompatibility, CRC Press, Liverpool, 141-195.

[46]   Ling, R.S. (1986) Observations on the Fixation of Implants to the Bony Skeleton. Clinical Orthopaedics and Related Research, 210, 80-96.

[47]   Wooley, P.H., Nasser, S. and Fitzgerald Jr., R.H. (1996) The Immune Response to Implant Materials in Humans. Clinical Orthopaedics & Related Research, 326, 63-70.

[48]   Bergmann, G., Deuretzbacher, G., Heller, M., Graichen, F., Rohlmann, A., Strauss, J. and Duda, G.N. (2001) Hip Contact Forces and Gait Patterns from Routine Activities. Journal of Biomechanics, 34, 859-871.

[49]   Ducheyne, P., Willems, G., Martens, M. and Helsen, J. (1984) In Vivo Metal-Ion Release from Porous Titanium-Fiber Material. Journal of Biomedical Materials Research, 18, 293-308.

[50]   Rae, T. (1981) The Toxicity of Metals Used in Orthopaedic Prostheses. An Experimental Study Using Cultured Human Synovial Fibroblasts. Journal of Bone and Joint Surgery, 63-B, 435-440.

[51]   MacDonald, S.J. (2004) Can a Safe Level for Metal Ions in Patients with Metal-On-Metal Total Hip Arthroplasties be Determined? Journal of Arthroplasty, 19, 71-77.

[52]   Dannenmaier, W.C., Haynes, D.W. and Nelson, C.L. (1985) Granulomatous Reaction and Cystic Bony Destruction Associated with High Wear Rate in a Total Knee Prosthesis. Clinical Orthopaedics and Related Research, 198, 224-230.

[53]   Tallroth, K., Eskola, A., Santavirta, S., Konttinen, Y.T. and Lindholm, T.S. (1989) Aggressive Granulomatous Lesions after Hip Arthroplasty. Journal of Bone and Joint Surgery, 71, 571-575.

[54]   Amstutz, H.C., Campbell, P., Kossovsky, N. and Clarke, I.C. (1992) Mechanism and Clinical Significance of Wear Debris-Induced Osteolysis. Clinical Orthopaedics and Related Research, 276, 7-18.

[55]   Goodfellow, J. (1992) Malignancy and Joint Replacement. Journal of Bone and Joint Surgery (British volume), 74-B, 645.

[56]   Apley, A.G. (1989) Malignancy and Joint Replacement: The Tip of an Iceberg? Journal of Bone and Joint Surgery, 71-B, 1.

[57]   Black, J. (1988) Does Corrosion Matter? Journal of Bone and Joint Surgery (British volume), 70-B, 517-520.

[58]   Hamblen, D.L. and Carter, R.L. (1984) Sarcoma and Joint Replacement. Journal of Bone and Joint Surgery, 66-B, 625-626.

[59]   Penman, H.G. and Ring, P.A. (1984) Osteosarcoma in Association with Total Hip Replacement. Journal of Bone and Joint Surgery, 66-B, 632-634.

[60]   Bagó-Granell, J., Aguirre-Canyadell, M., Nardi, J. and Tallada, N. (1984) Malignant Fibrous Histiocytoma of Bone at the Site of a Total Hip Arthroplasty. Journal of Bone and Joint Surgery, 66-B, 38-40.

[61]   Jasty, M., Jiranek, W. and Harris, W.H. (1992) Acrylic Fragmentation in Total Hip Replacements and Its Biological Consequences. Clinical Orthopaedics and Related Research, 285, 116-128.

[62]   Khan, W.S., Agarwal, M., Malik, A.A., Cox, A.G., Denton, J. and Holt, E.M. (2008) Chromium, Cobalt and Titanium Metallosis Involving a Nottingham Shoulder Replacement. Journal of Bone and Joint Surgery (British volume), 90, 502-505.

[63]   Albrektsson, T., Branemark, I.I., Hansson, H.A. and Lindstrom, J. (1981) Osseointegrated Titanium Implants. Acta Orthopaedica, 52, 155-170.

[64]   Meyer, U., Joos, U., Mythili, J., Stamm, T., Hohoff, A., Fillies, T., Stratmannc, U. and Wiesmann, H.P. (2004) Ultrastructural Characterization of the Implant/Bone Interface of Immediately Loaded Dental Implants. Biomaterials, 25, 1959-1967.

[65]   Albrektsson, T. and Linder, L. (1984) Bone Injury Caused by Curing Bone Cement. An in Vivo Study in Rabbit Tibia. Clinical Orthopaedics and Related Research, 183, 280.

[66]   Laing, P.G., Ferguson Jr., A.B. and Hodge, E.S. (1967) Tissue Reaction in Rabbit Muscle Exposed to Metallic Implants. Journal of Biomedical Materials Research, 1, 135-149.

[67]   Nkenke, E., Lehner, B., Weinzierl, K., Thams, U., Neugebauer, J., Steveling, H., Radespiel-Tröger, M. and Neukam, F.W. (2003) Bone Contact, Growth, and Density around Immediately Loaded Implants in the Mandible of Mini Pigs. Clinical Oral Implants Research, 14, 312-321.

[68]   Piattelli, A., Corigliano, M., Scarano, A., Costigliola, G. and Paolantonio, M. (1998) Immediate Loading of Titanium Plasma-Sprayed Implants: An Histologic Analysis in Monkeys. Journal of Periodontology, 69, 321-327.

[69]   Szmukler-Moncler, S., Salama, H., Reingewirtz, Y. and Dubruille, J.H. (1998) Timing of Loading and Effect of Micromotion on Bone-Dental Implant Interface: Review of Experimental Literature. Journal of Biomedical Materials Research, 43, 192-203.<192::AID-JBM14>3.0.CO;2-K

[70]   Slaets, E., Carmeliet, G., Naert, I. and Duyck, J. (2007) Early Trabecular Bone Healing around Titanium Implants: A Histologic Study in Rabbits. Journal of Periodontology, 78, 510-517.

[71]   Vandamme, K., Naert, I., Vander Sloten, J., Puers, R. and Duyck, J. (2008) Effect of Implant Surface Roughness and Loading on Peri-Implant Bone Formation. Journal of Periodontology, 79, 150-157.

[72]   Bloebaum, R.D., Rubman, M.H. and Hofmann, A.A. (1992) Bone Ingrowth into Porous-Coated Tibial Components Implanted with Autograft Bone Chips: Analysis of Ten Consecutively Retrieved Implants. Journal of Arthroplasty, 7, 483-493.

[73]   Hacking, S.A., Bobyn, J.D., Toh, K., Tanzer, M. and Krygier, J.J. (2000) Fibrous Tissue Ingrowth and Attachment to Porous Tantalum. Journal of Biomedical Materials Research, 52, 631-638.<631::AID-JBM7>3.0.CO;2-6

[74]   Hofmann, A.A., Bloebaum, R.D. and Bachus, K.N. (1997) Progression of Human Bone Ingrowth into Porous-Coated Implants. Acta Orthopaedica, 68, 161-166.

[75]   Pilliar, R.M., Lee, J.M. and Maniatopoulos, C. (1986) Observations on the Effect of Movement on Bone Ingrowth into Porous-Surfaced Implants. Clinical Orthopaedics and Related Research, 208, 108-113.

[76]   Kieswetter, K., Schwartz, Z., Dean, D.D. and Boyan, B.D. (1996) The Role of Implant Surface Characteristics in the Healing of Bone. Critical Reviews in Oral Biology & Medicine, 7, 329-345.

[77]   Branemark, P.I. and Albrektsson, T. (1982) Titanium Implants Permanently Penetrating Human Skin. Journal of Plastic Surgery and Hand Surgery, 16, 17-21.

[78]   Bloebaum, R.D., Bachus, K.N., Rubman, M.H. and Dorr, L.D. (1993) Postmortem Comparative Analysis of Titanium and Hydroxyapatite Porous Coated Femoral Implants Retrieved from the Same Patient. Journal of Arthroplasty, 8, 203-211.

[79]   Vandamme, K., Naert, I., Geris, L., Sloten, J.V., Puers, R. and Duyck, J. (2007) Histodynamics of Bone Tissue Formation around Immediately Loaded Cylindrical Implants in the Rabbit. Clinical Oral Implants Research, 18, 471-480.

[80]   Uhthoff, H.K. and Germain, J.P. (1977) The Reversal of Tissue Differentiation around Screws. Clinical Orthopaedics and Related Research, 123, 248-252.

[81]   Meyer, A.E., Baier, R.E., Natiella, J.R. and Meenaghan, M.A. (1988) Investigation of Tissue/Implant Interactions during the First Two Hours of Implantation. The Journal of Oral Implantology, 14, 363-379.

[82]   Novaes Jr., A.B., Souza, S.L., Barros, R.R., Pereira, K.K., Iezzi, G. and Piattelli, A. (2010) Influence of Implant Surfaces on Osseointegration. Brazilian Dental Journal, 21, 471-481.

[83]   Boyan, B.D., Lohmann, C.H., Dean, D., Sylvia, V.L., Cochran, D.L. and Schwartz, Z. (2001) Mechanisms Involved In Osteoblast Response to Implant Surface Morphology. Annual Review of Materials Research, 31, 357-371.

[84]   Bobyn, J.D., Pilliar, R.M., Cameron, H.U. and Weatherly, G.C. (1980) The Optimum Pore Size for the Fixation of Porous-Surfaced Metal Implants by the Ingrowth of Bone. Clinical Orthopaedics and Related Research, 150, 263-270.

[85]   Brady, R.A., Leid, J.G., Calhoun, J.H., Costerton, J.W. and Shirtliff, M.E. (2007) Osteomyelitis and the Role of Biofilms in Chronic Infection. FEMS Immunology & Medical Microbiology, 52, 13-22.

[86]   Costerton, J.W. (2005) Biofilm Theory Can Guide the Treatment of Device-Related Orthopaedic Infections. Clinical Orthopaedics and Related Research, 437, 7-11.

[87]   Costerton, J.W., Geesey, G.G. and Cheng, K.J. (1978) How Bacteria Stick. Scientific American, 238, 86-95.

[88]   Geesey, G.G., Richardson, W.T., Yeomans, H.G., Irvin, R.T. and Costerton, J.W. (1977) Microscopic Examination of Natural Sessile Bacterial Populations from an Alpine Stream. Canadian Journal of Microbiology, 23, 1733-1736.

[89]   Gristina, A.G. and Costerton, J.W. (1984) Bacteria-Laden Biofilms: A Hazard to Orthopedic Prostheses. Infections in Surgery, 3, 655-662.

[90]   Lawrence, J.R., Korber, D.R., Hoyle, B.D., Costerton, J.W. and Caldwell, D.E. (1991) Optical Sectioning of Microbial Biofilms. Journal of Bacteriology, 173, 6558-6567.

[91]   Marrie, T., Nelligan, J. and Costerton, J.A. (1982) Scanning and Transmission Electron Microscopic Study of an Infected Endocardial Pacemaker Lead. Circulation, 66, 1339-1341.

[92]   Nickel, J.C., Ruseska, I., Wright, J.B. and Costerton, J.W. (1985) Tobramycin Resistance of Pseudomonas aeruginosa Cells Growing as a Biofilm on Urinary Catheter Material. Antimicrobial Agents and Chemotherapy, 27, 619-624.

[93]   ZoBell, C.E. (1943) The Effect of Solid Surfaces upon Bacterial Activity. Journal of Bacteriology, 46, 39-56.

[94]   Costerton, J., Stewart, P. and Greenberg, E. (1999) Bacterial Biofilms: A Common Cause of Persistent Infections. Science, 284, 1318-1322.

[95]   James, G.A., Swogger, E., Wolcott, R., Pulcini, E.D., Secor, P., Sestrich, J., Costerton, J.W. and Stewart, P.S. (2008) Biofilms in Chronic Wounds. Wound Repair and Regeneration, 16, 37-44.

[96]   Williams, D.L. and Costerton, J.W. (2011) Using Biofilms as Initial Inocula in Animal Models of Biofilm-Related Infections. Journal of Biomedical Materials Research. Part B, 100, 1163-1169.

[97]   Costerton, J.W. (2007) The Microbiology of the Healthy Human Body. In: Costerton, J.W., Ed., The Biofilm Primer, Springer, Heidelberg, 107-128.

[98]   van der Borden, A.J., van der Werf, H., van der Mei, H.C. and Busscher, H.J. (2004) Electric Current-Induced Detachment of Staphylococcus epidermidis Biofilms from Surgical Stainless Steel. Applied and Environmental Microbiology, 70, 6871-6874.

[99]   Charnley, J. (1972) Postoperative infection after Total Hip Replacement with Special Reference to Air Contamination in the Operating Room. Clinical Orthopaedics and Related Research, 87, 167-187.

[100]   Nelson, C.L., McLaren, A.C., McLaren, S.G., Johnson, J.W. and Smeltzer, M.S. (2005) Is Aseptic Loosening Truly Aseptic? Clinical Orthopaedics and Related Research, 437, 25-30.

[101]   Uchida, K., Yayama, T., Kokubo, Y., Miyazaki, T., Nakajima, H., Negoro, K., Takeno, K., Mwaka, E.S., Orwotho, N.T., Shimadzu, M., Kobayashi, S. and Baba, H. (2009) Direct Detection of Pathogens in Osteoarticular Infections by Polymerase Chain Reaction Amplification and Microarray Hybridization. Journal of Orthopaedic Science, 14, 471-483.

[102]   Harris, K.A., Fidler, K.J., Hartley, J.C., Vogt, J., Klein, N.J., Monsell, F. and Novelli, V.M. (2002) Unique Case of Helicobacter sp. Osteomyelitis in an Immunocompetent Child Diagnosed by Broad-Range 16s PCR. Journal of Clinical Microbiology, 40, 3100-3103.

[103]   Stoodley, P., Nistico, L., Johnson, S., Lasko, L.A., Baratz, M., Gahlot, V., Ehrlich, G.D. and Kathju, S. (2008) Direct Demonstration of Viable Staphylococcus aureus Biofilms in an Infected Total Joint Arthroplasty: A Case Report. Journal of Bone and Joint Surgery, 90, 1751-1758.

[104]   Blenkinsopp, S.A., Khoury, A.E. and Costerton, J.W. (1992) Electrical Enhancement of Biocide Efficacy against Pseudomonas Aeruginosa Biofilms. Applied and Environmental Microbiology, 58, 3770-3773.

[105]   Patel, R., Osmon, D.R. and Hanssen, A.D. (2005) The Diagnosis of Prosthetic Joint Infection: Current Techniques and Emerging Technologies. Clinical Orthopaedics and Related Research, 437, 55-58.

[106]   van der Borden, A.J., Maathuis, P.G., Engels, E., Rakhorst, G., van der Mei, H.C., Busscher, H.J. and Sharma, P.K. (2007) Prevention of Pin Tract Infection in External Stainless Steel Fixator Frames Using Electric Current in a Goat Model. Biomaterials, 28, 2122-2126.

[107]   van der Borden, A.J., van der Mei, H.C. and Busscher, H.J. (2005) Electric Block Current Induced Detachment from Surgical Stainless Steel and Decreased Viability of Staphylococcus epidermidis. Biomaterials, 26, 6731-6735.

[108]   Hetrick, E.M. and Schoenfisch, M.H. (2006) Reducing Implant-Related Infections: Active Release Strategies. Chemical Society Reviews, 35, 780-790.

[109]   Williams, D.L., Haymond, B.S., Beck, J.P., Savage, P.B., Chaudhary, V., Epperson, R.T., Kawaguchi, B. and Bloebaum, R.D. (2012) In Vivo Efficacy of a Silicone-Cationic Steroid Antimicrobial Coating to Prevent Implant-Related Infection. Biomaterials, 33, 8641-8656.

[110]   Darouiche, R.O. (2007) Antimicrobial Coating of Devices for Prevention of Infection: Principles and Protection. The International Journal of Artificial Organs, 30, 820-827.

[111]   Kalicke, T., Schierholz, J., Schlegel, U., Frangen, T.M., Koller, M., Printzen, G., et al. (2006) Effect on Infection Resistance of a Local Antiseptic and Antibiotic Coating on Osteosynthesis Implants: An in Vitro and in Vivo Study. Journal of Orthopaedic Research, 24, 1622-1640.

[112]   Lockwood, N., Hergenrother, R., Patrick, L., Stucke, S., Steendam, R., Pacheco, E., Virmani, R., Kolodgie, F.D. and Hubbard, B. (2010) In Vitro and in Vivo Characterization of Novel Biodegradable Polymers for application as Drug-Eluting Stent Coatings. Journal of Biomaterials Science, Polymer Edition, 21, 529-552.

[113]   Lucke, M., Schmidmaier, G., Sadoni, S., Wildemann, B., Schiller, R., Haas, N.P. and Raschke, M. (2003) Gentamicin Coating of Metallic Implants Reduces Implant-Related Osteomyelitis in Rats. Bone, 32, 521-531.

[114]   Sinclair, K.D., Farnsworth, R.J., Loc-Carrillo, C., Williams, D.L. and Bloebaum, R.D. (2012) Model Development for Determining the Efficacy of a Combination Coating for the Prevention Perioperative Device Related Infections: A Pilot Study. Journal of Biomedical Materials Research. Part B, 101, 1143-1153.

[115]   Sinclair, K.D., Pham, T.X., Farnsworth, R.W., Williams, D.L., Loc-Carrillo, C., Horne, L.A., Ingebretsen, S.H. and Bloebaum, R.D. (2012) Development of a Broad Spectrum Polymer-Released Antimicrobial Coating for the Prevention of Resistant Strain Bacterial Infections. Journal of Biomedical Materials Research. Part A, 100, 2732-2738.

[116]   Williams, D.L., Sinclair, K.D., Jeyapalina, S. and Bloebaum, R.D. (2012) Characterization of a Novel Active Release Coating to Prevent Biofilm Implant-Related Infections. Journal of Biomedical Materials Research. Part B, 101, 1078-1089.

[117]   Zhao, L., Chu, P.K., Zhang, Y. and Wu, Z. (2009) Antibacterial Coatings on Titanium Implants. Journal of Biomedical Materials Research Part B, 91B, 470-480.