Urine Aluminum Concentration as a Possible Implant Biomarker of Pseudomonas aeruginosa Infection Using a Fluorine- and Phosphorus-Doped Ti-6Al-4V Alloy with Osseointegration Capacity

Joint prosthesis failure is mainly related to aseptic loosening and prosthetic joint infections, both associated with high morbidity and a substantial cost burden for patients and health systems. The development of a biomaterial capable of stimulating bone growth while minimizing bacterial adhesion would reduce the incidence of prosthetic failure. Using an in vivo rabbit model, this study evaluates the osseointegration effect of the fluorine (F)- and phosphorus (P)-doped bottle-shaped nanostructured (bNT) Ti-6Al-4V alloy and effectiveness of monitoring urine aluminum concentration to determine the presence of Pseudomonas aeruginosa infection in Ti-6Al-4V implants. Unlike chemically polished (CP) Ti-6Al-4V alloy implants, bNT Ti-6Al-4V alloy implants promoted osseointegration and showed effectiveness as a biomaterial marker. The bNT Ti-6Al-4V alloy implants were associated with a twofold increase in bone thickness and up to 15% greater bone density compared to the CP alloy. Additionally, bNT Ti-6Al-4V alloy implants allowed for discrimination between P. aeruginosa-infected and noninfected animals for 15 days postoperatively, as indicated by the decrease of aluminum concentration in urine, while this difference was only appreciable over the first 7 days when CP Ti-6Al-4V alloy implants were used. Therefore, bNT Ti-6Al-4V alloys could have clinical applications by detecting the infection and by avoiding aseptic loosening.

[1]  M. Arenas,et al.  Microbiological and Cellular Evaluation of a Fluorine-Phosphorus-Doped Titanium Alloy, a Novel Antibacterial and Osteostimulatory Biomaterial with Potential Applications in Orthopedic Surgery , 2018, Applied and Environmental Microbiology.

[2]  P. Chu,et al.  Nano Ag/ZnO-Incorporated Hydroxyapatite Composite Coatings: Highly Effective Infection Prevention and Excellent Osteointegration. , 2018, ACS applied materials & interfaces.

[3]  A. Ingle,et al.  Osteogenic Nanofibrous Coated Titanium Implant Results in Enhanced Osseointegration: In Vivo Preliminary Study in a Rabbit Model , 2018, Tissue Engineering and Regenerative Medicine.

[4]  Haobo Pan,et al.  Synergistic Bacteria Killing through Photodynamic and Physical Actions of Graphene Oxide/Ag/Collagen Coating. , 2017, ACS applied materials & interfaces.

[5]  K. Dirscherl,et al.  Pectin nanocoating of titanium implant surfaces ‐ an experimental study in rabbits , 2017, Clinical oral implants research.

[6]  Á. Soriano,et al.  Time trends in the aetiology of prosthetic joint infections: a multicentre cohort study. , 2016, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[7]  R. Sierra,et al.  Pseudomonas Prosthetic Joint Infections: A Review of 102 Episodes , 2016, Journal of bone and joint infection.

[8]  M. Arenas,et al.  Bacterial and fungal biofilm formation on anodized titanium alloys with fluorine , 2016, Journal of Materials Science: Materials in Medicine.

[9]  F. Haddad,et al.  The epidemiology of failure in total knee arthroplasty: avoiding your next revision. , 2016, The bone & joint journal.

[10]  W. Tato,et al.  Influence of fluoride content and pH on corrosion and tribocorrosion behaviour of Ti13Nb13Zr alloy in oral environment. , 2015, Journal of the mechanical behavior of biomedical materials.

[11]  M. Arenas,et al.  Correlation of the nanostructure of the anodic layers fabricated on Ti13Nb13Zr with the electrochemical impedance response , 2015 .

[12]  B. Katona,et al.  Examination of the Surface Phosphorus Content of Anodized Medical Grade Titanium Samples , 2015 .

[13]  M. Arenas,et al.  TiO2 nanotubes with tunable morphologies , 2014 .

[14]  Á. Soriano,et al.  Gram-negative prosthetic joint infection: outcome of a debridement, antibiotics and implant retention approach. A large multicentre study. , 2014, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[15]  Robin Patel,et al.  Clinical Characteristics and Outcomes of Prosthetic Joint Infection Caused by Small Colony Variant Staphylococci , 2014, mBio.

[16]  A. Sanz-Medel,et al.  Evaluation of the biological effect of Ti generated debris from metal implants: ions and nanoparticles. , 2014, Metallomics : integrated biometal science.

[17]  B. Fauconneau,et al.  If exposure to aluminium in antiperspirants presents health risks, its content should be reduced. , 2014, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[18]  Ming Ni,et al.  Enhanced osteointegration of medical titanium implant with surface modifications in micro/nanoscale structures , 2014 .

[19]  C. Exley,et al.  Human exposure to aluminium. , 2013, Environmental science. Processes & impacts.

[20]  E. Gómez-Barrena,et al.  Doped TiO2 anodic layers of enhanced antibacterial properties. , 2013, Colloids and surfaces. B, Biointerfaces.

[21]  M. Brandi,et al.  Painful prosthesis: approaching the patient with persistent pain following total hip and knee arthroplasty. , 2013, Clinical cases in mineral and bone metabolism : the official journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases.

[22]  J. Ariza,et al.  Early prosthetic joint infection: outcomes with debridement and implant retention followed by antibiotic therapy. , 2011, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[23]  A. Sanz-Medel,et al.  Titanium release in serum of patients with different bone fixation implants and its interaction with serum biomolecules at physiological levels , 2011, Analytical and bioanalytical chemistry.

[24]  D. Olson,et al.  Corrosion in Titanium Dental Implants/Prostheses - A Review , 2011 .

[25]  C. Domingo,et al.  Morphologies of nanostructured TiO2 doped with F on Ti–6Al–4V alloy , 2011 .

[26]  Robin Patel,et al.  Clinical practice. Infection associated with prosthetic joints. , 2009, The New England journal of medicine.

[27]  Mel S. Lee,et al.  Gram-negative prosthetic joint infections: risk factors and outcome of treatment. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[28]  Á. Soriano,et al.  Outcome of Acute Prosthetic Joint Infections Due to Gram-Negative Bacilli Treated with Open Debridement and Retention of the Prosthesis , 2009, Antimicrobial Agents and Chemotherapy.

[29]  J. Parvizi,et al.  Biology of implant osseointegration. , 2009, Journal of musculoskeletal & neuronal interactions.

[30]  S. Odum,et al.  Why Revision Total Hip Arthroplasty Fails , 2008, Clinical orthopaedics and related research.

[31]  C. Marculescu,et al.  Polymicrobial Prosthetic Joint Infections: Risk Factors and Outcome , 2008, Clinical orthopaedics and related research.

[32]  M. S. Patton,et al.  Levels of systemic metal ions in patients with intramedullary nails , 2008, Acta orthopaedica.

[33]  E. Gómez-Barrena,et al.  Evaluation of Quantitative Analysis of Cultures from Sonicated Retrieved Orthopedic Implants in Diagnosis of Orthopedic Infection , 2007, Journal of Clinical Microbiology.

[34]  G. Murrell,et al.  A sensitive stain for aluminum in undecalcified cancellous bone. , 2007, Journal of inorganic biochemistry.

[35]  J. Clohisy,et al.  Aseptic loosening of total joint replacements: mechanisms underlying osteolysis and potential therapies , 2007, Arthritis research & therapy.

[36]  L. Wolford,et al.  Factors to Consider in Joint Prosthesis Systems , 2006, Proceedings.

[37]  A. Sargeant,et al.  Ion concentrations from hip implants. , 2006, Journal of surgical orthopaedic advances.

[38]  N D Priest,et al.  The biological behaviour and bioavailability of aluminium in man, with special reference to studies employing aluminium-26 as a tracer: review and study update. , 2004, Journal of environmental monitoring : JEM.

[39]  I. Boissevain [Laboratory rabbit?]. , 2003, Tijdschrift voor diergeneeskunde.

[40]  J. Galante,et al.  Metal release and excretion from cementless titanium alloy total knee replacements. , 1999, Clinical orthopaedics and related research.

[41]  J. Galante,et al.  Metal Release in Patients Who Have Had a Primary Total Hip Arthroplasty. A Prospective, Controlled, Longitudinal Study* , 1998, The Journal of bone and joint surgery. American volume.

[42]  H. Rack,et al.  Titanium alloys in total joint replacement--a materials science perspective. , 1998, Biomaterials.

[43]  Joshua J. Jacobs,et al.  Corrosion of metal orthopaedic implants. , 1998, The Journal of bone and joint surgery. American volume.

[44]  P. Ducheyne,et al.  Titanium serum and urine levels in rabbits with a titanium implant in the absence of wear. , 1996, Biomaterials.

[45]  L. Munuera,et al.  Influence of bacterial strains on bone infection , 1996, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[46]  S. Sampath Release and excretion of metal in patients who have a total hip-replacement component made of titanium-base alloy. , 1992, The Journal of bone and joint surgery. American volume.

[47]  Greger Jl Dietary and other sources of aluminium intake. , 1992 .

[48]  J. Galante,et al.  Release and excretion of metal in patients who have a total hip-replacement component made of titanium-base alloy. , 1991, The Journal of bone and joint surgery. American volume.

[49]  J Savory,et al.  Water content of aluminum, dialysis dementia, and osteomalacia. , 1985, Environmental health perspectives.

[50]  J. Shuster,et al.  The influence of skeletal implants on incidence of infection. Experiments in a canine model. , 1985, The Journal of bone and joint surgery. American volume.

[51]  P. R. Wilson,et al.  Animal model of aluminum-induced osteomalacia: role of chronic renal failure. , 1983, Kidney international.