Antibacterial and Biocompatible Titanium-Copper Oxide Coating May Be a Potential Strategy to Reduce Periprosthetic Infection: An In Vitro Study

Abstract

Background Periprosthetic infections are devastating for patients and more efficacious preventive strategies are needed. Surface-modified implants using antibacterial coatings represent an option to cope with this problem; however, manufacturing limitations and cytotoxicity have curbed clinical translation. Among metals with antibacterial properties, copper has shown superior in vitro antibacterial performance while maintaining an acceptable cytotoxicity profile. A thin film containing copper could prevent early biofilm formation to limit periprosthetic infections. This pilot study presents the in vitro antibacterial effect, cytotoxicity, and copper ion elution pattern of a thin film of titanium-copper oxide (TiCuO). Questions/purposes (1) Do titanium alloy (Ti6Al4V) discs coated with a thin film of TiCuO reduce Staphylococcus epidermidis biofilm and planktonic cell density compared with uncoated discs? (2) Do Ti6Al4V discs coated with a thin film of TiCuO affect normal human osteoblast viability compared with untreated cells? (3) Is copper ion concentration generated by coated discs lower than previously published copper ion concentrations that cause 50% toxicity in similar human cell lines in vitro (TC50)? Methods Ninety Ti6Al4V discs (12.5 mm diameter; 1.25 mm thick) were used in this study. Seventy-two Ti6Al4V discs were coated with a thin film of either titanium oxide (TiO) or TiCuO containing 20%, 40%, or 80% copper using high-power impulse magnetron sputtering (HiPIMS). Eighteen Ti6Al4V discs remained uncoated for control purposes. We tested antibacterial properties of S epidermidis grown on The institution of one or more of the authors (GAN, RP, MK, CCW, PJJ, KEB, ADH, RJS) has received funding in excess of USD 100,000 from Codelco (Codelco Lab, Santiago, Chile; FP00076314-01-S01) and in excess of USD 10,000 from the Mayo Clinic. With the exception of one of the authors (RJS), the investigators have not personally received any money related to this study. One of the authors certifies that he (RJS), or a member of his immediate family, has received or may receive payments or benefits, during the study period, in an amount of USD 10,000 to USD 100,000 from Biomet Inc (Warsaw, IN, USA Clinical Orthopaedics and Related Research ®A Publication of The Association of Bone and Joint Surgeons® discs in wells containing growth medium. After 24 hours, planktonic bacteria as well as biofilms removed by sonication were quantitatively cultured. Annexin/Pi staining was used to quantify in vitro normal human osteoblast cell viability at 24 hours and Day 7, respectively. Copper elution was measured at Days 1, 2, 3, 7, 14, and 28 using an inductively coupled plasma mass spectrometer to analyze aliquots of culture medium. Copper ion concentration achieved at 24 hours was compared with previously published TC50 for gingival fibroblast, a phenotypically similar cell line with available data regarding copper ion exposure. Results Discs coated with TiCuO 80% copper showed greater biofilm and planktonic cell density re...

Advances in the local and targeted delivery of anti-infective agents for management of osteomyelitis

“…As discussed above, metals such as copper have significant antimicrobial activity, and therefore have been considered for incorporation into titanium alloys. Norambuena et al supplemented (“doped”) the alloy of a titanium surface with copper to form titanium-copper oxide (TiCuO) at various concentrations of copper [96]. In vitro studies showed that high doses of copper (80%) were most effective in reducing biofilm and planktonic growth of S. epidermidis [96], a coagulase-negative species of staphylococcus that is an important clinical cause of implant-associated osteomyelitis [2,6].…”

“…Norambuena et al supplemented (“doped”) the alloy of a titanium surface with copper to form titanium-copper oxide (TiCuO) at various concentrations of copper [96]. In vitro studies showed that high doses of copper (80%) were most effective in reducing biofilm and planktonic growth of S. epidermidis [96], a coagulase-negative species of staphylococcus that is an important clinical cause of implant-associated osteomyelitis [2,6]. Although microbial growth was reduced, no significant changes were observed in the viability of osteoblast cells, clarifying the potential clinical utility [96].…”

“…In vitro studies showed that high doses of copper (80%) were most effective in reducing biofilm and planktonic growth of S. epidermidis [96], a coagulase-negative species of staphylococcus that is an important clinical cause of implant-associated osteomyelitis [2,6]. Although microbial growth was reduced, no significant changes were observed in the viability of osteoblast cells, clarifying the potential clinical utility [96]. Further studies have demonstrated similar effects with a second heavy metal, silver, as discussed above [82].…”

Development of Copper Oxide Thin Film for Lossy Mode Resonance-Based Optical Fiber Sensor

“…Here we introduce the use of copper(II) oxide (CuO) thin film for this purpose. Copper oxide is a p-type semiconductor that fulfills the optical criteria for LMR generation and is considered as a very promising material for biomedical applications [7,8].…”

Design and development of novel antibacterial Ti-Ni-Cu shape memory alloys for biomedical application

“…Copper could prevent early biofilm formation to limit periprosthetic infections7. Similar with the long well known antibacterial alloying element Ag, copper ions can effectively bind to the thiol groups (a characteristic of many bacterial proteins, and play a structural and functional role in the bacterial cells), change the permeability of the bacterial cell membrane, cause the generation of reactive oxygen species, protein oxidation and DNA degradation in bacteria cells, thus causing the death of bacteria8.…”