Vet Comp Orthop Traumatol 2019; 32(01): 041-050
DOI: 10.1055/s-0038-1676292
Original Research
Georg Thieme Verlag KG Stuttgart · New York

Copper Bead Therapy in Severe Bone Infection: A Rabbit Tibial Model

Carmen C. Surdu-Bob
1   Low Temperature Plasma Laboratory, National Institute for Lasers, Plasma and Radiation Physics, Magurele, Romania
,
Ene Vlase
2   Unit of Animal Experimentation “Cantacuzino” National Institute for Medico-Military Research and Development, Bucharest, Romania
,
Florica Barbuceanu
3   Department of Morphopathology, Institute for Diagnosis and Animal Health, Bucharest, Romania
,
Danut Turcu
4   “Spiru Haret” University, Veterinary Medicine Faculty, Bucharest, Romania
,
Mariana Coman
5   Department of Radiology, Marie Sklodowska Curie Children's Hospital, Bucharest, Romania
,
Marius Badulescu
1   Low Temperature Plasma Laboratory, National Institute for Lasers, Plasma and Radiation Physics, Magurele, Romania
,
Mariana Oporanu
6   ROMVAC Company S.A., Jud. Ilfov, Bucharest, Romania
,
Cristin Coman
2   Unit of Animal Experimentation “Cantacuzino” National Institute for Medico-Military Research and Development, Bucharest, Romania
› Author Affiliations
Further Information

Publication History

16 January 2018

26 September 2018

Publication Date:
15 January 2019 (online)

Abstract

Objective We investigated the benefits of a local preventive therapy based on copper beads against severe bone infection using a rabbit open tibial fracture model.

Materials and Methods Cotton mesh balls soaked in a very high concentration of Staphylococcus aureus ATCC 6538 culture were inoculated in drilled holes of the tibiae of treated and control groups. The treated group was also implanted with small copper beads simultaneously, as prevention therapy.

Results Survival rate in the treated group was 67% compared with 25% in the control group (difference 40%, for a 95% confidence interval: 40%, 93.4%). The few remaining animals in the control group had bone lesions which developed into osteomyelitis, while the tibiae of treated group had clear signs of reparatory processes. Sixty days after inoculation, signs of local-only toxicity were observed in healthy tibia of a separate non-infected control group. Drawbacks of copper toxicity were weighed against the threat of septicaemia and also against prolonged use of powerful systemic antibiotic medications in severe bone contamination.

Cinical Significance It was found that the proposed therapy prevented septicaemia and the spread of infection, and it also induced reparatory processes. The findings of this study may be relevant in antisepsis of open fractures in less appropriate medical settings (such as military camps or remote locations), as well as in severe bone infections.

Author Contribution

Carmen Cristina Surdu-Bob and Cristin Coman contributed to conception of study, study design, acquisition of data and data analysis and interpretation. Ene Vlase contributed to study design, acquisition of data and data analysis and interpretation. Florica Barbuceanu, Danut Turcu, Mariana Coman, Marius Badulescu and Mariana Oporanu contributed to acquisition of data and data analysis and interpretation. Carmen Cristina Surdu-Bob and Cristin Coman drafted, revised and approved the submitted manuscript. Ene Vlase, Florica Barbuceanu, Danut Turcu, Mariana Coman, Marius Badulescu and Mariana Oporanu approved the submitted manuscript.


 
  • References

  • 1 Jennison T, McNally M, Pandit H. Prevention of infection in external fixator pin sites. Acta Biomater 2014; 10 (02) 595-603
  • 2 O'Brien CL, Menon M, Jomha NM. Controversies in the management of open fractures. Open Orthop J 2014; 8: 178-184
  • 3 Niikura T, Lee SY, Iwakura T, Sakai Y, Kuroda R, Kurosaka M. Antibiotic-impregnated calcium phosphate cement as part of a comprehensive treatment for patients with established orthopaedic infection. J Orthop Sci 2016; 21 (04) 539-545
  • 4 Surdu-Bob CC, Coman C, Barbuceanu F, Turcu D, Bercaru N, Badulescu M. The influence of foreign body surface area on the outcome of chronic osteomyelitis. Med Eng Phys 2016; 38: 870-876
  • 5 Gogia JS, Meehan JP, Di Cesare PE, Jamali AA. Local antibiotic therapy in osteomyelitis. Semin Plast Surg 2009; 23 (02) 100-107
  • 6 Tuleubaev B, Saginova D, Abiyev T, Davletbaev M, Koshanova A. Local antibiotic therapy of osteomyelitis using nonabsorbable implant (review) [article in Russian]. Georgian Med News 2016; 255: 21-26
  • 7 Anagnostakos K, Schröder K. Antibiotic-impregnated bone grafts in orthopaedic and trauma surgery: a systematic review of the literature. Int J Biomater 2012; 2012: 538061
  • 8 Wang X, Cheng F, Liu J. , et al. Biocomposites of copper-containing mesoporous bioactive glass and nanofibrillated cellulose: biocompatibility and angiogenic promotion in chronic wound healing application. Acta Biomater 2016; 46: 286-298
  • 9 Shirai T, Tsuchiya H, Shimizu T, Ohtani K, Zen Y, Tomita K. Prevention of pin tract infection with titanium-copper alloys. J Biomed Mater Res B Appl Biomater 2009; 91 (01) 373-380
  • 10 Ionita D, Ungureanu C, Demetrescu I. Electrochemical and antibacterial performance of CoCrMo alloy coated with hydroxyapatite or silver nanoparticles. J Mater Eng Perform 2013; 22 (11) 3584-3591
  • 11 Kizuki T, Matsushita T, Kokubo T. Antibacterial and bioactive calcium titanate layers formed on Ti metal and its alloys. J Mater Sci Mater Med 2014; 25 (07) 1737-1746
  • 12 Mauerer A, Lange B, Welsch GH. , et al. Release of Cu2+ from a copper-filled TiO2 coating in a rabbit model for total knee arthroplasty. J Mater Sci Mater Med 2014; 25 (03) 813-821
  • 13 Tolerable Upper Intake Levels for Vitamins and Minerals. European Food Safety Authority European Commission, 2006; ISBN: 92-9199-014-0
  • 14 Mineral Tolerance of Animals. Washington: The National Academies Press; 2005
  • 15 Dollwet HH, Sorenson JR. Roles of copper in bone maintenance and healing. Biol Trace Elem Res 1988; 18: 39-48
  • 16 Prinz C, Elhensheri M, Rychly J, Neumann HG. Antimicrobial and bone-forming activity of a copper coated implant in a rabbit model. J Biomater Appl 2017; 32 (02) 139-149
  • 17 Surdu-Bob CC, Badulescu M. Synthesis of metal spheres obtained in an anodic arc plasma in high vacuum. Paper presented at: Joint Conference of the 7th MC & WG Meetings. COST ACTION P21 2009; Bucharest
  • 18 Zatulovskaia YA, Ilyechova EY, Puchkova LV. The features of copper metabolism in the rat liver during development. PLoS One 2015; 10 (10) e0140797
  • 19 Platzman I, Brener R, Haick H, Tannenbaum R. Oxidation of polycrystalline copper thin films at ambient conditions. J Phys Chem C 2008; 112 (04) 1101-1108
  • 20 Hans M, Erbe A, Mathews S, Chen Y, Solioz M, Mücklich F. Role of copper oxides in contact killing of bacteria. Langmuir 2013; 29 (52) 16160-16166
  • 21 Hans M, Támara JC, Mathews S. , et al. Laser cladding of stainless steel with a copper–silver alloy to generate surfaces of high antimicrobial activity. Appl Surf Sci 2014; 320 (00) 195-199
  • 22 Hofmann-Amtenbrink M, Grainger DW, Hofmann H. Nanoparticles in medicine: current challenges facing inorganic nanoparticle toxicity assessments and standardizations. Nanomedicine (Lond) 2015; 11 (07) 1689-1694
  • 23 Nijhof MW, Stallmann HP, Vogely HC. , et al. Prevention of infection with tobramycin-containing bone cement or systemic cefazolin in an animal model. J Biomed Mater Res 2000; 52 (04) 709-715
  • 24 Arciola CR, Campoccia D, Ehrlich GD, Montanaro L. Biofilm-based implant infections in orthopaedics. In: Donelli G. , ed. Biofilm-Based Healthcare-Associated Infections. Vol I. Switzerland: Springer International Publishing; 2015: 38
  • 25 Cassat JE, Hammer ND, Campbell JP. , et al. A secreted bacterial protease tailors the Staphylococcus aureus virulence repertoire to modulate bone remodeling during osteomyelitis. Cell Host Microbe 2013; 13 (06) 759-772
  • 26 Chai H, Guo L, Wang X. , et al. Antibacterial effect of 317L stainless steel contained copper in prevention of implant-related infection in vitro and in vivo. J Mater Sci Mater Med 2011; 22 (11) 2525-2535
  • 27 Muller P, van Bakel H, van de Sluis B, Holstege F, Wijmenga C, Klomp LW. Gene expression profiling of liver cells after copper overload in vivo and in vitro reveals new copper-regulated genes. J Biol Inorg Chem 2007; 12 (04) 495-507
  • 28 Wu JP, Pickle S. Extended use of the intrauterine device: a literature review and recommendations for clinical practice. Contraception 2014; 89 (06) 495-503
  • 29 Fíca A, Lamas C, Olivares F. , et al. Cotrimoxazole in bone-related infections: toxicity and clinical and economic impact [article in Spanish]. Rev Chilena Infectol 2015; 32 (06) 609-617
  • 30 Oyewo EO, Don-Pedro KN. Acute toxicity and induced weight changes in laboratory tests with Mn and Cu against Tilapia guineensis (Dumeril) and Tympanotonus fuscatus (Linne). J Environ Biol 2006; 27 (2, Suppl): 327-334
  • 31 Ren L, Yang K, Guo L, Chai HW. Preliminary study of anti-infective function of a copper-bearing stainless steel. Mater Sci Eng C 2012; 32 (05) 1204-1209