Antibacterial Titanium Implants Biofunctionalized by Plasma Electrolytic Oxidation with Silver, Zinc, and Copper: A Systematic Review

Abstract

Patients receiving orthopedic implants are at risk of implant-associated infections (IAI). A growing number of antibiotic-resistant bacteria threaten to hamper the treatment of IAI. The focus has, therefore, shifted towards the development of implants with intrinsic antibacterial activity to prevent the occurrence of infection. The use of Ag, Cu, and Zn has gained momentum as these elements display strong antibacterial behavior and target a wide spectrum of bacteria. In order to incorporate these elements into the surface of titanium-based bone implants, plasma electrolytic oxidation (PEO) has been widely investigated as a single-step process that can biofunctionalize these (highly porous) implant surfaces. Here, we present a systematic review of the studies published between 2009 until 2020 on the biomaterial properties, antibacterial behavior, and biocompatibility of titanium implants biofunctionalized by PEO using Ag, Cu, and Zn. We observed that 100% of surfaces bearing Ag (Ag-surfaces), 93% of surfaces bearing Cu (Cu-surfaces), 73% of surfaces bearing Zn (Zn-surfaces), and 100% of surfaces combining Ag, Cu, and Zn resulted in a significant (i.e., >50%) reduction of bacterial load, while 13% of Ag-surfaces, 10% of Cu-surfaces, and none of Zn or combined Ag, Cu, and Zn surfaces reported cytotoxicity against osteoblasts, stem cells, and immune cells. A majority of the studies investigated the antibacterial activity against S. aureus. Important areas for future research include the biofunctionalization of additively manufactured porous implants and surfaces combining Ag, Cu, and Zn. Furthermore, the antibacterial activity of such implants should be determined in assays focused on prevention, rather than the treatment of IAIs. These implants should be tested using appropriate in vivo bone infection models capable of assessing whether titanium implants biofunctionalized by PEO with Ag, Cu, and Zn can contribute to protect patients against IAI.

TiAl6V4 Alloy Surface Modifications and Their Impact on Biofilm Development of S. aureus and S. epidermidis

“…This has led to the invention of many new types of titanium-based orthopedic materials with not only a higher resistance to corrosion and better tribological properties [14,15], but also improved mechanical properties [16][17][18][19]. In addition, biocompatibility [19] and resistance to bacterial infections [12,[20][21][22] can be positively influenced by those newly developed materials. As mentioned above, S. aureus and S. epidermidis are especially prone to cause device-related infections, and they are used in many biofilm-related studies in the field of orthopedics [6,[21][22][23][24][25][26][27].…”

“…In addition, biocompatibility [19] and resistance to bacterial infections [12,[20][21][22] can be positively influenced by those newly developed materials. As mentioned above, S. aureus and S. epidermidis are especially prone to cause device-related infections, and they are used in many biofilm-related studies in the field of orthopedics [6,[21][22][23][24][25][26][27].…”

Toward Bactericidal Enhancement of Additively Manufactured Titanium Implants

“…Similar to the method used for the preparation of the Ag coating, ion implantation [178], PEO [16], sol-gel [179], and electrodeposition [180] are applied in the preparation of copper coatings. For AM implants with complex geometries, PEO [16] and electrochemically assisted deposition [180] seem to be the superior methods.…”

“…Similar to the method used for the preparation of the Ag coating, ion implantation [178], PEO [16], sol-gel [179], and electrodeposition [180] are applied in the preparation of copper coatings. For AM implants with complex geometries, PEO [16] and electrochemically assisted deposition [180] seem to be the superior methods. Interestingly, the application of copper as an antibacterial active substance in implants is not only through surface modification; copper-containing titanium alloy has also received much interest from researchers [181][182][183].…”

“…They facilitate the controlled local release of antimicrobial agents that kill bacteria on the surface of the implant and around the tissue. Antibiotics [11], antibacterial active metals (such as silver (Ag) [12][13][14], copper (Cu) [15], zinc (Zn) [16]), and metal oxides [17] are widely applied in the study of implant antimicrobial surfaces. In a meta-analysis of 23 studies, Tsikopoulos et al showed that a combination of active and passive antibacterial surfaces reduced the risk of IAIs [18].…”