Surface Modification of Orthopedic and Dental Implants

The development of a new technology, IL-based, to modify the surface of metals has been developed by our research group. Ionic liquids (ILs) are a class of low temperature molten salts, comprised of an amphiphilic cationic moiety and a weekly coordinated anion1 (Figure 1 (a)). Despite having been described almost a century ago, ionic liquids recently attracted interest in a diverse array of applications ranging from synthetic processes in chemistry2 to a number of biological processes3 and utilization as active pharmaceutical ingredients (APIs)4. The most attractive property of ILs, is the flexibility or ‘tunability’ in the design of physical, chemical and biological properties by changing the structure of the cation and anion5. This possibility has helped to drive this phenomenal interest in the field of ILs. The feasibility of functionalization of titanium surface with IL has been investigated. The electronic structure of TiO2 plays a key role in the interaction mode between the oxide surface and other materials. Considering that titanium surfaces are highly charged, where Ti+ cations are at closer proximity to the surface and are coordinately unsaturated acting as Lewis acids (electron pair acceptor), the anions of ILs can easily adsorb onto these positively charged sites. The hypothesized mechanism of interaction between charged surface layers with the ILs is illustrated in Figure 1 (b). The counter cations would then assemble successively by the electron neutrality principle6.

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Figure 1. (a) Generic structure of Ionic Liquids and (b) Schematic representation of IL adsorbed on TiO2.

Initial experiments involving titanium nanoparticles were performed in order to verify the affinity of ILs with titanium surfaces with imidazolium derived ILs having as contra-ion the anions Br-, BF4 and NTf2-. TiO2 nanoparticles were used instead of bulk titanium in order to allow for a better understanding of the intermolecular interaction of selected ILs with the Ti oxide film (TiO2). Figure 2 (a) shows the hypothesized structure for coating process of nanoparticles. The interaction between TiO2 nanoparticles and IL was monitored by several thermal and spectroscopy techniques, which allowed identifying the interactions between IL-TiO2. Figure 1 (b) shows a TEM image of pure and coated nanoparticles. It is observed a thin film surrounding the nanoparticles which confirmed deposition of IL on TiO2 surface.

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Figure 2. (a) Representation of the coating process of TiO2 nanoparticles from Gindri et. al (2014) [7].

In order to assess potential application of this coating technology on the surface of dental implants, the interaction of dicationic imidazolium-based ionic liquids and titanium was further studied by dip coating titanium surfaces in amino acid based and NTf2- ILs. The varying alkyl chains lengths and anions in these ILs were used to understand how hydrophobicity and functionalized moieties can affect the coating on titanium surfaces. X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) were used to help elucidate the deposition profile and intermolecular interactions of the ILs, respectively. Figure 3 gives an overview for the dip coating and characterization procedure performed for all ILs. The concentration of deposited IL, and nature of amino acid functional group in anionic moieties were found to influence the deposition profile. It was also found that hydrophobicity influences the adhesion strength of ILs to titanium, with the most hydrophobic anion NTf2 having the highest adhesion strength.

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Figure 3. Representation of dip coating of titanium disks in IL and characterization of the coating interactions and morphology using XPS and AFM.8

After understanding the coating structure of ILs on Ti surfaces, the next step was to assess the potential compatibility of the coatings with mammalian and bacterial cells. Dental implants are exposed to large populations of bacteria upon placement, while trying to maintain attachment with bone and soft tissue cells for successful implant integration. Ideally, these coatings should mediate bacterial infiltration of an implant surface while remaining non-cytotoxic to host cells. Cytotoxicity has been broadly attributed to monocationic ILs, but not heavily investigated for dicationic imidazolium-based ILs. In order to evaluate the effect of our amino acid based ILs to bacterial and mammalian cells, IL-coated Ti disks were cultured with bone-forming (MC3T3-E1) cells, tissue forming (HGF-1) cells and separately with relevant oral bacteria strains, shown in Figure 4. It was found that the IL containing phenylalanine allowed for successful cell proliferation and differentiation, and also decreased both IC50 (concentration necessary to inhibit 50% of enzymatic activity) and the minimum inhibitory concentration (MIC), showing strong anti-microbial activity. This study shows that dicationic imidazolium-based ionic liquids are a potent strategy for applications requiring both anti-microbial activity and cell compatibility.

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Figure 4. Log colony Forming Units (CFU) per mL of oral bacteria after exposure to uncoated and IL 1 (phenylalanine containing) coated titanium [9].

Although titanium dental implants are successful because of their mechanical strength and corrosion resistance, the titanium surface is subjected to several corrosion and wear processes. Friction from insertion, chewing, and pH fluctuations in saliva can compromise the integrity of the implant surface, creating conditions that can potentially induce implant failure. Coatings to improve the corrosive and lubricating properties of dental implants have yet to be investigated, so Dicationic imidazolium-based ionic liquids were considered as a possible solution to improve these properties. IL-coated titanium samples were subjected to a series of electrochemical tests, shown in (Figure 5). to evaluate the corrosion resistance of the coating. To evaluate the lubricant properties, IL-coated samples were subjected to tribological wear testing. IL-coated samples were found to lower corrosion rate values as well as show enhanced lubrication through a significant reduction in the coefficient of friction and total wear volume loss in comparison to an uncoated control.

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Figure 5. Overview of electrochemical set-up used to evaluate the anti-corrosive properties of IL-coated titanium [10].

Through these studies, we have found that dicationic imidazolium-based ionic liquids act as stable coatings for titanium surfaces. In addition, these coatings exhibit corrosion-resistant, antimicrobial, and lubricative properties while maintaining compatibility with host cells. Due to these properties, ILs can be advantageously used as multifunctional coatings for dental implants to prevent failures and improve overall dental implant performance.

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(8) Gindri, I. M.; Siddiqui, D.A.; Frizzo, C.P.; Martins. M. A. P.; Rodrigues, D.C. Appl. Mater. Interfaces 2015.
(9) Gindri, I. M.; Palmer, K; Siddiqui, D. A.; Aghyarian, S.; Frizzo, C.P.; Martins. M. A. P.; Rodrigues, D.C. Appl. Mater. Interfaces 2016
(10) Gindri, I. M.; Siddiqui, D.A.; Frizzo, C.P.; Martins. M. A. P.; Rodrigues, D.C. Appl. Mater. Interfaces 2016