ICMCTF2014 Session D1: Surface Functionalization, Drug Delivery, and Anti-microbial Coatings

Titanium and titanium alloys have found several applications in the biomedical field due to their unique biocompatibility. However, there are problems associated with these materials in applications in which there is direct contact with blood, for instance, thrombogenesis and protein adsorption. Surface modification is one of the effective methods used to improve the performance of titanium and titanium alloys in these circumstances. In this study, oxygen (O₂) plasma treatment on diamond-like carbon (DLC) film surfaces is studied, taking into account the wetting and biocompatible properties. All the films were prepared on silicon (100) wafers and nickel-titanium by a plasma-based ion implantation (PBII) technique using acetylene (C₂H₂) as plasma source. The as-deposited DLC films were then treated with O₂ plasma using various radio frequency (RF) powers and treatment times in order to characterize the wettability and biocompatibility, compared to as-deposited DLC, fluorinated diamond-like carbon (F-DLC), titanium alloys and polymers. The thickness and structure of the films were evaluated using stylus profilometer and Raman spectroscopy. The wettability was assessed using a contact angle meter. The friction coefficient was measured using ball-on-disk friction testing. Cytotoxicity tests were performed using MTT assay and dyed fluorescence. The results indicate the O₂ plasma treatment on DLC film surfaces influenced to thickness change, but unaffected to structure of the films with various RF powers and treatment times. These films present their hydrophilic surfaces due to a low contact angle and high surface energy. Further, O₂ plasma treatment on DLC film surfaces exhibits low friction coefficient and less cytotoxicity on their surfaces. It is concluded that O₂ plasma treatment can be used to make hydrophilic DLC, making it a favorable wetting surface and improving the biocompatibility for biomedical applications.

By considering micro-arc oxidation (MAO) technique to grow bioactive ceramic layer over titanium surface, it provides a wide range of benefits for implant purposes, porous structure (acting as scaffold) and strong film adhesion (avoiding delaminating during service) in particular. The aim of this study is to fabricate a biocompatible titanium dioxide (TiO₂) coating over the titanium metal via MAO technique, followed by covalently grafting bone morphogenetic proteins (BMP-2/BMP-7). The experimental results revealed that the MAO coatings are porous structure which facilitate hydroxylation of TiO₂ coating to presumably absorb and anchor protein molecules, and then Ca²⁺ and PO₄^3- to form apatite. The in-vitro test suggested that it favors oesteoblast cell growth over the protein grafted TiO₂ surface of the titanium substrate.

Keywords: titanium; micro-arc oxidation (MAO); titanium dioxide (TiO₂); covalently grafting; bone morphogenetic protein (BMP).

Biofilms are fascinating and complex structures that nowadays are recognize that constitute the predominant mode of growth of many bacterial species. A biofilm is an assemblage structure of microbial cells irreversibly associated with a surface and enclosed in a matrix of primarily polysaccharide material, this structure provides protection to the microbial communities from predation, toxic substances such as antibiotics and physical perturbation. Biofilms have the potential to cause device-related and other chronic bacterial infections that have gradually come to predominate in modern medicine causing harm to millions of humans annually. The difficulty of eradicating biofilm bacteria with classic systemic antibiotic treatments is a prime concern of medicine because the bacteria in a biofilm can be up to a thousand times less susceptible to antimicrobial stress than their freely suspended counterparts. Oral biofilms are important due to their relationship with two of the most important diseases that can be present in the oral cavity; gingivitis and periodontitis. These diseases are the pathological manifestation of the host response against the bacterial challenge from the dental biofilm that colonize the dental surface. The term peri-implantitis describe a destructive inflammatory process affecting the soft and hard tissues around osseointegrated implants, leading to the formation of a peri-implant pocket and loss of supporting bone, this infection is caused by a biofilm and it is well known that bacterial adhesion on implant surfaces has a strong influence on healing and long-term outcome of dental implants. The first indication of the specific role of bacteria in peri-implant infections was originated from microscopic analysis of samples taken from failing implants that shown an abundance of motile rods, fusiform bacteria and spirochetes, whereas samples from successful implants contained only a small number of coccoid cells and very few rods. These findings revealed a site-specific disease process with microorganisms associated in patterns known from chronic periodontitis of natural teeth. The formation, properties and composition of oral biofilms an also some factors that can influence biofilm formation on a biomaterial surface, like chemical composition, surface energy, hydrophilicity and topography will be discussed. Finally, it is pointed out the importance of the understanding of the mechanisms of biofilm formation on different biomaterial surfaces in order to control and prevent the formation of this structure and to assure the long-term successful life of biomedical devices like dental implants.

The modification of implant surfaces with antimicrobial properties has an important route to solve problems, such as infections and fouling, in biomedical applications and healthcare. A number of strategies have been applied for the modification of surfaces to inhibit bacterial adhesion and growth. Due to the increasing problems with multi-resistant microorganisms, especially in hospital environments, numerous efforts have been taken to fabricate surfaces to possess or release an antimicrobial agent, e.g. silver, copper etc. Silver ions are very efficient at killing bacteria, and in contrast to antibiotics they are effective against a number of different bacterial strains, owing to their several mechanisms of action. Therefore, Oerlikon Balzers has developed new antimicrobial silver doped titanium nitride (TiN-Ag) and chromium nitride (CrN-Ag) coatings for orthopaedic and medical devices. The use of silver as an additional phase in a nitride matrix provides additional wear resistance due to its tribological properties. Nevertheless, the incorporation of silver into the coatings for use in implant and medical devices must be adjusted to ensure a good balance between tribological and biomaterial properties. The characterization of the properties of these materials as extensively as possible can give us an opportunity to improve their properties for a founded choice of application.

TiN-Ag and CrN-Ag coatings were developed by a combined arc/sputter process. The coatings were characterised using transmission electron microscopy ( TEM), energy-dispersive X-ray spectroscopy (EDX) and X-ray diffractometry (XRD). The formation of island shaped agglomerations having grain sizes of about 8-10 nm x 3-4 nm in TiN-Ag coating containing 2,5 at% of silver was observed. Ag release properties were assessed in NaNO3 buffer and the maximum concentration of Ag released from the coatings was determined. The antibacterial properties of the TiN-Ag and CrN-Ag surfaces against S. aureus were determined by plate count technique, a test method based on ASTM E-2180 standards. Both surfaces showed a reduction compared with controls of 3 logs in bacterial adhesion. In order to verify the applicability of the coated samples as biomaterials, samples were assayed in terms of their effect on fibroblast cells and the coated surfaces did not affect the cell functionality.

References:

1. Knetsch M. L. W and Koole L. H. Polymers 2011, 3, 340.

2. Ewald A. BioMedical Engineering OnLine, 2006, 5, 22.

3. Chopra I. Journal of Antimicrobial Chemotherapy, 2007, 59, 587

Recently, magnesium alloys are considered revolutionary metallic biomaterials due to their biodegradability and Young's modulus being similar to that of human bone. However, their applications are hampered by poor corrosion resistance as well as low wear resistance. Plasma-based surface modification techniques including sputtering, filtered cathodic vacuum arc, and ion implantation are useful and environmentally friendly compared to most chemical methods. We have applied these technologies to modify the surface properties of magnesium alloys to meet actual requiements. A metallic interlayer is usually prepared to improve the adhesion between the insulating ceramic coating and magnesium substrate. However, it also provides the possibility of galvanic corrosion in aqueous enviroments via the defects such as pores and cracks in the coatings. Ion implantation involves a process in which ions are accelerated and impinge into the surface. Different from surface coatings, an ion-implanted layer does not have an abrupt interface and layer delamination is thereby not a serious issue. Samples with a complex shape can also be processed easily with a more advanced technique termed plasma immersion ion implantation (PIII). In this talk, recent work related to magnesium research conducted in our laboratory is described and reviewed.

This study focuses on the effect of different Cu/Zr ratios in Cu-Zr-Ag-Al thin film metallic glass (TFMG) on corrosion, mechanical and anti-microbial properties. The thin films were prepared by DC magnetron sputtering with different ratios of Cu-Zr targets and a Ag-Al target. The chemical composition of the thin films was determined by field emission electron probe micro-analyzer (FE-EPMA). The morphology of cross section of thin films was examined by field emission scanning electron microscope (FE-SEM). The amorphous state was analyzed by X-ray diffractometer (XRD). The mechanical properties including hardness and elastic modulus were verified by nano-indention tester. Differential scanning calorimetry (DSC) is applied to evaluate if the thin films have glass transition temperature (Tg) and crystalline temperature (Tx), which is the thermal characteristic of metallic glass. The electrochemical corrosion behavior was investigated in 3 wt.% NaCl solution and PBS solution, which is a type of simulated body fluid (SBF), and is used in anti-microbial experiment to cultivate bacteria. Liquid culture methods and plate counting methods are used to determined the anti-microbial performance of thin films. With increasing Cu/Zr ratio, corrosion potential was improved up to 30%. It is also revealed that with small amount of Ag adding in Cu-Zr-Ag-Al system, anti-microbial efficiency against E. coli is significantly improved. Finally, the appropriate composition with better corrosion resistance, mechanical and anti-microbial properties can be controlled and achieved.

Bioinert alloys such as 316L stainless steel, Ti and TiVAl alloys have been extensively studied. Attempts to develop a bioactive coating onto them have been made. In the current study, a sputtering technique has been used to develop a bone-like apatite layer on the surfaces of TiVAl alloys with different degrees of surface roughness. Coatings were evaluated for their structure, morphology ad durability in simulated body fluid media. Results showed the formation of a stable, homogeneous, and nanostructured apatite layer with interconnected porosity, which make them potential for further evaluations for total bone replacement applications.