ICMCTF2010 Session TS3-2: Bioactive Coatings and Surface Biofunctionalization

Bioadhesive drug delivery platforms are desirable because they can adhere semi-permanently to tissues of interest and release drugs in a localized manner. Bioadhesive polymers have been investigated as particle carriers or as coating agents aiming to overcome the rapid elimination. By prolonging particle residence time, some types of bioadhesive polymers may establish specific interactions with the gastrointestinal mucosa allowing opportunity for target drug delivery. Numerous of drug molecules (particularly macromolecular drugs) presenting low oral bioavailability as well as low stability in the tract could be incorporated in such systems. Previous work has almost entirely concentrated on polymers or chemical strategies to improve bioadhesion. Polymer adhesives typically target mucin, instead of cells, allowing the devices to be rapidly cleared in mucous flows. Lectins have been successful as chemical modifications, binding specifically to cells. However, it may be possible to improve upon the chemical modifications by integrating topographical features which have previously been shown to direct and improve adhesion. Following research on gecko setae adhesion, nanowires and nanotubes have been shown to be highly adhesive due to Van der Waals forces arising from their increased surface area. Although it is known that nanostructures can enhance dry adhesion of films, no work has been carried out to investigate the adhesive properties of nanowire interfaces in physiological settings, particularly for drug delivery. Here we demonstrate that silicon-based nanowire interfaces can help anchor the particle to the cell surface and allow for greater residence time and localized drug release.

In particular, the adhesivity of devices with silicon nanowires was investigated under biological conditions, and showed superior bioadhesive properties in vitro. Adhesion studies under static and dynamic conditions, in conjunction with AFM studies, quantitatively show that nanowires adhere to cells better than conventionally used chemical bioadhesives. In vivo studies show enhanced retention with nanowire devices compared to uncoated devices. In combination with advancements in biosensing and microfabrication, the use of nanowires at a biointerface is a significant step in the direction of creating responsive drug release systems.

Up to date, wide variety of techniques including conventional photolithography, soft lithography, self-assembled monolayers (SAMs), direct writing, and laser ablation have been developed to functionalize the surface of interest with patterns to align cells and to control their functions. These techniques require masks, master stamps which may further need necessitates clean room instrumentation, long processing time, complex chemistry that may denature or degrade the deposited bio-organic layer. In addition, the requirement of mask and master stamps restrict the flexibility in patterning process while increasing the operating costs. In current study, we are introducing a versatile cell patterning approach; called freeform plasma generated maskless cell patterning.The freeform maskless patterning on biopolymer surface is done by the plasma nozzle system being able to create pattern on a substrate without using any chemical, solvent and mask. The plasma nozzle system is based on the principle of dielectric barrier discharges (DBD) operating with microsecond pulsed power supply and electrode system. To move the plasma nozzle system in freeform the nozzle system is integrated into data processing system, and the 3D motion system.

In current study, through freeform plasma generated maskless cell patterning approach the authors patterned mouse osteoblast cells on polyethylene. As working gas O2/He mixture was used. In order to create a line pattern on polymer surface, the plasma nozzle was navigated on a straight line with a 2mm/s speed. Following the patterning, the cells were deposited on the substrate to observe the effectiveness of effect of freeform plasma generated maskless cell patterning approach. The surface characterization was done by SEM and XPS. The SEM data showed that the surface functionalized with plasma nozzle system increased the surface roughness along the patterned line while rest of the substrate surface presented smooth surfaces. The XPS data showed that the atomic concentration of oxygen increased from 5% for virgin polymer to 18% for the center of the plasma treated line. This increment showed higher value on the line center and started to decrease by the lateral distance. The biological characterization has been done by Hoechst Stain 33258 through staining the nucleus of the patterned cells. The data showed that the cells only attached and survived on plasma functionalized patterned line while untreated surface showed no viability. Based on these data, we can say that it is possible to pattern the cells and dictate their shapes through freeform plasma generated maskless cell patterning approach.

Therefore in the frame of our examinations the surfaces of polyetherurethane and silicones, two typical flexible implant materials, have been modified by non-thermal electron beam processing. After doing this the new surfaces were characterized with regard to wetting behavior, surface energy, chemistry and morphology. The cell adhesion was examined too.

The results reveal that the electron beam is a proper tool for surface modification of polymers.

Experimental results show that TiO₂ coating can be grown on and well-adhered to β-Ti. The anatase phase formed under a low applied voltage, while the rutile phase formed under a high applied voltage, indicating that crystal structure is strongly influenced by applied voltage. A porous morphology was obtained in the TiO₂ coating regardless of the crystal structure and exhibited superior bone formation performance than β-Ti. In vivo analysis and in vitro test show similar trends. It is also noticeable that the R rich TiO₂ coating achieved better biocompatibility, osteogenesis performance. Therefore, a MAO-treated R rich TiO₂ coating can serve as a novel surface modification technique for β-Ti alloy implants.