ICMCTF2010 Session TS3-2: Bioactive Coatings and Surface Biofunctionalization

Tuesday, April 27, 2010 1:30 PM in Room Sunset
Tuesday Afternoon

Time Period TuA Sessions | Abstract Timeline | Topic TS3 Sessions | Time Periods | Topics | ICMCTF2010 Schedule

Start Invited? Item
1:30 PM Invited TS3-2-1 Engineering Nanostructured Devices for Bioadhesive Drug Delivery
Tejal Desai (University of California)

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.

2:10 PM TS3-2-3 Freeform Plasma Generated Maskless Cell Patterning for Tissue Engineering Applications
Eda Yildirim-Ayan (Drexel University); Halim Ayan (Murray State University); Daphne Pappas (U.S. Army Research Laboratory); Alexander Fridman, Wei Sun (Drexel University)

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.

2:30 PM TS3-2-4 Surface Modification of Polyurethane and Silicone for Therapeutic Medical Technics by Means of Electron Beam
Christiane Wetzel, Jessy Schönfelder, Wolfgang Schwarz (Fraunhofer Institute for Electron Beam and Plasma Technology, Germany); Richard Funk (University of Technology Dresden - Institute of Anatomy, Germnay)
To enhance biocompatibility of implant materials surface modification technologies are becoming in use steady more.

But concerning electron beam applications only little is reported for such purposes, despite of a few of advantages like adjustable degree of modification and efficacy in depth as well as simultaneous sterilising effects; in summary a careful treatment of sensible substrates by this method.

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.

2:50 PM TS3-2-5 Modification of the Surface of Polymer Implants by Deposition of Multifunctional Bioactive Nanostructured Films (MuBiNaFs) With and Without Stem Cells
Dmitry Shtansky, Irina Bashkova, Alexander Sheveiko (National University of Science and Technology "MISIS", Russia); M. Jimenez de Haro (Instituto de Ciencia de Materiales de Sevilla, Spain); A. Grigoryan (Central Research Dental Institute, Russia)
Recently, a new approach to design perspective films for metallic implants has been developed by our group. Multifunctional bioactive nanostructured films (MuBiNaFs) were deposited by magnetron sputtering of composite targets based on TiC0.5 and (Ti,Ta)C with various inorganic additives CaO, TiO2, ZrO2, Ca3(PO4)2, Si3N4, and Ca10(PO4)6(OH)2. While Teflon (polytetrafluoroethylene, PTFE) is widely used for the construction of surgical implants in restorative surgery, the surface of Teflon shows hydrophobic properties, cells do not attach the PTFE surface, and the interfacial bonding between the polymer surface and the surrounding bone is poor or does not exist at all. An effective way to promote the formation of bone-like layer on the polymer implant surface is the deposition of multifunctional bioactive film. The present work is focused on the investigation of the structure and properties of MuBiNaFs deposited on the surface of PTFE. The film morphology and phase composition were examined using X-ray diffraction, scanning electron microscopy, and Raman spectroscopy. The films were characterized in terms of their adhesion to PTFE substrate, hardness, elastic modulus, elastic recovery, wettability, electrochemical characteristics, friction and wear both under physiological solution (100 ml H2O + 0.9 g NaCl) and Dulbecko modified Eagle medium with Fetal calf serum. The biocompatibility and bioactivity of the films were evaluated by both in vitro and in vivo experiments. In vitro studies involved the investigation of adhesion, spreading and proliferation of human fibroblast cells. Two groups of the in vivo investigations were fulfilled. Polymer fibres, 15% porosity, with MuBiNaFs were implanted in the rat hip defect and hybrid implants [stem cells from rabbit adipose tissue/MuBiNaFs/PTFE porous membrane] were implanted in the rabbit calvarian defect. The MuBiNaFs/PTFE samples demonstrated hardness H=0.6 GPa, Young’s modulus E=5 GPa, and percentage of elastic recovery We=57-62% that is higher then that of PTFE sample without film (H=0.04 GPa, E=0.9 GPa, and We=31%). Static water contact angle measurements showed hydrophilic nature of the film surfaces. Critical load measurements using scratch tester with Al2O3 ball as counterpart material indicated high adhesion strength. Human fibroblasts were well adhered and spread on the surface of polymer coated with MuBiNaFs. The MuBiNaFs/PTFE implants revealed a high level of biocompatibility and osteointegration in the experiments in vivo.
3:10 PM Invited TS3-2-6 Nanotechnology for Improving Regenerative Medicine
Thomas Webster (Brown University)
Much work is needed to design more effective tissue engineering materials. This could not be more evident by the fact that the average lifetime of current orthopedic implants is less than 15 years. Frequently, current implants fail due to insufficient integration into juxtaposed tissues (for example, bone, vascular, etc.). Nanotechnology offers exciting alternatives to traditional implants since our tissues are composed of constituent nanostructured components. For example, bone is composed of nanofibered hydroxyapatite well-dispersed in a mostly collagen matrix. Thus, it stands to reason that cells are accustomed to interacting with nanostructured (not conventionally-structured) surfaces. For these reasons, we have synthesized novel nanophase (that is, materials with dimensions less than 100 nm in at least one direction) ceramics, metals, polymers, and composites thereof. To date, increased synthesis of bone, cartilage, vascular, and bladder tissue have been observed on nanophase compared to conventional materials. Recently, increased functions of neurons have also been observed on nanophase materials. In this manner, results of studies demonstrating increased tissue regeneration on nanophase compared to conventional materials pertinent for the regeneration of a wide range of tissues will be presented in this talk.
3:50 PM TS3-2-8 Osteoblast Growth Affected by Micro-arc Oxidized β-titanium Alloy
Hsien-Te Chen (Feng Chia University; China Medical University Hospital, Taiwan); Chi-Jen Chung (Central Taiwan University of Science and Technology, Taiwan); Tsai-Ching Yang (Feng Chia University, Taiwan, R.O.C.); I-Ping Chiang, Chin-Hsin Tang (China Medical University, Taiwan); Keh-Chang Chen, Ju-Liang He (Feng Chia University, Taiwan)
β-titanium (β-Ti) alloys are known for their excellent physical properties and biocompatibility, and are therefore considered as next-generation metals for orthopedics and dental implants. To improve the osseous integration between β-Ti alloys and bone, this study develops a titanium dioxide (TiO2) coating on the surface of β-Ti alloys by using micro-arc oxidation (MAO) technique. The anatase (A) rich and rutile (R) rich TiO2 layer, were formed on β-Ti, respectively. In vitro tests were carried out using pre-osteoblast cell (MC3T3-E1) to determine biocompatibility and osteogenesis performance. Biocompatibility includes cell adhesion, cell proliferation, and ALP activity, while the later includes osteopontin (OPN), osteocalcin (OCN) and calcium content. Cell morphology was also observed. In addition, raw β-Ti, A rich TiO2 and R rich TiO2 were implanted into the distal femora of Japanese white rabbits for 4, 8, and 12 weeks to evaluate its in vivo performance.

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.

4:10 PM TS3-2-9 Development of Surface Modification Techniques for the Covalent Attachment of Insulin-Like Growth Factor-1 (IGF-1) on PECVD Silica-Coated Titanium
Sunil Kumar, Endre Szili (University of South Australia); Mark DeNichilo (TGR BioSciences, Australia); Roger Smart (University of South Australia); Nicolas Voelcker (Flinders University of South Australia)
Osseointegration is a complex process governed by the interaction of many cell types including blood cells (erythrocytes, platelets and leukocytes), phagocytic cells (macrophages) and bone cells (osteoblasts and ostecoclasts) on or near the implant surface. The implant surface can be modified through a variety of methods in order to achieve control of some of these cellular interactions and consequently increase the degree of implant fixation with the surrounding bone tissue. In the work presented in this paper, titanium, a common bone implant material, was modified with hydroxylated silica deposited using plasma enhanced chemical vapour deposition (PECVD) to increase the surface hydrophilicity and generate reactive surface silanol groups. Subsequently, the silica-coated titanium surface was further modified through silanisation to generate surfaces bearing different reactive chemical functionalities consisting of aldehydes, epoxides and isocyanates, which can react with the amino groups of proteins and growth factors. 2,2,2-trifluoroethylamine (FEAM) was reacted on these surfaces to determine the coupling efficiency of the different surface chemical functionalities. The amino group of FEAM can react with an amino-reactive surface functional group to form a surface terminated with 3 fluorine atoms per FEAM molecule that can be detected by X-ray photoelectron spectroscopy. By analysing the techniques used for protein attachment with the FEAM model molecule, a successful method was found and later adapted for tethering IGF-1 molecules to the functionalised PECVD silica-coated titanium surface. Therefore, this simple method of preliminary testing protein reactivity may prove to be a cost effective strategy in the development of new biomaterial surfaces modified with tethered protein bioconjugation methods.
Time Period TuA Sessions | Abstract Timeline | Topic TS3 Sessions | Time Periods | Topics | ICMCTF2010 Schedule