ICMCTF2012 Session D2-1: Coatings for Biomedical Implants

Functional coatings presenting a variety of functional chemical groups can be readily prepared by plasma polymerisation in an easy one-step process. Applications of such films span over a range of fields from modification of biomaterials to protective coatings.

In my talk, I will present recent developments from our group on various biomaterial coatings prepared by plasma polymerisation which include chemical and biomolecular gradients, and antibacterial coatings based on silver nanoparticles and conventional antibiotics.

Surface gradients have become important tools for studying and guiding cellular responses such as migration, adhesion, differentiation, etc. We generate gradients of various surface chemistries via plasma co-polymerisation over a moving mask. We used these chemical gradients to direct differentiation of kidney (KSC) and embryonic stem cells. We found that KSC express proximal tubule markers at medium amine group surface concentration and adapt a podocyte-like morphology at high.We extended these surface chemical gradients to density gradients of bound ligands, proteins and nanoparticles. We developed gradients of two proteins because gradients of single protein (employed in cell studies up to now) are probably too simplistic to mimic natural biological processes. We also developed density gradients of nanoparticles to use as a tool to study the effect of nanoscale surface features on cell behaviour.

Antibacterial coatings are important for many biomedical applications. We developed unique coatings based on silver nanoparticles which allow control over the rate of release of silver ions. As we show, the rate of silver release can be tuned such that it allows normal adhesion and spreading of mammalian cell and preserves the antibacterial properties of the coatings. We also developed two platforms for release of conventional antibiotics such as vancomycin and levofloxacin. Delicate control over the rate of release was achieved by a plasma polymer overlayer of a controlled thickness.

References:

K. Vasilev et al “Tunable antibacterial coatings that support mammalian cell growth” Nano Lett 10 (1), 202–207 (2010)

K. Vasilev et al “A PEG-density gradient to control protein binding: creating gradients of two proteins”, Biomaterials 31, 392–397 (2010)

S. Simovic, D. Losic and K Vasilev “Controlled drug release from mesoporous materials by plasma polymer deposition” Chem Commun 46, 1317 - 1319 (2010)

R.V. Goreham, R. D. Short and K. Vasilev “A Novel Method for the Generation of Surface-Bound Nanoparticle Density Gradients” J Phys Chem C 115 (8), 3429-3433 (2011)

The study of the protein adsorption is relevant to understand the interactions biological media–foreign material since the adsorbed protein layer on the material surface mediates the interactions cell-material, greatly determining the biological response. The protein adsorption on solid surfaces is mainly driven by the surface properties; different studies have shown that properties such as hydrophobicity or roughness influence protein adsorption. Also, certain crystalline phases of a material have been mentioned as to induce a more biocompatible response than other crystalline or amorphous phases of the same material. However, this is not fully understood and more studies are needed to get a deeper understanding of the processes occurring when surfaces of the same material but with different atom ordering interact with biological media.

In the present study titanium oxide, a potential material for biocompatible cotaings for orthopaedic and dental implants, was chosen as the model material to study the influence of surface atom ordering on protein adsorption. Albumin (BSA) and Fibrinogen (Fib) were chosen as the model proteins. Quasi-amorphous and polycrystalline titanium oxide thin films (qa-TiO₂ and pc-TiO₂) were deposited on Si(100) substrates by Reactive Magnetron Sputtering. The atom ordering, wettability, surface energy, roughness, optical properties and chemical composition of the films were characterized. The films were immersed in BSA and Fib solutions and the protein adsorption was studied in-situ using dynamic and spectroscopic ellipsometry. Then, after 2400 s of immersion the adsorbed protein layer was studied ex-situ in a dried ambient using Atomic Force Microscopy and X-Ray Photoelectron Spectroscopy (XPS).

The results showed that the film roughness decreased with atom ordering; however, their water contact angle increased from 74° for qa-TiO₂ to 85° for pc-TiO₂. For both proteins a higher adsorption rate was observed on pc-TiO₂ characterized for a total Δ change 3 degrees higher compared to that one for qa-TiO₂. The surface mass density of the adsorbed protein layer was higher on pc-TiO₂. The N at. % calculated form XPS after protein adsorption evidenced a slightly higher protein adsorption on pc-TiO₂; for BSA adsorption on pc-TiO₂ the N at. % was ≈ 5.3 while on qa-TiO₂ it was ≈ 4.7%. For Fib adsorption the difference was more notorious with a N at. % ≈ 8.2 on q-aTiO₂ and ≈ 28% on pc-TiO₂. The Differences observed in the protein adsorption on the two films might be related to the changes in the films hydrophobicity induced by the different surface atom ordering.

Researches show that 90% of the population over the age of 40 suffers from some degree of degenerative joint disease. Surgeries to repair or replace damaged joints are increasingly needed in recent years. However, current artificial joints made of Ti6Al4V have limited service lifetime due to their low wear resistance. The debris caused by wear results in tissue inflammation, osteolysis, and loosening of the implants, which is the main failure mechanism of artificial joints. Diamond-like carbon (DLC) coatings exhibit low friction coefficient, high wear resistance, and excellent biocompatibility and thus they are very promising protective coatings for artificial joints to prolong their service lifetime. However, DLC often suffers from high internal stress and poor adhesion on Ti6Al4V due to their thermal expansion mismatch.

In this research, nanodiamond/DLC composite coatings were deposited on Ti6Al4V substrates. Initially, nanocrystalline diamond particles were deposited on Ti6Al4V substrates by microwave plasma enhanced chemical vapor deposition to enhance adhesion and wear resistance of DLC. DLC thin film was then deposited on the predeposited substrate by ion beam deposition. Scanning electron microscopy, Raman spectroscopy and X-ray diffraction were used to characterize the microstructure of the Diamond/DLC composite. Nanoindentation and scratch tests were used to study the hardness and adhesion property of the films. The friction and wear tests were conducted using both ball- and pin- on-disc techniques. The results show that the nanocrystalline diamond particles can significantly enhance the adhesion between DLC thin film and Ti6Al4V substrate as well as the hardness and wear resistance of DLC.

Argon plasma surface treatment was introduced for the modification of the surface of drug-eluting stent (DES) coated with polymers in order to prevent the initial burst release of the drug. Currently, the implantation of DES is the most powerful way to treat coronary artery disease. DES elutes anti-proliferative drugs that suppress the proliferation of smooth muscle cells in the stented segment of the artery. Despite the impressive reduction in restenosis, DES still has a disadvantage for not preventing restenosis at the implant site due to the relatively vast drug release from the stent surface in the early stage of the release.

To solve the problem, we focused on argon plasma treatment. Argon gas is an inert gas without the risk of damaging the surface of the stent by surface treatment. In this experiment, polymers were used as drug-reservoir materials, where it was necessary to achieve the controllable and sustainable drug release from the polymers. Three biocompatible polymer films were selected as base drug-reservoir materials: hydrophilic 2-metacryloyloxyethyl phosphorylcholine (MPC), hydrophobic poly (ethylene-co-vinyl acetate) (EVA), and less hydrophobic polyurethane (PU). Structural analyses were carried out using scanning electron microscopy (SEM), atomic force microscopy (AFM), water contact angle measurements, and X-ray photon spectroscopy (XPS). By changing processing time of argon plasma from 5 sec to 45 sec, it was found that the initial burst release of drug, especially with EVA and PU films, was suppressed. These experimental results of the plasma treatment could provide a new and alternative approach to a controllable and sustainable drug release system.