Multifunctional calcium phosphate based coatings on titanium implants with integrated trace elements.

For decades, the main focus of titanium implants developed to restore bone functionality was on improved osseointegration. Additional antimicrobial properties have now become desirable, due to the risk that rising antibiotic resistance poses for implant-associated infections. To this end, the trace elements of copper and zinc were integrated into calcium phosphate based coatings by electrochemically assisted deposition. In addition to their antimicrobial activity, zinc is reported to attract bone progenitor cells through chemotaxis and thus increase osteogenic differentiation, and copper to stimulate angiogenesis. Quantities of up to 68.9 ± 0.1 µg cm- 2 of copper and 56.6 ± 0.4 µg cm- 2 of zinc were deposited; co-deposition of both ions did not influence the amount of zinc but slightly increased the amount of copper in the coatings. The release of deposited copper and zinc species was negligible in serum-free simulated body fluid. In protein-containing solutions, a burst release of up to 10 µg ml-1 was observed for copper, while zinc was released continuously for up to 14 days. The presence of zinc was beneficial for adhesion and growth of human mesenchymal stromal cells in a concentration-dependent manner, but cytotoxic effects were already visible for coatings with an intermediate copper content. However, co-deposited zinc could somewhat alleviate the adverse effects of copper. Antimicrobial tests with E. coli revealed a decrease in adherent bacteria on brushite without copper or zinc of 60%, but if the coating contained both ions there was almost no bacterial adhesion after 12 h. Coatings with high zinc content and intermediate copper content had the overall best multifunctional properties.

Surface modification of titanium-based alloys with bioactive molecules using electrochemically fixed nucleic acids.

A new method of surface modification for titanium (alloys) with bioactive molecules was developed with the intention of providing a new basis of implant adaptation for particular requirements of certain medical indications. Nucleic acid single strands are fixed electrochemically via their termini (regiospecifically) by growing an oxide layer on Ti6Al7Nb anodically. It could be shown that they are accessible to subsequent hybridization with complementary strands at physiological pH. Amount of nucleic acids immobilized and hybridized were determined radioanalytically using 32P-labelled nucleic acids. Stable fixation was attained at and above potentials of 4 V(SCE). Up to 4 pmol/cm2 of nucleic acid single strands could be immobilized and hybridization efficiencies up to 1.0 were reached. Hybridization efficiency was found to depend on surface density of immobilized oligonucleotides, while hybridization rates increased when MgCl2 was added. A conjugate consisting of an oligonucleotide complementary to the immobilized strand and the hexapeptide GRGDSP with RGD as an integrin recognition site was synthesized. This conjugate was able to bind to integrins on osteoblasts. It was shown that this conjugate binds to the anchor strand fixed on Ti6Al7Nb to an extent comparable with the unconjugated complementary strand.

Valacyclovir for the management of herpes viral infections.

The Herpesviridae family (Types 1-8) continues to inflict considerable morbidity and social stigma upon humanity. Once infected with the herpes viruses, especially Types 1-3, they establish permanent residence within our nervous system and reactivate during periods of stress, trauma, and/or other precipitating factors. To date, there is no cure for herpes viral infections but antivirals can attenuate the symptoms and duration of episodic outbreaks. Prophylactic therapy can suppress recurrences. The first antiviral with selective activity against virus-infected cells is considered to be acyclovir. Our article will highlight the clinical indications of the current generation, valacyclovir, which is a prodrug of acyclovir. We consider valacyclovir as a second-generation antiviral, having taken into account the initial selectivity and safety profile of its progenitor, acyclovir.

Electrochemical behavior of titanium-based materials - are there relations to biocompatibility?

For biomedical applications the physico-chemical properties of oxide layers, always present in titanium-based materials, are of special interest because the biological system is in direct contact only with these oxides. Using electrochemical impedance spectroscopy and galvanostatic polarization it is shown that the different compositions of c.p.-titanium, Ti6Al4V, and Ti6Al7Nb result in different physico-chemical properties of air formed passive layers and anodic oxide layers. This may have a direct impact on the biocompatibility of these materials. Results of impedance spectroscopy distinctly differ in the flatband potentials as well as in the donor densities of air-formed passive layers with Ti6Al7Nb showing an approximately 50% smaller donor density than the other materials. Anodic galvanostatic polarization results in voltage-charge density curves with distinct differences in the Faraday efficiency epsilon of the oxide formation between Ti6Al7Nb and c.p.-titanium/Ti6Al4V, especially for low current densities. These effects correlate strongly with the donor densities in the air formed passive films of the examined materials. SEM-images of anodic oxide layers show a blister containing surface morphology of the outer part of the oxide layers for all materials. This morphology is probably caused by oxygen evolution, a process which relies on the transfer of electrons through the growing anodic oxide layers and strongly depends on the donor density in the air formed passive layers. Again, the much more pronounced morphology on c.p. titanium/Ti6Al4V agrees with the different donor densities in the air formed passive layers on the materials. These findings correlate with the good biocompatibility of Ti6Al7Nb and suggest that conduction mechanisms, in air formed passive layers and anodic oxide layers, contribute to processes that determine the biocompatibility of these materials.