Improving antimicrobial release kinetics from hydrophobic polymer implants via ion pairing to combat biomedical-device related infection

Purpose The aim of this study is to improve the drug release properties of antimicrobial agents from hydrophobic biomaterials using using an ion pairing strategy. In so doing antimicrobial agents may be eluted and maintained over a sufficient time period thereby preventing bacterial colonisation and subsequent biofilm formation on medical devices. Methods The model antimicrobial agent was chlorhexidine and the selected fatty acid counter ions were capric acid, myristic acid and stearic acid. The polymethyl methacrylate films were loaded with 2% of fatty acid:antimicrobial agent at the following molar ratios; 0.5:1M, 1:1M and 2:1M and thermally polymerized using azobisisobutyronitrile initiator. Drug release experiments were subsequently performed over a 3-month period and the mass of drug released under sink conditions (pH 7.0, 37oC) quantified using a validated HPLC-UV method. Results In all platforms, a burst of chlorhexidine release was observed over the initial 24-hour period. Similar release kinetics were observed between the formulations during the initial 28 days. However, as time progressed, the chlorhexidine baseline plateaued after 56 days whereas formulations containing the counterions appeared to continuously elute linearly with time. As can be observed in figure 1, the rank order of total chlorhexidine release in the presence of 0.5M fatty acid was myristic acid (40%) > capric acid (35%) > stearic acid (30%)> chlorhexidine baseline (15%). Conclusion The incorporation of fatty acids within the formulation significantly improved chlorhexidine solubility within both the monomer and the polymer and enhanced the drug release kinetics over the period of study. This is attributed to the greater diffusivity of chlorhexidine through PMMA in the presence of fatty acids. In th absence of fatty acids, chlorhexidine release was facilitated by dissolution of surface associated drug particles. This study has illustrated the ability of fatty acids to modulate chlorhexidine release from a model biomaterial through enhanced diffusivity. This strategy may prove advantageous for improved medical devices with enhanced resistance to infection.

The human micro-vascular enclothelial cells in vitro interaction with atomic-nitrogen-doped diamond-like carbon thin films

This paper reports the initial response of atomic nitrogen doped diamond like carbon (DLC) to endothelial cells in vitro. The introduction of nitrogen atoms/molecules to the diamond like carbon structures leads to an atomic structural change favorable to the attachment of human micro-vascular enclothelial cells. Whilst the semi-conductivity induced by nitrogen in DLC is thought to play a part, the increase in the inion-bonded N atoms and N-2 molecules in the atomic doped species (with the exclusion of the charged species) seems to contribute to the improved attachment of human microvascular endothelial cells. The increased endothelial attachment is associated with a lower work function and slightly higher water contact angle in the atomic doped films, where the heavy charged particles are excluded. The films used in the study were synthesized by the RF PECVD technique followed by post deposition doping with nitrogen, and afterwards the films were characterized by XPS, Raman spectroscopy, SIMS and Kelvin probe. The water contact angles were measured, and the counts of the adherent endothelial cells on the samples were carried out. This study is relevant and contributory to improving biocompatibility of surgical implants and prostheses.

Liquid monomer-powder particle interaction in acrylic bone cement

It is known that the method used to mix the liquid monomer and powder of PMMA bone cement influences the quality of the cement that is used in total joint replacements. Mixing theory indicates that the interaction between the liquid monomer and the powder is affected by a number of parameters, such as cement viscosity and degree of agitation, with this knowledge utilized in the design of cement mixing devices. Therefore, the objectives of this study were to: (i) obtain information on the interaction of the liquid monomer and the powder in the case of an PMMA bone cement, (ii) show how this knowledge can be applied to the design of an automated cement mixing device, and (iii) compare the porosity, bending modulus, and bending strength of one commercially-available cement prepared using the automated mixer and prepared using a conventional mixer that is in current clinical use. Experimental data indicated that increasing the velocity and decreasing the viscosity of the systems produced cement that improved mechanical properties, which may contribute to better mechanical integrity and, hence, reduced tendency for aseptic loosening, of cemented hip implants.

Experimentally elevated plasma testosterone levels do not influence singing behaviour of male blue tits (Parus caeruleus) during the early breeding season

Sexual selection theory suggests that females might prefer males on the basis of testosterone (T)-dependent secondary sexual traits such as song. Correlational studies have linked high plasma T-levels to high diurnal song output. This has been confirmed in experiments where T-levels were kept high at times when natural T-levels have decreased. However, surprisingly little is known about the relation between T-levels during the early breeding season and song. In many passerine birds males sing at a high rate at dawn early in the breeding season, referred to as the dawn chorus. In blue tits (Parus caeruleus), the dawn chorus coincides with the fertile period of the female, whereas diurnal song occurs throughout the breeding season. Previous studies on blue tits showed that characteristics of the dawn chorus correlate with male reproductive success. We experimentally elevated plasma T-levels in male blue tits during the pre-fertile and fertile period. Our aim was to test whether increased plasma T-levels affect dawn song characteristics and increase the amount of diurnal song. Although T-implants successfully raised circulating T-levels, we did not find any difference between T- and control males in temporal performance measures of dawn song or in diurnal song output. Our results suggest that either there is no direct causal link between song output or quality and individual T-levels, or experimental manipulations of T-levels using implants do not permit detection of such effects during the early breeding season. Although we cannot exclude that individual T-levels are causally linked to other (e.g. structural) song parameters, our results cast doubt on T-dependence as the mechanisms that enforces honesty on song as a sexually selected trait.

Tooth loss and implant outcomes in patients refractory to treatment in a periodontal practice

Aim: The aim of this study was to investigate the factors associated with continued significant tooth loss due to periodontal reasons during maintenance following periodontal therapy in a specialist periodontal practice in Norway.
Material and Methods: A case-control design was used. Refractory cases were patients who lost multiple teeth during a maintenance period of 13.4 (range 8-19) years following definitive periodontal treatment in a specialist practice. Controls were age- and gender-matched maintenance patients from the same practice. Characteristics and treatment outcomes were assessed, and all teeth classified as being lost due to periodontal disease during follow-up were identified. The use of implants in refractory cases and any complications relating to such a treatment were recorded.
Results: Only 27 (2.2%) patients who received periodontal treatment between 1986 and 1998 in a specialist practice met the criteria for inclusion in the refractory to treatment group. Each refractory subject lost 10.4 (range 4-16) teeth, which represented 50% of the teeth present at baseline. The rate of tooth loss in the refractory group was 0.78 teeth per year, which was 35 times greater than that in the control group. Multivariate analysis indicated that being in the refractory group was predicted by heavy smoking (p=0.026), being stressed (p=0.016) or having a family history of periodontitis (p=0.002). Implants were placed in 14 of the refractory patients and nine (64%) of these lost at least one implant. In total, 17 (25%) of the implants placed in the refractory group were lost during the study period.
Conclusions: A small number of periodontal maintenance patients are refractive to treatment and go on to experience significant tooth loss. These subjects also have a high level of implant complications and failure. Heavy smoking, stress and a family history of periodontal disease were identified as factors associated with a refractory outcome.