Examination of surface properties and in vitro biological performance of amorphous diamond-like carbon-coated polyurethane

Despite the emerging use of diamond-like carbon (DLC) as a coating for medical devices, few studies have examined the resistance of DLC coatings onto medical polymers to both microbial adherence and encrustation. In this study, amorphous DLC of a range of refractive indexes (1.7-1.9) and thicknesses (100-600 nm) was deposited onto polyurethane, a model polymer, and the resistance to microbial adherence (Escherichia coli; clinical isolate) and encrustation examined using in vitro models. In comparison to the native polymer, the advancing and receding contact angles of DLC-coated polyurethane were lower, indicating greater hydrophilic properties. No relationship was observed between refractive index, thickness, and advancing contact angle, as determined using multiple correlation analysis. The resistances of the various DLC-coated polyurethane films to encrustation and microbial adherence were significantly greater than that to polyurethane; however, there were individual differences between the resistances of the various DLC coatings. In general, increasing the refractive index of the coatings (100 nm thickness) decreased the resistance of the films to both hydroxyapatite and struvite encrustation and to microbial adherence. Films of lower thicknesses (100 and 200 nm; of defined refractive index, 1.8), exhibited the greatest resistance to encrustation and to microbial adherence. In conclusion, this study has uniquely illustrated both the microbial antiadherence properties and resistance to urinary encrustation of DLC-coated polyurethane. The resistances to encrustation and microbial adherence were substantial, and in light of this, it is suggested that DLC coatings of low thickness and refractive index show particular promise as coatings of polymeric medical devices. (c) 2006 Wiley Periodicals, Inc.

Factors affecting in vitro adherence of ureteral stent biofilm isolates to polyurethane

Adherence of bacteria to biomaterials is the first stage in the development of a device-related infection. The adherence of bacterial cells to biomaterials may be influenced by surface characteristics of the cell, its growth conditions and the biomaterial surface chemistry. Following growth in human urine, the cell surface,hydrophobicity and zeta potential of two ureteral stent biofilm isolates, Enterococcus faecalis and Escherichia coli, were significantly altered. In addition, the adherence of human urine-grown Enterococcus faecalis and Escherichia coli to polyurethane was significantly increased by up to 52.1% and 58.6%, respectively. Treatment of the polyurethane with human urine rendered the polymer surface more hydrophilic (mean advancing water contact angle reduced from 97.59 degrees to 26.37 degrees). However, organisms grown in human urine showed less adherence (up to 90.4%) to the treated polymer than those grown in Mueller-Hinton broth. The results presented in this study indicate that in vivo conditions should be simulated as far as possible when carrying out in vitro bacterial adherence assays, especially if assessing novel methods for reduction of adherence. (C) 1997 Elsevier Science B.V.

Biological efficacy of electroless-deposited silver on plasma activated polyurethane

Silver coating of catheters has been shown to have inhibitory effects on bacterial growth and adhesion to catheter surfaces. In this study, plasma-modification was used to enhance the adhesion of an electroless silver coating on polyurethane. Both the antibacterial and antiadhesive properties of these coatings were investigated. Bacterial growth was inhibited in cultures exposed to silver-treated polyurethane compared to unmodified polyurethane. Higher growth inhibition was observed for polyurethane surfaces with lower silver coverage. Bacterial adhesion was completely inhibited on all silver-coated surfaces.

Evaluation of a poly(vinyl pyrollidone)-coated biomaterial for urological use

The associated problems of bacterial biofilm formation and encrustation that may cause obstruction or blockage of urethral catheters and ureteral stents often hinders the effective use of biomaterials within the urinary tract. In this in vitro study, we have investigated the surface properties of a hydrophilic polyvinyl pyrollidone) (PVP)-coating applied to polyurethane and determined its suitability for use as a urinary tract biomaterial by comparing its lubricity and ability to resist bacterial adherence and encrustation with that of uncoated polyurethane and silicone. The PVP-coated polyurethane was significantly more hydrophilic and more lubricious than either uncoated polyurethane or silicone. Adherence of a hydrophilic Escherichia coli isolate to PVP-coated polyurethane and uncoated polyurethane was similar but significantly less than adherence to silicone. Adherence of a hydrophobic Enterococcus faecalis isolate to PVP-coated polyurethane and silicone was similar but was significantly less than adherence to uncoated polyurethane. Struvite encrustation was similar on the PVP-coated polyurethane and silicone but significantly less than on uncoated polyurethane. Furthermore, hydroxyapatite encrustation was significantly less on the PVP-coated polyurethane than on either uncoated polyurethane or silicone. The results suggest that the PVP-coating could be useful in preventing complications caused by bacterial biofilm formation and the deposition of encrustation on biomaterials implanted in the urinary tract and, therefore, warrants further evaluation. (C) 2002 Elsevier Science Ltd. All rights reserved.

High-solid-content hydroxyapatite slurry for the production of bone substitute scaffolds

Key to various bone substitute scaffold production techniques is the development of free-flowing ceramic slurry with optimum theological properties. The aim is to achieve a colloidal suspension with as high a solid content as possible while maintaining a low viscosity which easily penetrates the pores of relevant sacrificial templates. The following investigation describes the optimization of a hydroxyapatite slip and demonstrates its potential application in scaffold production. Using predominantly spherical particles of hydroxyapatite of between 0.82 mu m and 16.2 mu m, coupled with a 2 wt % addition of the anionic polyelectrolyte, ammonium polyacrylate, an 80 wt % (55.9 vol %) hydroxyapatite solid loaded slip with a viscosity of approximately 126 mPa s has been developed. Its ability to infiltrate and replicate porous preforms has been shown using polyurethane foam. The enhanced particle packing achieved has allowed for the production of scaffolds with highly dense and uniform grain structures. The results represent a significant improvement in current slurry production techniques and can be utilized to develop high-density ceramic bone substitute scaffolds.

Multi-Study Assessment of Vaginal Cytokines and Microflora in the Safety Evaluation of Intravaginal Rings in Pig-Tailed Macaques

BACKGROUND: HIV microbicide trials have emphasized the need to evaluate the safety of topical microbicides and delivery platforms in an animal model prior to conducting clinical efficacy trials. An ideal delivery device should provide sustainable and sufficient concentrations of effective products to prevent HIV transmission while not increasing transmission risk by either local mucosal inflammation and/or disruption of the normal vaginal microflora.

METHODS: Safety analyses of macaque-sized elastomeric silicone and polyurethane intravaginal rings (IVRs) loaded with candidate antiretroviral (ARV) drugs were tested in four studies ranging in duration from 49 to 73 days with retention of the IVR being 28 days in each study. Macaques were assigned to 3 groups; blank IVR, ARV-loaded IVR, and naïve. In sequential studies, the same macaques were used but rotated into different groups. Mucosal and systemic levels of cytokines were measured from vaginal fluids and plasma, respectively, using multiplex technology. Changes in vaginal microflora were also monitored. Statistical analysis (Mann-Whitney test) was used to compare data between two groups of unpaired samples (with and without IVR, and IVR with and without ARV) for the groups collectively, and also for individual macaques.

RESULTS: There were few statistically significant differences in mucosal and systemic cytokine levels measured longitudinally when the ring was present or absent, with or without ARVs. Of the 8 proinflammatory cytokines assayed a significant increase (p = 0.015) was only observed for IL8 in plasma with the blank and ARV loaded IVR (median of 9.2 vs. 5.7 pg/ml in the absence of IVR). There were no significant differences in the prevalence of H2O2-producing lactobacilli or viridans streptococci, or other microorganisms indicative of healthy vaginal microflora. However, there was an increase in the number of anaerobic gram negative rods in the presence of the IVR (p= < 0.0001).

CONCLUSIONS: IVRs with or without ARVs neither significantly induce the majority of potentially harmful proinflammatory cytokines locally or systemically, nor alter the lactobacillus or G. vaginalis levels. The increase in anaerobic gram negative rods alone suggests minimal disruption of normal vaginal microflora. The use of IVRs as a long-term sustained delivery device for ARVs is promising and preclinical studies to demonstrate the prevention of transmission in the HIV/SHIV nonhuman primate model should continue.

Pharmacokinetics of UC781-loaded intravaginal ring segments in rabbits: a comparison of polymer matrices

UC781 is a potent and poorly water-soluble nonnucleoside reverse transcriptase inhibitor being investi- gated as a potential microbicide for preventing sexual transmission of HIV-1. This study was designed to evaluate the in vivo release and pharmacokinetics of UC781 delivered from matrix-type intravaginal ring segments in rabbits. Three polymer matrices (polyurethane, ethylene vinyl acetate copolymer, and silicone elastomer) and two drug loadings (5 and 15 mg/segment) were evaluated in at least one of two independent studies for up to 28 days in vivo. Inter-study comparison of in vivo release, vaginal tissue, and plasma concentrations for similar formulations demonstrated good reproducibility of the animal model. Mean estimates for a 28-day in vivo release ranged from 0.35 to 3.17 mg UC781 per segment. Mean proximal vaginal tissue levels (adjacent to the IVR segment) were 8– 410 ng/g and did not change significantly with time for most formulations. Distal vaginal tissue levels of UC781 were 6- to 49-fold lower than proximal tissue levels. Mean UC781 plasma levels were low for all formulations, at 0.09–0.58 ng/mL. All formulations resulted in similar UC781 concentrations in vaginal tissue and plasma, except the low loading polyurethane group which provided significantly lower levels. Loading dependent release and pharmacokinetics were only clearly observed for the polyurethane matrix. Based on these results, intravaginal ring segments loaded with UC781 led to vaginal tissue concen- trations ranging from below to approximately two orders of magnitude higher than UC781’s EC50 under in vitro conditions (2.8 ng/mL), with little influence by polymer matrix or UC781 loading. Moreover, these findings support the use of rabbit vaginal pharmacokinetic studies in preclinical testing of microbicide intravaginal rings.

Comparative Characterisation of 3-D Hydroxyapatite Scaffolds Developed via Replication of Synthetic Polymer Foams and Natural Marine Sponges

The production of complex inorganic forms, based on naturally occurring scaffolds offers an exciting avenue for the construction of a new generation of ceramic-based bone substitute scaffolds. The following study reports an investigation into the architecture (porosity, pore size distribution, pore interconnectivity and permeability), mechanical properties and cytotoxic response of hydroxyapatite bone substitutes produced using synthetic polymer foam and natural marine sponge performs. Infiltration of polyurethane foam (60 pores/in2) using a high solid content (80wt %), low viscosity (0.126Pas) hydroxyapatite slurry yielded 84-91% porous replica scaffolds with pore sizes ranging from 50µm - 1000µm (average pore size 577µm), 99.99% pore interconnectivity and a permeability value of 46.4 x10-10m2. Infiltration of the natural marine sponge, Spongia agaricina, yielded scaffolds with 56- 61% porosity, with 40% of pores between 0-50µm, 60% of pores between 50-500µm (average pore size 349 µm), 99.9% pore interconnectivity and a permeability value of 16.8 x10-10m2. The average compressive strengths and compressive moduli of the natural polymer foam and marine sponge replicas were 2.46±1.43MPa/0.099±0.014GPa and 8.4±0.83MPa /0.16±0.016GPa respectively. Cytotoxic response proved encouraging for the HA Spongia agaricina scaffolds; after 7 days in culture medium the scaffolds exhibited endothelial cells (HUVEC and HDMEC) and osteoblast (MG63) attachment, proliferation on the scaffold surface and penetration into the pores. It is proposed that the use of Spongia agaricina as a precursor material allows for the reliable and repeatable production of ceramic-based 3-D tissue engineered scaffolds exhibiting the desired architectural and mechanical characteristics for use as a bone 3 scaffold material. Moreover, the Spongia agaricina scaffolds produced exhibit no adverse cytotoxic response.