Plasma-modified biomaterials for self-antimicrobial applications.

The surface compatibility and antibacterial properties of biomaterials are crucial to tissue engineering and other medical applications, and plasma-assisted technologies have been employed to enhance these characteristics with good success. Herein, we describe and review the recent developments made by our interdisciplinary team on self-antimicrobial biomaterials with emphasis on plasma-based surface modification. Our results indicate that a self-antibacterial surface can be produced on various types of materials including polymers, metals, and ceramics by plasma treatment. Surface characteristics such as roughness, microstructure, chemistry, electronegativity, free energy, hydrophilicity, and interfacial physiochemistry are important factors and can be tailored by using the appropriate plasma-assisted processing parameters. In particular, mechanistic studies reveal that the interfacial physiochemical processes, biocidal agents, and surface free energy are predominantly responsible for the antibacterial effects of plasma-modified biomaterials.

Gentamicin-loaded strontium-containing hydroxyapatite bioactive bone cement--an efficient bioactive antibiotic drug delivery system.

Modified strontium-containing hydroxyapatite (Sr-HA) bone cement was loaded with gentamicin sulfate to generate an efficient bioactive antibiotic drug delivery system for treatment of bone defects. Gentamicin release and its antibacterial property were determined by fluorometric method and inhibition of Staphylococcus aureus (S. aureus) growth. Gentamicin was released from Sr-HA bone cement during the entire period of study and reached around 38% (w/w) cumulatively after 30 days. Antibacterial activity of the gentamicin loaded in the cements is clearly confirmed by the growth inhibition of S. aureus. The results of the amount and duration of gentamicin release suggest a better drug delivery efficiency in Sr-HA bone cement over polymethylmethacrylate bone cement. Bioactivity of the gentamicin-loaded Sr-HA bone cement was confirmed with the formation of apatite layer with 1.836 ± 0.037 µm thick on day 1 and 5.177 ± 1.355 µm thick on day 7 after immersion in simulated body fluid. Compressive strengths of the gentamicin-loaded Sr-HA cement reached 132.60 ± 10.08 MPa, with a slight decrease from the unloaded groups by 4-9%. Bending moduli of Sr-HA cements with and without gentamicin were 1.782 ± 0.072 GPa and 1.681 ± 0.208 GPa, respectively. On the contrary, unloaded Sr-HA cement obtained slightly larger bending strength of 35.48 ± 2.63 MPa comparing with 33.00 ± 1.65 MPa for loaded cement. No statistical difference was found on the bending strengths and modulus of gentamicin-loaded and -unloaded Sr-HA cements. Sr-HA bone cement loaded with gentamicin was proven to be an efficient drug delivery system with uncompromised mechanical properties and bioactivity.

In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds.

Effective antiviral agents are urgently needed to combat the possible return of severe acute respiratory syndrome (SARS). Commercial antiviral agents and pure chemical compounds extracted from traditional Chinese medicinal herbs were screened against 10 clinical isolates of SARS coronavirus by neutralisation tests with confirmation by plaque reduction assays. Interferon-beta-1a, leukocytic interferon-alpha, ribavirin, lopinavir, rimantadine, baicalin and glycyrrhizin showed antiviral activity. The two interferons were only active if the cell lines were pre-incubated with the drugs 16 h before viral inoculation. Results were confirmed by plaque reduction assays. Antiviral activity varied with the use of different cell lines. Checkerboard assays for synergy were performed showing combinations of interferon beta-1a or leukocytic interferon-alpha with ribavirin are synergistic. Since the clinical and toxicity profiles of these agents are well known, they should be considered either singly or in combination for prophylaxis or treatment of SARS in randomised placebo controlled trials in future epidemics.

Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings.

BACKGROUND: The clinical response of patients with severe acute respiratory syndrome (SARS) to a combination of lopinavir/ritonavir and ribavirin was examined after establishing the in vitro antiviral susceptibility of the SARS associated coronavirus to a panel of antiviral agents. METHODS: The in vitro susceptibility of the prototype of SARS associated coronavirus to a panel of nucleoside analogues and protease inhibitors currently licensed for clinical use was studied. Forty one patients with SARS followed for 3 weeks were treated with a combination of lopinavir/ritonavir and ribavirin. The clinical progress and virological outcomes were monitored and compared with 111 patients treated with ribavirin only who served as historical controls. RESULTS: In vitro antiviral activity against SARS associated coronavirus was demonstrated for lopinavir and ribavirin at concentrations of 4 micro g/ml and 50 micro g/ml, respectively, only at 48 hours. The adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p<0.001) at day 21 after the onset of symptoms. The adverse outcome remained significantly lower in the treatment group than in the controls-both those diagnosed early (p<0.001) and those diagnosed later in the course of the epidemic (p = 0.002)-but there was no significant difference in adverse outcome rates between the two time periods (p = 0.548). No time related difference in outcome was observed in the control groups. A reduction in steroid usage and nosocomial infections was seen in patients initially treated with lopinavir/ritonavir, and these patients had a decreasing viral load and rising peripheral lymphocyte count. Multivariate analysis showed that age, hepatitis B carrier status, and lack of treatment with this antiviral combination were independent predictors of an adverse outcome. Lopinavir/ritonavir treatment was associated with a better outcome even when adjusted for baseline lactate dehydrogenase level. CONCLUSIONS: The apparent favourable clinical response with lopinavir/ritonavir and ribavirin supports further randomised placebo controlled trials in patients with SARS.