A simple way to track single gold-loaded alginate microcapsules using x-ray CT in small animal longitudinal studies.

The use of alginate based microcapsules to deliver drugs and cells with a minimal host interaction is increasingly being proposed. A proficient method to track the position of the microcapsules during such therapies, particularly if they are amenable to commonly used instrumentation, would greatly help the development of such treatments. Here we propose to label the microcapsules with gold nanoparticles to provide a bright contrast on small animal x-ray micro-CT systems enabling single microcapsule detection. The microcapsules preparation is based on a simple protocol using inexpensive compounds. This, combined with the widespread availability of micro-CT apparatus, renders our method more accessible compared with other methods. Our labeled microcapsules showed good mechanical stability and low cytotoxicity in-vitro. Our post-mortem rodent model data strongly suggest that the high signal intensity generated by the labeled microcapsules permits the use of a reduced radiation dose yielding a method fully compatible with longitudinal in-vivo studies. FROM THE CLINICAL EDITOR: The authors of this study report the development of a micro-CT based tracking method of alginate-based microcapsules by incorporating gold nanoparticles in the microcapsules. They demonstrate the feasibility of this system in rodent models, where due to the high signal intensity, even reduced radiation dose is sufficient to track these particles, providing a simple and effective method to track these commonly used microcapsules and allowing longitudinal studies.

Efficacy of antimicrobial polymer coatings in an animal model of bacterial infection associated with foreign body implants.

OBJECTIVES: To assess support discs, comprising polyethylene terephthalate (PET), coated with different polymer/levofloxacin combinations for antimicrobial activity in an animal model of infection, in order to explore the use of specific polymer coatings incorporating levofloxacin as a means of reducing device-related infections. METHODS: Aliphatic polyester-polyurethanes containing different ratios of poly(lactic acid) diol and poly(caprolactone) diol were prepared, blended with levofloxacin and then used to coat support discs. The in vitro levofloxacin release profiles from these discs were measured in aqueous solution. Mice were surgically implanted with the coated discs placed subcutaneously and infection was initiated by injection of 10(6) cfu of Staphylococcus aureus into the subcutaneous pocket containing the implant. After 5, 10, 20 and 30 days, the discs were removed, and the number of bacteria adhering to the implant and the residual antimicrobial activity of the discs were determined. RESULTS: In vitro, the release of levofloxacin from the coated discs occurred at a constant rate and then reached a plateau at different timepoints, depending on the polymer preparation used. In vivo, none of the discs coated with polymer blends containing levofloxacin was colonized by S. aureus, whereas 94% of the discs coated with polymer alone were infected. All discs coated with levofloxacin-blended polymers displayed residual antimicrobial activity for at least 20 days post-implantation. CONCLUSIONS: Bioerodable polyester-polyurethane polymer coatings containing levofloxacin can prevent bacterial colonization of implants in an intra-operative model of device-related infections.

Biodegradable injectable polyurethanes: synthesis and evaluation for orthopaedic applications.

Biodegradable polyurethanes offer advantages in the design of injectable or preformed scaffolds for tissue engineering and other medical implant applications. We have developed two-part injectable prepolymer systems (prepolymer A and B) consisting of lactic acid and glycolic acid based polyester star polyols, pentaerythritol (PE) and ethyl lysine diisocyanate (ELDI). This study reports on the formulation and properties of a series of cross linked polyurethanes specifically developed for orthopaedic applications. Prepolymer A was based on PE and ELDI. Polyester polyols (prepolymer B) were based on PE and dl-lactic acid (PEDLLA) or PE and glycolic acid (PEGA) with molecular weights 456 and 453, respectively. Several cross linked porous and non-porous polyurethanes were prepared by mixing and curing prepolymers A and B and their mechanical and thermal properties, in vitro (PBS/37 degrees C/pH 7.4) and in vivo (sheep bi-lateral) degradation evaluated. The effect of incorporating beta-tricalcium phosphate (beta-TCP, 5 microns, 10 wt.%) was also investigated. The cured polymers exhibited high compressive strength (100-190 MPa) and modulus (1600-2300 MPa). beta-TCP improved mechanical properties in PEDLLA based polyurethanes and retarded the onset of in vitro and in vivo degradation. Sheep study results demonstrated that the polymers in both injectable and precured forms did not cause any surgical difficulties or any adverse tissue response. Evidence of new bone growth and the gradual degradation of the polymers were observed with increased implant time up to 6 months.

Self-assembled gold coating enhances X-ray imaging of alginate microcapsules.

Therapeutic biomolecules produced from cells encapsulated within alginate microcapsules (MCs) offer a potential treatment for a number of diseases. However the fate of such MCs once implanted into the body is difficult to establish. Labelling the MCs with medical imaging contrast agents may aid their detection and give researchers the ability to track them over time thus aiding the development of such cellular therapies. Here we report the preparation of MCs with a self-assembled gold nanoparticle (AuNPs) coating which results in distinctive contrast and enables them to be readily identified using a conventional small animal X-ray micro-CT scanner. Cationic Reversible Addition-Fragmentation chain Transfer (RAFT) homopolymer modified AuNPs (PAuNPs) were coated onto the surface of negatively charged alginate MCs resulting in hybrids which possessed low cytotoxicity and high mechanical stability in vitro. As a result of their high localized Au concentration, the hybrid MCs exhibited a distinctive bright circular ring even with a low X-ray dose and rapid scanning in post-mortem imaging experiments facilitating their positive identification and potentially enabling them to be used for in vivo tracking experiments over multiple time-points.