No abstract

While the infection rate of orthopedic implants is low, the required treatment, which can involve six weeks of antibiotic therapy and two additional surgical operations, is life threatening and expensive, and thus motivates the development of a one-stage re-implantation procedure. Polyelectrolyte multilayers incorporating gentamicin were fabricated using the layer-by-layer deposition process for use as a device coating to deal with an existing bone infection in a direct implant exchange operation. The films eluted about 70% of their payload in vitro during the first three days and subsequently continued to release drug for more than four additional weeks, reaching a total average release of over 550 μg/cm 2 . The coatings were demonstrated to be bactericidal against Staphylococcus aureus, and degradation products were generally nontoxic towards MC3T3-E1 murine preosteoblasts. Film-coated titanium implants were compared to uncoated implants in an in vivo S. aureus bone infection model. After a direct exchange procedure, the antimicrobial-coated devices yielded bone homogenates with a significantly lower degree of infection than uncoated devices at both day four (p < 0.004) and day seven (p < 0.03). This study has demonstrated that a self-assembled ultrathin film coating is capable of effectively treating an experimental bone infection in vivo and lays the foundation for development of a multi-therapeutic film for optimized, synergistic treatment of pain, infection, and osteomyelitis.

The functional success of a biomedical implant critically depends on its stable bonding with the host tissue. Aseptic implant loosening accounts for over half of all joint replacement failures. Various materials, including metals and plastic, confer mechanical integrity to the device, but often these materials are not suitable for direct integration with the host tissue, which leads to implant loosening and patient morbidity. We describe a self-assembled, osteogenic, polymer-based conformal coating that promotes stable mechanical fixation of an implant in a surrogate rodent model. A single modular, polymer-based multilayered coating was deposited using a water-based layer-by-layer approach, by which each element was introduced on the surface in nanoscale layers. Osteoconductive hydroxyapatite (HAP) and osteoinductive bone morphogenetic protein 2 (BMP-2) contained within the nanostructured coating acted synergistically to induce osteoblastic differentiation of endogenous progenitor cells within the bone marrow, without indications of a foreign body response. The tuned release of BMP-2, controlled by a hydrolytically degradable poly(β-amino ester), was essential for tissue regeneration and, in the presence of HAP, the modular coating encouraged the direct deposition of highly cohesive trabecular bone on the implant surface. The bone-implant interfacial tensile strength was significantly higher than standard bone cement, did not fracture at the interface, and had long-term stability. Collectively, these results suggest that the multilayered coating system promotes biological fixation of orthopedic and dental implants to improve surgical outcomes by preventing loosening and premature failure.

Fluorophore-induced plasmonic current is generated when an excited fluorophore in close proximity to a metal nanoparticle film nonradiatively transfers energy to the metal, resulting in an electrical current across the film. Although a growing literature reports the use of surface plasmons for fluorescence enhancement as well as plasmons for current generation, little has been published hitherto regarding the electrical current generation via the fluorophore excitation of plasmons. Our "plasmon to current" technique utilizes electron transport between closely spaced metal nanoparticles, generating a measurable electrical signal upon excitation of a proximal fluorophore. This induced electrical signal is found to be strongly dependent on the magnitude of the fluorophore extinction coefficient. In other words the electrical signal contains photophysical information pertaining to the fluorophore, potentially leading to the direct detection of fluorescence without the need for traditional detectors such as photomultiplier tubes and charge coupled devices. In addition, we demonstrate the dependence of this current on fluorophore concentration and excitation laser polarization. Fluorophore-induced plasmonic current holds potential as a novel molecular detection platform with simplified instrumentation, compatible with a variety of fluorescent probes.

Electrically triggered drug delivery represents an attractive option for actively and remotely controlling the release of a therapeutic from an implantable device (e.g., a “pharmacy-on-a-chip”). Here we report the fabrication of nanoscale thin films that can release precise quantities of a small molecule drug in response to application of a small, anodic electric potential of at least +0.5 V versus Ag/AgCl. Films containing negatively charged Prussian Blue (PB) nanoparticles and positively charged gentamicin, a small hydrophilic antibiotic, were fabricated using layer-by-layer (LbL) assembly. When oxidized, the PB nanoparticles shift from negatively charged to neutral, inducing dissolution of the film. Films with thicknesses in the range 100–500 nm corresponding to drug loadings of 1–4 μg/cm2 were characterized. We demonstrate control over the drug dosage by tuning the film thickness as well as the magnitude of the applied voltage. Drug release kinetics ranging from triggered burst release to on/off, or pulsatile release, were achieved by applying different electric potential profiles. Finally, the in vitro efficacy of the released drug was confirmed against Staphylococcus aureus bacteria. Given the versatility of an external electrical stimulus and the ability of LbL assembly to conformally coat a variety of substrates regardless of size, shape, or chemical composition, we maintain that electrically controlled release of a drug from an LbL-coated surface could have applications in both implantable medical devices and transdermal drug delivery systems.