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.
Here we present a new bifunctional layer-by-layer (LbL) construct made by combining a permanent microbicidal polyelectrolyte multilayered (PEM) base film with a hydrolytically degradable PEM top film that offers controlled and localized delivery of therapeutics. Two degradable film architectures are presented: 1) bolus release of an antibiotic (gentamicin) to eradicate initial infection at the implant site, or 2) sustained delivery of an anti-inflammatory drug (diclofenac) to cope with inflammation at the site of implantation due to tissue injury. Each degradable film was built on top of a permanent base film that imparts the implantable device surface with microbicidal functionality that prevents the formation of biofilms. Controlled-delivery of gentamicin was demonstrated over hours and diclofenac over days. Both drugs retained their efficacy upon release. The permanent microbicidal base film was biocompatible with A549 epithelial cancer cells and MC3T3-E1 osteoprogenitor cells, while also preventing bacteria attachment from turbid media for the entire duration of the two weeks studied. The microbicidal base film retains its functionality after the biodegradable films have completely degraded. The versatility of these PEM films and their ability to prevent biofilm formation make them attractive as coatings for implantable devices.
In a recent paper, our laboratory has shown that fluorophores in close proximity to a non-continuous metal nanoparticle film can induce a detectable electrical current in the film. This current was found directly proportional to the fluorophore extinction coefficient and concentration when excited with p-polarized light. This finding threatens to change the way we both think about and use fluorescence spectroscopy as no longer do we have to use and are limited by traditional photodetectors and associated optics to collect and measure fluorescence signatures. This approach holds potential to significantly simplify fluorescence-based instrumentation. In this paper, we significantly expand upon our previous findings and show that plasmonic current is a function of the nanoparticle size and spacing in the film, which is explained by the concentric sphere model for nanoparticle capacitance. We also demonstrate the dependence of plasmonic current on the relative permittivity of the solvent, and that in an excess of salt, the fluorophore-induced current is significantly greater than the background current. This paves the way for downstream plasmonic assays in a variety of biological media. In addition, we have measured plasmonic current as a function of both applied bias voltage and temperature, allowing for the optimization of the fluorophore-induced plasmonic current. These findings allow for not only a better understanding of plasmonic current but also its optimization as it relates to fluorescence-based detection.
In this work, we report the surface-based electrical detection of singlet oxygen using the emerging fluorophore-induced plasmonic current (PC) technique. By this method, we utilize the fluorescent “turn on” response of the well-known singlet oxygen sensor green (SOSG) singlet oxygen (1O2) fluorescent probe for the generation of fluorophore-induced PC in a silver nanoparticle film. To demonstrate the potential utility of this new technique, a photosensitizing molecule is used to generate 1O2 in a solution containing the SOSG probe. The resulting change in SOSG fluorescence quantum yield and extinction coefficient permits stronger energy transfer from the SOSG probe to a proximal silver nanoparticle island film located in the near-electric field of the probe. This yields an increase in the induced electric current flow, allowing for the detection of the 1O2 analyte. To the author’s knowledge, this represents the first detection of the reactive oxygen species 1O2 utilizing fluorophore-induced PC methodology and even broader electrical detection of 1O2. This is significant as it opens the possibility for 1O2 detection methods which do not require a traditional “photodetector” and associated optics, simplifying the instrumentation over existing fluorescence detection methods and potentially even lowering the cost.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.