Standardized quantification of biofilm in a novel rabbit model of periprosthetic joint infection.

Periprosthetic joint infection (PJI) is one of the most devastating complications of total joint arthroplasty. The underlying pathogenesis involves the formation of bacterial biofilm that protects the pathogen from the host immune response and antibiotics, making eradication difficult. The aim of this study was to develop a rabbit model of knee PJI that would allow reliable biofilm quantification and permit the study of treatments for PJI. In this work, New Zealand white rabbits ( n = 19 ) underwent knee joint arthrotomy, titanium tibial implant insertion, and inoculation with Xen36 (bioluminescent Staphylococcus aureus) or a saline control after capsule closure. Biofilm was quantified via scanning electron microscopy (SEM) of the tibial explant 14 d after inoculation ( n = 3 noninfected, n = 2 infected). Rabbits underwent debridement, antibiotics, and implant retention (DAIR) ( n = 6 ) or sham surgery ( n = 2 noninfected, n = 6 infected) 14 d after inoculation, and they were sacrificed 14 d post-treatment. Tibial explant and periprosthetic tissues were examined for infection. Laboratory assays supported bacterial infection in infected animals. No differences in weight or C-reactive protein (CRP) were detected after DAIR compared to sham treatment. Biofilm coverage was significantly decreased with DAIR treatment when compared with sham treatment (61.4 % vs. 90.1 %, p < 0 .0011) and was absent in noninfected control explants. In summary, we have developed an experimental rabbit hemiarthroplasty knee PJI model with bacterial infection that reliably produces quantifiable biofilm and provides an opportunity to introduce treatments at 14 d. This model may be used to better understand the pathogenesis of this condition and to measure treatment strategies for PJI.

Hyperthermia-mediated changes in the tumor immune microenvironment using iron oxide nanoparticles.

Iron oxide nanoparticles (IONPs) have often been investigated for tumor hyperthermia. IONPs act as heating foci in the presence of an alternating magnetic field (AMF). It has been shown that hyperthermia can significantly alter the tumor immune microenvironment. Typically, mild hyperthermia invokes morphological changes within the tumor, which elicits a secretion of inflammatory cytokines and tumor neoantigens. Here, we focused on the direct effect of IONP-induced hyperthermia on the various tumor-resident immune cell subpopulations. We compared direct intratumoral injection to systemic administration of IONPs followed by application of an external AMF. We used the orthotopic 4T1 mouse model, which represents aggressive and metastatic breast cancer with a highly immunosuppressive microenvironment. A non-inflamed and 'cold' microenvironment inhibits peripheral effector lymphocytes from effectively trafficking into the tumor. Using intratumoral or systemic injection, IONP-induced hyperthermia achieved a significant reduction of all the immune cell subpopulations in the tumor. However, the systemic delivery approach achieved superior outcomes, resulting in substantial reductions in the populations of both innate and adaptive immune cells. Upon depletion of the existing dysfunctional tumor-resident immune cells, subsequent treatment with clinically approved immune checkpoint inhibitors encouraged the repopulation of the tumor with 'fresh' infiltrating innate and adaptive immune cells, resulting in a significant decrease of the tumor cell population.

Uncovering the Magnetic Particle Imaging and Magnetic Resonance Imaging Features of Iron Oxide Nanocube Clusters.

Multifunctional imaging nanoprobes continue to garner strong interest for their great potential in the detection and monitoring of cancer. In this study, we investigate a series of spatially arranged iron oxide nanocube-based clusters (i.e., chain-like dimer/trimer, centrosymmetric clusters, and enzymatically cleavable two-dimensional clusters) as magnetic particle imaging and magnetic resonance imaging probes. Our findings demonstrate that the short nanocube chain assemblies exhibit remarkable magnetic particle imaging signal enhancement with respect to the individually dispersed or the centrosymmetric cluster analogues. This result can be attributed to the beneficial uniaxial magnetic dipolar coupling occurring in the chain-like nanocube assembly. Moreover, we could effectively synthesize enzymatically cleavable two-dimensional nanocube clusters, which upon exposure to a lytic enzyme, exhibit a progressive increase in magnetic particle imaging signal at well-defined incubation time points. The increase in magnetic particle imaging signal can be used to trace the disassembly of the large planar clusters into smaller nanocube chains by enzymatic polymer degradation. These studies demonstrate that chain-like assemblies of iron oxide nanocubes offer the best spatial arrangement to improve magnetic particle imaging signals. In addition, the nanocube clusters synthesized in this study also show remarkable transverse magnetic resonance imaging relaxation signals. These nanoprobes, previously showcased for their outstanding heat performance in magnetic hyperthermia applications, have great potential as dual imaging probes and could be employed to improve the tumor thermo-therapeutic efficacy, while offering a readable magnetic signal for image mapping of material disassemblies at tumor sites.

Exploring the chelation-based plant strategy for iron oxide nanoparticle uptake in garden cress (Lepidium sativum) using magnetic particle spectrometry.

Although iron is one of Earth's most abundant elements, its availability to plants remains an agricultural challenge, particularly in high pH environments. At high pH, iron forms insoluble ferric oxide-hydroxides that makes it inaccessible to plants. It is estimated that 30% of the world's cropland is too alkaline for optimal plant growth. Staple crops, like rice, are particularly susceptible to iron deficiency, thereby, necessitating the need for continued research in developing iron-based fertilizers. Recent studies have demonstrated the potential of using iron oxide nanoparticles (IONPs) as fertilizers to address iron deficiency in plants, but some studies have generated conflicting results. One of the major challenges associated in investigating IONP plant uptake and translocation is the inability to distinguish between intact IONPs versus leached iron ions. In this study, we utilized a new approach based on magnetic particle spectrometry (MPS) to monitor the uptake and distribution of different sized (10 and 20 nm) chelated IONPs in plants. We exposed garden cress (Lepidium sativum) plants to EDTA-capped IONPs and observed an 8-fold enhancement in total biomass and 1.4 times increase in chlorophyll production compared to plants treated with a commercial chelated iron fertilizer (Fe-EDTA). Moreover, we demonstrated that the uptake and tissue distribution of IONPs can be quantitatively monitored using MPS, and the results of the analysis were validated by atomic absorption spectroscopy, which is the conventional method used to study IONP plant uptake. Our study demonstrates that MPS is a reliable, sensitive, and effective analytical tool for the development of IONP-based fertilizers.

Applications and challenges of using 3D printed implants for the treatment of birth defects.

Pediatric implants are a special subclass of a vast number of clinically used medical implants, uniquely designed to address the needs of young patients who are at the onset of their developmental growth stage. Given the vulnerability of the implant receiver, it is crucial that the implants manufactured for small children with birth-associated defects be given careful considerations and great attention to design detail to avoid postoperative complications. In this review, we focus on the most common types of medical implants manufactured for the treatment of birth defects originating from both genetic and environmental causes. Particular emphasis is devoted toward identifying the implant material of choice and manufacturing approaches for the fabrication of pediatric prostheses. Along this line, the emerging role of 3D printing to enable customized implants for infants with congenital disorders is presented, as well as the possible complications associated with prosthetic-related infections that is prevalent in using artificial implants for the treatment of birth malformations.

A novel synthetic route for high-index faceted iron oxide concave nanocubes with high T2 relaxivity for in vivo MRI applications.

Iron oxide nanoparticles (IONPs) with high-index facets have shown great potential as high performance T2 contrast agents for MRI. Previous synthetic approaches focused mainly on ion-directed or oxidative etching methods. Herein, we report a new synthetic route for preparing high-index faceted iron oxide concave nanocubes using a bulky coordinating solvent. Through the systematic replacement of a non-coordinating solvent, 1-octadecene, with trioctylamine, the solvent interaction with the nanoparticle surface is modified, thereby, promoting the growth evolution of the IONPs from spherical to concave cubic morphology. The presence of the bulky trioctylamine solvent results in particle size increase and the formation of nanoparticles with enhanced shape anisotropy. A well-defined concave nanocube structure was evident from the early stages of particle growth, further confirming the important role of bulky coordinating solvents in nanoparticle structural development. The unique concave nanocube morphology has a direct influence on the magnetic properties of the IONPs, ultimately leading to an ultra-high T2 relaxivity (862.2 mM-1 s-1), and a 2-fold enhancement in T2*-weighted in vivo MRI contrast compared to spherical IONP analogs.

Magnetic Glycol Chitin-Based Hydrogel Nanocomposite for Combined Thermal and d-Amino-Acid-Assisted Biofilm Disruption.

Bacterial biofilms are highly antibiotic resistant microbial cell associations that lead to chronic infections. Unlike free-floating planktonic bacterial cells, the biofilms are encapsulated in a hardly penetrable extracellular polymeric matrix and, thus, demand innovative approaches for treatment. Recent advancements on the development of gel-nanocomposite systems with tailored therapeutic properties provide promising routes to develop novel antimicrobial agents that can be designed to disrupt and completely eradicate preformed biofilms. In our study, we developed a unique thermoresponsive magnetic glycol chitin-based nanocomposite containing d-amino acids and iron oxide nanoparticles, which can be delivered and undergoes transformation from a solution to a gel state at physiological temperature for sustained release of d-amino acids and magnetic field actuated thermal treatment of targeted infection sites. The d-amino acids in the hydrogel nanocomposite have been previously reported to inhibit biofilm formation and also disrupt existing biofilms. In addition, loading the hydrogel nanocomposite with magnetic nanoparticles allows for combination thermal treatment following magnetic field (magnetic hyperthermia) stimulation. Using this novel two-step approach to utilize an externally actuated gel-nanocomposite system for thermal treatment, following initial disruption with d-amino acids, we were able to demonstrate in vitro the total eradication of Staphylococcus aureus biofilms, which were resistant to conventional antibiotics and were not completely eradicated by separate d-amino acid or magnetic hyperthermia treatments.

M3Ag17(SPh)12 Nanoparticles and Their Structure Prediction.

Although silver nanoparticles are of great fundamental and practical interest, only one structure has been determined thus far: M4Ag44(SPh)30, where M is a monocation, and SPh is an aromatic thiolate ligand. This is in part due to the fact that no other molecular silver nanoparticles have been synthesized with aromatic thiolate ligands. Here we report the synthesis of M3Ag17(4-tert-butylbenzene-thiol)12, which has good stability and an unusual optical spectrum. We also present a rational strategy for predicting the structure of this molecule. First-principles calculations support the structural model, predict a HOMO-LUMO energy gap of 1.77 eV, and predict a new "monomer mount" capping motif, Ag(SR)3, for Ag nanoparticles. The calculated optical absorption spectrum is in good correspondence with the measured spectrum. Heteroatom substitution was also used as a structural probe. First-principles calculations based on the structural model predicted a strong preference for a single Au atom substitution in agreement with experiment.