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.
Anthropogenic carbon dioxide (CO2) emission is one of the biggest global threats that we are confronted with in the 21st century. A lack of prompt action to mitigate the atmospheric CO2 level could lead to global catastrophic events. As a result of the significance of the aforementioned threat, multiple nations have agreed to enact carbon capture, storage, utilization, and sequestration (CCUS) technologies at academic and industrial scales with the aim of lowering the atmospheric CO2 level. Although there are many reviews on CCUS technologies, there is a lack of comprehensive review on CO2 conversion to more economically valuable products, such as nanomaterials. Carbon dioxide capture and conversion into nanomaterials is an interesting research topic in many ways because it contributes to our fundamental knowledge of material conversion, provides alternative ways to reduce atmospheric pollution, and yields lucrative products, which has not been explored broadly. Aside from the positive outcomes, we have a moral obligation to rectify a global threat caused by anthropogenic emission. Herein, we present current methods of converting CO2 into organic and inorganic nanomaterials with a focus on operating conditions and challenges as well as the potential of nanomaterials in specifically biomedical applications as opposed to extensively reviewed energy-related uses. Moreover, our review emphasizes the toxicity issues related to using such nanomaterials in biological settings based on literature and other comparable studies.
Self-assembly of small molecules via non-covalent interactions such as ionic bonds, hydrogen bonding, van der Waals interactions, and p-p interactions among aromatic units is regarded as one of the major forces contributing to cellular life. This is due to the fact that having a supramolecular structure is vital for peptides, proteins, DNA, lipids, and other important molecules to maintain their structural integrity and to perform biological functions. Electron microscopic techniques have been widely used to reveal the nanoscale structural features of bio-inspired self-assemblies, which have broadened our understanding of their structure-property relationships in complex biological systems. Electron microscopy has also been applied to observe predetermined self-assemblies of biomolecules for a variety of biomedical applications including drug delivery, gene delivery, tissue engineering, and antimicrobials, as well as bio-inspired ceramic nanostructures, electrochemical sensors, and carbon electrodes. However, recent studies related to neurodegenerative diseases, including Alzheimer’s, Parkinson’s, chronic traumatic encephalopathy, and phenylketonuria (PKU), have shown that these diseases are likely linked to the nonproteinaceous building blocks which can form amyloid-like fibrils, emphasizing the need for further investigation of the self-assembly of metabolites such as amino acids. In our study, we investigated the self-assembly of both aliphatic and aromatic amino acids including phenylalanine, which is directly related to PKU. We also determined the effects of anaerobic conditions on the self-assembled nanostructures by observing the changes in structural and stability properties in different self-assembly conditions. Using scanning electron microscopy, we were able to demonstrate concentration dependent formation
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.
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.
Monodisperse Fe3O4 nanoparticles (NPs) with excellent water dispersibility and stability were prepared by the introduction of the carboxyl group (−COOH) on the surface of the as-prepared oleyl-capped Fe3O4 NPs. Controlled introduction of the COOH moieties on the NP surface was carried out by a simple ligand exchange reaction using two types of phosphonic acid ligands with dodecyl moiety and the terminal COOH group. The degree of modification of the COOH group on the particle surface was controlled by tuning the molar ratios of the two phosphonic acids. During the ligand exchange reaction, no change was observed in the crystal structure and morphology of the Fe3O4 NPs. The results of Fourier transform infrared (FT-IR) spectroscopy confirmed that the two ligands were bound to the Fe3O4 NP surface through their phosphoric acid functional groups. The surface coverage and molar ratios of the two ligands were evaluated by thermal gravimetric analysis (TGA) and via proton nuclear magnetic resonance (1H NMR) measurements, respectively. Results obtained from the thermal analyses were consistent with the initial molar ratios of the ligands used in the reaction, which reflect on the efficiency of the developed ligand exchange process. Our COOH-modified Fe3O4 NPs could be dispersed in water by deprotonation for over 6 months and exhibit a typical ferrofluid behavior without the addition of other surfactants and dispersants, showing high dispersion stability. Furthermore, the magnetic induction heating performance of the Fe3O4 NPs in aqueous dispersions was evaluated and the specific absorption rate (SAR) value was estimated to be 38.3 W/g Fe. These results suggest that our COOH-modified Fe3O4 NPs with the desired number of COOH surface moieties can be advantageous for applications such as precise surface design, water-based ferrofluid, and hyperthermia treatment.
Bacterial biofilms associated with orthopedic implants are notorious cell associations of pathogens that show resistance against antibiotic medications and the host immune response. The presence of hard-to-penetrate extracellular polymeric substances in the biofilm provides a protective shield against the different modes of action of conventional antimicrobial agents. To address the severe complications associated with biofilm-related infections in medical implants such as prosthetic joint infections (PJIs), we have developed a treatment approach that is based on a thermoresponsive hydrogel nanocomposite system, containing D-amino acids (D-AAs) and engineered gold nanorods (AuNRs), which can undergo sol-to-gel transformation at physiological temperatures for site-specific sustained drug release. Our two-step approach that utilizes a light-actuated AuNR hydrogel composite system for a combination of photothermal treatment (PTT), following initial biofilm disruption with D-AAs, is filling a current gap to develop alternative therapies that have the potential to advance a whole range of PJI medical treatment technologies. Using this two-step approach, we were able to successfully demonstrate in vitro the effective disruption and total eradication of Staphylococcus aureus biofilms formed on different metal alloys (Ti-based, CoCr, and Ta-based alloys) used in the manufacture of prosthetic joints. Moreover, this nanocomposite treatment is safe, does not lead to thermal damage of the surrounding soft tissues, and is localized to the disruption of the biofilms on the surface of the metal alloys. This treatment modality, when adapted to an open surgical approach that is compatible to current irrigation and debridement (I&D) medical procedures, has great potential to combat chronic PJIs and may help to preserve the implant, thereby decreasing the morbidity and mortality of the alternative revision surgery procedures.
Nitrogen-doped TiO2 has a great potential as a photocatalyst under visible light irradiation with applications in the removal of air and water pollutants, and the treatment of bacterial contaminations. In this study, nitrogen-doped TiO2 nanoparticles were synthesized via the sol–gel method and a post-annealing heat treatment approach. The effects of annealing treatment on the photocatalyst crystalline size and degree of crystallinity were analyzed. Methylene blue dye was used as the model water contaminant for the evaluation of the photoactivity of the synthesized nitrogen-doped TiO2 nanoparticles. The degradation of methylene blue was attributed to three mechanisms, i.e., adsorption, photocatalysis, and direct light photolysis. A kinetic model was developed to distinguish the impact of these three different mechanisms on the removal of contaminants. Adsorption and photocatalysis are heterogeneous processes for removing water organic contaminants. The characterization analysis demonstrates that they are relevant to the microstructures and surface chemical compositions of nitrogen-doped TiO2 photocatalysts. The processing–structure–performance relationship helped to determine the optimal processing parameters for nitrogen-doped TiO2 photocatalyst to achieve the best performance. While we used methylene blue as the model contaminant, the generalized quantitative model framework developed in this study can be extended to other types of contaminants after proper calibration.
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.
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.
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.
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.
Magnetic iron oxide nanoparticles(IONPs) are heavily explored as diagnostic and therapeutic agents due to their low cost, tunable properties, and biocompatibility. In particular, upon excitation with an alternating current(AC) magnetic field, the NPs generate localized heat that can be exploited for therapeutic hyperthermia treatment of diseased cells or pathogenic microbes. In this review, we focus on how structural changes and inter-particle interactions affect the heating efficiency of iron oxide-based magnetic NPs. Moreover, we present an overview of the different approaches to evaluate the heating performance of IONPs and introduce a new theranostic modality based on magnetic imaging guided–hyperthermia.
M4Ag44(p-MBA)30 molecular nanoparticles, where M is an alkali metal, have recently been shown to have exceptional stability, which confers unique traits to this molecule. In particular, the synthesis is straightforward, produces a truly single-sized molecular product, and has a quantitative yield. Here we describe in detail the results of experimental and theoretical studies on the synthesis, structure, stability, and electronic and optical properties of M4Ag44(p-MBA)30, including ESI-MS, NMR, optical absorption, IR, TGA, and other measurements as well as DFT and TDDFT calculations. This work deepens our understanding of this important Ag molecule, which should facilitate its use in a wide range of fundamental studies and applications.