Lipid and smooth muscle architectural pathology in the rabbit atherosclerotic vessel wall using Q-space cardiovascular magnetic resonance.

BACKGROUND: Atherosclerosis is an arterial vessel wall disease characterized by slow, progressive lipid accumulation, smooth muscle disorganization, and inflammatory infiltration. Atherosclerosis often remains subclinical until extensive inflammatory injury promotes vulnerability of the atherosclerotic plaque to rupture with luminal thrombosis, which can cause the acute event of myocardial infarction or stroke. Current bioimaging techniques are unable to capture the pathognomonic distribution of cellular elements of the plaque and thus cannot accurately define its structural disorganization. METHODS: We applied cardiovascular magnetic resonance spectroscopy (CMRS) and diffusion weighted CMR (DWI) with generalized Q-space imaging (GQI) analysis to architecturally define features of atheroma and correlated these to the microscopic distribution of vascular smooth muscle cells (SMC), immune cells, extracellular matrix (ECM) fibers, thrombus, and cholesteryl esters (CE). We compared rabbits with normal chow diet and cholesterol-fed rabbits with endothelial balloon injury, which accelerates atherosclerosis and produces advanced rupture-prone plaques, in a well-validated rabbit model of human atherosclerosis. RESULTS: Our methods revealed new structural properties of advanced atherosclerosis incorporating SMC and lipid distributions. GQI with tractography portrayed the locations of these components across the atherosclerotic vessel wall and differentiated multi-level organization of normal, pro-inflammatory cellular phenotypes, or thrombus. Moreover, the locations of CE were differentiated from cellular constituents by their higher restrictive diffusion properties, which permitted chemical confirmation of CE by high field voxel-guided CMRS. CONCLUSIONS: GQI with tractography is a new method for atherosclerosis imaging that defines a pathological architectural signature for the atheromatous plaque composed of distributed SMC, ECM, inflammatory cells, and thrombus and lipid. This provides a detailed transmural map of normal and inflamed vessel walls in the setting of atherosclerosis that has not been previously achieved using traditional CMR techniques. Although this is an ex-vivo study, detection of micro and mesoscale level vascular destabilization as enabled by GQI with tractography could increase the accuracy of diagnosis and assessment of treatment outcomes in individuals with atherosclerosis.

Monitoring Therapeutic Responses to Silicified Cancer Cell Immunotherapy Using PET/MRI in a Mouse Model of Disseminated Ovarian Cancer.

Current imaging approaches used to monitor tumor progression can lack the ability to distinguish true progression from pseudoprogression. Simultaneous metabolic 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) offers new opportunities to overcome this challenge by refining tumor identification and monitoring therapeutic responses to cancer immunotherapy. In the current work, spatial and quantitative analysis of tumor burden were performed using simultaneous [18F]FDG-PET/MRI to monitor therapeutic responses to a novel silicified cancer cell immunotherapy in a mouse model of disseminated serous epithelial ovarian cancer. Tumor progression was validated by bioluminescence imaging of luciferase expressing tumor cells, flow cytometric analysis of immune cells in the tumor microenvironment, and histopathology. While PET demonstrated the presence of metabolically active cancer cells through [18F]FDG uptake, MRI confirmed cancer-related accumulation of ascites and tissue anatomy. This approach provides complementary information on disease status without a confounding signal from treatment-induced inflammation. This work provides a possible roadmap to facilitate accurate monitoring of therapeutic responses to cancer immunotherapies.

The brains of aged mice are characterized by altered tissue diffusion properties and cerebral microbleeds.

BACKGROUND: Brain aging is a major risk factor in the progression of cognitive diseases including Alzheimer's disease (AD) and vascular dementia. We investigated a mouse model of brain aging up to 24 months old (mo). METHODS: A high field (11.7T) MRI protocol was developed to characterize specific features of brain aging including the presence of cerebral microbleeds (CMBs), morphology of grey and white matter, and tissue diffusion properties. Mice were selected from age categories of either young (3 mo), middle-aged (18 mo), or old (24 mo) and fed normal chow over the duration of the study. Mice were imaged in vivo with multimodal MRI, including conventional T2-weighted (T2W) and T2*-weighted (T2*W) imaging, followed by ex vivo diffusion-weighted imaging (DWI) and T2*W MR-microscopy to enhance the detection of microstructural features. RESULTS: Structural changes observed in the mouse brain with aging included reduced cortical grey matter volume and enlargement of the brain ventricles. A remarkable age-related change in the brains was the development of CMBs found starting at 18 mo and increasing in total volume at 24 mo, primarily in the thalamus. CMBs presence was confirmed with high resolution ex vivo MRI and histology. DWI detected further brain tissue changes in the aged mice including reduced fractional anisotropy, increased radial diffusion, increased mean diffusion, and changes in the white matter fibers visualized by color-coded tractography, including around a large cortical CMB. CONCLUSIONS: The mouse is a valuable model of age-related vascular contributions to cognitive impairment and dementia (VCID). In composite, these methods and results reveal brain aging in older mice as a multifactorial process including CMBs and tissue diffusion alterations that can be well characterized by high field MRI.

Ablation of the calpain-targeted site in cardiac myosin binding protein-C is cardioprotective during ischemia-reperfusion injury.

Cardiac myosin binding protein-C (cMyBP-C) phosphorylation is essential for normal heart function and protects the heart from ischemia-reperfusion (I/R) injury. It is known that protein kinase-A (PKA)-mediated phosphorylation of cMyBP-C prevents I/R-dependent proteolysis, whereas dephosphorylation of cMyBP-C at PKA sites correlates with its degradation. While sites on cMyBP-C associated with phosphorylation and proteolysis co-localize, the mechanisms that link cMyBP-C phosphorylation and proteolysis during cardioprotection are not well understood. Therefore, we aimed to determine if abrogation of cMyBP-C proteolysis in association with calpain, a calcium-activated protease, confers cardioprotection during I/R injury. Calpain is activated in both human ischemic heart samples and ischemic mouse myocardium where cMyBP-C is dephosphorylated and undergoes proteolysis. Moreover, cMyBP-C is a substrate for calpain proteolysis and cleaved by calpain at residues 272-TSLAGAGRR-280, a domain termed as the calpain-target site (CTS). Cardiac-specific transgenic (Tg) mice in which the CTS motif was ablated were bred into a cMyBP-C null background. These Tg mice were conclusively shown to possess a normal basal structure and function by analysis of histology, electron microscopy, immunofluorescence microscopy, Q-space MRI of tissue architecture, echocardiography, and hemodynamics. However, the genetic ablation of the CTS motif conferred resistance to calpain-mediated proteolysis of cMyBP-C. Following I/R injury, the loss of the CTS reduced infarct size compared to non-transgenic controls. Collectively, these findings demonstrate the physiological significance of calpain-targeted cMyBP-C proteolysis and provide a rationale for studying inhibition of calpain-mediated proteolysis of cMyBP-C as a therapeutic target for cardioprotection.

Assessing the multiscale architecture of muscular tissue with Q-space magnetic resonance imaging: Review.

Contraction of muscular tissue requires the synchronized shortening of myofibers arrayed in complex geometrical patterns. Imaging such myofiber patterns with diffusion-weighted MRI reveals architectural ensembles that underlie force generation at the organ scale. Restricted proton diffusion is a stochastic process resulting from random translational motion that may be used to probe the directionality of myofibers in whole tissue. During diffusion-weighted MRI, magnetic field gradients are applied to determine the directional dependence of proton diffusion through the analysis of a diffusional probability distribution function (PDF). The directions of principal (maximal) diffusion within the PDF are associated with similarly aligned diffusion maxima in adjacent voxels to derive multivoxel tracts. Diffusion-weighted MRI with tractography thus constitutes a multiscale method for depicting patterns of cellular organization within biological tissues. We provide in this review, details of the method by which generalized Q-space imaging is used to interrogate multidimensional diffusion space, and thereby to infer the organization of muscular tissue. Q-space imaging derives the lowest possible angular separation of diffusion maxima by optimizing the conditions by which magnetic field gradients are applied to a given tissue. To illustrate, we present the methods and applications associated with Q-space imaging of the multiscale myoarchitecture associated with the human and rodent tongues. These representations emphasize the intricate and continuous nature of muscle fiber organization and suggest a method to depict structural "blueprints" for skeletal and cardiac muscle tissue.

Association between tumor architecture derived from generalized Q-space MRI and survival in glioblastoma.

While it is recognized that the overall resistance of glioblastoma to treatment may be related to intra-tumor patterns of structural heterogeneity, imaging methods to assess such patterns remain rudimentary. METHODS: We utilized a generalized Q-space imaging (GQI) algorithm to analyze magnetic resonance imaging (MRI) derived from a rodent model of glioblastoma and 2 clinical datasets to correlate GQI, histology, and survival. RESULTS: In a rodent glioblastoma model, GQI demonstrated a poorly coherent core region, consisting of diffusion tracts <5 mm, surrounded by a shell of highly coherent diffusion tracts, 6-25 mm. Histologically, the core region possessed a high degree of necrosis, whereas the shell consisted of organized sheets of anaplastic cells with elevated mitotic index. These attributes define tumor architecture as the macroscopic organization of variably aligned tumor cells. Applied to MRI data from The Cancer Imaging Atlas (TCGA), the core-shell diffusion tract-length ratio (c/s ratio) correlated linearly with necrosis, which, in turn, was inversely associated with survival (p = 0.00002). We confirmed in an independent cohort of patients (n = 62) that the c/s ratio correlated inversely with survival (p = 0.0004). CONCLUSIONS: The analysis of MR images by GQI affords insight into tumor architectural patterns in glioblastoma that correlate with biological heterogeneity and clinical outcome.

Alterations in Multi-Scale Cardiac Architecture in Association With Phosphorylation of Myosin Binding Protein-C.

BACKGROUND: The geometric organization of myocytes in the ventricular wall comprises the structural underpinnings of cardiac mechanical function. Cardiac myosin binding protein-C (MYBPC3) is a sarcomeric protein, for which phosphorylation modulates myofilament binding, sarcomere morphology, and myocyte alignment in the ventricular wall. To elucidate the mechanisms by which MYBPC3 phospho-regulation affects cardiac tissue organization, we studied ventricular myoarchitecture using generalized Q-space imaging (GQI). GQI assessed geometric phenotype in excised hearts that had undergone transgenic (TG) modification of phospho-regulatory serine sites to nonphosphorylatable alanines (MYBPC3(AllP-/(t/t))) or phospho-mimetic aspartic acids (MYBPC3(AllP+/(t/t))). METHODS AND RESULTS: Myoarchitecture in the wild-type (MYBPC3(WT)) left-ventricle (LV) varied with transmural position, with helix angles ranging from -90/+90 degrees and contiguous circular orientation from the LV mid-myocardium to the right ventricle (RV). Whereas MYBPC3(AllP+/(t/t)) hearts were not architecturally distinct from MYBPC3(WT), MYBPC3(AllP-/(t/t)) hearts demonstrated a significant reduction in LV transmural helicity. Null MYBPC3((t/t)) hearts, as constituted by a truncated MYBPC3 protein, demonstrated global architectural disarray and loss in helicity. Electron microscopy was performed to correlate the observed macroscopic architectural changes with sarcomere ultrastructure and demonstrated that impaired phosphorylation of MYBPC3 resulted in modifications of the sarcomere aspect ratio and shear angle. The mechanical effect of helicity loss was assessed through a geometric model relating cardiac work to ejection fraction, confirming the mechanical impairments observed with echocardiography. CONCLUSIONS: We conclude that phosphorylation of MYBPC3 contributes to the genesis of ventricular wall geometry, linking myofilament biology with multiscale cardiac mechanics and myoarchitecture.

Improved molecular fingerprint analysis employing multi-branched gold nanoparticles in conjunction with surface-enhanced Raman scattering.

Vibrational spectroscopy is a powerful analytical tool that assesses molecular properties based on spectroscopic signatures. In this study, the effect of gold nanoparticle morphology (spherical vs multi-branched) was assessed for the characterization of a Raman signal (ie, molecular fingerprint) that may be helpful for numerous medical applications. Multi-branched gold nanoparticles (MBAuNPs) were fabricated using a green chemistry method which employed the reduction of gold ion solute by 2-[4-(2-hydroxyethyl)-1-piperazyl] ethane sulfonic acid. Two types of reporter dyes, indocyanine (IR820 and IR792) and carbocyanine (DTTC [3,3'-diethylthiatricarbocyanine iodide] and DTDC [3,3'-diethylthiadicarbocyanine iodide]), were functionalized to the surface of the MBAuNPs and stabilized with denatured bovine serum albumin, thus forming the surface-enhanced Raman spectroscopy tag. Fluorescein isothiocyanate-conjugated anti-epidermal growth factor receptor to the surface-enhanced Raman spectroscopy tags and the properties of the resulting conjugates were assessed through determination of the Raman signal. Using the MBAuNP Raman probes synthesized in this manner, we demonstrated that MBAuNP provided significantly more surface-enhanced Raman scattering signal when compared with the associated spherical gold nanoparticle of similar size and concentration. MBAuNP enhancements were retained in the surface-enhanced Raman spectroscopy tags complexed to anti-epidermal growth factor receptor, providing evidence that this could be a useful biological probe for enhanced Raman molecular fingerprinting. Furthermore, while utilizing IR820 as a novel reporter dye linked with MBAuNP, superior Raman signal fingerprint results were obtained. Such results provide significant promise for the use of MBAuNP in the detection of numerous diseases for which biologically specific surface markers exist.

Antibacterial Nanostructured Polyhydroxybutyrate Membranes for Guided Bone Regeneration.

The principle of guided bone regeneration (GBR) in orthopedic, cranio-maxillofacial and dental tissue engineering applications is to create a secluded space for the treatment of large bone defects while excluding fibrous connective tissue formation at the defect area. In dental surgeries, a GBR membrane is placed near the dental implant in post-extraction sockets to grow new bone at the implant site, along with inhibiting infection due to the microbial nature of the mouth flora. Poly[(R)-3-hydroxybutyric acid] (PHB) is a natural polyester synthesized by a wide variety of microorganisms which has been proposed for various biomedical applications. In this study, to improve the performance of PHB as a GBR, a NaOH based alkaline treatment was designed to create nanofeatured PHB membranes. The newly fabricated nanofeatured PHB membranes were investigated for GBR applications. The results showed that a quick, simple, and inexpensive sodium hydroxide treatment modified the nanostructured surface morphology and chemistry of the PHB membranes by inducing hydrolysis of the ester bonds in the PHB backbone creating carboxylic surface functional groups, which increased the hydrophilicity of the PHB surfaces. Cytocompatibility studies showed increased proliferation of human osteoblasts (bone forming cells) on the NaOH treated PHB membranes compared to the untreated ones. Importantly, in vitro bacterial studies with Staphylococcus aureus (S. aureus) indicated that the NaOH-treated PHB surfaces inhibited S. aureus growth more than 60% after 48 hours of culture compared to the untreated PHB membrane. Thus, this study, for the first time, showed that nanofeatured PHB membranes modified with a NaOH treatment may be a useful anti-bacterial, osteoconductive GBR membrane for numerous orthopedic, cranio-maxillofacial and dental tissue engineering applications.

Patterns of intersecting fiber arrays revealed in whole muscle with generalized Q-space imaging.

The multiscale attributes of mammalian muscle confer significant challenges for structural imaging in vivo. To achieve this, we employed a magnetic resonance method, termed "generalized Q-space imaging", that considers the effect of spatially distributed diffusion-weighted magnetic field gradients and diffusion sensitivities on the morphology of Q-space. This approach results in a subvoxel scaled probability distribution function whose shape correlates with local fiber orientation. The principal fiber populations identified within these probability distribution functions can then be associated by streamline methods to create multivoxel tractlike constructs that depict the macroscale orientation of myofiber arrays. We performed a simulation of Q-space input parameters, including magnetic field gradient strength and direction, diffusion sensitivity, and diffusional sampling to determine the optimal achievable fiber angle separation in the minimum scan time. We applied this approach to resolve intravoxel crossing myofiber arrays in the setting of the human tongue, an organ with anatomic complexity based on the presence of hierarchical arrays of intersecting myocytes. Using parameters defined by simulation, we imaged at 3T the fanlike configuration of the human genioglossus and the laterally positioned merging fibers of the styloglossus, inferior longitudinalis, chondroglossus, and verticalis. Comparative scans of the excised mouse tongue at 7T demonstrated similar midline and lateral crossing fiber patterns, whereas histological analysis confirmed the presence and distribution of these myofiber arrays at the microscopic scale. Our results demonstrate a magnetic resonance method for acquiring and displaying diffusional data that defines highly ordered myofiber patterns in architecturally complex tissue. Such patterns suggest inherent multiscale fiber organization and provide a basis for structure-function analyses in vivo and in model tissues.

Generalized Q-space MRI reveals macroscopic patterns of tumor architecture in vivo.

Current approaches for studying tumor activity in patients involve molecular characterization in excised tissue or biopsied samples. Recognizing that tumors are composed of heterogeneous arrays of cells and their environment, there is a compelling rationale to explore the macroscopic organization of tumor tissue. We present a novel methodology for probing the micro-structural constituents of tumors in vivo utilizing generalized Q-space MRI. This approach employs varying magnetic field gradients and diffusion sensitivities to yield voxel-scale probability distribution functions of proton diffusivity, and then maps multi-voxel cellular alignment with tractography. Using this methodology, we describe the presence of macroscopic organizational features in patients with head and neck cancers, specifically depicting regional differences between the geometrically coherent periphery and incoherent core region. Such methods may comprise a method for assessing attributes of tumor biology in vivo and for predicting the response of such tumors to various drugs and interventions.

Lubricin: a novel means to decrease bacterial adhesion and proliferation.

This study investigated the ability of lubricin (LUB) to prevent bacterial attachment and proliferation on model tissue culture polystyrene surfaces. The findings from this study indicated that LUB was able to reduce the attachment and growth of Staphylococcus aureus on tissue culture polystyrene over the course of 24 h by approximately 13.9% compared to a phosphate buffered saline (PBS)-soaked control. LUB also increased S. aureus lag time (the period of time between the introduction of bacteria to a new environment and their exponential growth) by approximately 27% compared to a PBS-soaked control. This study also indicated that vitronectin (VTN), a protein homologous to LUB, reduced bacterial S. aureus adhesion and growth on tissue culture polystyrene by approximately 11% compared to a PBS-soaked control. VTN also increased the lag time of S. aureus by approximately 43%, compared to a PBS-soaked control. Bovine submaxillary mucin was studied because there are similarities between it and the center mucin-like domain of LUB. Results showed that the reduction of S. aureus and Staphylococcus epidermidis proliferation on mucin coated surfaces was not as substantial as that seen with LUB. In summary, this study provided the first evidence that LUB reduced the initial adhesion and growth of both S. aureus and S. epidermidis on a model surface to suppress biofilm formation. These reductions in initial bacteria adhesion and proliferation can be beneficial for medical implants and, although requiring more study, can lead to drastically improved patient outcomes.

Multi-scale strategy to eradicate Pseudomonas aeruginosa on surfaces using solid lipid nanoparticles loaded with free fatty acids.

Infections are both frequent and costly in hospitals around the world, leading to longer hospital stays, overuse of antibiotics, and excessive costs to the healthcare system. Moreover, antibiotic resistant organisms, such as Pseudomonas aeruginosa are increasing in frequency, leading to 1.7 million infections per year in USA hospitals, and 99,000 deaths, both due to the evolution of antibiotic resistance and the formation of biofilms on medical devices. In particular, respiratory infections are costly, deadly to 4.5 million persons per year worldwide, and can spread to the lungs through the placement of endotracheal tubing. In this study, towards a reduction in infections, solid lipid nanoparticles were formulated from free fatty acids, or natural lipophilic constituents found in tissues of the body. A strategy was developed to target infections by producing coatings made of non-toxic chemistries lauric acid and oleic acid delivered by core-shell solid lipid nanoparticles that act against bacteria by multiple mechanisms at the nanoscale, including disruption of bacteria leading to DNA release, and reducing the adhesion of dead bacteria to ~1%. This is the first such study to explore an anti-infection surface relying on these multi-tier strategies at the nanoscale.

Enhanced efficacy of superparamagnetic iron oxide nanoparticles against antibiotic-resistant biofilms in the presence of metabolites.

Antibiotic resistance and the lack of new antibacterial agents cause major challenges for the treatment of infections. Here, we describe a simple, broad-spectrum, and low-cost dual-sided approach which uses superparamagnetic iron oxide particles (SPION) in combination with fructose metabolites as an alternative to existing antibacterial strategies. This strategy offers further improved efficacy of SPION against persistent gram-positive and gram-negative bacteria infections by manipulating the biofilm metabolic microenvironment and outperforms vancomycin (the antibiotic of last resort), creating a new nanotechnology-driven approach.

Short communication: Carboxylate functionalized superparamagnetic iron oxide nanoparticles (SPION) for the reduction of S. aureus growth post biofilm formation.

Biofilms formed by antibiotic resistant Staphylococcus aureus (S. aureus) continue to be a problem for medical devices. Antibiotic resistant bacteria (such as S. aureus) often complicate the treatment and healing of the patient, yet, medical devices are needed to heal such patients. Therefore, methods to treat these Biofilms once formed on medical devices are badly needed. Due to their small size and magnetic properties, superparamagnetic iron oxide nanoparticles (SPION) may be one possible material to penetrate Biofilms and kill or slow the growth of bacteria. In this study, SPION were functionalized with amine, carboxylate, and isocyanate functional groups to further improve their efficacy to disrupt the growth of S. aureus Biofilms. Without the use of antibiotics, results showed that SPION functionalized with carboxylate groups (followed by isocyanate then amine functional groups then unfunctionalized SPION) significantly disrupted Biofilms and retarded the growth of S. aureus compared to untreated Biofilms (by over 35% after 24 hours).

Effects of different sterilization techniques and varying anodized TiO2 nanotube dimensions on bacteria growth.

Infection of titanium (Ti)-based orthopedic implants is a growing problem due to the ability of bacteria to develop a resistance to today's antibiotics. As an attempt to develop a new strategy to combat bacteria functions, Ti was anodized in the present study to possess different diameters of nanotubes. It is reported here for the first time that Ti anodized to possess 20 nm tubes then followed by heat treatment to remove fluorine deposited from the HF anodization electrolyte solution significantly reduced both S. aureus and S. epidermidis growth compared to unanodized Ti controls. It was further found that the sterilization method used for both anodized nanotubular Ti and conventional Ti played an important role in the degree of bacteria growth on these substrates. Overall, UV light and ethanol sterilized samples decreased bacteria growth, while autoclaving resulted in the highest amount of bacteria growth. In summary, this study indicated that through a simple and inexpensive process, Ti can be anodized to possess 20 nm tubes that no matter how sterilized (UV light, ethanol soaking, or autoclaving) reduces bacteria growth and, thus, shows great promise as an antibacterial implant material.

Superparamagnetic iron oxide nanoparticles (SPION) for the treatment of antibiotic-resistant biofilms.

Bacterial infections caused by antibiotic-resistant strains are of deep concern due to an increasing prevalence, and are a major cause of morbidity in the United States of America. In particular, medical device failures, and thus human lives, are greatly impacted by infections, where the treatments required are further complicated by the tendency of pathogenic bacteria, such as Staphylococcus aureus, to produce antibiotic resistant biofilms. In this study, a panel of relevant antibiotics used clinically including penicillin, oxacillin, gentamicin, streptomycin, and vancomycin are tested, and although antibiotics are effective against free-floating planktonic S. aureus, either no change in biofilm function is observed, or, more frequently, biofilm function is enhanced. As an alternative, superparamagnetic iron oxide nanoparticles (SPION) are synthesized through a two-step process with dimercaptosuccinic acid as a chelator, followed by the conjugation of metals including iron, zinc, and silver; thus, the antibacterial properties of the metals are coupled to the superparamagnetic properties of SPION. SPION might be the ideal antibacterial treatment, with a superior ability to decrease multiple bacterial functions, target infections in a magnetic field, and had activity better than antibiotics or metal salts alone, as is required for the treatment of medical device infections for which no treatment exists today.

Fructose-enhanced reduction of bacterial growth on nanorough surfaces.

Patients on mechanical ventilators for extended periods of time often face the risk of developing ventilator-associated pneumonia. During the ventilation process, patients incapable of breathing are intubated with polyvinyl chloride (PVC) endotracheal tubes (ETTs). PVC ETTs provide surfaces where bacteria can attach and proliferate from the contaminated oropharyngeal space to the sterile bronchoalveolar area. To overcome this problem, ETTs can be coated with antimicrobial agents. However, such coatings may easily delaminate during use. Recently, it has been shown that changes in material topography at the nanometer level can provide antibacterial properties. In addition, some metabolites, such as fructose, have been found to increase the efficiency of antibiotics used to treat Staphylococcus aureus (S. aureus) infections. In this study, we combined the antibacterial effect of nanorough ETT topographies with sugar metabolites to decrease bacterial growth and biofilm formation on ETTs. We present for the first time that the presence of fructose on the nanorough surfaces decreases the number of planktonic S. aureus bacteria in the solution and biofilm formation on the surface after 24 hours. We thus envision that this method has the potential to impact the future of surface engineering of biomaterials leading to more successful clinical outcomes in terms of longer ETT lifetimes, minimized infections, and decreased antibiotic usage; all of which can decrease the presence of antibiotic resistant bacteria in the clinical setting.

The use of superparamagnetic nanoparticles for prosthetic biofilm prevention.

As with all surgical procedures, implantation comes with the added risk of infection. The goal of this in vitro study was to explore the use of superparamagnetic iron oxide nanoparticles (SPION) as a multifunctional platform to prevent biofilm formation. Results showed for the first time decreased Staphylococcus epidermidis numbers when exposed to 100 microg/ml of SPION for 12 hours and this trend continued for up to 48 hours. Prevention of colony assembly, a prerequisite to biofilm formation, was also observed at lower SPION dosages of 10 microg/ml after 12 hours. Coupled with previous studies demonstrating enhanced bone cell functions in the presence of the same concentration of SPION, the present results provided much promise for the use of SPION for numerous anti-infection orthopedic applications.