silicon and Inflammation

Topics: Aging; Animals; Anti-Inflammatory Agents; Arthritis; Autoimmune Diseases; Blood Coagulation; Bone and Bones; Cartilage; Chemical Phenomena; Chemistry, Physical; Connective Tissue; Embryonic and Fetal Development; Exudates and Transudates; Fibronectins; Fibrosis; Gene Expression Regulation; Glycosaminoglycans; Humans; Inflammation; Macrophages; Molecular Structure; Organ Specificity; Proteoglycans; Silicon; Wound Healing

Intranasal delivery is the most preferred route of drug administration for treatment of a range of nasal conditions including chronic rhinosinusitis (CRS), caused by an infection and inflammation of the nasal mucosa. However, localised delivery of lipophilic drugs for persistent nasal inflammation is a challenge especially with traditional topical nasal sprays. In this study, a composite thermoresponsive hydrogel is developed and tuned to obtain desired rheological and physiochemical properties suitable for intranasal administration of lipophilic drugs. The composite is comprised of drug-loaded porous silicon (pSi) particles embedded in a poloxamer 407 (P407) hydrogel matrix. Mometasone Furoate (MF), a lipophilic corticosteroid (log P of 4.11), is used as the drug, which is loaded onto pSi particles at a loading capacity of 28 wt%. The MF-loaded pSi particles (MF@pSi) are incorporated into the P407-based thermoresponsive hydrogel (HG) matrix to form the composite hydrogel (MF@pSi-HG) with a final drug content ranging between 0.1 wt% to 0.5 wt%. Rheomechanical studies indicate that the MF@pSi component exerts a minimal impact on gelation temperature or strength of the hydrogel host. The in-vitro release of the MF payload from MF@pSi-HG shows a pronounced increase in the amount of drug released over 8 h (4.5 to 21-fold) in comparison to controls consisting of pure MF incorporated in hydrogel (MF@HG), indicating an improvement in kinetic solubility of MF upon loading into pSi. Ex-vivo toxicity studies conducted on human nasal mucosal tissue show no adverse effect from exposure to either pure HG or the MF@pSi-HG formulation, even at the highest drug content of 0.5 wt%. Experiments on human nasal mucosal tissue show the MF@pSi-HG formulation deposits a quantity of MF into the tissues within 8 h that is >19 times greater than the MF@HG control (194 ± 7 μg of MF/g of tissue vs. <10 μg of MF/g of tissue, respectively).

Topics: Administration, Intranasal; Humans; Hydrogels; Inflammation; Mometasone Furoate; Porosity; Silicon

We investigated the biosafety and implantation feasibility of a new phakic refractive lens (PRL) in rabbit eyes.. Short PRLs (S-PRLs), large PRLs (L-PRLs), and large-grooved PRLs (LG-PRLs), were prepared by molding medical-grade liquid silicon. The cytotoxicity and cellular adhesion of the PRLs was assessed in vitro. To assess implantation feasibility, the S-PRL, L-PRL, and LG-PRL were implanted in the posterior chamber of rabbit eyes and the relative position was assessed by optical coherence tomography. The intraocular pressures (IOP) were compared between the S-PRL, L-PRL, LG-PRL, and control groups to evaluate the PRL biosafety after implantation.. The in vitro assays showed that cell viability and cellular adhesion in the S-PRL, L-PRL and LG-PRL groups was not significantly different to those in the control group throughout the study. After implantation into the posterior chamber of rabbit eyes, there were no obvious signs of inflammation or increases in IOP at each time point relative to the control group, demonstrating good biosafety of the PRL. The relative positions of the L-PRLs and LG-PRLs in the posterior chamber were appropriate and the retention frequencies were high.. The newly developed LG-PRL showed good biosafety with negligible in vitro cytotoxicity, ocular inflammation, or fluctuations in IOP. The LG-PRL provided the best implantation feasibility. The grooves on the LG-PRL provided channels for aqueous humor circulation. The LG-PRL is a promising type of PRL with an appropriate size and surface structure for effective correction of refractive errors in rabbit eyes.

Topics: Animals; Containment of Biohazards; Feasibility Studies; Inflammation; Lens Implantation, Intraocular; Lenses, Intraocular; Myopia; Phakic Intraocular Lenses; Rabbits; Refraction, Ocular; Silicon

Dry eye disease (DED) is the most common chronic eye disease characterized by ocular surface inflammation that affects hundreds of millions of people worldwide. The diagnosis and monitoring of DED require fast and reliable tools in the clinical setting. Matrix metalloproteinase 9 (MMP-9) has been proven to be a reliable indicator of DED owing to its close relationship with inflammation. A novel biosensor based on silicon nanowire-based field-effect transistor (SiNW FET) devices was fabricated for the quantitative measurement of MMP-9 in human tears. A modified controllable process was applied to improve the uniformity of the SiNWs in size and stabilize their performance with optical calibration at low salt concentrations for clinical application. With this protocol, correlation analysis proved the high agreement between the biosensor and enzyme-linked immunosorbent assay (correlation coefficient of 0.92 for DED patients and 0.90 for healthy controls). A diagnostic sensitivity of 86.96% and specificity of 90% were achieved in human tear samples from DED patients and healthy subjects in real-world clinical settings. Furthermore, the tear MMP-9 concentrations monitored using the device correlated with the therapeutic response of the patients with DED. Our enhanced SiNW biosensor device demonstrated its potential as an alternative tool for real-time diagnosis and monitoring for prognostic prediction toward point-of-care testing for DED.

Topics: Biosensing Techniques; Dry Eye Syndromes; Humans; Inflammation; Matrix Metalloproteinase 9; Nanowires; Silicon; Tears

The lack of drugs that target both disease progression and tissue preservation makes it difficult to effectively manage rheumatoid arthritis (RA). Here, we report a porous silicon-based nanomedicine that efficiently delivers an antirheumatic drug to inflamed synovium while degrading into bone-remodeling products. Methotrexate (MTX) is loaded into the porous silicon nanoparticles using a calcium silicate based condenser chemistry. The calcium silicate-porous silicon nanoparticle constructs (pCaSiNPs) degrade and release the drug preferentially in an inflammatory environment. The biodegradation products of the pCaSiNP drug carrier are orthosilicic acid and calcium ions, which exhibit immunomodulatory and antiresorptive effects. In a mouse model of collagen-induced arthritis, systemically administered MTX-loaded pCaSiNPs accumulate in the inflamed joints and ameliorate the progression of RA at both early and established stages of the disease. The disease state readouts show that the combination is more effective than the monotherapies.

Topics: Animals; Antirheumatic Agents; Arthritis, Rheumatoid; Calcium; Drug Carriers; Inflammation; Methotrexate; Mice; Nanomedicine; Porosity; Silicon

To describe an outbreak of late-onset toxic anterior segment syndrome (TASS) after the implantation of a specific hydrophilic acrylic intraocular lens (IOL).. University Hospitals of Leuven, Belgium.. Retrospective, single-center, observational study.. All eyes undergoing cataract surgery with a monofocal, toric, or enhanced depth-of-focus (EDoF) Synthesis (Cutting Edge) IOL between August 2019 and March 2020 were reviewed. Data were collected on the surgical procedure, postoperative course, time until onset of symptoms, clinical features, and additional treatments. A laboratory surface analysis of all 3 IOL subtypes was performed in the Intermountain Ocular Research Center at the University of Utah, USA. Furthermore, other possible causes of prolonged postoperative inflammation rather than the IOL itself were investigated.. Among the 203 eyes included, 28 TASS cases were identified (13.8%), among which 25 received a monofocal IOL, and 3 received an EDoF IOL. The mean time until onset was 28.9 (±19.9) days. Patients presented with anterior chamber cells (92.9%), deposits on the IOL (57.1%), or fibrinous inflammation (35.7%). 4 eyes (14.3%) underwent a surgical intervention, whereas 24 eyes showed a resolution of inflammation with topical therapy alone. Laboratory analysis showed the presence of both aluminum and silicon particles on the monofocal IOL, silicon particles only on the EDoF IOL, and no particles on the toric IOL surface.. This report describes an outbreak of atypical, late-onset TASS after cataract surgery, possibly correlated with aluminum and silicon contamination of the IOL surfaces.

Topics: Aluminum; Cataract; Eye Diseases; Humans; Inflammation; Lens Implantation, Intraocular; Lenses, Intraocular; Phacoemulsification; Retrospective Studies; Silicon; Visual Acuity

With advances in electronics and fabrication technology, intracortical microelectrodes have undergone substantial improvements enabling the production of sophisticated microelectrodes with greater resolution and expanded capabilities. The progress in fabrication technology has supported the development of biomimetic electrodes, which aim to seamlessly integrate into the brain parenchyma, reduce the neuroinflammatory response observed after electrode insertion and improve the quality and longevity of electrophysiological recordings. Here we describe a protocol to employ a biomimetic approach recently classified as nano-architecture. The use of focused ion beam lithography (FIB) was utilized in this protocol to etch specific nano-architecture features into the surface of non-functional and functional single shank intracortical microelectrodes. Etching nano-architectures into the electrode surface indicated possible improvements of biocompatibility and functionality of the implanted device. One of the benefits of using FIB is the ability to etch on manufactured devices, as opposed to during the fabrication of the device, facilitating boundless possibilities to modify numerous medical devices post-manufacturing. The protocol presented herein can be optimized for various material types, nano-architecture features, and types of devices. Augmenting the surface of implanted medical devices can improve the device performance and integration into the tissue.

Topics: Animals; Automation; Biomarkers; Brain; Cell Count; Electrodes, Implanted; Electrophysiological Phenomena; Inflammation; Ions; Microelectrodes; Nanoparticles; Neurons; Printing; Rats; Silicon

Inflammatory bowel disease (IBD) affects a confined area of the intestine and, therefore, administration of drugs via oral route is preferable. However, obstacles such as changes in the pH along gastrointestinal tract (GIT), enzymatic activity, and intraluminal pressure may cause low drug availability in the target tissue when delivered orally. Previous studies have pointed out the benefits of using micron-sized particles for targeting inflamed intestinal mucosa and nanoparticles for delivery of anti-inflammatory agents to the affected epithelial cells. We hypothesized that by combining the benefits of micro- and nano- particles, we could create a more efficient delivery system for budesonide, a glucocorticosteroid commonly used for anti-inflammatory IBD therapy. The aim of this study was to develop a novel multistage system for oral delivery designed to increase concentrations budesonidein the inflamed intestinal tissue. The multistage system consists of Stage 1 mesoporous silicon microparticles (S1MP) loaded with stage 2 poly-lactic-glycolic acid (PLGA) budesonide-encapsulating nanoparticles (BNP). BNP were efficiently loaded into S1MP (loading efficiency of 45.9 ± 14.8%) due to the large pore volume and high surface area of S1MP and exhibited controlled release profiles with enhanced drug dissolution rate in biologically relevant pHs. Due to the robustness in acidic pH and their geometry, S1MP protected the loaded budesonide in the acidic (gastric) pH with only 20% release. This allowed for the prolonged release of the BNP in the higher pH conditions (intestinal pH). The sustained release of BNP could facilitate accumulation in the inflamed tissue, enabling BNP to penetrate inflamed mucosa and release active budesonide to the target site. The multistage systems of S1MP and BNP were further evaluated in three-dimensional (3D) in vitro model of IBD and were found to (1) increase accumulation of BNP in the inflamed areas, (2) restore the barrier function of Caco-2 inflamed monolayer, and (3) significantly reduce pro-inflammatory cytokine release almost to the level of the healthy control.

Topics: Anti-Inflammatory Agents; Budesonide; Caco-2 Cells; Cell Line, Tumor; Delayed-Action Preparations; Drug Carriers; Drug Delivery Systems; Drug Liberation; Humans; Hydrogen-Ion Concentration; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa; Nanoparticles; Particle Size; Polylactic Acid-Polyglycolic Acid Copolymer; Silicon; Solubility

Injectable silk hydrogels are ideal carriers of therapeutic agents due to their biocompatibility and low immunogenicity. Injectable silk hydrogels for bone regeneration have been previously developed but often utilize expensive biologics. In this study, we have developed an injectable silk composite incorporated with a triphasic ceramic called MSM-10 (54 Mg

Topics: Alkaline Phosphatase; Animals; Bombyx; Bone Regeneration; Cell Proliferation; Collagen; Compressive Strength; Elastic Modulus; Humans; Hydrogels; Hydrogen-Ion Concentration; Inflammation; Injections; Ions; Magnesium; Male; Mice, Inbred C57BL; Osteoblasts; Platelet Endothelial Cell Adhesion Molecule-1; Silicon; Silk; Strontium

In a low inflammatory skin environment, Langerhans cells (LCs) - but not dermal dendritic cells (dDCs) - contribute to the pivotal process of tolerance induction. Thus LCs are a target for specific-tolerance therapies. LCs reside just below the stratum corneum, within the skin's viable epidermis. One way to precisely deliver immunotherapies to LCs while remaining minimally invasive is with a skin delivery device such as a microprojection arrays (MPA). Today's MPAs currently achieve rapid delivery (e.g. within minutes of application), but are focussed primarily at delivery of therapeutics to the dermis, deeper within the skin. Indeed, no MPA currently delivers specifically to the epidermal LCs of mouse skin. Without any convenient, pre-clinical device available, advancement of LC-targeted therapies has been limited. In this study, we designed and tested a novel MPA that delivers ovalbumin to the mouse epidermis (eMPA) while maintaining a low, local inflammatory response (as defined by low erythema after 24 h). In comparison to available dermal-targeted MPAs (dMPA), only eMPAs with larger projection tip surface areas achieved shallow epidermal penetration at a low application energy. The eMPA characterised here induced significantly less erythema after 24 h (p = 0.0004), less epidermal swelling after 72 h (p < 0.0001) and 52% less epidermal cell death than the dMPA. Despite these differences in skin inflammation, the eMPA and dMPA promoted similar levels of LC migration out of the skin. However, only the eMPA promoted LCs to migrate with a low MHC II expression and in the absence of dDC migration. Implementing this more mouse-appropriate and low-inflammatory eMPA device to deliver potential immunotherapeutics could improve the practicality and cell-specific targeting of such therapeutics in the pre-clinical stage. Leading to more opportunities for LC-targeted therapeutics such as for allergy immunotherapy and asthma.

Topics: Animals; Cell Movement; Cell Survival; Dermis; Drug Carriers; Drug Liberation; Epidermal Cells; Epidermis; Inflammation; Langerhans Cells; Mice; Mice, Inbred BALB C; Models, Theoretical; Ovalbumin; Polycarboxylate Cement; Silicon; Skin; Transdermal Patch

Biomedical coatings for orthopedic implants should facilitate osseointegration and mitigate implant-induced inflammatory reactions. In our study, Ca-Si coatings with Sr-containing nanowire-like structures (NW-Sr-CS) were achieved via hydrothermal treatment. In order to identify the effect of nanowire-like topography and Sr dopant on the biological properties of Ca-Si-based coatings, the original Ca-Si coating, Ca-Si coatings modified with nanoplate (NP-CS) and similar nanowire-like structure (NW-CS) were fabricated as the control. Surface morphology, phase composition, surface area, zeta potential and ion release of these coatings were characterized. The in vitro osteogenic activities and immunomodulatory properties were evaluated with bone marrow stromal cells (BMSCs) and RAW 264.7 cells, a mouse macrophage cell line. Compared with the CS and NP-CS coatings, the NW-CS coating possessed a larger surface area and pore volume, beneficial protein adsorption, up-regulated the expression levels of integrin β1, Vinculin and focal adhesion kinase and promoted cell spreading. Furthermore, the NW-CS coating significantly enhanced the osteogenic differentiation and mineralization as indicated by the up-regulation of ALP activity, mineralized nodule formation and osteoblastogenesis-related gene expression. With the introduction of Sr, the NW-Sr-CS coatings exerted a greater effect on the BMSC proliferation rate, calcium sensitive receptor gene expression as well as PKC and ERK1/2 phosphorylation. In addition, the Sr-doped coatings significantly up-regulated the ratio of OPG/RANKL in the BMSCs. The NW-Sr-CS coatings could modulate the polarization of macrophages towards the wound-healing M2 phenotype, reduce the mRNA expression levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and enhance anti-inflammatory cytokines (IL-1ra, IL-10). The Sr-doped nanowire modification may be a valuable approach to enhance osteogenic activities and reduce inflammatory reactions.

Topics: Adsorption; Alkaline Phosphatase; Animals; Calcium; Cell Adhesion; Cell Proliferation; Coated Materials, Biocompatible; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation; Inflammation; Ions; Macrophages; Mesenchymal Stem Cells; Mice; Nanowires; Osteoblasts; Osteoclasts; Osteogenesis; Phosphorylation; Protein Kinase C; Rats; RAW 264.7 Cells; Silicon; Strontium; Surface Properties; X-Ray Diffraction

Study evaluated effect of silicon-rich water intake on systemic inflammation and functional characteristics of peritoneal macrophages (PMs) of rats that were chronically exposed to dietary aluminum.. One month-old female Wistar Albino rats were administered aluminum chloride dissolved in distilled water (1.6mg/kg body weight in 0.5mL) by gavage for 90days. The rats were then given standard (6mg/L) or silicon-rich water (19mg/L silicon) (n=7/group). Control rats underwent sham gavage and received standard or silicon-rich water (n=7/group). Blood was assessed for cytokine levels. Unstimulated and lipopolysaccharide (LPS)-stimulated PMs were assessed in terms of phagocytic activity and cytokine secretion in vitro.. Chronic exposition to dietary aluminum and silicon-rich drinking water did not change serum TNF-α levels. Aluminum increased serum IL-2 and this was reversed by silicon-rich water. The aluminum-exposed rats had higher serum sICAM-1 than sham-gavaged, unrelated to type of water. LPS-stimulated PMs from aluminum-intoxicated animals exhibited low phagocytic activity and release of TNF-α, this was significantly improved by silicon-rich water intake. In the presence of silicon-rich water, LPS-stimulated and unstimulated PMs from aluminum-exposed rats produced significantly more IL-10.. Chronic ingestion of aluminum, increases systemic and peritoneal inflammation and PM dysfunction. The presence of high levels of the natural aluminum antagonist silicon in the drinking water restored IL-10 and TNF-α PM secretion, preventing prolonged inflammation. Thus, silicon intake can decrease the immunotoxicity of aluminum.

Topics: Aluminum Chloride; Animals; Cytokines; Dietary Exposure; Drinking; Female; Inflammation; Lipopolysaccharides; Macrophage Activation; Macrophages, Peritoneal; Rats, Wistar; Silicon; Water

It is known that good mechanical properties, low modulus to reduce stress-shielding effect, favorable osteogenic activity and limited inflammatory response are critical factors for orthopedic implants to induce excellent osteointegration. In this study, Ti-20% Ta metal-metal composite (referred as Ti-Ta) which consisted of Ti- and Ta-rich phases was fabricated via the strategy of powder metallurgy. Micro-arc oxidation (MAO) was employed to modify the surface of Ti-Ta composite. The surfaces of Ti-Ta composite after MAO treatment at an applied voltage of 250 (referred as MAO-250 V) or 300 V (referred as MAO-300 V) exhibited three distinct zones with significantly different morphological features and surface chemistry. Osteoblast-like SaOS-2 cells were found to be preferential to attach on the Ta-rich phase and its surrounding areas, exhibiting an area-dependent adhesion tendency. However, the attachment of Raw 264.7 macrophages was found to be insensitive to the surface characteristics. The proliferation and differentiation of SaOS-2 cells cultured on various surfaces basically followed the trend: MAO-modified surfaces > Ti-Ta surface > Ti surface. The Ti-Ta and MAO-modified surfaces were found to inhibit the inflammatory response and polarize macrophages to anti-inflammatory M2 phenotype compared to Ti surface. Moreover, the microenvironments created by Ti-Ta, MAO-250 V and MAO-300 V/macrophage interactions promoted the proliferation and differentiation of SaOS-2 cells compared to that created by Ti/macrophage interactions. MAO-300 V surface exhibited further enhanced positive osteo-immunomodulatory effects compared to Ti-Ta surface. Together, the Ti-20% Ta metal-metal composite modified by MAO at an applied voltage of 300 V is considered as a promising implant material for orthopedic applications.

Topics: Animals; Calcium; Cell Proliferation; Cell Survival; Cells, Cultured; Coated Materials, Biocompatible; Cytokines; Humans; Inflammation; Mice; Osteogenesis; Particle Size; RAW 264.7 Cells; Silicon; Surface Properties; Tantalum; Titanium

Aluminum consumption has been associated with various neurodegenerative diseases. Previous studies suggest that regular beer intake reverses the pro-oxidant and inflammatory statuses induced by aluminum nitrate intoxication. This paper aims to evaluate the in vitro antioxidant capacity and acetylcholinesterase inhibitory activity of non-alcoholic beer (NABeer), silicon or hops, as well as their effect on animal behavior (e.g. curiosity, immobilization, rearing, grooming, swimming) and brain antioxidant enzyme (activity and gene expression) and anti-inflammatory status in aluminum nitrate intoxicated rats. Male Wistar rats were divided into five groups: 1) Control, 2) Aluminum nitrate (450 μg/kg/day), 3) Aluminum nitrate plus NABeer, 4) Aluminum nitrate plus hops, and 5) Aluminum nitrate plus silicon. Hops showed the highest in vitro antioxidant capacity and silicon the highest anticholinesterase activity. In the Aluminum group the brain aluminum/silicon ratio increased with impairment of brain antioxidant and inflammatory statuses. NABeer, silicon and hops block the negative effect on the in vivo antioxidant and inflammatory statuses induced by Aluminum nitrate and improve swimming and rearing behavioral tests. The various positive results suggest that NABeer is useful as a functional multi-target drink in the prevention of some neurodegenerative events caused by aluminum intoxication. More studies are required to conclude present results.

Topics: Acetylcholinesterase; Aluminum Compounds; Animals; Antioxidants; Behavior, Animal; Beverages; Brain; Butyrylcholinesterase; Cholinesterase Inhibitors; Humulus; Inflammation; Male; Memory; Motor Activity; Nitrates; Rats, Wistar; Silicon

Toxicology and bedside medical condition monitoring is often desired to be both ultrasensitive and noninvasive. However, current biomarker analyses for these purposes are mostly offline and fail to detect low marker quantities. Here, we report a system called dLABer (detection of living animal's exhaled breath biomarker) that integrates living rats, breath sampling, microfluidics, and biosensors for the automated tracking of breath-borne biomarkers. Our data show that dLABer could selectively detect (online) and report differences (of up to 10

Topics: Animals; Biomarkers; Biosensing Techniques; Breath Tests; Humans; Inflammation; Interleukin-6; Male; Nanowires; Particulate Matter; Rats, Wistar; Silicon; Transistors, Electronic

Interleukin-1b (IL-1b) and interleukin-10 (IL-10) biomarkers are one of many antigens that are secreted in acute stages of inflammation after left ventricle assisted device (LVAD) implantation for patients suffering from heart failure (HF). In the present study, we have developed a fully integrated electrochemical biosensor platform for cytokine detection at minute concentrations. Using eight gold working microelectrodes (WEs) the design will increase the sensitivity of detection, decrease the time of measurements, and allow a simultaneous detection of varying cytokine biomarkers. The biosensor platform was fabricated onto silicon substrates using silicon technology. Monoclonal antibodies (mAb) of anti-human IL-1b and anti-human IL-10 were electroaddressed onto the gold WEs through functionalization with 4-carboxymethyl aryl diazonium (CMA). Cyclic voltammetry (CV) was applied during the WE functionalization process to characterize the gold WE surface properties. Finally, electrochemical impedance spectroscopy (EIS) characterized the modified gold WE. The biosensor platform was highly sensitive to the corresponding cytokines and no interference with other cytokines was observed. Both cytokines: IL-10 and IL-1b were detected within the range of 1pgmL

Topics: Antibodies, Immobilized; Biosensing Techniques; Cytokines; Dielectric Spectroscopy; Gold; Heart Failure; Heart Ventricles; Humans; Inflammation; Interleukin-10; Interleukin-1beta; Silicon

Quantum dots (QDs) are nanocrystalline semiconductor materials that have been tested for biological applications such as cancer therapy, cellular imaging and drug delivery, despite the serious lack of information of their effects on mammalian cells. The present study aimed to evaluate the potential of Si/SiO2 QDs to induce an inflammatory response in MRC-5 human lung fibroblasts. Cells were exposed to different concentrations of Si/SiO2 QDs (25-200 μg·mL(-1)) for 24, 48, 72 and 96 h. The results obtained showed that uptake of QDs was dependent on biocorona formation and the stability of nanoparticles in various biological media (minimum essential medium without or with 10% fetal bovine serum). The cell membrane damage indicated by the increase in lactate dehydrogenase release after exposure to QDs was dose- and time-dependent. The level of lysosomes increased proportionally with the concentration of QDs, whereas an accumulation of autophagosomes was also observed. Cellular morphology was affected, as shown by the disruption of actin filaments. The enhanced release of nitric oxide and the increase in interleukin-6 and interleukin-8 protein expression suggested that nanoparticles triggered an inflammatory response in MRC-5 cells. QDs decreased the protein expression and enzymatic activity of matrix metalloproteinase (MMP)-2 and MMP-9 and also MMP-1 caseinase activity, whereas the protein levels of MMP-1 and tissue inhibitor of metalloproteinase-1 increased. The present study reveals for the first time that silicon-based QDs are able to generate inflammation in lung cells and cause an imbalance in extracellular matrix turnover through a differential regulation of MMPs and tissue inhibitor of metalloproteinase-1 protein expression.

Topics: Autophagy; Extracellular Matrix; Homeostasis; Humans; Inflammation; Lung; Lysosomes; Quantum Dots; Silicon

The aim of this study was to investigate the effects of dietary silicon-enriched spirulina (SES) on atherosclerosis.. Hamsters (six per group) on a high-fat (HF) diet received SES or non-enriched spirulina (both at 57 mg/kg body weight) daily. This corresponded to 0.57 mg silicon/kg body weight daily.. The HF diet induced dyslipidemia, insulin resistance, oxidative stress, and vascular dysfunction. Compared with the HF group, SES attenuated increases of lipemia and prevented insulin resistance (IR) (P = 0.001). SES protected against oxidative stress through a reduction of heart (P = 0.006) and liver (P < 0.0001) nicotinamide adenine dinucleotide phosphate-oxidase activity and by sparing the activity of superoxide dismutase (P = 0.0017) and glutathione peroxidase (P = 0.01861). SES decreased inflammation, lowering tumor necrosis factor-α (P = 0.0006) and interleukin-6 levels (P = 0.0112), decreasing polymorphonuclear cells and preventing nuclear factor-κB activity (P = 0.0259). SES corrected plasma level of monocyte chemoattractant protein-1 (P = 0.0380), which was increased by the HF diet. Finally, SES supplementation prevented vascular and endothelial functions assessed respectively by the contractile response to the agonist phenylephrine and the relaxation induced by acetylcholine.. SES protects against metabolic imbalance, inflammation, oxidative stress, and vascular dysfunction induced by an HF diet, and could prevent the atherogenic processes. Synergistic effects between spirulina and silicon were observed.

Topics: Animals; Atherosclerosis; Biomarkers; Cricetinae; Cytokines; Diet, High-Fat; Dietary Supplements; Drug Synergism; Dyslipidemias; Endothelium, Vascular; Glutathione Peroxidase; Heart; Inflammation; Inflammation Mediators; Insulin Resistance; Liver; Male; Oxidative Stress; Silicon; Spirulina; Superoxide Dismutase; Trace Elements

Myocardial infarction (MI), commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia, which is an increasing problem in terms of morbidity, mortality and healthcare costs worldwide. Along with the idea to develop nanocarriers that efficiently deliver therapeutic agents to target the heart, in this study, we aimed to test the in vivo biocompatibility of different sizes of thermally hydrocarbonized porous silicon (THCPSi) microparticles and thermally oxidized porous silicon (TOPSi) micro and nanoparticles in the heart tissue. Despite the absence or low cytotoxicity, both particle types showed good in vivo biocompatibility, with no influence on hematological parameters and no considerable changes in cardiac function before and after MI. The local injection of THCPSi microparticles into the myocardium led to significant higher activation of inflammatory cytokine and fibrosis promoting genes compared to TOPSi micro and nanoparticles; however, both particles showed no significant effect on myocardial fibrosis at one week post-injection. Our results suggest that THCPSi and TOPSi micro and nanoparticles could be applied for cardiac delivery of therapeutic agents in the future, and the PSi biomaterials might serve as a promising platform for the specific treatment of heart diseases.

Topics: Animals; Biocompatible Materials; Cells, Cultured; Drug Carriers; Drug Delivery Systems; Fibrosis; Gene Expression Regulation; Inflammation; Male; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Porosity; Rats; Rats, Sprague-Dawley; Silicon

Sensory receptors in human skin transmit a wealth of tactile and thermal signals from external environments to the brain. Despite advances in our understanding of mechano- and thermosensation, replication of these unique sensory characteristics in artificial skin and prosthetics remains challenging. Recent efforts to develop smart prosthetics, which exploit rigid and/or semi-flexible pressure, strain and temperature sensors, provide promising routes for sensor-laden bionic systems, but with limited stretchability, detection range and spatio-temporal resolution. Here we demonstrate smart prosthetic skin instrumented with ultrathin, single crystalline silicon nanoribbon strain, pressure and temperature sensor arrays as well as associated humidity sensors, electroresistive heaters and stretchable multi-electrode arrays for nerve stimulation. This collection of stretchable sensors and actuators facilitate highly localized mechanical and thermal skin-like perception in response to external stimuli, thus providing unique opportunities for emerging classes of prostheses and peripheral nervous system interface technologies.

Topics: Electrodes; Humans; Inflammation; Movement; Nanotechnology; Nanotubes, Carbon; Pressure; Prosthesis Design; Silicon; Skin; Skin, Artificial; Temperature; Touch Perception

Hydrogels may be the ideal vitreous substitutes due to their wonderful physical features and biocompatibility. However, their drawbacks, short residence time, and biodegradation in vivo, have led to the fact that none of them have been approved for clinical use. In this study, we developed a novel approach of using a foldable capsular vitreous body (FCVB) injected with polyvinylalcohol (PVA) hydrogel as a vitreous substitute for long-term tamponade. The 3% PVA hydrogel that was cross-linked by gamma irradiation showed good rheological and physical properties and had no toxicity in vitro. After 180 days retention, the 3% PVA hydrogel inside FCVB remained transparent and showed good viscoelasticity without biodegradation and showed good biocompatibility and retina support. This new approach may develop into a valuable tool to improve the stability performance of PVA hydrogel as a vitreous substitute and to extend the application function of FCVB for long-term implantation in vitreous cavity.

Topics: Animals; Cataract; Cells, Cultured; Drug Delivery Systems; Electroretinography; Eye; Fibroblasts; Humans; Hyaluronic Acid; Hydrogel, Polyethylene Glycol Dimethacrylate; Inflammation; Mice; Polyvinyl Alcohol; Rabbits; Retina; Silicon; Vitrectomy; Vitreous Body

It has been well established that the bone marrow (BM) is a radiosensitive tissue, but the radiosensitivity of the heart is poorly understood. In this study, we investigated the comparative effects of ²⁸Silicon (²⁸Si) ions (one type of heavy ion found in space) on tissue from the heart and the BM of exposed mice. We gave adult male CBA/CaJ mice a whole-body exposure to a total dose of 0, 0.1, 0.25, or 0.5 Gy of 300 MeV/nucleon (n) ²⁸Si ions, using a fractionated schedule (two exposures, 15 days apart that totaled each selected dose). The heart and BM were collected from 5 mice per treatment group at various times up to 6 months post-irradiation. In each mouse, we obtained tissue lysates from the heart and from the total population of BM cells for measuring the levels of cleaved poly (ADP-ribose) polymerase (cleaved PARP, a marker of apoptotic cell death) and the levels of activated nuclear factor-kappa B (NF-κB) and selected NF-κB-regulated cytokines known to be involved in inflammatory responses. Our data showed that, up to 6 months post-irradiation, the levels of apoptotic cell death and inflammatory responses in tissues from the heart and BM collected from exposed mice were statistically higher than those in sham controls. Hence, these findings are suggestive of chronic apoptotic cell death and inflammation in both tissues after exposure to ²⁸Si ions. In summary, our data are indicative of a possible association between exposure to ²⁸Si ions during space flight and long-term health risk.

Topics: Animals; Apoptosis; Bone Marrow; Cytokines; Heart; Inflammation; Male; Mice; Mice, Inbred CBA; Myocardium; NF-kappa B; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Radioisotopes; Silicon; Whole-Body Irradiation

The purpose of this study is to investigate the antioxidant and anti-inflammatory properties of silicon (Si) in the RAW 264.7 murine macrophage cell line. Lipopolysaccharide (LPS) was used to induce inflammatory conditions, and cells were treated with 0, 1, 5, 10, 25, 50, and 100 μM Si in the form of sodium metasilicate. Tert-butylhydroquinone (TBHQ), a well-known antioxidative substance, was used as a positive control to assess the degree of antioxidative and anti-inflammatory properties of Si. Sodium metasilicate at 100 μM suppressed LPS-induced nitric oxide generation from macrophages 36 h after treatment. In addition, 50 μM sodium metasilicate decreased interleukin-6 production, and the degree of suppression was comparable to that of 10 μM TBHQ treatment. LPS-induced messenger RNA (mRNA) expression of tumor necrosis factor-α and inducible nitric oxide synthase was significantly decreased by 1, 5, 10, and 50 μM sodium metasilicate. Cyclooxygenase-2 mRNA expression was also suppressed by 1, 5, 25, and 50 μM sodium metasilicate. Based on these data, Si has the ability to suppress the production of inflammatory cytokines and mediators, possibly through the suppression of radical scavenger activity and down-regulation of gene expression of inflammatory mediators.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Cell Line; Cyclooxygenase 2; Down-Regulation; Inflammation; Inflammation Mediators; Interleukin-6; Lipopolysaccharides; Macrophages; Mice; RNA, Messenger; Silicates; Silicon

Four cylindrical silicon tissue cages (TC, internal volume: 6.7 ± 0.11 cm(3)) were inserted subcutaneously in 29 young healthy cats. A mild inflammatory reaction was induced by intracaveal injection of 1 mL of a 2%λ-carrageenan solution. TC exudate was subsequently sampled at predetermined times (up to 120 h) to measure exudate leucocyte counts and the concentrations of protein and eicosanoids. TC remained in situ for 9-10 months and were well tolerated. Leucocyte counts peaked at 34 h (50.1 ± 57.6 × 10(3) cells/mm(3) ) and returned towards baseline after 72 h. Protein concentration increased from 26.2 ± 2.7 g/L to a peak of 35.9 ± 6.0 g/L at 12 h before returning to baseline at 48 h. Exudate prostaglandin (PG)E(2) concentration peaked at 24 h (11.7 ± 13.7 ng/mL) and returned to baseline by 120 h. Repeated collection of fluid from noninjected cages did not increase transudate PGE(2). Ketoprofen (2 mg/kg, subcutaneously) suppressed exudate PGE(2) at 24 h. The carrageenan-stimulated TC model is an ethical and novel means of investigating soft tissue inflammation in the cat, in which exudate PGE(2) acts as surrogate marker of cyclooxygenase-2 activity. This model will facilitate the investigation of in vivo pharmacokinetics and pharmacodynamics of anti-inflammatory drugs in this species.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Carrageenan; Cat Diseases; Cats; Diffusion Chambers, Culture; Dinoprostone; Disease Models, Animal; Exudates and Transudates; Inflammation; Injections, Subcutaneous; Leukocyte Count; Silicon

Polysilicon nanowire biosensors have been fabricated using a top-down process and were used to determine the binding constant of two inflammatory biomarkers. A very low cost nanofabrication process was developed, based on simple and mature photolithography, thin film technology, and plasma etching, enabling an easy route to mass manufacture. Antibody-functionalized nanowire sensors were used to detect the proteins interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) over a wide range of concentrations, demonstrating excellent sensitivity and selectivity, exemplified by a detection sensitivity of 10 fM in the presence of a 100,000-fold excess of a nontarget protein. Nanowire titration curves gave antibody-antigen dissociation constants in good agreement with low-salt enzyme-linked immunosorbent assays (ELISAs). This fabrication process produces high-quality nanowires that are suitable for low-cost mass production, providing a realistic route to the realization of disposable nanoelectronic point-of-care (PoC) devices.

Topics: Antigen-Antibody Reactions; Biomarkers; Biosensing Techniques; Crystallization; Enzyme-Linked Immunosorbent Assay; Inflammation; Interleukin-8; Membranes, Artificial; Nanowires; Polymers; Silicon; Surface Properties; Tumor Necrosis Factor-alpha

Nanotechnology, such as nanoelectronic biosensors, is bringing new opportunities and tools to the studies of cell biology, clinical applications, and drug discovery. In this study, crystalline silicon nanowire based field-effect transistors fabricated using top-down approach were employed to parallelly detect pro-inflammatory cytokines in the complex biological fluids (cell culture medium and blood samples) with high specificity and femtomolar sensitivity. Using this technique, the dynamic secretion of TNF-alpha and IL6 was revealed during the immune response of macrophages and rats to the stimulation of bacteria endotoxin. This technique could provide a unique platform to examine the profile of complex immune responses for fundamental studies and diagnosis.

Topics: Biosensing Techniques; Conductometry; Cytokines; Equipment Design; Equipment Failure Analysis; Humans; Inflammation; Nanotechnology; Nanotubes; Silicon; Transistors, Electronic

Mesoporous silicon particles hold great potential in improving the solubility of otherwise poorly soluble drugs. To effectively translate this feature into the clinic, especially via oral or parenteral administration, a thorough understanding of the interactions of the micro- and nanosized material with the physiological environment during the delivery process is required. In the present study, the behaviour of thermally oxidized porous silicon particles of different sizes interacting with Caco-2 cells (both non-differentiated and polarized monolayers) was investigated in order to establish their fate in a model of intestinal epithelial cell barrier. Particle interactions and TNF-α were measured in RAW 264.7 macrophages, while cell viabilities, reactive oxygen species and nitric oxide levels, together with transmission electron microscope images of the polarized monolayers, were assessed with both the Caco-2 cells and RAW 264.7 macrophages. The results showed a concentration and size dependent influence on cell viability and ROS-, NO- and TNF-α levels. There was no evidence of the porous nanoparticles crossing the Caco-2 cell monolayers, yet increased permeation of the loaded poorly soluble drug, griseofulvin, was shown.

Topics: Animals; Caco-2 Cells; Cell Death; Cell Membrane Permeability; Cell Survival; Epithelial Cells; Griseofulvin; Humans; Inflammation; Intestines; Intracellular Space; Macrophages; Mice; Nanoparticles; Nitric Oxide; Oxidation-Reduction; Porosity; Reactive Oxygen Species; Silicon; Solubility; Temperature; Tumor Necrosis Factor-alpha

In this study, the effect of insertion speed on long-term tissue response and insertion mechanics was investigated. A dummy silicon parylene-coated probe was used in this context and implanted in the rat brain at 10 μm/s (n = 6) or 100 μm/s (n = 6) to a depth of 9 mm. The insertion mechanics were assessed by the dimpling distance, and the force at the point of penetration, at the end of the insertion phase, and after a 3-min rest period in the brain. After 6 weeks, the tissue response was evaluated by estimating the amount of gliosis, inflammation, and neuronal cell loss with immunohistochemistry. No difference in dimpling, penetration force, or the force after a 3-min rest period in the brain was observed. However, the force at the end of the insertion phase was significantly higher when inserting the probes at 100 μm/s compared to 10 μm/s. Furthermore, an expected tissue response was seen with an increase of glial and microglial reactivity around the probe. This reaction was similar along the entire length of the probe. However, evidence for a neuronal kill zone was observed only in the most superficial part of the implant. In this region, the lesion size was also greatest. Comparison of the tissue response between insertion speeds showed no differences.

Topics: Analysis of Variance; Animals; Brain; Electrodes, Implanted; Gliosis; Immunohistochemistry; Inflammation; Male; Mechanical Phenomena; Microelectrodes; Prosthesis Implantation; Rats; Rats, Wistar; Silicon

For tissue engineering of gastrointestinal organs, in situ implantation of constructs in the omentum is performed to utilize the body as a bioreactor for tissue generation. In this approach, constructs are fabricated into tubes, using stents, and implanted in the omentum to induce vascularization. In order to evaluate the constructs and its environment during the period of in situ tissue engineering in the rat model, micro-computed tomography imaging was performed. Imaging using micro-computed tomography was useful in localization of the position of the construct, evaluation of implant site tissue, degree of peripheral inflammation to neighbouring tissues and migration of the implanted construct. Images also enable the estimation of the dimensions of the construct and imaging of cyst formations or fluid accumulations on the luminal side of the tubular construct or ascites formation. Since micro-computed tomography is a non-invasive method, it can be repeated for evaluation of implanted constructs if in situ tissue engineering is performed over longer periods.

Topics: Animals; Bone Substitutes; Equipment Design; Esophagus; Inflammation; Omentum; Rats; Rats, Sprague-Dawley; Silicon; Stents; Tissue Engineering; Tissue Scaffolds; X-Ray Microtomography

Leukocyte beta2 integrins Mac-1 and p150,95 are promiscuous cell-surface receptors that recognise and mediate cell adhesion to a variety of adsorbed and denatured proteins. We used albumin as a model protein to study whether leukocyte adhesion and activation depended on the nm-scale topography of a protein adlayer. Albumin adsorbed from the native conformation gave rise to different adlayer topographies and different amounts of adsorbed protein on hydrophobic and relatively hydrophilic polystyrene and silanised silicon-wafer surfaces, whereas adsorption of pre-denatured Alb resulted in similar adlayer topographies and similar amounts of adsorbed protein on these surfaces. All three distinct protein-adlayer topographies supported adhesion of in vitro differentiated, macrophage-like U937 and THP-1 cells, but did not support adhesion of their promonocytic precursors. Human monocytes freshly isolated from peripheral blood did not adhere to adsorbed albumin, not even in the presence of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1alpha chemokines. Adhesion of the macrophage-like cells to albumin in any of the three topographies was inhibited by antibodies against beta2 integrins, but not by antibodies against beta1 integrins, and did not induce secretion of the proinflammatory cytokine tumour necrosis factor-alpha.

Topics: Adsorption; Albumins; Apoptosis; Biocompatible Materials; CD18 Antigens; Cell Adhesion; Cell Line; Cell Membrane; Chemokine CCL4; Cytokines; Dose-Response Relationship, Drug; Edetic Acid; Humans; Inflammation; Leukocytes; Macrophage Inflammatory Proteins; Macrophages; Microscopy, Atomic Force; Monocytes; Polystyrenes; Protein Conformation; Protein Denaturation; Proteins; Silicon; Spectrometry, X-Ray Emission; Surface Properties; Time Factors; Tumor Necrosis Factor-alpha; U937 Cells

Implantable silicon microelectrode array technology is a useful technique for obtaining high-density, high-spatial resolution sampling of neuronal activity within the brain and holds promise for a wide range of neuroprosthetic applications. One of the limitations of the current technology is inconsistent performance in long-term applications. Although the brain tissue response is believed to be a major cause of performance degradation, the precise mechanisms that lead to failure of recordings are unknown. We observed persistent ED1 immunoreactivity around implanted silicon microelectrode arrays implanted in adult rat cortex that was accompanied by a significant reduction in nerve fiber density and nerve cell bodies in the tissue immediately surrounding the implanted silicon microelectrode arrays. Persistent ED1 up-regulation and neuronal loss was not observed in microelectrode stab controls indicating that the phenotype did not result from the initial mechanical trauma of electrode implantation, but was associated with the foreign body response. In addition, we found that explanted electrodes were covered with ED1/MAC-1 immunoreactive cells and that the cells released MCP-1 and TNF-alpha under serum-free conditions in vitro. Our findings suggest a potential new mechanism for chronic recording failure that involves neuronal cell loss, which we speculate is caused by chronic inflammation at the microelectrode brain tissue interface.

Topics: Animals; Astrocytes; Brain; Cell Count; Cell Death; Cytokines; Diagnostic Imaging; Ectodysplasins; Electrodes, Implanted; Glial Fibrillary Acidic Protein; Gliosis; Immunohistochemistry; Inflammation; Macrophages; Male; Membrane Proteins; Naphthalenes; Neurofilament Proteins; Neurons; Oxepins; Phosphopyruvate Hydratase; Rats; Rats, Inbred F344; Silicon; Time Factors

Determination of the ability of a medical device to interact with the immune system currently involves assessment of the immunogenic potential and biocompatibility of the device or an extract of the device. However, implants are often in the body for extended periods of time and/or are placed by a surgical procedure that in and of itself will generate an acute inflammatory response. This symposium discussed studies that have been performed to evaluate the immunogenicity of various devices consisting of several different compositions (i.e., silicone, metals, and latex) in contact with different anatomical sites, the ability of a device to modulate an inflammatory response generated by a surgical procedure or trauma, and the response of the body to a material left in place for extended periods of time. This symposium brought together scientists from many different disciplines to begin to identify and fill in the gaps in this area.

Topics: Animals; Biocompatible Materials; Equipment and Supplies; Humans; Hypersensitivity; Immunity, Cellular; Inflammation; Latex; Materials Testing; Prostheses and Implants; Silicon; Toxicity Tests

Cristobalite is a crystalline silicon dioxide that elicits pulmonary inflammation and fibrosis in humans and experimental animals. Exposure of rats to aerosols of respirable cristobalite for 8 days led to a rapid influx of neutrophils and macrophages into alveolar and tissue compartments of the lung followed by a more gradual accumulation of T lymphocytes. This inflammatory response persisted throughout 52 weeks after the end of the exposure. For some variables studied there appeared to be a cyclical nature to the response. Statistical analysis of alveolar cell populations and lung tissue weight, protein, and hydroxyproline showed significant time-dependent fluctuations. Histologic analysis revealed a progressive deposition of collagen and type II cell hyperplasia centered on airways, however, there appeared to be some correlation between fluctuations in alveolar cell populations and overall tissue pathology. The observed cellular and biochemical fluctuations and the persistence of the inflammatory response may be due to the presence of silica in the lung, which serves as a source of repetitive stimulation of lung cells.

Topics: Aerosols; Animals; Bronchoalveolar Lavage Fluid; Hydroxyproline; Inflammation; Lung; Lymphocytes; Male; Organ Size; Proteins; Rats; Rats, Inbred F344; Silicon; Silicon Dioxide; Time Factors

Sprague-Dawley rats were exposed 6 hr/day, 5 days a week, for 28 days to tetramethoxysilane (TMOS) at concentrations of 0, 1, 5, and 10 ppm (Phase I study) and to 0, 15, 30, and 45 ppm (Phase II study). All of the rats exposed to 45 ppm TMOS died or were sacrificed in a moribund state during the 28-day study period. Statistically significant changes were observed in food consumption, body weights, and clinical chemistry parameters in the animals exposed to 30 ppm TMOS. Males exposed to 15 ppm TMOS showed a significant decrease in total protein. No effects were seen in rats exposed to 1, 5, and 10 ppm TMOS. Histopathological lesions related to TMOS exposure were observed in the respiratory tract tissues and eyes of rats exposed to 15, 30, and 45 ppm TMOS. The principal types of lesions observed were ulceration, inflammation, and necrosis of epithelium. At 45 ppm, changes at these sites were severe and present in all animals. Changes at 30 ppm, while occurring in all rats, were much less severe than those seen at 45 ppm. At 15 ppm, the changes were minimal and occurred only in three males and five females. The data of this study showed that TMOS has a steep dose-response curve with no observable effects at 10 ppm, very minimal effects at 15 ppm, moderate to severe effects at 30 ppm, and severe effects and lethality at 45 ppm.

Topics: Administration, Inhalation; Air Pollutants, Occupational; Animals; Blood Chemical Analysis; Body Weight; Cornea; Eating; Female; Inflammation; Male; Nasal Mucosa; Organ Size; Rats; Rats, Inbred Strains; Silanes; Silicon

It has been recognized that storage inflammation in organs of uraemic patients is due to silicone particle migration from tubing segments of the haemodialysis circuit to blood. Nevertheless, iatrogenic storage of foreign material containing Si has been also observed in long-term dialysis patients which, in our Unit, used only PVC or PU-PVC tubings. The origin and the nature of the particulate has been investigated in vivo and in vitro on bioptical samples as well as on cuprophan dialyser and PVC tubing eluates. This study carried out by means of TEM, SEM and microprobe EDS revealed the presence of variously shaped material and particles containing Si in bioptical samples and in eluates. Si containing contaminants were not demonstrated in eluates filtered in absence of the dialyser. This result suggests that leachable products can result from the dialyser and that such release can be an additional risk for uraemic patients.

Topics: Electron Probe Microanalysis; Humans; Inflammation; Kidneys, Artificial; Microscopy, Electron; Silicon; Uremia