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Magnesium batteries have attracted great attention as an alternative to Li-ion batteries but still suffer from limited choice of positive electrode materials. V2O5 exhibits high theoretical capacities, but previous studies have been mostly limited to α-V2O5. Herein, we report on the ß-V2O5 polymorph as a Mg intercalation electrode. The structural changes associated with the Mg2+ (de-) intercalation were analyzed by a combination of several characterization techniques: in situ high resolution X-ray diffraction, scanning transmission electron microscopy, electron energy-loss spectroscopy, and X-ray absorption spectroscopy. The reversible capacity reached 361 mAh g-1, the highest value found at room temperature for V2O5 polymorphs.
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Vascular access is the lifeline for hemodialysis patients and the single most important component of the hemodialysis procedure. Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis patients, but nearly 60% of AVFs created fail to successfully mature due to early intimal hyperplasia development and poor outward remodeling. There are currently no therapies available to prevent AVF maturation failure. First, we showed the important regulatory role of nitric oxide (NO) on AVF development by demonstrating that intimal hyperplasia development was reduced in an overexpressed endothelial nitric oxide synthase (NOS3) mouse AVF model. This supported the rationale for the potential application of NO to the AVF. Thus, we developed a self-assembled NO releasing nanomatrix gel and applied it perivascularly at the arteriovenous anastomosis immediately following rat AVF creation to investigate its therapeutic effect on AVF development. We demonstrated that the NO releasing nanomatrix gel inhibited intimal hyperplasia formation (more than 70% reduction), as well as improved vascular outward remodeling (increased vein diameter) and hemodynamic adaptation (lower wall shear stress approaching the preoperative level and less vorticity). Therefore, direct application of the NO releasing nanomatrix gel to the AVF anastomosis immediately following AVF creation may enhance AVF development, thereby providing long-term and durable vascular access for hemodialysis.
Assuntos
Fístula Arteriovenosa , Remodelação Vascular , Animais , Fístula Arteriovenosa/terapia , Humanos , Hiperplasia , Camundongos , Óxido Nítrico , Ratos , RoedoresRESUMO
Layered 2D (PbI2 )1- x (BiI3 )x materials exhibit a nonlinear dependence in structural and charge transport properties unanticipated from the combination of PbI2 and BiI3 . Within (PbI2 )1- x (BiI3 )x crystals, phase integration yields deceptive structural features, while phase boundary separation leads to new conductance switching behavior observed as large peaks in current during current-voltage (I-V) measurements (±100 V). Temperature- and time-dependent electrical measurements demonstrate that the behavior is attributed to ionic transport perpendicular to the layers. High-resolution transmission electron microscopy reveals that the structure of (PbI2 )1- x (BiI3 )x is a "brick wall" consisting of two phases, Pb-rich and Bi-rich. These brick-like features are 10s nm a side and it is posited that iodide ion transport at the interfaces of these regions is responsible for the conductance switching action.
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Hemorrhagic blood loss from traumatic injury is the leading cause of death in severe accidents and combat injuries. Treating and stopping blood loss in a timely and effective manner is essential for the survival of the patient. Currently, QuikClot and dry fibrin sealant dressing are well-known approaches for hemostatic treatment. However, these dressings have limitations in slowing blood loss such as being brittle, low blood absorption, and a poor sealant of the injury site. Temperature-sensitive gels may have potential as a platform for delivery of coagulation factors to improve hemostasis and wound sealing in the treatment of traumatic injuries. Here, we developed a temperature-sensitive triblock copolymer (poly ethylene oxide (PEO)-poly propylene oxide (PPO)-poly ethylene oxide (PEO)) containing fibrinogen to promote blood coagulation through gel formation at body temperature. This temperature sensitive solution-to-gel (sol-gel) transition does not require cross-linking agents or UV photoinitiation. We determined that 22 wt % (weight percent) copolymers with and without fibrinogen was the maximum concentration for sol-gel transition at body temperature. Rheology results further confirmed this sol-gel transition of 22 wt % copolymers at body temperature. We showed that fibrinogen itself promoted blood coagulation. Additionally, 22 wt % copolymer with fibrinogen successfully demonstrated stable blood coagulation within the gel compared to 22 wt % copolymer without fibrinogen. Twenty-two weight percent copolymers with and without fibrinogen also exhibited excellent biocompatibility based on cell viability, proliferation, and morphology analysis. In addition, treatment of 22 wt % copolymers did not stimulate pro-inflammatory TNF-α production from differentiated human monocytes. Our results suggest that 22 wt % of a temperature-sensitive copolymer gel containing fibrinogen has great potential as a hemostatic agent stimulating coagulation and providing immediate wound coverage for protection through a sol-gel transition at body temperature.
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Cardiovascular disease is the number one cause of death in the U.S and results in the loss of approximately one million lives and more than 400 billion U.S. dollars for treatments every year. Recently, tissue engineered blood vessels have been studied and developed as promising replacements for treatment with autologous veins. Here, we summarize the cell sources and methods to make tissue-engineered blood vessels (TEBVs), the recent progress in TEBV related research, and also the recent progress in TEBV related clinical studies.
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Vasos Sanguíneos , Doenças Cardiovasculares/terapia , Engenharia Tecidual , HumanosRESUMO
The unusual Au3+ ternary halide AuPb2I7 has been isolated from reactions of AuI, PbI2, and I2. AuPb2I7 crystallizes in the triclinic P1Ì space group as micron-scale needles with cell dimensions a = 4.5170(3) Å, b = 7.3847(4) Å, c = 12.2970(7) Å, α = 76.374(4)°, ß = 83.711(4)°, γ = 72.987(3)° at room temperature with ρ = 6.538 g/cm3 and has no structural phase transition down to 100 K. The title compound has a unique three-dimensional structure composed of [Pb2I7]3- pseudolayers extending in [010] bridged by square planar Au3+ at an oblique angle in the [001] direction. The pseudolayers are composed of 1/∞[Pb2I2]2+ chains propagating down [100] linked by square planar I- ions through [010]. AuPb2I7 has a bandgap of 1.17 eV and is stable in air for several days, before degrading to PbI2, Au0, and I2. Density functional theory calculations show that AuPb2I7 is an indirect bandgap semiconductor where the bandgap stems predominantly from Au-I metal-ligand charge transfer.
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The major concern of pancreatic islet transplantation is that the implanted islets are exposed to the immune system of the recipient. To overcome this challenge, the peptide amphiphile (PA) nanomatrix gel was used for immunoisolation of islets through microencapsulation. The PA can self-assemble to form a nanomatrix gel with an extracellular matrix-mimicking, islet nurturing microenvironment and a semipermeable immune barrier. In this study, the islet protective effect of the PA nanomatrix gel was evaluated by coculture of PA-encapsulated human islets with differentiated U937 cells (human monocyte cell-line) for 3 and 7 days. The coculture of the bare islets with the differentiated U937 cells stimulated proinflammatory cytokine (IL-1ß and TNF-α) secretion and caused islet death after 7 days, which simulated an early inflammatory response environment after islet transplantation. The PA-encapsulated islets, however, did not stimulate proinflammatory cytokine secretion and maintained islet viability up to 7 days. More insulin-producing ß cells were observed when islets were PA-encapsulated than control islets with the differentiated U937 cells for 7 days compared to the bare islets. This result was also confirmed by dithizone staining analysis. Further evaluation of islet functionality was assessed by a glucose-stimulated insulin secretion test. The PA-encapsulated islets showed greater insulin secretion response to glucose stimulation than the bare islets with the differentiated U937 cells after 3 and 7 days. These results demonstrated that islet encapsulation with the PA nanomatrix gel was able to improve islet survival and function in the presence of inflammatory responses, which will increase the success rate of islet engraftment and the efficacy of islet transplantation.
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BACKGROUND: Chronic rhinosinusitis (CRS) is often associated with persistent bacterial infection despite the use of systemic antibiotics. Topically administered antibiotics are an alternative strategy, but require effective local concentrations, prolonged mucosal contact time, minor systemic absorption, and minimal depletion. The objectives of the current study were to analyze the in vitro release rate and in vivo drug delivery tolerance and pharmacokinetics of a ciprofloxacin-coated sinus stent (CSS). METHODS: The CSS (2 mg) was created from biodegradable poly-D/L-lactic acid. After analyzing in vitro release profile, CSSs were placed unilaterally in maxillary sinuses of 16 rabbits via dorsal sinusotomy. Animals were euthanized between 1 and 3 weeks postoperatively. Ciprofloxacin concentrations in the sinus tissue and plasmas were assessed using high-performance liquid chromatography. Radiological and histological evaluations were performed. RESULTS: In the in vitro release profile, an initial burst release was observed over the first 24 hours, followed by sustained release through the 14-day time point. In the rabbit model, ciprofloxacin was continuously released from the stent up to 3 weeks at doses >50 ng/mL. Histologic examination found no evidence of inflammation, epithelial ulceration, or bony reaction upon euthanization of the animals at 21 days. Computed tomography also demonstrated no signs of mucosal edema or opacification in the sinus. CONCLUSION: The CSS was safe in this preclinical model and sustained release was observed in both the in vitro and in vivo analyses. The innovative stent design coated with ciprofloxacin may provide a unique therapeutic strategy for chronic rhinosinusitis (CRS).
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Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Ciprofloxacina/administração & dosagem , Ciprofloxacina/farmacocinética , Stents Farmacológicos , Seio Maxilar/metabolismo , Animais , Antibacterianos/sangue , Ciprofloxacina/sangue , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Seio Maxilar/anatomia & histologia , Seio Maxilar/diagnóstico por imagem , Coelhos , Mucosa Respiratória/anatomia & histologia , Mucosa Respiratória/diagnóstico por imagem , Mucosa Respiratória/metabolismo , Tomografia Computadorizada por Raios XRESUMO
UNLABELLED: For three-dimensional tissue engineering scaffolds, the major challenges of hydrogels are poor mechanical integrity and difficulty in handling during implantation. In contrast, electrospun scaffolds provide tunable mechanical properties and high porosity; but, are limited in cell encapsulation. To overcome these limitations, we developed a "hybrid nanosack" by combination of a peptide amphiphile (PA) nanomatrix gel and an electrospun poly (ε-caprolactone) (ePCL) nanofiber sheet with porous crater-like structures. This hybrid nanosack design synergistically possessed the characteristics of both approaches. In this study, the hybrid nanosack was applied to enhance local angiogenesis in the omentum, which is required of tissue engineering scaffolds for graft survival. The ePCL sheet with porous crater-like structures improved cell and blood vessel penetration through the hybrid nanosack. The hybrid nanosack also provided multi-stage fibroblast growth factor-2 (FGF-2) release kinetics for stimulating local angiogenesis. The hybrid nanosack was implanted into rat omentum for 14days and vascularization was analyzed by micro-CT and immunohistochemistry; the data clearly demonstrated that both FGF-2 delivery and porous crater-like structures work synergistically to enhance blood vessel formation within the hybrid nanosack. Therefore, the hybrid nanosack will provide a new strategy for engineering scaffolds to achieve graft survival in the omentum by stimulating local vascularization, thus overcoming the limitations of current strategies. STATEMENT OF SIGNIFICANCE: For three-dimensional tissue engineering scaffolds, the major challenges of hydrogels are poor mechanical integrity and difficulty in handling during implantation. In contrast, electrospun scaffolds provide tunable mechanical properties and high porosity; but, are limited in cell encapsulation. To overcome these limitations, we developed a "hybrid nanosack" by combination of a peptide amphiphile (PA) nanomatrix gel and an electrospun poly (ε-caprolactone) (ePCL) nanofiber sheet with porous crater-like structures. This design synergistically possessed the characteristics of both approaches. In this study, the hybrid nanosack was applied to enhance local angiogenesis in the omentum, which is required of tissue engineering scaffolds for graft survival. The hybrid nanosack was implanted into rat omentum for 14days and vascularization was analyzed by micro-CT and immunohistochemistry. We demonstrate that both FGF-2 delivery and porous crater-like structures work synergistically to enhance blood vessel formation within the hybrid nanosack. Therefore, the hybrid nanosack will provide a new strategy for engineering scaffolds to achieve graft survival in the omentum by stimulating local vascularization, thus overcoming the limitations of current strategies.
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Materiais Biocompatíveis/farmacologia , Nanofibras/química , Neovascularização Fisiológica/efeitos dos fármacos , Omento/irrigação sanguínea , Alicerces Teciduais/química , Animais , Ensaio de Imunoadsorção Enzimática , Fator 2 de Crescimento de Fibroblastos/farmacologia , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Cinética , Omento/efeitos dos fármacos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Poliésteres/farmacologia , Porosidade , Ratos , Microtomografia por Raio-XRESUMO
Inflammatory responses play a critical role in tissue-implant interactions, often limiting current implant utility. This is particularly true for cardiovascular devices. Existing stent technology does little to avoid or mitigate inflammation or to influence the vasomotion of the artery after implantation. We have developed a novel endothelium-mimicking nanomatrix composed of peptide amphiphiles that enhances endothelialization while decreasing both smooth muscle cell proliferation and platelet adhesion. Here, we evaluated whether the nanomatrix could prevent inflammatory responses under static and physiological flow conditions. We found that the nanomatrix reduced monocyte adhesion to endothelial cells and expression of monocyte inflammatory genes (TNF-α, MCP-1, IL-1ß, and IL-6). Furthermore, the nitric-oxide releasing nanomatrix dramatically attenuated TNF-α-stimulated inflammatory responses as demonstrated by significantly reduced monocyte adhesion and inflammatory gene expression in both static and physiological flow conditions. These effects were abolished by addition of a nitric oxide scavenger. Finally, the nanomatrix stimulated vasodilation in intact rat mesenteric arterioles after constriction with phenylephrine, demonstrating the bioavailability and bioactivity of the nanomatrix, as well as exhibiting highly desired release kinetics. These results demonstrate the clinical potential of this nanomatrix by both preventing inflammatory responses and promoting vasodilation, critical improvements in stent and cardiovascular device technology.
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Inflamação/prevenção & controle , Nanocompostos/uso terapêutico , Stents/efeitos adversos , Vasodilatação/efeitos dos fármacos , Animais , Artérias/efeitos dos fármacos , Artérias/patologia , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Humanos , Inflamação/patologia , Monócitos/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Nanocompostos/química , Óxido Nítrico/metabolismo , Peptídeos/química , Adesividade Plaquetária/efeitos dos fármacos , RatosRESUMO
Pancreatic islet transplantation has been validated as a treatment for type 1 diabetes since it maintains consistent and sustained type 1 diabetes reversal. However, one of the major challenges in pancreatic islet transplantation is the body's natural immune response to the implanted islets. Immunosuppressive drug treatment is the most popular immunomodulatory approach for islet graft survival. However, administration of immunosuppressive drugs gives rise to negative side effects, and long-term effects are not clearly understood. A bioartificial pancreas is a therapeutic approach to enable pancreatic islet transplantation without or with minimal immune suppression. The bioartificial pancreas encapsulates the pancreatic islets in a semi-permeable environment which protects islets from the body's immune responses, while allowing the permeation of insulin, oxygen, nutrients, and waste. Many groups have developed various types of the bioartificial pancreas and tested their efficacy in animal models. However, the clinical application of the bioartificial pancreas still requires further investigation. In this review, we discuss several types of bioartificial pancreases and address their advantages and limitations. We also discuss recent advances in bioartificial pancreas applications with microfluidic or micropatterning technology.
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Electrospinning has been widely used to fabricate scaffolds imitating the structure of natural extracellular matrix (ECM). However, conventional electrospinning produces tightly compacted nanofiber layers with only small superficial pores and a lack of bioactivity, which limit the usefulness of electrospinning in biomedical applications. Thus, a porous poly(ε-caprolactone) (PCL)/gelatin composite electrospun scaffold with crater-like structures was developed. Porous crater-like structures were created on the scaffold by a gas foaming/salt leaching process; this unique fiber structure had more large pore areas and higher porosity than the conventional electrospun fiber network. Various ratios of PCL/gelatin (concentration ratios: 100/0, 75/25, and 50/50) composite electrospun scaffolds with and without crater-like structures were characterized by their microstructures, surface chemistry, degradation, mechanical properties, and ability to facilitate cell growth and infiltration. The combination of PCL and gelatin endowed the scaffold with both structural stability of PCL and bioactivity of gelatin. All ratios of scaffolds with crater-like structures showed fairly similar surface chemistry, degradation rates, and mechanical properties to equivalent scaffolds without crater-like structures; however, craterized scaffolds displayed higher human mesenchymal stem cell (hMSC) proliferation and infiltration throughout the scaffolds after 7-day culture. Therefore, these results demonstrated that PCL/gelatin composite electrospun scaffolds with crater-like structures can provide a structurally and biochemically improved three-dimensional ECM-mimicking microenvironment.
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Gelatina/química , Nanofibras/química , Poliésteres/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Linhagem Celular , Proliferação de Células , Sobrevivência Celular , Humanos , Células-Tronco Mesenquimais/citologia , Nanofibras/ultraestrutura , PorosidadeRESUMO
BACKGROUND: A triple antibiotic mixture (ciprofloxacin; CF, metronidazole; MN, and minocycline; MC) has been used for dental root canal medicaments in pulp regeneration therapy. However, tooth discolorations, cervical root fractures, and inadequate pulp-dentin formation have been reported due to the triple antibiotic regimen. Therefore, an antibiotic encapsulated biomimetic nanomatrix gel was developed to minimize the clinical limitations and maximize a natural healing process in root canal infections. In this study, minimal bacterial concentrations (MBC) of the selected antibiotics (CF and MN) were tested in 14 representative endodontic bacterial species. Then MBC of each CF and MN were separately encapsulated within the injectable self-assembled biomimetic nanomatrix gel to evaluate antibacterial level on Enterococcus faecalis and Treponema denticola. RESULTS: Antibiotic concentrations lower than 0.2 µg/mL of CF and MN demonstrated antibacterial activity on the 14 endodontic species. Furthermore, 6 different concentrations of CF and MN separately encapsulated with the injectable self-assembled biomimetic nanomatrix gel demonstrated antibacterial activity on Enterococcus faecalis and Treponema denticola at the lowest tested concentration of 0.0625 µg/mL. CONCLUSIONS: These results suggest that each CF and MN encapsulated within the injectable self-assembled biomimetic nanomatrix gel demonstrated antibacterial effects, which could be effective for the root canal disinfection while eliminating MC. In the long term, the antibiotic encapsulated injectable self-assembled biomimetic nanomatrix gel can provide a multifunctional antibiotic delivery method with potential root regeneration. Further studies are currently underway to evaluate the effects of combined CF and MN encapsulated within the injectable self-assembled biomimetic nanomatrix gel on clinical samples.
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In the title compound, 2C6H11N2 (+)·P2Se8 (2-) or [EMIM]2P2Se8 (EMIM = 1-ethyl-3-methyl-imidazolium), the anions, located about inversion centers between EMIM cations, exhibit a cyclo-hexane-like chair conformation. The cations are found in columns along the a axis, with centroid-centroid distances of 3.8399â (3) and 4.7530â (2)â Å. The observed P-Se distances and Se-P-Se angles agree with other salts of this anion.
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Four new nickel thiophosphate anions have been isolated as 1-ethyl-3-methylimidazolium (EMIM) salts: [EMIM](2)[Ni(P(2)S(8))(2)] (1), [EMIM](3)[Ni(P(3)S(9))(P(2)S(8))] (2), [EMIM](4)[Ni(P(3)S(9))(2)] (3), and [EMIM](7)[(NiP(3)S(8))(4)(PS(4))] (4). Single crystals of each were prepared by ionothermal reaction of the elements in [EMIM][BF(4)]. 1 can also be obtained from [EMIM][CF(3)SO(3)]. In all four anions, Ni atoms are octahedrally coordinated and P atoms are tetrahedrally coordinated. In the anion found in 1, two tridentate 1,3-P(2)S(8)(2-) ligands are cis to each other. The anion in 2 contains two different tridentate thiophosphate ligands, 1,3-P(2)S(8)(2-) and P(3)S(9)(3-), whereas the anion in 3 consists of two P(3)S(9)(3-) ligands coordinated to the central Ni atom. The anion in 4 is complex, consisting of four NiP(3)S(8)(-) clusters surrounding a central PS(4) tetrahedron; within the NiP(3)S(8)(-) groups, one P atom is directly bound to Ni. The discovery of these four new compounds demonstrates the versatility of ionothermal methods for the synthesis of novel thiophosphates.