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Bismuth (Bi) is used to treat certain diseases, however the Bi powder or colloids used in medicine must be nonpolluting and safe. The use of electrical discharge machines (EDMs) to produce nano-Bi powder is a green process. A nonpolluting and safe nano-Bi colloid can be produced swiftly and easily in deionized water using the electrical spark discharge method, adjusting the discharge pulse width Ton, Toff and the discharge current IP of the EDM. Transmission electron microscopy (TEM), energy-dispersive x-ray spectroscopy, the Zetasizer technique, ultraviolet–visible spectroscopy (UV–Vis), and other techniques were used to analyze a nano-Bi colloid prepared under various discharge parameters to optimize the preparation of Bi nanoparticles (Bi-NPs) using EDMs. The results of this study indicated that Bi-NP colloids were successfully prepared using EDM. TEM images revealed that the NPs were smaller than 50 nm with only the Bi element in the colloid. Furthermore, the zeta potential of the nano-Bi colloid exceeded 30 mV, which indicated that the suspension of the colloid was excellent. A UV–Vis absorption peak was observed at approximately 234–237 nm. [ABSTRACT FROM AUTHOR]

Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide, accounting for 10% of the global cancer burden. Rectal cancer accounts for around 30% of CRC cases, and patients with resectable rectal cancer are often given preoperative radiotherapy (PRT) to reduce the rate of local recurrence. The human plasma proteome is an exceptionally complex proteome and ideal to study due to its ability to reflect the presence of diseases such as cancer and the ease of obtaining blood samples. Previous proteomic studies involving rectal cancer patients have mostly focused on the identification of proteins involved in resistance to radiotherapy. Objective: The aim of this study was to investigate the overall effects of PRT on plasma protein expression in rectal cancer patients, as there is a lack of such studies. Methods: Here, we have used mass spectrometry and subsequent statistical analyses to analyze the plasma samples of 30 rectal cancer patients according to PRT status (positive or negative) and tumor stage (II or III). Results and Conclusions: We discovered 42 proteins whose levels differed significantly between stage II and III rectal cancer patients who did or did not receive PRT. This study shows that PRT, although localized to the pelvis, leads to measurable, tumor stage-specific changes in plasma protein expression. Future studies of plasma proteins should, when relevant, take this into account and be aware of the widespread effects that PRT has on the plasma proteome. [ABSTRACT FROM AUTHOR]

Background Usually serum albumin is measured with dye‐binding assay as bromocresol green (BCG) and bromocresol purple (BCP) methods. The aim of this paper was to examine the differences in albumin measurements between the Advia2400 BCG method (AlbBCG), Dimension RxL BCP (AlbBCP) and capillary zone electrophoresis (CZE). Methods Albumin concentrations from 165 serum samples were analysed using AlbBCG, AlbBCP and CZE. CZE was employed to estimate different serum protein fractions. Influence of globulins on albumin concentration discrepancies between methods was estimated as well as the impact of the albumin method on aCa concentrations. Medcalc was employed for statistical analysis, setting a value of P < 0.05 as significant. Results Correlation of AlbBCG and AlbBCP was r = 0.948 (p < 0.0001), but mean difference was large. Bland-Altman plots showed greater bias at lower albumin concentrations. AlbBCG were positively biased versus CZE (3.54 g/L). There was good agreement between CZE and ALbBCP (< 1 g/L). The AlbBCG assay bias shows a good correlation with alpha-1-globulin concentrations (r = 0.758); moderate and weak correlations were observed with CRP (r = 0.729) and alpha-2-globulin (r = 0.585); we found no correlation with beta-globulin (r = 0.120) or gamma-globulin (r = –0.303). Mean aCa based on AlbBCG and AlbBCP methods were 2.34 ± 0.15 mmol/L and 2.46 ± 0.16 mmol/L (p < 0.01), with a mean BCG-BCP difference of –0.12. Conclusion Albumin results from the BCP and BCG methods may result in unacceptable differences and clinical confusion, especially at lower albumin concentrations. Serum acute phase proteins contribute to overestimating the albumin concentration using AlbBCG. [ABSTRACT FROM AUTHOR]

The Semi-solid Control Diagram (SSCD) is a new tool designed for the study of different excipients and different semi-solid dosage forms. It can be used to review and evaluate different formulations and/or batches and facilitate the selection of one of them that will present the most suitable galenic characteristics for topical application. It is also useful to track stability studies by comparing the diagrams, which allows to measure the impact of subjecting the formulation to different conditions and times to be examined. In this study, the Semi-solid Control Diagram (SSCD) is used as an instrument for studying and evaluating semi-solid pharmaceutical dosage forms, by comparing several different semisolid preparations (lipogels). With these results, the tool is validated and the best formulation has been discriminated from the others. [ABSTRACT FROM AUTHOR]

Introduction: Fluid management is a cornerstone of treatment in acute pancreatitis (AP). Methods: Identification of existing randomized prospective trials of patients with AP, in which intravenous fluid management was a significant parameter in the experimental design, was undertaken using the PubMed and ENDOBASE databases. Results: Included patients in the seven studies identified were on the whole very unwell with deaths occurring in six trials. Fluid regimens in AP included crystalloid alone, combinations of crystalloid and colloid and in two studies, plasma. In most studies, patients with premorbid major organ failure and advanced age were excluded. Study entry within 6 h of presentation occurred in three trials. Initial fluid administration rates varied from 1 to 2 mL/kg/h to 15 mL/kg/h. Rapid fluid rates were associated with increased morbidity and mortality except in one study in which a high fluid regimen (20 mL/kg bolus within 4 h of presentation followed by 3 mL/kg) led to a better clinical outcome than a more conservative regimen. Use of Ringer's lactate led to improved surrogate outcome markers compared to that of normal saline in one study. Administration of colloid as part of the fluid management was associated with lower morbidity and lower fluid requirements. Conclusion: Rapid infusion of crystalloid very early in the course of AP may be beneficial but rapid infusion of fluid later in the course of the illness may be deleterious. Colloid administration and the use of Ringer's lactate solution in preference to normal saline may improve outcome. [ABSTRACT FROM AUTHOR]

Synthesis and storage of thyroglobulin as well as synthesis of thyroid hormones and their release into the circulation are important functions of thyroid, which were studied in fine needle aspiration (FNA) smears from thyroid lesions. Evidence of thyroglobulin synthesis was demonstrated in neoplastic and nonneoplastic follicular cells, especially in Hürthle cells, in the form of colloid inclusions. Whereas the pinocytic vesicles containing colloid at the luminal end of in nonneoplastic and neoplastic follicular cells indicated engulfment of colloid for synthesis of thyroid hormones (T3 and T4), the marginal vacuoles (MVs) (fire-flare appearance) at the basal aspects of follicular cells suggested their release on way to the interfollicular capillaries. The morphological evidence of secretary activity could also be demonstrated in medullary thyroid carcinoma (MTC) in the form of azurophilic granules, marginal vacuoles, and intracytoplasmic lumina (ICL) with secretions; the secretory material, likely to be amyloid, present in MTC cells, and their release to the extracellular space was confirmed by positive immunocytochemical staining for calcitonin. It was found that nuclear grooves and related intranuclear cytoplasmic inclusions (INCIs) in papillary thyroid carcinoma (PTC) possibly represent an initial step of a degenerative process leading to formation of inactive cerebriform nuclei. Based on observation regarding formation and release of precursor substances for psammoma bodies (PBs), it was also suggested that PBs may not represent a process of dystrophic calcification over infarcted/dead papillae but suggest an active biological process, which leads to inhibition of growth of neoplastic cells and acts as a barrier against spread of PTC. [ABSTRACT FROM AUTHOR]

In this study, Compritol ATO-based Resveratrol colloidal carriers (CCCs) were prepared and subjected to characterization and evaluation. In most formulae, the use of a binary-mixture of surfactants improved the physicochemical properties. CCC6 (containing P407/P188 as bi-surfactants) attained the highest drug loading, release efficiency during 24 h and occlusive effect for 48 h; in addition, it showed a uniform particle size distribution within the desired range. In-vivo studies were done based on the analysis of anti-oxidant markers [catalase (CAT), reduced glutathione (GSH) and superoxide dismutase (SOD)], anti-inflammatory markers [interleukin 6 (IL-6), interleukin 8 (IL-8) and rat Nuclear factor-kappa B (NF-κB)] and anti-wrinkling markers [matrix metalloproteinase (MMP-1) and Granulocyte-macrophage colony-stimulating factor (GM-CSF)], after UVB-irradiation. Results were significantly different when comparing the positive control and the negative control groups (p < 0.05). Rats pre-treated with CCC6 showed a great amelioration, and the level of the biochemical markers was significantly different compared to those of the positive control group and those pre-treated with the drug suspension (p < 0.05). Also, the high skin protective effect of CCC6 was proved by visual and histopathological examination of the rats’ skin. Therefore, the current study proves the beneficial effects of the designed dermal Resveratrol-loaded colloidal system. [ABSTRACT FROM AUTHOR]

The present study evaluated drug distribution and clinical safety in treating patients with cystic craniopharyngioma (CP) with intracavitary radiotherapy using phosphorus-32 (32P) colloid. In total, 40 patients who were recently diagnosed with primary or recurrent cystic CP were enrolled into the study. Patients underwent stereotactic intracavitary therapy and were administered 32P colloid and iopamidol-300 (1:1 dilution). Head computed tomography (CT) scans were performed 2 h after surgery in order to assess drug distribution and leakage. Results obtained from the ophthalmic examination (visual acuity, visual field and fundus), enhanced head magnetic resonance imaging and/or CT scans, blood analysis, coagulation tests, electrolyte tests, pituitary hormone level analysis, and hepatic and renal function tests were compared between the 0.5, 1, 1.5 and 2 mCi groups. The 32P colloid per minute radioactive count was quantitatively measured in urine and blood samples using a CAPRAC well-type NaI γ counter at 1, 3 and 7 days post-surgery. In total, 6, 2 and 1 case(s) from the 2, 1.5 and 1 mCi groups, respectively, demonstrated heterogeneous drug distribution and intracavitary cerebrospinal fluid leakage. Furthermore, out of 24 patients, no significant differences were identified in blood analysis, blood biochemical measurements and pituitary hormone levels prior to and 7 days after surgery. Blood 32P deposition returned to normal levels within 3 days after surgery, whereas urine deposition returned to normal within 7 days after surgery. Methods utilized in the present study were advantageous in terms of convenience, speed and low cost, therefore, these techniques are suitable for continuous monitoring of patient 32P colloid deposition. [ABSTRACT FROM AUTHOR]

Peptic ulcer like condition requires delivery of anti-ulcer medicament locally in the stomach. Pediatric and geriatric convenience by ease of administration with enhanced gastric residence time achieved by formulating floating in situ gelling system. Using ionic cross linking method floating in situ gelling system of Minocycline HCl is prepared. Trials batches were prepared to optimize the concentration of sodium alginate, calcium carbonate and various grades of HPMC Prepared formulations were evaluated for viscosity, gel strength, pH, drug content, in vitro buoyancy and in vitro drug release. A 3²factorial design was applied to check effect of varying concentration of sodium alginate (X1) and HPMC K100M CR (X2) on the dependent variables such as viscosity, gelling strength, time required for complete release and floating lag time. Kinetic of drug release, regression analysis and analysis of variance were performed. Trial batch T1 to T4 shows optimum range of sodium alginate, T5 to T7 optimizes the concentration of calcium carbonate and batch B1 to B12 shows that HPMC K100 M CR is having maximum sustaining ability besides uniform raft formation. Formulation F8 was found to be optimum with sodium alginate (2%w/v) and HPMC K100M CR (1.5%w/v), shows release up to 12 hours. Floating in situ gelling system was successfully formulated using sodium alginate as gelling polymer and HPMC K100M CR as a release retardant polymer. [ABSTRACT FROM AUTHOR]

Patients with traumatic brain injury (TBI) are often resuscitated with crystalloids in the emergency department (ED) to maintain cerebral perfusion. The purpose of this study was to evaluate whether crystalloid resuscitation volume impacts mortality in TBI patients. This was a retrospective study of trauma patients with head abbreviated injury scale score ≥2, who received crystalloids during ED resuscitation between 2004 and 2013. Clinical characteristics and volume of crystalloids received in the ED were collected. Patients who received <2 L of crystalloids were categorized as low volume (LOW), whereas those who received ≥2 L were considered high volume (HIGH). Mortality and outcomes were compared. Multivariable regression analysis was used to determine the odds of mortality while controlling for confounders. Over 10 years, 875 patients met inclusion criteria. Overall mortality was 12.5 per cent. Seven hundred and forty-two (85%) were in the LOW cohort and 133 (15%) in the HIGH cohort. Gender and age were similar between the groups. The HIGH cohort had lower admission systolic blood pressure (128 vs 138 mm Hg, P = 0.001), lower Glasgow coma scale score (10 vs 12, P < 0.001), higher head abbreviated injury scale (3.8 vs 3.3, P < 0.001), and higher injury severity score (25 vs 18, P < 0.001). The LOW group had a lower unadjusted mortality (10 vs 26%, P < 0.001). Multivariable analysis adjusting for confounders demonstrated that those resuscitated with ≥2 L of crystalloids had increased odds of mortality (adjusted odds ratio 2.25, P = 0.005). Higher volume crystalloid resuscitation after TBI is associated with increased mortality, thus limited resuscitation for TBI patients may be indicated. [ABSTRACT FROM AUTHOR]

We present a novel approach for detection of cancerous kidney tissue areas by measuring surface enhanced Raman scattering (SERS) spectra of extracellular fluid taken from kidney tissue. The method is based on spectral analysis of the cancerous and normal tissue areas in order to find the specific spectral markers. The samples were prepared by sliding the kidney tissue over a substrate-calcium fluoride optical window. For producing the SERS signal, the dried extracellular fluid film was covered by silver nanoparticle colloidal solution. In order to suppress fluorescence background, the measurements of the dried samples were performed in the NIR spectral region with the Raman excitation wavelength of 1,064 nm. The most significant spectral differences-spectral markers-were found in the wavenumber region between 400 and 1,800 cm−1, where spectral bands related to various vibrations of carbohydrates, amino acids, and nucleic acids are located. Spectral markers in the SERS spectra are different from those in IR absorption spectra. The SERS spectroscopic method has a potential to be used directly during the surgery. [ABSTRACT FROM AUTHOR]

In this work, we present a methodology for the determination of the depth of demineralization in dental enamel caused by extended use of an Over-The-Counter (OTC) whitening product. Teeth whitening is a very common practice in Dentistry, but concerns have been raised regarding the invasiveness of the treatment, especially regarding OTC products, that can be used without medical supervision and sometimes with concentrations of active agent that exceed the allowed regulations. In this work, we studied tooth enamel samples, treated with a whitening product during an extended period of time, both directly on the enamel surface and in the cross-section. Specimens were analyzed using microbeam X-Ray Fluorescence (micro-XRF) using polycapillary optics to obtain a spot down to 25 μm. Due to the relatively large spot size of our setup point analysis of the cross-sections would be inadequate. This way, line scans were performed instead, before and after whitening, and using appropriate data treatment the depth of demineralization was inferred. The used methodology indicated an average demineralization depth of 25 μm, the same order of magnitude as the aprismatic enamel layer. [ABSTRACT FROM AUTHOR]

Background and objectives: Post-operative airway symptoms can be troublesome to patients following an uneventful general anesthesia with endotracheal intubation. In this study, we compared the effectiveness of lubricating an endotracheal tube with betamethasone gel or lidocaine jelly with using an unlubricated tube in reducing the incidence and severity of postoperative sore throat, hoarseness and cough. Methods: This was a prospective, randomized, single-blind comparative study carried out among 120 ASA I and II patients aged 18-65 years undergoing elective surgery under general anesthesia with endotracheal intubation. Patients were randomly divided into three groups of 40 patients each. Endotracheal tube used for patients in group C was unlubricated, while that for group B and group L were lubricated up to 15 cm mark with 2.5 ml of 0.05% betamethasone gel or 2% lidocaine jelly respectively. Incidence and severity of postoperative sore throat, hoarseness and cough were observed at 1, 6 and 24 h following extubation. Results: At 24 h following extubation, group B had the lowest incidence of postoperative sore throat among the three groups (group B: 12.5% vs group L: 37.5% vs group C: 25%; p = 0.036). Severity of postoperative sore throat at 24 h was less with betamethasone (score 0: 87.5%, 1: 10%) compared with lidocaine (score 0: 62.5%, 1: 37.5%) and control (score 0:75%, 1: 20%) (p = 0.006). Observations at other times and of other variables were comparable. Conclusion: Wide spread application of 0.05% betamethasone gel to lubricate the endotracheal tube significantly reduces the incidence and severity of sore throat at 24 h of extubation but not of hoarseness or cough. [ABSTRACT FROM AUTHOR]

Science-based selection of the base-carrier for a combined gel dosage form containing phenylacetic-acid derivatives was studied. One-factor dispersion analysis with repeated observations was used. For this, gels with nine bases were prepared and characterized qualitatively. According to the results, one composition was eliminated from further experiments because of thermal instability. The release of active substances (benzketozone and diclofenac sodium) from the proposed gels was determined by Kruvchinsky equilibrium dialysis. The experiments confirmed that the base-carrier type influences significantly the release of active substances from gel compositions. Dispersion analysis results showed that a carrier based on Carbomer 934P gave the optimum release of active substances. [ABSTRACT FROM AUTHOR]

Background Functional hyposplenism (FH) is indicated by an anatomically present spleen that fails to take up radiolabeled colloid. The occurrence of FH has been reported in a small group of renal transplant recipients based on hematologic parameters. The aim of this study was to replicate this association in a larger group of renal transplant recipients with the use of technetium-99m–stannous colloid liver-spleen scan to assess the spleen function. Methods This survey based on single samples enrolled 101 unselected adult patients with functional kidney grafts >180 days after transplantation. All patients underwent 99m Tc-stannous colloid scan to assess spleen function as well as bone marrow uptake of radiocolloid along with an anatomic and blood flow study of the spleen and kidney with the use of Doppler sonography. Results The prevalence of hyposplenism was 32.7% (33/101) for the cohort, and increased uptake of radiocolloid by the bone marrow was seen in 9.9% (10/101). According to the multivariate analysis, the frequency of hyposplenism was significantly influenced by indirect bilirubin and hemoglobin, and direct bilirubin and neutrophil count remained as independent predictors of bone marrow uptake. Conclusions This study demonstrated that a group of renal transplant recipients has FH. In addition, bone marrow uptake might be interpreted as liver dysfunction. In this situation, the small amount of contrast (spleen compared with liver) would leave hyposplenism undiagnosed. Further prospective and longitudinal clinical studies are needed to determine the clinical impact of this condition on the management of renal transplant recipients. [ABSTRACT FROM AUTHOR]

In colloid science, aggregation is problematic for small particles in the production and use of chemicals and pharmaceuticals, and makes it difficult to explore the properties and applications of nanomaterials. Herein, we reported the fabrication of ultra-stable colloidal porous Pt-Au-Ag nanoparticles (Pt-Au-Ag PoreNPs) with a particle size of 10 nm and a ligament size of 2 nm by selective removal of Ag from Pt-Au-Ag alloy nanoparticles. The resulting PoreNPs are very stable and keep monodisperse in organic solvent for 100 days under natural daylight. Transmission electron microscope and ultraviolet–visible spectroscopy show that neither aggregations nor changes in light absorbance occurred to Pt-Au-Ag PoreNPs. [ABSTRACT FROM AUTHOR]

Importance: Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk.Objective: To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume.Design, Setting, and Participants: Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014.Intervention: Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months.Main Outcomes and Measures: The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis).Results: Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, -27 Agatston units; 95% CI, -80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group.Conclusions and Relevance: Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding.Trial Registration: clinicaltrials.gov Identifier: NCT00799617. [ABSTRACT FROM AUTHOR]

Oral infectious diseases may lead to bone loss, which makes it difficult to achieve satisfactory restoration. The rise of multidrug resistant bacteria has put forward severe challenges to the use of antibiotics. Silver (Ag) has long been known as a strong antibacterial agent. In clinic, gelatin sponge with colloid silver is used to reduce tooth extraction complication. To investigate how this material affect infected bone defects, methicillin-resistant Staphylococcus aureus (MRSA) infected 3-mm-diameter cranial defects were created in adult female Sprague-Dawley rats. One week after infection, the defects were debrided of all nonviable tissue and then implanted with gelatin sponge with colloid silver (gelatin/Ag group) or gelatin alone (gelatin group). At 2 and 3 days after debridement, significantly lower mRNA expression levels of IL-6 and TNF-α and lower plate colony count value were detected in gelatin/Ag group than control. Micro-CT analysis showed a significant increase of newly formed bone volume fraction (BV/TV) in gelatin/Ag treated defects. The HE stained cranium sections also showed a faster rate of defect closure in gelatin/Ag group than control. These findings demonstrated that gelatin sponge with colloid silver can effectively reduce the infection caused by MRSA in cranial defects and accelerate bone healing process. [ABSTRACT FROM AUTHOR]

The aim of the present study is the formulation of mefenamic acid ethosomal gel by hot and cold methods. To prepare the mefenamic acid transdermal gel, ethosomes was selected as colloidal carriers. Ethosomes were prepared by cold and hot methods. The obtained ethosomes were characterized with vesicular diameter, zeta potential, drug content, entrapment efficiency and in-vitro diffusion studies. The five formulations of ethosomes prepared by cold and hot methods were compared. Among the 10 formulations of ethosomes, E5 was considered as the best formulation because of its mean vesicular diameter of 854 nm, zeta potential of 20 mV, drug content of 96.3%, entrapment efficiency of 94.4%, sustained drug release for 12 hr, i.e. 94.4. Then the E5 formulations was incorporated into gel. A comparative study was made between the plain gel and the ethosomal gel. The Ethosomal gel was considered the best because of its highest drug content spreadability, pH (6.9) and the sustained drug release profile for 12 hr. By comparison, the cold method shows better results. [ABSTRACT FROM AUTHOR]

Bone Morphogenic Protein 2 (BMP2) can induce ectopic bone. This ability, which first motivated the widespread application of BMP2 in fracture healing and spinal arthrodesis has, more recently, been indicated as one of several serious adverse effects associated with the supra-physiological doses of BMP2 relied upon for clinical efficacy. Key to harnessing BMPs and other agents safely and effectively will be the ability to localize activity at a target site at substantially reduced doses. Clay (Laponite) nanoparticles can self assemble into gels under physiological conditions and bind growth factors for enhanced and localized efficacy. Here we show the ability to localize and enhance the activity of BMP2 to achieve ectopic bone formation at doses within the sub-microgram per ml range of concentrations sufficient to induce differentiation of responsive cell populations in vitro and at approximately 3000 fold lower than those employed in clinical practice. [ABSTRACT FROM AUTHOR]

Ionic liquid gel materials offer a way to further utilise ionic liquids in technological applications. Combining the controlled and directed assembly of gels, with the diverse applications of ionic liquids, enables the design of a heady combination of functional tailored materials, leading to the development of task specific/functional ionic liquid gels. This review introduces gels and gel classification, focusing on ionic liquid gels and their potential roles in a more sustainable future. Ionic liquid gels provide the ability to build functionality at every level, the solid component, the ionic liquid, and any incorporated active functional agents. This allows materials to be custom designed for a vast assortment of applications. This diverse class of materials has the potential to yield functional materials for green and sustainable chemistry, energy, electronics, medicine, food, cosmetics, and more. The discussion of the development of ionic liquid gel materials for applications in green and sustainable chemistry centres on uses of ionic liquid gels in catalysis and energy. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) have attracted intensive research interest and have been recently incorporated in polymers, medical devices, hydrogels and burn dressings to control the proliferation of microorganisms. In this study a novel silver antibacterial coating was deposited for the first time on hydrogel fibers through an in-situ photo-chemical reaction. Hydrogel blends obtained by mixing different percentages of silver-treated and untreated fibers were characterized by thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). Four different fluids, such as phosphate buffered saline (PBS), simulated body fluid (SBF), chemical simulated wound fluid (cSWF), and deionized water (DI water), were used for evaluating the swelling properties. The results obtained confirmed that the presence of silver did not affect the properties of the hydrogel. Moreover, the results obtained through inductively coupled plasma mass spectrometry (ICP-MS) demonstrated very low silver release values, thus indicating the perfect adhesion of the silver coating to the substrate. Good antibacterial capabilities were demonstrated by any hydrogel blend on Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ) through agar diffusion tests and optical density readings. [ABSTRACT FROM AUTHOR]

Purpose Radioactive seed implants are widely used to treat cancer patients, most commonly those with prostate cancer. However, the seeds have a tendency to migrate after placement in patients, a phenomenon that can result in unfavorable outcomes. The ability of the seed strand to migrate was investigated by examining the impact of the strand surface on the velocity of its movement inside oil and gel media. Methods and materials We investigated the motion of smooth surface strands and strands with different grooved helical profiles after they were placed in oil and gel media. Three patterns of grooved helices were studied (60, 140, and 300 rotations per meter). The movement of the strands through a tube filled with the medium was recorded by the motion sensor, and the drag forces on the individual strands were calculated and compared for the oil and gel media. Results The strands with 60, 140, and 300 rotations/meter grooved helical surfaces demonstrated less mobility in both oil and gel than the strands with a smooth surface. The strand with the highest number of helical grooves per meter recorded the largest drag force and moved more slowly in both media. Conclusions The differential in the motion of the smooth strand and the strands with grooved surfaces can be attributed to the increased surface area of the grooved strands. This finding is significant since it will impact, theoretically, the design, and thus the migration of seed implants that are used to treat cancer patients, particularly those with prostate cancer. [ABSTRACT FROM AUTHOR]

IMPORTANCE Septic shock is a clinical emergency that occurs in more than 230 000 US patients each year. OBSERVATIONS AND ADVANCES In the setting of suspected or documented infection, septic shock is typically defined in a clinical setting by low systolic (≤90 mm Hg) or mean arterial blood pressure (≤65 mm Hg) accompanied by signs of hypoperfusion (eg, oliguria, hyperlactemia, poor peripheral perfusion, or altered mental status). Focused ultrasonography is recommended for the prompt recognition of complicating physiology (eg, hypovolemia or cardiogenic shock), while invasive hemodynamic monitoring is recommended only for select patients. In septic shock, 3 randomized clinical trials demonstrate that protocolized care offers little advantage compared with management without a protocol. Hydroxyethyl starch is no longer recommended, and debate continues about the role of various crystalloid solutions and albumin. CONCLUSIONS AND RELEVANCE The prompt diagnosis of septic shock begins with obtainment of medical history and performance of a physical examination for signs and symptoms of infection and may require focused ultrasonography to recognize more complex physiologic manifestations of shock. Clinicians should understand the importance of prompt administration of intravenous fluids and vasoactive medications aimed at restoring adequate circulation, and the limitations of protocol-based therapy, as guided by recent evidence. INSET: Box. Areas of Uncertainty in the Diagnosis and Treatment of.... [ABSTRACT FROM AUTHOR]

The increasing interest in chitosan-based biomaterials stems from its desirable physicochemical properties. Although calcium phosphates have been mixed with chitosan to form injectable scaffolds, its application for bone tissue engineering has been limited and is still being explored to improve its clinical translatability. We report a biocomposite comprised of preformed chitosan cryogel with dispersed biphasic calcium phosphate that can flow under moderate pressure allowing passage through a small gauge needle, while maintaining sufficient integrity and strength during injection for gel recovery. The formed samples were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction analysis and protein adsorption measurements. Composite with 1% w/v biphasic calcium phosphate (CSG1) resulted in a homogeneous and rigid final structure. Injectable composite cryogel CSG1 (2.5 ± 0.2 N, 23G needle) exhibited good protein adsorption and biocompatibility. Results of subcutaneous implantation in rats reveal relatively high presence of polymorphonuclear cells but with no fibrous encapsulation with the composites, allowing further infiltration of cells within the sample implants. The biocomposite system presents a less-invasive delivery of bone filling material for stabilizing pathologic fractures. [ABSTRACT FROM AUTHOR]

Interventional oncology procedures such as thermal ablation are becoming widely used for many tumours in the liver, kidney and lung. Thermal ablation refers to the focal destruction of tissue by generating cytotoxic temperatures in the treatment zone. Hydrodissection – separating tissues with fluids – protects healthy tissues adjacent to the ablation treatment zone to improve procedural safety, and facilitate more aggressive power application or applicator placement. However, fluids such as normal saline and 5% dextrose in water (D5W) can migrate into the peritoneum, reducing their protective efficacy. As an alternative, a thermo-gelable poloxamer 407 (P407) solution has been recently developed to facilitate hydrodissection procedures. We hypothesise that the P407 gel material does not provide convective heat dissipation from the ablation site, and therefore may alter the heat transfer dynamics compared to liquid materials during hydrodissection-assisted thermal ablation. The purpose of this study was to investigate the heat dissipation mechanics within D5W, liquid P407 and gel P407 hydrodissection barriers. Overall it was shown that the gel P407 dissipated heat primarily through conduction, whereas the liquid P407 and D5W dissipated heat through convection. Furthermore, the rate of temperature change within the gel P407 was greater than liquid P407 and D5W. Testing to evaluate thein vivoefficacy of the fluids with different modes of heat dissipation seems warranted for further study. [ABSTRACT FROM PUBLISHER]

In anesthesia and intensive care, treatment benefits that were claimed on the basis of small or modest-sized trials have repeatedly failed to be confirmed in large randomized controlled trials. A well-designed small trial in a homogeneous patient population with high event rates could yield conclusive results; however, patient populations in anesthesia and intensive care are typically heterogeneous because of comorbidities. The size of the anticipated effects of therapeutic interventions is generally low in relation to relevant endpoints. For regulatory purposes, trials are required to demonstrate efficacy in clinically important endpoints, and therefore must be large because clinically important study endpoints such as death, sepsis, or pneumonia are dichotomous and infrequently occur . The rarer endpoint events occur in the study population; that is, the lower the signal-to-noise ratio, the larger the trials must be to prevent random events from being overemphasized. In addition to trial design, sample size determination on the basis of event rates, clinically meaningful risk ratio reductions and actual patient numbers studied are among the most important characteristics when interpreting study results. Trial size is a critical determinant of generalizability of study results to larger or general patient populations. Typical characteristics of small single-center studies responsible for their known fragility include low variability of outcome measures for surrogate parameters and selective publication and reporting. For anesthesiology and intensive care medicine, findings in volume resuscitation research on intravenous infusion of colloids exemplify this, since both the safety of albumin infusion and the adverse effects of the artificial colloid hydroxyethyl starch have been confirmed only in large-sized trials. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop biocompatible, biodegradable dental implant coatings capable of withstanding the mechanical stresses imparted during implant placement. Two techniques were developed to deposit uniform silk fibroin protein coatings onto dental implants. Two novel coating techniques were implemented to coat titanium shims, studs, and implants. One technique involved electrodeposition of the silk directly onto the titanium substrates. The second technique consisted of melting electrogels and dispensing the melted gels onto the titanium to form the coatings. Both techniques were tested for coating reproducibility using a stylus profilometer and a dial thickness gauge. The mechanical strength of adhered titanium studs was assessed using a universal mechanical testing machine. Uniform, controllable coatings were obtained from both the electrodeposition and melted electrogel coating techniques, tunable from 35 to 1654 µm thick under the conditions studied, and able to withstand delamination during implantation into implant socket mimics. Mechanical testing revealed that the adhesive strength of electrogel coatings, 0.369 ± 0.09 MPa, rivaled other biologically derived coating systems such as collagen, hydroxyapatite, and chitosan (0.07–4.83 MPa). These novel silk-based techniques offer a unique approach to the deposition of safe, simple, mechanically robust, biocompatible, and degradable implant coatings. [ABSTRACT FROM AUTHOR]

The ability to estimate the diffusion coefficient of a solute within hydrogels has important application in the design and analysis of hydrogels used in drug delivery, tissue engineering, and regenerative medicine. A number of mathematical models have been derived for this purpose; however, they often rely on fitted parameters and so have limited predictive capability. Herein we assess the ability of the obstruction-scaling model to provide reasonable estimates of solute diffusion coefficients within hydrogels, as well as the assumption that a hydrogel can be represented as an entangled polymer solution of an equivalent concentration. Fluorescein isothiocyanate dextran solutes were loaded into sodium alginate solutions as well as hydrogels of different polymer volume fractions formed from photoinitiated cross-linking of methacrylate sodium alginate. The tracer diffusion coefficients of these solutes were measured using fluorescence recovery after photobleaching (FRAP). The measured diffusion coefficients were then compared to the values predicted by the obstruction-scaling model. The model predictions were within ± 15% of the measured values, suggesting that the model can provide useful estimates of solute diffusion coefficients within hydrogels and solutions. Moreover, solutes diffusing in both sodium alginate solutions and hydrogels were demonstrated to experience the same degree of solute mobility restriction given the same effective polymer concentration, supporting the assumption that a hydrogel can be represented as an entangled polymer solution of equivalent concentration. [ABSTRACT FROM AUTHOR]

An in situ-formed hydrogel was synthesized by enzymatic cross-linking of poly(γ-glutamic acid)–tyramine conjugates (PGA–Tyr) using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The gelation time ranged from 25 s to 5 min was accomplished by tuning the concentration of HRP, H2O2/Tyr molar ratio and the degree of substitution (DS) of Tyr groups. The storage modulus (G′), cross-link density, and mesh size can be tailored by controlling the H2O2/Tyr ratio and DS. The rheological analysis indicated that the storage modulus (G′) can be tailored from approximately 40 to over 1100 Pa with the increasing H2O2/Tyr ratio and DS. The bovine serum albumin (BSA) was used as model protein and encapsulated into the hydrogel during the enzyme-mediated cross-linking reaction. Controlled release of BSA in vitrofrom the PGA–Tyr hydrogel was obtained. The release rate and cumulative release amount of encapsulated BSA were manipulated by controlling the H2O2/Tyr ratio and DS. More than 90% of encapsulated BSA was released from the hydrogel with low cross-link density and lager mesh size in 60 h, while only 68% of BSA was released from the hydrogel with high cross-link density and small mesh size. The results indicated that the PGA–Tyr hydrogel is a promising material for the controlled release of therapeutic protein or peptides. [ABSTRACT FROM AUTHOR]

Purpose To study the safety and efficacy of implanting a hydrogel corneal inlay (Raindrop Near Vision Inlay) concurrently with performing laser in situ keratomileusis (LASIK) to treat myopic presbyopia and to compare the results with results of the same treatment in emmetropic and hyperopic patients. Setting Two private clinics, Tijuana and Monterrey, Mexico. Design Prospective nonrandomized clinical trial. Methods Bilateral myopic LASIK was performed and a corneal inlay was concurrently implanted in the nondominant eye under a flap created using a femtosecond laser. Primary safety outcomes were the retention of corrected distance (CDVA) and near (CNVA) visual acuities. Efficacy was evaluated on the basis of uncorrected near (UNVA), intermediate (UIVA), and distance (UDVA) visual acuities. A patient questionnaire was used to assess the preoperative and postoperative incidence of visual symptoms, the ability to perform common tasks with no correction, and patient satisfaction with vision. Results Thirty eyes were enrolled. At each postoperative visit, the mean CDVA and CNVA were within one half line of preoperative measurements and no eye lost 2 or more lines of CDVA. The mean binocular UDVA, UIVA, and UNVA were better than 20/25 Snellen at all postoperative visits. By 6 months, 93% of patients had a binocular Snellen acuity of 20/25 or better across all visual ranges. According to patient questionnaires, 1 year after surgery, visual symptoms were at preoperative levels, 98% of all visual tasks could be easily performed without correction, and 90% of patients were satisfied or very satisfied with their overall vision. Conclusion A hydrogel corneal inlay with concurrent LASIK was safe and effective for treating myopic presbyopia. Financial Disclosure Drs. Garza and Chayet are consultants to and investigators for Revision Optics, Inc. [ABSTRACT FROM AUTHOR]

Nanocrystals, a carrier-free colloidal delivery system in nano-sized range, is an interesting approach for poorly soluble drugs. Nanocrystals provide special features including enhancement of saturation solubility, dissolution velocity and adhesiveness to surface/cell membranes. Several strategies are applied for nanocrystals production including precipitation, milling, high pressure homogenization and combination methods such as Nano- Edge™, SmartCrystal and Precipitation-lyophilization-homogenization (PLH) technology. For oral administration, many publications reported useful advantages of nanocrystals to improve in vivo performances i.e. pharmacokinetics, pharmacodynamics, safety and targeted delivery which were discussed in this review. Additionally, transformation of nanocrystals to final formulations and future trends of nanocrystals were also described. [ABSTRACT FROM AUTHOR]

Although hyaluronate is an attractive biomaterial for many biomedical applications, hyaluronate hydrogels are generally formed using chemical cross-linking reagents that may cause unwanted side effects, including toxicity. We thus propose to design and prepare ionically cross-linkable hyaluronate compounds that can form gels in the presence of counter-ions. This study is based on the hypothesis that introduction of alginate to hyaluronate backbones (hyaluronate- g -alginate) could allow for gel formation in the presence of calcium ions. Here, we demonstrated ease of formation of cross-linked structures with calcium ions without additional chemical cross-linking reagents in hyaluronate- g -alginate (HGA) gels. The mechanical properties of HGA gels were regulated through changes in polymer composition and calcium concentration. We also confirmed that HGA gels could be useful in regenerating cartilage in a mouse model following subcutaneous injection into the dorsal region with primary chondrocytes. This finding was supported by histological and immunohistochemical analyses, glycosaminoglycan quantification and chondrogenic marker gene expression. This approach to the design and tailoring of ionically cross-linkable biomedical polymers may be broadly applicable to the development of biomaterials, especially in the drug delivery and tissue engineering fields. [ABSTRACT FROM AUTHOR]

Hydrogels designed to sustainably release bioactive molecules are extensively used to enhance tissue repair and regenerative therapies. Along this line, numerous efforts are made to control the molecular release rate and amount. In contrast, few efforts are made to control the molecular release pattern, and, subsequently, modulate the spatial organization of newly forming tissues, including blood vessels. Therefore, using a hydrogel printed to release vascular endothelial growth factor (VEGF) into a pre-defined pattern, this study demonstrates that spatial distribution of VEGF is important in guiding growth direction of new blood vessels, and also in retaining the structural integrity of pre-existing vasculature. Guided by a computational model, we fabricated a patch composed of micro-sized VEGF-releasing poly(ethylene glycol) diacrylate (PEGDA) hydrogel cylinders using an ink-jet printer. Interestingly, hydrogel printed with computationally optimized spacing created anisotropically aligned vasculature exclusively when the printed gel pattern was placed parallel to pre-existing blood vessels. In contrast, vascular sprouting from placing the printed gel pattern perpendicular to pre-existing vessels resulted in deformation and structural disintegration of the original vasculature. We envision that this study will be useful to better understand angiogenesis-modulated neovascularization and further improve the treatment quality for various wounds and tissue defects. [ABSTRACT FROM AUTHOR]

Numerous hormones are known to be endogenously secreted in a pulsatile manner. In particular, gonadotropin replacing hormone (GnRH) is released in rhythmic pulses, and disruption of this rhythm is associated with pathologies of reproduction and sexual development. In an effort to develop an implantable, rhythmic delivery system, a scheme has been demonstrated involving a negative feedback instability between a pH-sensitive membrane and enzymes that convert endogenous glucose to hydrogen ion. A bench prototype system based on this scheme was previously shown to produce near rhythmic oscillations in internal pH and in GnRH delivery over a period of one week. In the present work, a systematic study of conditions permitting such oscillations is presented, along with a study of factors causing period of oscillations to increase with time and ultimately cease. Membrane composition, glucose concentration, and surface area of marble (CaCO 3 ), which is incorporated as a reactant, were found to affect the capacity of the system to oscillate, and the pH range over which oscillations occur. Accumulation of gluconate − and Ca 2 + in the system over time correlated with lengthening of oscillation period, and possibly with cessation of oscillations. Enzyme degradation may also be a factor. These studies provide the groundwork for future improvements in device design. [ABSTRACT FROM AUTHOR]

The chemical construction of complexcolloidosomes consisting ofa molecularly crowded polyelectrolyte-enriched interior surroundedby a continuous shell of closely packed silica nanoparticles is studiedusing optical and fluorescence microscopy, high-resolution X-ray microcomputedtomography, and synchrotron radiation X-ray tomographic microscopy.The colloidosomes are prepared by addition of partially hydrophobicsilica nanoparticles to dodecane dispersions of positively or negativelycharged coacervate microdroplets consisting of aqueous mixtures ofpoly(diallyldimethylammonium chloride) (PDDA) and adenosine 5′-triphosphate(ATP) or PDDA and poly(acrylic acid) (PAA), respectively. Interfacialassembly of the nanoparticles produces a polydisperse population ofwell-defined PDDA/PAA droplets with diameters ranging from 50 to 950μm. In contrast, reconstruction of the PDDA/ATP coacervate interioroccurs on addition of the silica nanoparticles to produce a nanoparticle-stabilizedoil-in-coacervate-in-oil multiphase emulsion. Transfer of the coacervate-containingcolloidosomes into water and replication of their internal structureare achieved by addition of tetramethoxysilane, which serves as botha cross-linking and silicification agent to produce mineralized PDDA/PAAor PDDA/ATP microstructures with a uniform solidified texture or multichamberedinterior, respectively. The integration of colloidosome and coacervatetechnologies offers a route to a new type of multifunctional microcompartmentalizedsystem based on the membrane-mediatedincarceration of molecularly crowded chemical environments. [ABSTRACT FROM AUTHOR]

A novel strategy is reported forsensing chemical bond breakagein hydrogels at low levels of mechanical stress using a mechanochemicalreaction cascade to generate fluorescence. Hydrogels are promisingsubstrates and frameworks for cell growth and tissue engineering,particularly for cardiovascular repair and cartilage replacement.For these applications, it is important to maintain careful controlover gel mechanical properties so that these hydrogels not only matchthe properties of the desired tissue for replacement but also retaintheir integrity for extended periods. Since the failure of hydrogelsbegins with the breakage of cross-links within the structure, methodsare needed to sense these initial events for monitoring the performanceof implants. In this work, it was hypothesized that nonspecific covalentbond breakage would produce radicals that would react with water toproduce reactive oxygen species, which in turn could activate fluorophoressensitive to these. A series of multiarm poly(ethylene glycol) hydrogelswere synthesized with a variety of cross-links of different bond dissociationenergies. It was found that gels loaded with the masked fluorophore3′-(p-aminophenyl) fluorescein became fluorescentduring compression, even with as little as 5 kPa of pressure. Theeffect of compression on fluorescence activation was found to dependprimarily on the strength of the cross-linking functional group. Futurestudies include utilizing this system to image mechanical variabilityin heterogeneous gel structures. [ABSTRACT FROM AUTHOR]

Hydrogels are natural or synthetic polymer networks that have high water-absorbing capacity and closely mimic native extracellular matrices. As hydrogel-based cell delivery systems are being increasingly employed in regenerative medicine, several advances have been made in the hydrogel chemistry and modification for enhanced control of cell fate and functions, and modulation of cell and tissue responses against oxidative stress and inflammation in the tissue environment. This review aims to provide the state-of-the-art overview of the recent advances in field, discusses new perspectives and challenges in the regeneration of specific tissues, and highlights some of the limitations of current systems for possible future advancements. [ABSTRACT FROM AUTHOR]

Environmentally sensitive hydrogels as one of the most potential drug delivery systems have gained considerable interest in recent years. In the present study, we synthesized a newly temperature-responsive composite hydrogel based on attapulgite (ATP) and poly (N-isopropylacrylamide) (PNIPAM) as the localized drug carriers for drug delivery. The as-prepared ATP/PNIPAM hydrogel has large aperture which significantly improved the quantity of adsorption of drugs, exhibiting the excellent properties of drug release. The scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X-ray diffraction (XRD) were used to characterize the ATP/PNIPAM. The swelling/deswelling behaviors and the release of ciprofloxacin lactate were studied. When the temperature was below the low critical solution temperature (LCST), the swelling property of hydrogels was excellent and the swelling rate was large. And, the drug release rate increased with the increase of the content of attapulgite in the composite hydrogel when it was put in the buffer solution (pH 7.38) at 37.0 °C. Therefore, the composite hydrogels might be very useful for its application in biomedical fields. [ABSTRACT FROM AUTHOR]

Craniosynostosis is the premature fusion of cranial sutures, which can result in progressive cranial deformations, increased intracranial pressure, and restricted brain growth. Most cases of craniosynostosis require surgical reconstruction of the cranial vault with the goal of increasing the intracranial volume and correcting the craniofacial deformities. However, patients often experience rapid post-operative bone regrowth, known as re-synostosis, which necessitates additional surgical intervention. Bone morphogenetic protein (BMP) inhibitors have tremendous potential to treat re-synostosis, but the realization of a clinically viable inhibitor-based therapeutic requires the development of a delivery vehicle that can localize the release to the site of administration. Here, we present an in situ rapidly crosslinking injectable hydrogel that has the properties necessary to encapsulate co-administered proteins and demonstrate that the delivery of rmGremlin1 via our hydrogel system delays bone regrowth in a weanling mouse model of re-synostosis. Our hydrogel is composed of two mutually reactive poly(ethylene glycol) macromolecules, which when mixed crosslink via a bio-orthogonal Cu free click reaction. Hydrogels containing Gremlin caused a dose dependent inhibition of bone regrowth. In addition to craniofacial applications, our injectable click hydrogel has the potential to provide customizable protein, small molecule, and cell delivery to any site accessible via needle or catheter. [ABSTRACT FROM AUTHOR]

The development of pancreatic ductal adenocarcinoma (PDAC) is heavily influenced by local stromal tissues, or desmoplasia. Biomimetic hydrogels capable of mimicking tumor niches are particularly useful for discovering the role of independent matrix cues on cancer cell development. Here, we report a photo-curable and bio-orthogonal thiol-ene (i.e., cross-linked by mutually reactive norbornene and thiol groups via photoinitiation) hydrogel platform for studying the growth, morphogenesis, drug resistance, and cancer stem cell marker expression in PDAC cells cultured in 3D. The hydrogels were prepared from multi-arm poly(ethylene glycol)-norbornene cross-linked with protease-sensitive peptide to permit cell-mediated matrix remodeling. Collagen 1 fibrils were incorporated into the covalent network while cytokines (e.g., EGF and TGF-β1) were supplemented in the culture media for controlling cell fate. We found that the presence of collagen 1 enhanced cell proliferation and Yes-associated protein (YAP) translocation to cell nuclei. Cytokines and collagen 1 synergistically up-regulated MT1-MMP expression and induced cell spreading, suggestive of epithelial-mesenchymal transition (EMT) in the encapsulated cells. Furthermore, PDAC cells cultured in 3D developed chemo-resistance even in the absence of collagen 1 and cytokines. This phenotype is likely a consequence of the enrichment of pancreatic cancer stem cells that expressed high levels of CD24, sonic hedgehog (SHH), and vascular endothelial growth factor (VEGF). [ABSTRACT FROM AUTHOR]

Despite the recent expansion of peptide drugs, delivery remains a challenge due to poor localization and rapid clearance. Therefore, a hydrogel-based platform technology was developed to control and sustain peptide drug release via matrix metalloproteinase (MMP) activity. Specifically, hydrogels were composed of poly(ethylene glycol) and peptide drugs flanked by MMP substrates and terminal cysteine residues as crosslinkers. First, peptide drug bioactivity was investigated in expected released forms (e.g., with MMP substrate residues) in vitro prior to incorporation into hydrogels. Three peptides (Qk (from Vascular Endothelial Growth Factor), SPARC 113 , and SPARC 118 (from Secreted Protein Acidic and Rich in Cysteine)) retained bioactivity and were used as hydrogel crosslinkers in full MMP degradable forms. Upon treatment with MMP2, hydrogels containing Qk, SPARC 113 , and SPARC 118 degraded in 6.7, 6, and 1 days, and released 5, 8, and, 19% of peptide, respectively. Further investigation revealed peptide drug size controlled hydrogel swelling and degradation rate, while hydrophobicity impacted peptide release. Additionally, Qk, SPARC 113 , and SPARC 118 releasing hydrogels increased endothelial cell tube formation 3.1, 1.7, and 2.8-fold, respectively. While pro-angiogenic peptides were the focus of this study, the design parameters detailed allow for adaptation of hydrogels to control peptide release for a variety of therapeutic applications. [ABSTRACT FROM AUTHOR]

Optimal wound dressings should be capable of mechanical wound protection and also facilitate the healing process via maintenance of suitable environmental conditions and the controlled delivery of bioactive molecules. Hydrogels present suitable properties for wound-dressing applications such as good biocompatibility, together with a high water content, the latter of which is important for the maintenance of a moist environment and ready removal from the wound with a minimal level of associated pain. However, their properties as drug delivery systems can be improved by the use of cyclodextrins as cross-linking agents. Cyclodextrins have been extensively used as 'carriers' on food, textile, cosmetic and, most especially, in the pharmaceutical industry in view of their powerful complexation abilities and biocompatibilities, together with further desirable characteristics. The conjugation of cyclodextrins with hydrogels may allow the achievement of an optimal wound-dressing material, because the hydrogel component will maintain the moist environment required for the healing process, and the cyclodextrin moiety has the ability to protect and modulate the release of bioactive molecules. Therefore, this review aims to gather information regarding cyclodextrin-based hydrogels for possible wound-dressing applications. [ABSTRACT FROM AUTHOR]

Althoughseveral strategies are now available to enzymaticallycross-link linear polymers to hydrogels for biomedical use, littleprogress has been reported on the use of dendritic polymers for thesame purpose. Herein, we demonstrate that horseradish peroxidase (HRP)successfully catalyzes the oxidative cross-linking of a hyperbranchedpolyglycerol (hPG) functionalized with phenol groups to hydrogels.The tunable cross-linking results in adjustable hydrogel properties.Because the obtained materials are cytocompatible, they have greatpotential for encapsulating living cells for regenerative therapy.The gel formation can be triggered by glucose and controlled wellunder various environmental conditions. [ABSTRACT FROM AUTHOR]

Toovercome the poor pharmacokinetic conditions of short double-strandedRNA molecules in RNA interference therapies, cationic nanohydrogelparticles can be considered as alternative safe and stable carriersfor oligonucleotide delivery. For understanding key parameters duringthis process, two different types of well-defined cationic nanohydrogelparticles were synthesized, which provided nearly identical physicochemicalproperties with regards to their material composition and resultingsiRNA loading characteristics. Yet, according to the manufacturingprocess using amphiphilic reactive ester block copolymers of pentafluorophenylmethacrylate (PFPMA) and tri(ethylene glycol)methyl ether methacrylate(MEO3MA) with similar compositions but different molecularweights, the resulting nanohydrogel particles differed in size aftercross-linking with spermine (average diameter 40 vs 100 nm). Thisaffected their knockdown potential significantly. Only the 40 nm sizedcationic nanogel particles were able to generate moderate gene knockdownlevels, which lasted, however, up to 3 days. Interestingly, primarycell uptake and colocalization studies with lysosomal compartmentsrevealed that only these small sized nanogels were able to avoid acidiccompartments of endolysosomal uptake pathways, which may contributeto their knockdown ability exclusively. To that respect, this size-dependentintracellular distribution behavior may be considered as an essentialkey parameter for tuning the knockdown potential of siRNA nanohydrogelparticles, which may further contribute to the development of advancedsiRNA carrier systems with improved knockdown potential. [ABSTRACT FROM AUTHOR]

The in vitro antioxidant activity and the in vivo wound healing performance of the exopolysaccharide EPS22, produced by Pseudomonas stutzeri AS22, were investigated. Antioxidant activity was evaluated by three different tests. The scavenging effect on DPPH radicals at a concentration of 1 mg/ml was 80 ± 1.41%. The reducing power reached a maximum of 1.26 ± 0.02 at 2 mg/ml. Moreover, EPS22 showed good chelating ability and chelated almost 88.5 ± 0.7% of ferrous ions at 0.75 mg/ml. The rheological characterization of EPS22 gel (0.5%) showed a pseudoplastic behavior, high elasticity, good mechanical strength and stability with high water-absorption ability. The application of the EPS22 gel on dermal full-thickness excision wounds in a rat model every two days, enhanced significantly wound healing activity and a total closure was achieved after 12 days of wound induction. Further, histological examination of biopsies showed advanced tissue regeneration, characterized by the presence of well-organized stratum of both derma and epidermis. [ABSTRACT FROM AUTHOR]

Hydrogels closely resemble the extracellular matrix (ECM) and can support cell proliferation while new tissue is formed, making them materials of choice as tissue engineering scaffolds. However, their sometimes-poor mechanical properties can hinder their application. The addition of meshes of nanofibers embedded in their matrix forms a composite that draws from the advantages of both components. Given that these materials are still in the early stages of development, there is a lack of uniformity across methods for characterizing their mechanical properties. Here, we propose a simple metric to enable comparisons between materials. The fibrous constituent improves the mechanical properties of the hydrogel, while the biocompatibility and functionality of the gels are maintained or even improved. [ABSTRACT FROM AUTHOR]

The organ distribution of intravenously injected nanoparticles is determined by the composition of the blood protein adsorption pattern occurring after injection. This is exploited in the concept of 'differential protein adsorption' for drug targeting, which is briefly discussed. The surface properties of the nanoparticles determine the adsorption patterns, by controlling the surface properties one can generate adsorption patterns required for achieving the desired organ distribution. The efficiency of this principle is shown by reviewing different organ distributions achieved using various polymeric nanoparticles with different surface properties. Surface modification can be obtained by polymer adsorption and can create nanoparticles circulating in the blood, or accumulating in targets such as bone marrow and brain. The protein adsorption patterns were analyzed using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Here, adsorption patterns of dendritic polymer nanoparticles were investigated, where the used polymer was dendritic polyglycerol sulfate. They showed reduced opsonization and preferential adsorption of apolipoprotein A-I with brain targeting potential. In perspective, the principle of surface property modification by polymer/stabilizer adsorption can be transferred to intravenous drug nanocrystals. A hybrid system of nanocrystal and polymeric nanoparticles is suggested, the polymeric nanoparticle with nanocrystal core. [ABSTRACT FROM AUTHOR]