Ionically crosslinked alginate hydrogels have been extensively explored for encapsulation and immunoisolation of living cells/tissues to develop implantable cell therapies, such as islet encapsulation for bioartificial pancreas. Chemical instability of these hydrogels during long-term implantation hinders the development of viable cell therapy. The exchange between divalent crosslinking ions (e.g., Ca+2) with monovalent ions from physiological environment causes alginate hydrogels to degrade, resulting in exposure of the donor tissue to the host's immune system and graft failure. The goal of this study was to improve stability of alginate hydrogels by utilizing covalent click crosslinking while preserving other biomedically viable hydrogel properties. Alginate was first functionalized to contain either pendant alkyne or azide functionalities, and subsequently reacted via click chemistry to form click gel capsules. Alginate functionalization was confirmed by NMR and gel permeation chromatography. When compared with Ca+2 capsules, click capsules exhibited superior stability in ionic media, while showing higher permeability to small size diffusants and similar molecular weight cut-off and water swelling. Physicochemical properties of click alginate hydrogels demonstrate their potential utility for therapeutic cell encapsulation and other biomedical applications. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1120-1132, 2015.

Emerging technologies result when advances and innovation in technology lead to discoveries. Often emerging technologies stimulate novel research in medical product development that contribute to new approaches to manufacturing and can improve the quality of products. By supporting investments in agency coordination, staff training and professional development, regulatory science research, stakeholder engagement, and enhancing opportunities for expert input, the U.S. Food and Drug Administration plays a critical role in translating innovations into novel safe and effective medical products that improve the public health.

Oversulfated chrondroitin sulfate (OSCS) was recently identified as a contaminant of heparin and was associated with serious adverse events in patients treated with heparin.Because heparin is a common component of blood collection tubes, we tested the effect of OSCS on the laboratory analysis of plasma.Blood from healthy volunteers (N=50) was collected into tubes containing various mixtures of heparin and OSCS.Samples were inspected for microclots and were analyzed for a panel of 28 routine laboratory tests.No microclots were observed in tubes that contained only heparin but were detected in 18%, 88% and 76% of plasma samples containing 5%, 15%, 20% OSCS (%weight relative to heparin), respectively.OSCS at the highest dose (20%) caused a systematic bias for the following 6 tests: Lactate Dehydrogenase: 18% (12% to 24%); Triiodothyronine: -5.7% (-8.1% to -3.3%); Potassium: -2.8% (-4.2% to -1.4%);Total Protein: 2.5% (1.4% to 3.6%); Chloride: -1.4% (-1.8% to -1.0%) and Uric Acid: 1% (0.5% to 1.4%).In summary, OSCS contamination of heparin was found to potentially affect the anticoagulation of plasma and the analytical performance of several routine clinical laboratory tests.

Iron-crosslinked hyaluronic acid hydrogel (FeHA) has been used to reduce postsurgical adhesions in patients undergoing open, gynecological surgery. The performance of FeHA gel as an adhesion barrier device is influenced by many factors, including the physicochemical gel properties, which, in turn, depend on the chemistry and conditions of the device manufacturing. In this work, we demonstrate the effect of reaction pH on rheology and homogeneity of FeHA gels formulated in house and also compare the viscoelastic properties of FeHA gels with that of uncrosslinked HA solution of similar HA concentration and ionic strength. Dynamic mechanical analyses provide evidence that the reaction of HA with Fe(III) ions leads to the formation of "weak" gels. The viscoelastic properties and homogeneity of FeHA gels vary depending on the pH at which crosslinking was initiated. When solution pH, at the start of crosslinking, varied between 1.5 and 3, the low-shear rate viscosity of FeHA varied between 10,000 and 40,000 cPoise (10-40 Pa s). The highest steady-state shear viscosity and viscoelasticity were measured when pH was around 2.6, which is similar to the pH-dependent viscoelasticity of pure HA solution. Initiating HA crosslinking at pH ≤ 3 led to relatively homogenous solutions, while crosslinking higher pH > 3 caused instantaneous gel precipitation and inhomogeneities. Sensitivity of FeHA gel properties to small variations in reaction pH clearly supports the need for a tight manufacturing control during medical device fabrication.

Hyaluronic acid (HA), in linear or cross-linked form, is a common component of cosmetics, personal care products, combination medical products, and medical devices. In all cases, the ability of the HA solution or gel to wet surfaces and/or disrupt and lubricate interfaces is a limiting feature of its mechanism of action. We synthesized ferric ion-cross-linked networks of HA based on an adhesion barrier, varied the degree of cross-linking, and performed wetting goniometry, viscometry, and dynamic mechanical analysis. As cross-linking increases, so do contact angle, viscosity, storage modulus, and loss modulus; thus, wetting and lubrication are compromised. These findings have implications in medical device materials, such as adhesion barriers and mucosal drug delivery vehicles.

A critical metrology issue for pharmaceutical industries is the application of analytical techniques for the characterization of drug delivery systems to address interrelationships between processing, structure, and drug release. In this study, cast coatings were formed from solutions of poly(styrene-b-isobutylene-b-styrene) (SIBS) and tetracycline in tetrahydrofuran (THF). These coatings were characterized by several imaging modalities, including time-of-flight secondary ion mass spectrometry (TOF-SIMS) for chemical imaging and analysis, atomic force microscopy (AFM) for determination of surface structure and morphology, and laser scanning confocal microscopy (LSCM), which was used to characterize the three-dimensional structure beneath the surface. The results showed phase separation between the drug and copolymer regions. The size of the tetracycline phase in the polymer matrix ranged from hundreds of nanometers to tens of microns, depending on coating composition. The mass of drug released was not found to be proportional to drug loading, because the size and spatial distribution of the drug phase varied with drug loading and solvent evaporation rate, which in turn affected the amount of drug released.

The Food and Drug Administration received complaints of Huber needles creating cores in the septa of ports of gastric banding devices. One of these complaints represented a cluster of similar events, even though no deviations from design specifications or recommended practices were subsequently identified by the manufacturer. The authors conducted this comparative investigation of off-the-shelf Huber needles and ports from several manufacturers to determine if engineering parameters could be identified that could account for the coring complaints. Huber needles from ten manufacturers were evaluated for coring using intravascular access ports from five manufacturers. A detailed optical analysis was also performed to identify needle features that would possibly account for coring. The majority of the tested needles performed as they should, i.e., they perforated the port septa without creating cores. However, needles that did produce cores were found to have sharp edges at the heel edge of the needle lumen, the edge of the ground bevel opposite from the needle tip that opens to the inner surface of the cannula tube. Manufacturing processes, which dulled or rounded the sharp heel of the bevel after bevel grinding, prevented coring. As a result of this investigation one manufacturer voluntarily recalled their product and another manufacturer implemented coring testing as part of their quality control. To prevent coring needles from entering the market as a result of manufacturing flaws, optical inspection of the heel edge and coring testing should be performed as part of routine quality control.

With the advent of nanotechnology, silver nanoparticles increasingly are being used in coatings, especially in medical device applications, to capitalize on their antimicrobial properties. The attractiveness of nanoparticulate silver systems is the expected increased antimicrobial efficacy relative to their bulk counterparts, which may be attributed to an increased silver ion (Ag+) solubility, and hence availability, that arises from capillarity effects in small, nanometer-sized particles. However, a change of the material upon which the antimicrobial nanoparticulate silver is deposited (herein called "substrate") may affect the availability of Ag+ ions and the intended efficacy of the device. We utilize both theory and experiment to determine the effect of substrate on ion release from silver particles in electrochemical environments and find that substrate surface charge, chemical reactivity or affinity of the surface for Ag+ ions, and wettability of the surface all affect availability of Ag+ ions, and hence antimicrobial efficacy. It is also observed that with time of exposure to deionized water, Ag+ ion release increases to a maximum value at 5 min before decreasing to undetectable levels, which is attributed to coarsening of the nanoparticles, and which subsequently reduces the solubility and availability of Ag+ ions. This coarsening phenomenon is also predicted by the theoretical considerations and has been confirmed experimentally by transmission electron microscopy.

Timely identification of biothreat organisms from large numbers of clinical or environmental samples in potential outbreak or attack scenario is critical for effective diagnosis and treatment. This study aims to evaluate the potential of resequencing arrays for this purpose. Albeit suboptimal, this report demonstrated that respiratory pathogen microarray version 1 can identify Bacillus anthracis, Francisella tularensis, Yersinia pestis and distinguish them from benign 'near neighbor' species in a single assay. Additionally, the sequence information can discriminate strains and possibly the sources of the strains. With further development, it is possible to use resequencing microarrays for biothreat surveillance.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Exquisite control over positioning nanoscale components on a protein scaffold allows bottom-up self-assembly of nanodevices. Using cowpea mosaic virus, modified to express cysteine residues on the capsid exterior, gold nanoparticles were attached to the viral scaffold to produce specific interparticle distances (see picture). The nanoparticles were then interconnected using thiol-terminated conjugated organic molecules that act as "molecular wires", resulting in a 3D spherical conductive network, which is only 30 nm in diameter.

Reported herein are the synthesis, electrochemical and structural characterization of wire-like Ru-2-alkynyl Compounds, Ru-2(ap)(4)(Ln)(x), where ap is 2-anilinopyridinate, and Ln is -(C equivalent to CC6H4)nSCH(2)CH(2)SiMe(3) With n = 1 (1) and 2 (2), and x can be 1 (a) and 2 (b). Reactions between Ru-2(ap)(4)Cl and one equiv. of LiLn yielded the mono-alkynyl compound only, while the use of 4-5 equiv. of LiLn resulted in a mixture of both the mono and bis-alkynyl species. Single crystal X-ray diffraction studies of compounds 1a and 1b revealed structural similarities to Ru-2(ap)(4)(C2Ph) and Ru-2(ap)(4)(C2Ph)(2), respectively. Magnetic, spectroscopic and voltammetric measurements also revealed a minimal perturbation on electronic structures due to the functionalization of OPE ligands with thiol-TMSE group (-SCH2CH2SiMe3). Most significantly, it can be estimated based on the structure of la that the Ru-OPE2-S- linkage in 2a is significantly longer than the depth of C11 thiol SAM and hence enables the insertion of 2a into the latter. (c) 2005 Elsevier B.V. All rights reserved.