Oligo(ethylene glycol)-oligo(propylene glycol)-oligo(ethylene glycol) (OEG-OPG-OEG) triblock copolymers are hydrogel forming and extensively investigated in the field of drug release due to their biocompatibility and thermo-sensitivity. Here the synthesis and characterization of OEG-OPG-OEG based polymer networks from methacrylated oligomers by photo-irradiation are reported. Two precursors were selected to have comparable hydrophilicity (80 wt% OEG content) but different molecular weights of Mn = 8400 g·mol-1 and 14600 g·mol-1. The precursor solutions were prepared in concentration 10 to 30 wt%. The resulting polymer networks prepared from high Mn precursors exhibited higher swellability at equilibrium (up to 3400%) and mechanical properties in the range of G’ ∼ 0.1 to 1 kPa at 5 °C compared to networks based on low Mn precursors. A more significant thermo-sensitive behavior in terms of swellability, volumetric contraction and mechanical transition, starting at 30 °C could also be observed for the networks based on high Mn precursors, thus promoting future application in the field of drug release.

In this report we develop a complete mathematical model for a porous scaffold from nitinol (NiTi – intermetallic phase) with a shape memory effect (SME), fabricated layerwise via the selective laser sintering (SLS) process. The operation of the SME bio-fluidic MEMS involves such physical process as a heat transfer, a phase transformation with a temperature hysteresis, stress-strain and electrical resistance variations accompanied the phase transformation. The simulations were conducted for the electro- and a thermo- mechanical hysteresis phenomenon, during the SME in the porous nitinol structures of the cylinder shape, which allow to formulate a recommendations for SLS. Previously done the temperature evolution of electrical resistivity was compared with our present calculations as a function of the laser-processing parameters for three dimensional nitinol samples. This model can be used for an estimation of a drug delivery system route during a porous phase volume changing.

The rapid synthesis of gold nanoparticles (AuNPs) was done by solution plasma sputtering (SPS) process in the presence of a biopolymer, sodium alginate. We utilized the alginate polymer in order to meet three important requirements: (1) to promote the generation of plasma in liquid environment, (2) to provide colloidal stability, and (3) to render biocompatibility to the AuNPs. The effect of sodium alginate concentration (varied as 0.2, 0.5, and 0.9 %w/v) and plasma sputtering time on the particle size and the physical absorption property of the AuNPs were studied. The results indicated that preparation of AuNPs in alginate gel matrix was successful by the SPS process in one step without any reducing agents. This technique has high potential as a novel strategy to produce AuNPs suspended in alginate aqueous solution which is suitable for biomedical application.

The ability of nano secondary ion mass spectrometry (NanoSIMS) to locate and analyze Raman active gold core nanoparticles (R-AuNPs) in a biological system is compared with the standard analysis using the scanning electron microscope (SEM). The same cell with R-AuNPs on and inside the macrophage was analyzed with both techniques to directly compare them. SEM analysis showed a large number of nanoparticles within the cell. Subsequent NanoSIMS analysis showed fewer R-AuNPs with lower spatial resolution. SEM was determined to be superior to NanoSIMS for the analysis of inorganic nanoparticles in complex biological systems.

In this paper, we provide the investigation about the controlled surface functionalization of acrylic toner particles for electro photography (“laser printing”) with sodium hydroxide and the subsequent carbodiimide-mediated coupling of numerous functional amines onto the generated carboxylic group. Various chemically valuable functionalities, comprising of thiol, alkyne and azide, were bound onto the particles’ surface and allow for further versatile modifications via huisgen cycloaddition as well as thiol-ene reaction. The functionalization of the acrylic toner surface with alkyne, azide and carboxylic groups increased the cell viability up to 178 % ± 22 % and might offer an interesting path for new applications using common laser printing techniques.

In order to explore the feasibility for preparing defined crosslinked particulate structures, oligo(ε-caprolactone) [oCL] derived microparticles (MPs) were crosslinked in non-molten, non-dissolved, i.e. solid state in aqueous suspension by applying a controlled regime with well-defined polymer network precursors either with or without photoinitiator. The MPs (diameter ∼ 40 μm) were prepared by an oil-in-water emulsion process from linear 2oCL or 4-arm star-shaped 4oCL with methacrylate end groups. Crosslinking was initiated by UV-laser irradiation (308 nm) at room temperature. Conversion of methacrylate was monitored by ATR-FTIR spectroscopy and crosslinking was confirmed by a lack of MP dissolution in dichloromethane. In a quantitative evaluation of swelling by dynamic light scattering, higher swelling ratios were detected for particles synthesized with photoinitiator. Wrinkled particle surfaces and distorted particle shapes were observed by light microscopy in the solvent-swollen state and by scanning electron microscopy after deswelling. This work indicated some limitations due to internal inhomogeneity of the MP, but particle crosslinking in solid state was generally possible and may be further improved by higher chain mobility during crosslinking.

Polymer-based, degradable microparticles (MP) are attractive delivery vehicles for vaccines as the polymer properties can be specifically tailored and the carrier can be loaded with adjuvant. For all newly developed carrier systems it is important to analyze cellular uptake efficiency and the specific effects mediated by the encapsulated agent when phagocytosed by the cells, which is barely reported so far. By the encapsulation of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) labeled with fluoresceinisothiocyanat (FITC) in poly[(rac-lactide)-co-glycolide] (PLGA) MP, the MP was fluorescent and used to visualize the phagocytic uptake. Since encapsulated MDP can activate dendritic cells (DC) via the cytosolic nucleotide-binding oligomerization domain receptors (NOD), it can be investigated whether only cells that have phagocytosed the MP are activated or whether bystander effects occur, resulting in activation of cells, which did not take up MDP-FITC loaded MP. Here, it is demonstrated that increasing MP concentrations in the culture medium had no impact on the viability of DC and that the MP uptake efficiency was dose dependent. Interestingly, it could be shown by the CD86 expression, that only DC, which had engulfed MP, were significantly stronger activated than DC, which had not phagocytosed MDP-FITC loaded MP. On the one hand these results indicate that sufficient amounts of MDP were released from the PLGA carriers into the cytosol of the DC. On the other hand, based on the correlation of uptake and activation on the single cell level, minimal MP induced bystander effects may be expected for in vivo applications.

The micro- and nanostructured phase behavior of non-woven hybrid electrospun fibers of Polycaprolactone (PCL-f), Polycaprolactone/α-Alumina (PCL/AA) and Polycaprolactone/Hydroxyapatite (PCL/HA) were elucidated. Nanoparticles of Hydroxyapatite featured 7-20 nm while α-Alumina was 500 nm in average size. Analysis by Transmission Electron Microscopy (TEM), Small-Angle Light Scattering (SALS), Polarized Optical Microscopy (POM) and Differential Scanning Calorimetry (DSC) enabled us to suggest a simple structural model for the series of hybrid fibers. PCL with a molecular weight of 70,000 g/mol was dissolved in chloroform. POM exhibited qualitative birefringent regions for all samples at the microscale level. Furthermore, polarized light distinguished between amorphous and micro-ordered structures along the fibers. On the other hand, SALS patterns suggested a needle-like morphology for all fibers. The influence of both, Hydroxyapatite and α-Alumina, was apparent in the SALS patterns of the PCL semicrystalline phase. Thermal analysis by DSC showed that the crystalline phase of PCL was disrupted by the presence of the inorganic nanoparticles. TEM micrographs showed that Hydroxyapatite and α-Alumina nanoparticles were embedded along the structure of PCL microfibers.

Optical biosensor for monitoring proteolytic activity is constructed by DNA-directed immobilization of enzymes onto porous Silicon nanostructures. This sensor configuration allows both protease recycling and easy surface regeneration for subsequent biosensing analysis by means of mild dehybridization conditions. We demonstrate real-time analysis of minute quantities of proteases paving the way for substrate profiling and the identification of cleavage sites. The biosensor is compatible with common proteomic methods and allows for a successful downstream mass spectrometry analysis of the reaction products.

Amphiphilic diacetylenes (DAs) can self-assemble into photopolymerizable liposomes that can be used to construct effective pathogen sensors. Here, modified commercial inkjet printers are used to disperse DAs into water, facilitating self-assembly. The liposomes are of similar size, but are significantly less polydisperse than liposomes formed using conventional sonication methods. The process is efficient, readily scalable and tolerant of structural modification. The derivitization of approximately 5% of the DA head groups and the incorporation of fluorophores into the hydrophobic bilayer allows for the preparation of novel multifluorophore PDA sensing systems that can provide enhanced bacterial discrimination in a single experiment by way of a fluorescent fingerprint.

In the presented study, a new application for distyrylbenzene oligoelectrolyte, named DSBN+, as a marker for bioimaging is presented. DSBN+ is a water-soluble, conjugated oligoelectrolyte (COE) with novel photophysical and solvatochromatic properties. Previous studies have shown that this compound spontaneously inserts into bilayer membranes in both synthetic and microbial living systems and can facilitate visualization of cell membranes through fluorescence imaging. In the presented research, we seek to further study and exploit the multifunctional nature of DSBN+ in terms of membrane interactions and photophysical properties for visualization of membranous structures of more complex mammalian cells, namely a human cervical carcinoma (HeLa) cell line. Obtained results confirm the possibility of applying DSBN+ as a fluorescent dye for bioimaging of membranes in human cell cultures systems, both in live-cell imaging and in the studies required formaldehyde fixation. Due to the defined structure of this conjugated oligoelectrolyte we suspect that it will display organelle membrane selectivity, but this has to be further investigated.

Nanobiosensors have drawn significant research interest in recent years owing to the advantages of label-free, electrical detection. However, nanobiosensors fabricated by bottom-up process are limited in terms of yield and device uniformity due to the challenges in assembly. Nanobiosensors fabricated by top-down process, on the other hand, exhibit better uniformity but require time and costly processes and materials to achieve the critical dimensions required for high sensitivity. In this report, we introduce a top-down nanobiosensor based on polysilicon nanoribbon. The polysilicon nanoribbon devices can be fabricated by conventional photolithography with only materials and equipments used in the standard CMOS process, thus resulting in great time and cost efficiency, as well as scalability. The devices show great response to pH changes with a wide dynamic range and high sensitivity. Biomarker detection is also demonstrated with clinically relevant sensitivity. Such results suggest that polysilicon nanoribbon devices exhibit great potential toward a highly efficient, reliable and sensitive biosensing platform.

Hydrogels consisting of the conducting polymer PEDOT:PSS and the biopolymer gellan gum (GG) were characterized using electrical, mechanical and rheological methods. Compression testing and rheological analysis showed that the gels weakened with increasing PEDOT:PSS content. In contrast, the increasing PEDOT:PSS content resulted in an increasing electrical conductivity.

Poly(3,4-ethylenedioxythiophene) (PEDOT) was polymerized with the biological dopants dextran sulphate and chondroitin sulphate. Polymer physical and mechanical properties were investigated using quartz crystal microgravimetry with dissipation monitoring and atomic force microscopy, revealing polymer shear modulus and interfacial roughness to be significantly altered as a function of the dopant species. The adsorption of fibronectin, an important extracellular protein that is critical for a range of cellular functions and processes, was investigated using QCM-D, revealing protein adsorption to be increased on the DS doped PEDOT film relative to the CS doped film. PEDOT films have traditionally been doped with synthetic counterions such as polystyrene sulphonate (PSS), however the incorporation of biological molecules as the counterion, which has been shown to improve polymer biofunctionality, has received far less attention. In particular, there has been little detailed study on the impact of incorporating polyelectrolyte biomolecules into the PEDOT polymer matrix on fundamental polymer properties which are critical for biomedical applications. This investigation provides a detailed characterization of the interfacial and mechanical properties of biologically doped PEDOT films, as well as the efficacy of the composite films to bind and retain extracellular proteins of the type that are critical to the biocompatibility of the polymeric material.

Thin-films of magnetic nanoparticles (MNPs) with high coercivities are deposited onto surfaces for use in data storage applications. This usually requires specialist clean-room facilities, sputtering equipment and high temperatures to achieve the correct crystallographic phases. One possible cheaper and more environmentally friendly alternative could be to use biomolecules. Many biomineralization and biotemplating molecules have been identified that are able to template a wide range of technologically relevant materials using mild, aqueous chemistry under physiological reaction conditions. Here, we have designed a dual affinity peptide (DAP) sequence to template MNPs onto a surface. One end of the DAP has a high binding affinity for SiO2 and the other for MNPs of the L10 phase of CoPt, a high coercivity magnetic material. Images of the biomineralized substrates show that nanoparticles of CoPt are localized onto the areas that were functionalized with the biotemplating DAP. Magnetic force microscopy (MFM) plots of the biotemplated nanoparticles show that there is magnetic contrast on the patterned surface.

We introduce a new approach for fabricating hollow microneedles using vertically-aligned carbon nanotubes (VA-CNTs) for rapid transdermal drug delivery. Here, we discuss the fabrication of the microneedles emphasizing the overall simplicity and flexibility of the method to allow for potential industrial application. By capitalizing on the nanoporosity of the CNT bundles, uncured polymer can be wicked into the needles ultimately creating a high strength composite of aligned nanotubes and polymer. Flow through the microneedles as well as in vitro penetration of the microneedles into swine skin is demonstrated. Furthermore, we present a trade study comparing the difficulty and complexity of the fabrication process of our CNT-polymer microneedles with other standard microneedle fabrication approaches.

The United States dependence on fossil fuels has become mandatory over the past few decades. The fuel shortage during the 1970s and after Hurricane Katrina has catalyzed a need for creating alternative energy sources, improving the efficacy of these alternative energy sources, and enhancing energy sustainability. The U.S. Department of Energy has set goals to replace 30% of the liquid petroleum transportation fuel with biofuels and to replace 25% of industrial organic chemicals with biomass-derived chemicals by 2025. In the southeast United States, subterranean termites are prevalent and microbes in their gut degrade wood based materials such as cellulose which produce simple sugars that can be used to produce bioethanol. Upon seasonal change, subterranean termites undergo less enzymatic activity and wood-eating capability limiting the amount of sugars that may be produced. This limited activity sparks an interest to investigate this poorly understood phenomenon of how temperature may affect the enzymatic activity in subterranean termites’ guts. In this study, we report the development thermoresponsive biomaterial nanofiber mats containing cellulose to model cellulase activity. Using electrospinning techniques, poly(N-vinylcaprolactam) celluose fiber mats have been prepared via alkaline hydrolysis and labeled with fluorescent tags. Subterranean termites (reticulitermes species) were feed fiber mats for 10 consecutive days to assess enzyme mapping and kinetics. Fluorescent microscopy images confirmed spatial and temporal localization of cellulase enzyme throughout the termite gut upon time and temperature change. These novel high affinity enzyme detection membranes show promise towards future biofuel production.

Silicatein is general catalyst for synthesis of silica structure in siliceous sponges. However, the advent of biomimetic silicification by this recombinant version is limited by its poor yield. To overcome this limitation, we employed a cathepsin L as an alternative to silicatein. Cathepsin L has high sequence identity and similarity with silicatein alpha except cysteine other than serine residues at the active site. Here, we expressed recombinant hypothetical cathepsin-like protein (CAT) from Nematostella vectensis, displaying not only protease activity but also silica condensing activity. To increase the silica forming activity, some residues including cysteine in active site were changed into silicatein conserved residues. The mutant silicatein-like cathepsin (SLC) revealed increased protein stability in comparison with that of CAT when expressed in E. coli. The silica forming activity of SLC was comparable to that of SIL. SLC produced silica particles of size less than 50 nm which were increased to 200∼300 nm in the presence of a structure-directing agent, Triton X-100. Protein immobilization by SLC-mediated silicification was performed using bovine carbonic anhydrase under ambient conditions. Immobilized protein retained its enzymatic activity for a longer time and was reused up to several times. In conclusion, CAT from Nematostella vectensis was evolved to a more soluble and available biosilica forming protein that can be applied for various silica-based materials.

Nanoporous gold (np-Au) with its high surface area to volume ratio, tunable pore morphology, ease of surface modification with well-studied thiol chemistry, as well as integration with conventional microfabrication techniques is a promising candidate for controlled drug delivery studies. While it has been demonstrated that np-Au can retain and release drugs, release mechanisms and governing parameters are unclear. This paper reports on the effect of film thickness and morphology on the molecular release from np-Au films.