Overcoming the rise in local deposit resistance during electrophoretic deposition via suspension replenishing.

Nanomaterials have unique properties, functionalities, and excellent performance, and as a result have gained significant interest across disciplines and industries. However, currently, there is a lack of techniques that can assemble as-synthesized nanomaterials in a scalable manner. Electrophoretic deposition (EPD) is a promising method for the scalable assembly of colloidally stable nanomaterials into thick films and arrays. In EPD, an electric field is used to assemble charged colloidal particles onto an oppositely charged substrate. However, in constant voltage EPD the deposition rate decreases with increasing deposition time, which has been attributed in part to the fact that the electric field in the suspension decreases with time. This decreasing electric field has been attributed to two probable causes, (i) increased resistance of the particle film and/or (ii) the growth of an ion-depletion region at the substrate. Here, to increase EPD yield and scalability we sought to distinguish between these two effects and found that the growth of the ion-depletion region plays the most significant role in the increase of the deposit resistance. Here, we also demonstrate a method to maintain constant deposit resistance in EPD by periodic replenishing of suspension, thereby improving EPD's scalability.

PEGDA hydrogel structure from semi-dilute concentrations: insights from experiments and molecular simulations.

The efficacy of hydrogel materials used in biomedical applications is dependent on polymer network topology and the structure of water-laden pore space. Hydrogel microstructure can be tuned by adjusting synthesis parameters such as macromer molar mass and concentration. Moreover, hydrogels beyond dilute conditions are needed to produce mechanically robust and dense networks for tissue engineering and/or drug delivery systems. Thus, this study utilizes a combined experimental and molecular simulation approach to characterize structural features for 4.8 and 10 kDa poly (ethylene glycol) diacrylate (PEGDA) hydrogels formed from a range of semi-dilute solution concentrations. The connection between chain-chain interactions in polymer solutions, hydrogel structure, and equilibrium swelling behavior is presented. Bulk rheology analysis revealed an entanglement concentration for PEGDA pre-gel solutions around 28 wt% for both macromers studied. A similar transition in swelling behavior was revealed around the same concentration where hydrogel capacity to retain water was drastically reduced. To understand this transition, the hydrogel structure was characterized using the swollen polymer network hypothesis and compared to pore size distributions from molecular dynamics simulations. We find in both approaches a structural transition concentration at the hydrogel swelling inflection point that is comparable to the entanglement concentration. Calculated mesh sizes from theory are compared with computationally determined average maximum pore diameters; mesh sizes from theory yielded greater feature sizes across all concentrations considered. Molecular simulations are further used to assess pore dynamics, which are shown to vary in distribution shape and number of modes compared to the time-averaged hydrogel pore features. Altogether, this work provides insights into hydrogel network features and their dynamic behavior at physiological conditions (37 °C) as a basis for hydrogel design beyond dilute conditions for biomedical applications.

Chelating Agent Functionalized Substrates for the Formation of Thick Films via Electrophoretic Deposition.

Incorporating nanoparticles into devices for a wide range of applications often requires the formation of thick films, which is particularly necessary for improving magnetic power storage, microwave properties, and sensor performance. One approach to assembling nanoparticles into films is the use of electrophoretic deposition (EPD). This work seeks to develop methods to increase film thickness and stability in EPD by increasing film-substrate interactions via functionalizing conductive substrates with various chelating agents. Here, we deposited iron oxide nanoparticles onto conductive substrates functionalized with three chelating agents with different functional moieties and differing chelating strengths. We show that increasing chelating strength can increase film-substrate interactions, resulting in thicker films when compared to traditional EPD. Results will also be presented on how the chelating strength relates to film formation as a function of deposition conditions. Yield for EPD is influenced by deposition conditions including applied electric field, particle concentration, and deposition time. This work shows that the functionalization of substrates with chelating agents that coordinate strongly with nanoparticles (phosphonic acid and dopamine) overcome parameters that traditionally hinder the deposition of thicker and more stable films, such as applied electric field and high particle concentration. We show that functionalizing substrates with chelating agents is a promising method to fabricate thick, stable films of nanoparticles deposited via EPD over a larger processing space by increasing film-substrate interactions.

Piezoelectric and Magnetoelectric Scaffolds for Tissue Regeneration and Biomedicine: A Review.

Electric fields are ubiquitous throughout the body, playing important role in a multitude of biological processes including osteo-regeneration, cell signaling, nerve regeneration, cardiac function, and DNA replication. An increased understanding of the role of electric fields in the body has led to the development of devices for biomedical applications that incorporate electromagnetic fields as an intrinsically novel functionality (e.g., bioactuators, biosensors, cardiac/neural electrodes, and tissues scaffolds). However, in the majority of the aforementioned devices, an implanted power supply is necessary for operation, and therefore requires highly invasive procedures. Thus, the ability to apply electric fields in a minimally invasive manner to remote areas of the body remains a critical and unmet need. Here, we report on the potential of magnetoelectric (ME)-based composites to overcome this challenge. ME materials are capable of producing localized electric fields in response to an applied magnetic field, which the body is permeable to. Yet, the use of ME materials for biomedical applications is just beginning to be explored. Here, we present on the potential of ME materials to be utilized in biomedical applications. This will be presented alongside current state-of-the-art for in vitro and in vivo electrical stimulation of cells and tissues. We will discuss key findings in the field, while also identifying challenges, such as the synthesis and characterization of biocompatible ME materials, challenges in experimental design, and opportunities for future research that would lead to the increased development of ME biomaterials and their applications.

Elucidating the role of electrophoretic mobility for increasing yield in the electrophoretic deposition of nanomaterials.

HYPOTHESIS: Catalysts, chemical, gas, and bio- sensing devices fabricated from porous nanoparticle films show better performance and sensitivity than their bulk material counterparts because of their high specific surface area. Electrophoretic deposition (EPD) technique is a cost-effective, fast, versatile, and easy to perform method to fabricate porous nanoparticle films. However, conventional EPD is currently limited by the fact that the deposition rate decreases with time, resulting in an eventual plateau in the deposit yield. Here, we sought to overcome this limitation by establishing and leveraging the critical role of the particle's electrophoretic mobility in EPD kinetics. EXPERIMENTS: To identify the impact of electrophoretic mobility on EPD yield we used alumina nanoparticles suspended in ethanol as a model system. Changes in particle mobility were monitored via changes in the effective pH (pHe) of the suspension during EPD. We also developed a new suspension replenish EPD approach that allows us to maintain near-constant particle mobility and particle concentration with time thereby increasing yield. FINDINGS: We observed that in conventional EPD the particle mobility of the alumina nanoparticles decreased with time, resulting in a halting of deposition. Further, using the suspension replenish EPD, we observed a linear increase in the mass of the deposited film with time, overcoming the plateau limitation of conventional EPD.

Sol-Gel-Based Electrospray Synthesis of Barium Titanate Nanoparticles.

Barium titanate nanoparticles are desirable for a wide range of applications, spanning electronics to biomedicine. Here, we present an electrospray-based method for the synthesis of barium titanate nanomaterials, where their morphology can be altered, forming either particles or rods. As-electrosprayed particles are amorphous and spherical, but upon calcination in the presence of sodium chloride their morphology can vary from particles to rods as the calcination time is increased. The processing-structure-property relationships in these materials are discussed.

Molecular Modeling of Complex Cross-Linked Networks of PEGDA Nanogels.

Poly(ethylene glycol) (PEG)-based nanogels are attractive for biomedical applications due to their biocompatibility, versatile end group chemistry, and ability to sterically shield encapsulated drug molecules. The characteristics of a hydrogel network govern the encapsulation and efficient delivery of drug molecules for a target application. A molecular-level description of network topology can complement experimental investigations to understand its effects on the structural properties of these nanogels. In this work, atomistic molecular simulations of heterogeneous, nonideal PEG-diacrylate (PEGDA) nanogels are presented. The effects of cross-linking density and topological features on the structural properties of PEGDA nanogels were studied. The average functionality was controlled to systematically study the effect of cross-linking density on the radius of gyration, shape, and mesh size of the nanogels. For a given average functionality, the impact of distinct network topologies on the structural properties was also studied. The aspect ratios, based on the gyration tensor, were calculated to characterize the shapes of these nanogels for different topologies. Nanogel structures with higher cross-linking densities showed a globular shape, while structures with lower cross-linking density showed shape anisotropy. The distribution and connectivity of the cross-linked junctions played a key role in determining the size and shape anisotropy of PEGDA nanogels; the number of unreacted chain ends and their connectivity directly affected the anisotropy. The mesh size, denoted by the limiting "free volume element" present in the nanogel samples, does not show a significant change with increasing average functionality. This work provides insight into the structural properties of heterogeneous hydrogels that aid the design of nonideal nanogel networks for a targeted drug delivery application.

Guide column array: a versatile approach to aligning and patterning ceramic nanofibers.

Ceramic fibers have been manufactured via electrospinning for a variety of applications, including microelectronics, gas sensing, and memory systems. Preferentially ordering ceramic fibers as uniaxially aligned mats, as layered arrays, or as patterned structures has enormous potential to enhance current applications and add utility to electrospun ceramic fibers. Here, we developed a versatile guide column array-based method for manufacturing uniaxially aligned and patterned arrays of ceramic fibers. The guide column array was designed to control the electrospinning jet via electrostatic interactions between the electrified jet and the electrodes, resulting in fibers that preferentially oriented during deposition. A relationship between the ceramic precursor solution conductivity was correlated to the optimal operating voltage for the realization of aligned ceramic nanofibers using the guide column array.

Magnetic field sensors using arrays of electrospun magnetoelectric Janus nanowires.

The fabrication and characterization of the first magnetoelectric sensors utilizing arrays of Janus magnetoelectric composite nanowires composed of barium titanate and cobalt ferrite are presented. By utilizing magnetoelectric nanowires suspended across electrodes above the substrate, substrate clamping is reduced when compared to layered thin-film architectures; this results in enhanced magnetoelectric coupling. Janus magnetoelectric nanowires are fabricated by sol-gel electrospinning, and their length is controlled through the electrospinning and calcination conditions. Using a directed nanomanufacturing approach, the nanowires are then assembled onto pre-patterned metal electrodes on a silicon substrate using dielectrophoresis. Using this process, functional magnetic field sensors are formed by connecting many nanowires in parallel. The observed magnetic field sensitivity from the parallel array of nanowires is 0.514 ± .027 mV Oe-1 at 1 kHz, which translates to a magnetoelectric coefficient of 514 ± 27 mV cm-1 Oe-1.

Thermal Decomposition Synthesis of Iron Oxide Nanoparticles with Diminished Magnetic Dead Layer by Controlled Addition of Oxygen.

Decades of research focused on size and shape control of iron oxide nanoparticles have led to methods of synthesis that afford excellent control over physical size and shape but comparatively poor control over magnetic properties. Popular synthesis methods based on thermal decomposition of organometallic precursors in the absence of oxygen have yielded particles with mixed iron oxide phases, crystal defects, and poorer than expected magnetic properties, including the existence of a thick "magnetically dead layer" experimentally evidenced by a magnetic diameter significantly smaller than the physical diameter. Here, we show how single-crystalline iron oxide nanoparticles with few defects and similar physical and magetic diameter distributions can be obtained by introducing molecular oxygen as one of the reactive species in the thermal decomposition synthesis. This is achieved without the need for any postsynthesis oxidation or thermal annealing. These results address a significant challenge in the synthesis of nanoparticles with predictable magnetic properties and could lead to advances in applications of magnetic nanoparticles.

Size Control of Porous Silicon-Based Nanoparticles via Pore-Wall Thinning.

Photoluminescent silicon nanocrystals are very attractive for biomedical and electronic applications. Here a new process is presented to synthesize photoluminescent silicon nanocrystals with diameters smaller than 6 nm from a porous silicon template. These nanoparticles are formed using a pore-wall thinning approach, where the as-etched porous silicon layer is partially oxidized to silica, which is dissolved by a hydrofluoric acid solution, decreasing the pore-wall thickness. This decrease in pore-wall thickness leads to a corresponding decrease in the size of the nanocrystals that make up the pore walls, resulting in the formation of smaller nanoparticles during sonication of the porous silicon. Particle diameters were measured using dynamic light scattering, and these values were compared with the nanocrystallite size within the pore wall as determined from X-ray diffraction. Additionally, an increase in the quantum confinement effect is observed for these particles through an increase in the photoluminescence intensity of the nanoparticles compared with the as-etched nanoparticles, without the need for a further activation step by oxidation after synthesis.

Matrix metalloproteinase-sensitive hydrogel microparticles for pulmonary drug delivery of small molecule drugs or proteins.

Hydrogel microparticles are particularly attractive for pulmonary drug delivery. Their size can be engineered for efficient delivery into the bronchi, where they subsequently swell, avoiding macrophage uptake. In this study, enzyme-responsive peptide functionalized poly(ethylene glycol) (PEG) based hydrogel microparticles were synthesized by an emulsion polymerization. Here, we demonstrate that these microparticles are nontoxic and demonstrated their viability as a drug carrier by studying the encapsulation and release of three types of drugs: a hydrophobic (dexamethasone), a hydrophilic (methylene blue) and a protein (horseradish peroxidase)-based drug. The release of each of these three drugs was studied in the presence of varying concentrations of matrix metalloproteinase (MMP). Each of the three types of drugs were able to be encapsulated in the microparticles, and we further showed that the protein is still functional after release.

Enzyme-responsive hydrogel microparticles for pulmonary drug delivery.

Poly(ethylene glycol) based hydrogel microparticles were developed for pulmonary drug delivery. Hydrogels are particularly attractive for pulmonary delivery because they can be size engineered for delivery into the bronchi, yet also swell upon reaching their destination to avoid uptake and clearance by alveolar macrophages. To develop enzyme-responsive hydrogel microparticles for pulmonary delivery a new synthesis method based on a solution polymerization was developed. This method produces spherical poly(ethylene glycol) (PEG) microparticles from high molecular weight poly(ethylene glycol) diacrylate (PEGDA)-based precursors that incorporate peptides in the polymer chain. Specifically, we have synthesized hydrogel microparticles that degrade in response to matrix metalloproteinases that are overexpressed in pulmonary diseases. Small hydrogel microparticles with sizes suitable for lung delivery by inhalation were obtained from solid precursors when PEGDA was dissolved in water at a high concentration. The average diameter of the particles was between 2.8 and 4 µm, depending on the molecular weight of the precursor polymer used and its concentration in water. The relation between the physical properties of the particles and their enzymatic degradation is also reported, where an increased mesh size corresponds to increased degradation.

Janus-type bi-phasic functional nanofibers.

Multiferroic materials hold enormous potential for a variety of applications, including tunable microelectronics and multiphase memories. This paper describes a new type of multiferroic materials with a Janus-type architecture prepared by co-electrospinning sol-gel precursors of barium titanate and cobalt ferrite.

Suitability of porous silicon microparticles for the long-term delivery of redox-active therapeutics.

Thermal oxidation of porous Si microparticles provides an inert carrier for the long-term release of the anthracycline drug daunorubicin. Without prior oxidation, porous Si undergoes an undesirable side reaction with this redox active drug.

Real-time monitoring of sustained drug release using the optical properties of porous silicon photonic crystal particles.

A controlled and observable drug delivery system that enables long-term local drug administration is reported. Biodegradable and biocompatible drug-loaded porous Si microparticles were prepared from silicon wafers, resulting in a porous 1-dimensional photonic crystal (rugate filter) approx. 12 µm thick and 35 µm across. An organic linker, 1-undecylenic acid, was attached to the Si-H terminated inner surface of the particles by hydrosilylation and the anthracycline drug daunorubicin was bound to the carboxy terminus of the linker. Degradation of the porous Si matrix in vitro was found to release the drug in a linear and sustained fashion for 30 d. The bioactivity of the released daunorubicin was verified on retinal pigment epithelial (RPE) cells. The degradation/drug delivery process was monitored in situ by digital imaging or spectroscopic measurement of the photonic resonance reflected from the nanostructured particles, and a simple linear correlation between observed wavelength and drug release was observed. Changes in the optical reflectance spectrum were sufficiently large to be visible as a distinctive red to green color change.

Sustained Release of a Monoclonal Antibody from Electrochemically Prepared Mesoporous Silicon Oxide.

Nanostructured mesoporous silica (SiO(2)) films are used to load and release the monoclonal antibody bevacizumab (Avastin) in vitro. A biocompatible and biodegradable form of mesoporous SiO(2) is prepared by electrochemical etching of single crystalline Si, followed by thermal oxidation in air at 800 °C. Porous SiO(2) exhibits a negative surface charge at physiological pH (7.4), allowing it to spontaneously adsorb the positively charged antibody from an aqueous phosphate buffered saline solution. This electrostatic adsorption allows bevacizumab to be concentrated by >100× (300 mg bevacziumab per gram of porous SiO(2) when loaded from a 1 mg mL(-1) solution of bevacziumab). Drug loading is monitored by optical interferometric measurements of the thin porous film. A two-component Bruggeman effective medium model is employed to calculate percent porosity and film thickness, and is further used to determine the extent of drug loading into the porous SiO(2) film. In vitro drug release profiles are characterized by an enzyme-linked immunosorbent assay (ELISA), which confirms that the antibody is released in its active, VEGF-binding form. The nanostructured delivery system described here provides a sustained release of the monoclonal antibody where approximately 98% of drug is released over a period of one month.