Meiyu Gai

Guidable Thermophoretic Janus Micromotors Containing Gold Nanocolorifiers for Infrared Laser Assisted Tissue Welding

Current wound sealing systems such as nanoparticle‐based gluing of tissues allow almost immediate wound sealing. The assistance of a laser beam allows the wound sealing with higher controllability due to the collagen fiber melting which is defined by loss of tertiary protein structure and restoration upon cooling. Usually one employs dyes to paint onto the wound, if water absorption bands are absent. In case of strong bleeding or internal wounds such applications are not feasible due to low welding depth in case of water absorption bands, dyes washing off, or the dyes becoming diluted within the wound. One possible solution of these drawbacks is to use autonomously movable particles composing of biocompatible gold and magnetite nanoparticles and biocompatible polyelectrolyte complexes. In this paper a proof of principle study is presented on the utilization of thermophoretic Janus particles and capsules employed as dyes for infrared laser‐assisted tissue welding. This approach proves to be efficient in sealing the wound on the mouse in vivo. The temperature measurement of single particle level proves successful photothermal heating, while the mechanical characterizations of welded liver, skin, and meat confirm mechanical restoration of the welded biological samples.

Micro-contact printing of PEM thin films: effect of line tension and surface energies

Polyelectrolyte multilayer (PEM) thin films are popular candidates for surface coating due to their versatility, tunability and simple production method. Often these films are used in a 2D structured manner for creating defined cell scaffolds or electronic applications. Although these films were successfully printed in the past, the conditions and energies necessary for a successful printing were only investigated as isolated parameters or as a function of the substrate but not the PEM surface energy and therefore the dominating forces remained controversial. We hereby present a theory and method for microcontact printing of condensed polyelectrolyte multilayer thin films, based on surface energies and the line tension. The theory relies on the surface energy of the substrate, stamp and PEM as well as the PEM line tension ratios to create the desired pattern. The presented theory is able to predict the printability, quality and resolution limit of a chosen system and was evaluated with experiments. A reduction of the production time from the beginning of PEM assembly to the final pattern from several hours down to 30 minutes was achieved while increasing reproducibility and resolution of the printed patterns at the same time. We would like to point out that this approach can generally be used for any kind of adsorbed thin film on substrates.

Patterned Microstructure Fabrication: Polyelectrolyte Complexes vs Polyelectrolyte Multilayers

Polyelectrolyte complexes (PEC) are formed by mixing the solutions of oppositely charged polyelectrolytes, which were hitherto deemed “impossible” to process, since they are infusible and brittle when dry. Here, we describe the process of fabricating free-standing micro-patterned PEC films containing array of hollow or filled microchambers by one-step casting with small applied pressure and a PDMS mould. These structures are compared with polyelectrolyte multilayers (PEM) thin films having array of hollow microchambers produced from a layer-by-layer self-assembly of the same polyelectrolytes on the same PDMS moulds. PEM microchambers “cap” and “wall” thickness depend on the number of PEM bilayers, while the “cap” and “wall” of the PEC microchambers can be tuned by varying the applied pressure and the type of patterned mould. The proposed PEC production process omits layering approaches currently employed for PEMs, reducing the production time from ~2 days down to 2 hours. The error-free structured PEC area was found to be significantly larger compared to the currently-employed microcontact printing for PEMs. The sensitivity of PEC chambers towards aqueous environments was found to be higher compared to those composed of PEM.

Polylactic Acid Sealed Polyelectrolyte Multilayer Microchambers for Entrapment of Salts and Small Hydrophilic Molecules Precipitates.

Efficient depot systems for entrapment and storage of small water-soluble molecules are of high demand for wide variety of applications ranging from implant based drug delivery in medicine and catalysis in chemical processes to anticorrosive systems in industry where surface-mediated active component delivery is required on a time and site specific manner. This work reports the fabrication of individually sealed hollow-structured polyelectrolyte multilayer (PEM) microchamber arrays based on layer-by-layer self-assembly as scaffolds and microcontact printing. These PEM chambers are composed out of biocompatible polyelectrolytes and sealed by a monolayer of hydrophobic biocompatible and biodegradable polylactic acid (PLA). Coating the chambers with hydrophobic PLA allows for entrapment of a microair-bubble in each chamber that seals and hence drastically reduces the PEM permeability. PLA@PEM microchambers are proven to enable prolonged subaqueous storage of small hydrophilic salts and molecules such as crystalline NaCl, doxicycline, and fluorescent dye rhodamine B. The presented microchambers are able to entrap air bubbles and demonstrate a novel strategy for entrapment, storage, and protection of micropackaged water-soluble substances in precipitated form. These chambers allow triggered release as demonstrated by ultrasound responsiveness of the chambers. Low-frequency ultrasound exposure is utilized for microchamber opening and payload release.

Forecastable and Guidable Bubble-Propelled Microplate Motors for Cell Transport

Cell transport is important to renew body functions and organs with stem cells, or to attack cancer cells with immune cells. The main hindrances of this method are the lack of understanding of cell motion as well as proper transport systems. In this publication, bubble-propelled polyelectrolyte microplates are used for controlled transport and guidance of HeLa cells. Cells survive attachment on the microplates and up to 22 min in 5% hydrogen peroxide solution. They can be guided by a magnetic field whereby increased friction of cells attached to microplates decreases the speed by 90% compared to pristine microplates. The motion direction of the cell-motor system is easier to predict due to the cell being opposite to the bubbles.

In-situ NIR-laser mediated bioactive substance delivery to single cell for EGFP expression based on biocompatible microchamber-arrays

&NA; Controlled drug delivery and gene expression is required for a large variety of applications including cancer therapy, wound healing, cell migration, cell modification, cell‐analysis, reproductive and regenerative medicine. Controlled delivery of precise amounts of drugs to a single cell is especially interesting for cell and tissue engineering as well as therapeutics and has until now required the application of micro‐pipettes, precisely placed dispersed drug delivery vehicles, or injections close to or into the cell. Here we present surface bound micro‐chamber arrays able to store small hydrophilic molecules for prolonged times in subaqueous conditions supporting spatiotemporal near infrared laser mediated release. The micro‐chambers (MCs) are composed of biocompatible and biodegradable polylactic acid (PLA). Biocompatible gold nanoparticles are employed as light harvesting agents to facilitate photothermal MC opening. The degree of photothermal heating is determined by numerical simulations utilizing optical properties of the MC, and confirmed by Brownian motion measurements of laser‐irradiated micro‐particles exhibiting similar optical properties like the MCs. The amount of bioactive small molecular cargo (doxycycline) from local release is determined by fluorescence spectroscopy and gene expression in isolated C2C12 cells via enhanced green fluorescent protein (EGFP) biosynthesis. Graphical abstract Laser mediated release of small hydrophilic molecule doxycycline from biodegradable and biocompatible surface bound microchambers arrays is demonstrated by controlled EGFP expression of a targeted cell in a cell colony. Figure. No caption available.

Polylactic acid sealed polyelectrolyte complex microcontainers for controlled encapsulation and NIR-Laser based release of cargo

Surface mediated drug delivery is important for a large variety of applications, especially in medicine to control cell growth, prevent blood platelet activation on implants or for self-disinfecting devices (e.g. catheters). In industrial applications, controlled release of substances from surfaces is needed in a broad range of applications from anti-corrosion systems to anti-biofouling. Polyelectrolyte multilayers (PEM) based microcontainers (MCs) require several days production time, while MCs composed out of polylactic acid (PLA) are entirely hydrophobic, offering no functionality. We hereby present an approach to fabricate PLA coated synthetic as well as biopolymer based biodegradable polyelectrolyte complex MCs able to encapsulate small hydrophilic cargo within less than one hour. The chambers facilitate laser controlled release of cargo within submerged conditions.

Hydrodynamic electrospray ionization jetting of calcium alginate particles: effect of spray-mode, spraying distance and concentration

Hydrodynamic electrospray ionization jetting was applied for generating and characterizing calcium cross-linked alginate microparticles. These microparticles show different diameters and aspect ratios for three electrospray modes (dripping, conejet and multijet modes), four spraying distances (5, 10, 15 and 20 cm), and six spraying concentrations. Comparing the three different electrospray modes, we found that the conejet mode results in the smallest particle diameters, lowest aspect ratio and smallest variations over the parameter space mentioned above. For all spraying modes, the resultant particle diameters become independent of the spraying distance at a sprayed solute concentration ≥ 2.5%. The aspect ratio of microparticles varies significantly for different spraying modes and distances. An increasing aspect ratio of all spray modes was determined for sodium alginate spraying concentrations ≤ 1.5% and spraying distances of 20 cm; this phenomenon can be explained with the chain ejection effect. This systematic investigation offers a basic database for industrial applications of hydrodynamic electrospray ionization.

Effect of a Controlled Release of Epinephrine Hydrochloride from PLGA Microchamber Array: In Vivo Studies

This paper presents the synthesis of highly biocompatible and biodegradable poly(lactide- co-glycolide) (PLGA) microchamber arrays sensitive to low-intensity therapeutic ultrasound (1 MHz, 1-2 W, 1 min). A reliable method was elaborated that allowed the microchambers to be uniformly filled with epinephrine hydrochloride (EH), with the possibility of varying the cargo amount. The maximum load of EH was 4.5 μg per array of 5 mm × 5 mm (about 24 pg of EH per single microchamber). A gradual, spontaneous drug release was observed to start on the first day, which is especially important in the treatment of acute patients. Ultrasound triggered a sudden substantial release of EH from the films. In vivo real-time studies using a laser speckle contrast imaging system demonstrated changes in the hemodynamic parameters as a consequence of EH release under ultrasound exposure. We recorded a decrease in blood flow as a vascular response to EH release from a PLGA microchamber array implanted subcutaneously in a mouse. This response was immediate and delayed (1 and 2 days after the implantation of the array). The PLGA microchamber array is a new, promising drug depot implantable system that is sensitive to external stimuli.