Design of two complementary copolymers that work as a glue for cell-laden collagen gels.

We designed two types of copolymers that play a role of "polymeric glue". They introduced surface adhesive functions to cell-laden collagen gels. The present study realised surface functionalisation of naturally derived hydrogels and suggested a novel method for manipulating living cells. This method is potentially useful for in vitro reconstruction of 3D living tissue since it enabled versatile and cytocompatible hydrogel surface modification by a simple procedure without any special equipment.

Crosslinked Poly(N-Isopropylacrylamide)-Based Microfibers as Cell Manipulation Materials with Prompt Cell Detachment.

Stimuli-responsive smart materials are a key to the realization of next-generation medical technologies. Among them, the temperature-responsive polymer poly(N-isopropylacrylamide) (PNIPAAm) is attracting particular attention because it is easy to use in physiological conditions. PNIPAAm-grafted surfaces can undergo temperature-modulated cell adhesion and detachment without proteolytic enzymes, and can be used as cell-separating materials through selective cell adhesion/detachment. However, cell detachment at reduced temperatures is problematic because it takes several hours. A novel thermoresponsive crosslinked microfiber system that can greatly reduce the cell detachment time is introduced in this study. The crosslinked fibers provide temperature-dependent volume change, and enable cell detachment within 10 min of reducing the temperature, which is one-sixth of the time required in previous studies. The prompt cell detachment is thought to arise from a completely new mechanism derived from fiber swelling. This system will make a significant contribution as a novel cell manipulating system for next-generation medical technology.

Adsorption-Desorption Control of Fibronectin in Real Time at the Liquid/Polymer Interface on a Quartz Crystal Microbalance by Thermoresponsivity.

The cell manipulation technique using thermoresponsive polymers is currently attracting much attention for applications in the medical field. To achieve arbitrary and accurate cell control, it is necessary to intensely research fibronectin behavior. A smart surface, which has thermoresponsive wettability and which can adsorb or desorb fibronectin repeatedly without the presence of cells, was fabricated by an electrospinning method. The fabricated coating changed its structure as the temperature was changed, and this transformation could substitute for the pulling force generated by the cytoskeletal contraction of cells. Moreover, a coated quartz crystal microbalance was able to detect the fibronectin behavior as frequency shifts, which could be used in the estimation of the mass shift with the aid of suitable equations. This coating and measurement system can contribute greatly not only to the development in the medical field centered on biomaterial manipulation technologies, but also to the improvement of medical instruments.

Chemomechanical Motion of a Self-Oscillating Gel in a Protic Ionic Liquid.

An autonomous swelling-deswelling oscillation of polymer gels in a hydrated protic ionic liquid (PIL) as a proton source for the Belousov-Zhabotinsky (BZ) reaction is presented. Methylammonium hydrogen sulfate ([maH+ ][HSO4 - ]) was employed as the PIL because it provides stable redox oscillation in the BZ reaction. Due to the significantly higher pKa for [maH+ ][HSO4 - ] than those for conventional proton sources for the BZ reaction, chemomechanical oscillation can be expected under weaker acidic conditions. The self-oscillating polymer was designed as a ternary random copolymer of N-isopropylacrylamide, N-(3-aminopropyl)methacrylamide, and the Ru(bpy)3 moiety as a catalyst for the BZ reaction. The copolymer exhibited spontaneous soluble-insoluble oscillation in hydrated [maH+ ][HSO4 - ] containing NaBrO3 and malonic acid. Macroscopic swelling-deswelling oscillation of the porous bulk gel prepared by covalently connecting microgel particles was also observed.

Thermoresponsive Surface-Grafted Gels: Controlling the Bulk Volume Change Properties by Surface-Localized Polymer Grafting with Various Densities.

We prepared poly(N-isopropylacrylamide-r-N-3-(aminopropyl)methacrylamide) (poly(NIPAAm-r-NAPMAm)) gels with poly NIPAAm (PNIPAAm) grafted only in the surface region (so-called thermoresponsive surface-grafted gels) with various graft densities and investigated the effect of the graft density on the bulk volume change properties, shrinking and swelling, in response to temperature changes. Initiators for atom-transfer radical polymerization (ATRP) and structurally analogous compounds were introduced at certain ratios onto the surface regions of the gels, and a subsequent activator regeneration by electron transfer ATRP of NIPAAm was conducted in aqueous media. The graft densities and molecular weights of the grafted polymers were evaluated from the increment in the dry mass of the gels and the amount of introduced ATRP initiators, which was measured by elemental analyses. Three-dimensional measuring laser microscopy revealed that the prepared gels had graft-density-dependent fine wrinkle structures on their surfaces. The surface-grafted gels induced the formation of skin layers during the shrinking process in response to a temperature increase, and their permeability strongly depended on the graft density. The graft density also controlled the kinetics of the swelling behavior in response to a temperature decrease. These physical properties were discussed on the basis of Young's modulus of the surface determined by an atomic force microscopy force curve measurement and the homogeneity of the surface polymer network observed by cryo-scanning electron microscopy. This makes it possible to arbitrarily control the characteristics of gels as open or semiclosed systems, which was uniquely determined by the designs of the surface gel networks.

Protic Ionic Liquids for the Belousov-Zhabotinsky Reaction: Aspects of the BZ Reaction in Protic Ionic Liquids and Its Use for the Autonomous Coil-Globule Oscillation of a Linear Polymer.

Herein, we describe the physicochemical aspects of the Belousov-Zhabotinsky (BZ) reaction in hydrated protic ionic liquids (PILs) combined with different cations with a hydrogen sulfate ([HSO4-]) anion. PILs were prepared from the neutralization reactions of sulfuric acid with 13 different aliphatic amines. The amine structure was selected to investigate the effect of the number of active protons, alkyl chain length (hydrophilicity), and cationic linearity on the mechanism of the BZ reaction. The pKa values of PILs were significantly higher (pKa = 1.0-2.5) than those of inorganic acids (H2SO4 = -3.0; HNO3 = -1.4), the conventional proton source in a BZ reaction. A periodic redox oscillation was observed in Ru(bpy)3 when appropriate amounts of BZ reaction substrates (NaBrO3 oxidant; malonic acid reductant) were added to the hydrated PILs. A long-lasting BZ oscillation was realized when hydrophilic cations (ammonium, ethylammonium, and dimethylethylammonium) were employed. Interestingly, a large ΔA5000 (oscillation amplitude of absorbance for the scale of the oscillation stability observed after 5000 s from the initiation of the BZ reaction) was achieved for PILs possessing less than four carbon atoms in their cationic structure. The apparent BZ oscillation activation energy (Ea) in the hydrated PILs was estimated to be ∼40 kJ mol-1, which is 30 kJ mol-1 less than that observed in a conventional system. The catalytic reaction in the BZ reaction subprocess suppresses the total activation energy of the reaction. To realize long-lasting self-oscillating polymeric materials acting under milder condition, we demonstrated an autonomous coil-globule polymer chain transition (BZ-driven) that directly converts chemical energy to mechanical motion in hydrated PILs without freely diffusing Ru(bpy)3 metal catalyst. Ethylammonium hydrogen sulfate ([ea-H+][HSO4-]) is selected as the suitable proton source for the BZ reaction. A well-defined self-oscillating polymer that incorporated Ru(bpy)3 metal catalyst into the polymer backbone accompanied by good compatibility in hydrated [ea-H+][HSO4-] is successfully prepared by ATRP, followed by postmodification of the metal catalyst. The rhythmic solubility changes of the polymer under milder conditions, realized by combination with PILs, will expand the potential applications of PILs to novel functional materials.

Reversible conformational changes in the parallel type G-quadruplex structure inside a thermoresponsive hydrogel.

The novel property of reversible regulation of parallel type G-quadruplexes with moderate temperature changes was discovered in thermoresponsive hydrogels using a universal chiroptical spectrophotometer 1 (UCS-1). This study is the first to report the regulation of the ssDNA steric structure by using a poly(N-isopropylacrylamide) (PNIPAAm) gel.

A surface-grafted thermoresponsive hydrogel in which the surface structure dominates the bulk properties.

A surface-grafted hydrogel was successfully synthesized by immobilization of the ATRP initiator at the surface region of the gel and the subsequent ARGET ATRP step. This is the first example of a bulk hydrogel with a dense surface-localized layer of a grafted polymer and "active" permeation control of the gel.