Temperature-Adaptative Self-Oscillating Gels: Toward Autonomous Biomimetic Soft Actuators with Broad Operating Temperature Region.

Self-oscillating gel systems exhibiting an expanded operating temperature and accompanying functional adaptability are showcased. The developed system contains nonthermoresponsive main-monomers, such as N,N-dimethylacrylamide (DMAAm) or 2-acrylamido-2-methylpropane sulfonic acid (AMPS) or acrylamide (AAm) or 3-(methacryloylamino)propyl trimethylammonium chloride (MAPTAC). The gels volumetrically self-oscillate within the range of the conventional (20.0 °C) and extended (27.0 and 36.5 °C) temperatures. Moreover, the gels successfully adapt to the environmental changes; they beat faster and smaller as the temperature increases. The period and amplitude are also controlled by tuning the amount of main-monomers and N-(3-aminopropyl) acrylamide. Furthermore, the record amplitude in the bulk gel system consisting of polymer strand and cross-linker at 36.5 °C is achieved (≈10.8%). The study shows new self-oscillation systems composed of unprecedented combinations of materials, giving the community a robust material-based insight for developing more life-like autonomous biomimetic soft robots with various operating temperatures and beyond.

SMiPoly: Generation of a Synthesizable Polymer Virtual Library Using Rule-Based Polymerization Reactions.

Recent advances in machine learning have led to the rapid adoption of various computational methods for de novo molecular design in polymer research, including high-throughput virtual screening and inverse molecular design. In such workflows, molecular generators play an essential role in creation or sequential modification of candidate polymer structures. Machine learning-assisted molecular design has made great technical progress over the past few years. However, the difficulty of identifying synthetic routes to such designed polymers remains unresolved. To address this technical limitation, we present Small Molecules into Polymers (SMiPoly), a Python library for virtual polymer generation that implements 22 chemical rules for commonly applied polymerization reactions. For given small organic molecules to form a candidate monomer set, the SMiPoly generator conducts possible polymerization reactions to generate an exhaustive list of potentially synthesizable polymers. In this study, using 1083 readily available monomers, we generated 169,347 unique polymers forming seven different molecular types: polyolefin, polyester, polyether, polyamide, polyimide, polyurethane, and polyoxazolidone. By comparing the distribution of the virtually created polymers with approximately 16,000 real polymers synthesized so far, it was found that the coverage and novelty of the SMiPoly-generated polymers can reach 48 and 53%, respectively. Incorporating the SMiPoly library into a molecular design workflow will accelerate the process of de novo polymer synthesis by shortening the step to select synthesizable candidate polymers.

Functional Output Regression for Machine Learning in Materials Science.

In recent years, there has been a rapid growth in the use of machine learning in material science. Conventionally, a trained predictive model describes a scalar output variable, such as thermodynamic, electronic, or mechanical properties, as a function of input descriptors that vectorize the compositional or structural features of any given material, such as molecules, chemical compositions, or crystalline systems. In machine learning of material data, on the other hand, the output variable is often given as a function. For example, when predicting the optical absorption spectrum of a molecule, the output variable is a spectral function defined in the wavelength domain. Alternatively, in predicting the microstructure of a polymer nanocomposite, the output variable is given as an image from an electron microscope, which can be represented as a two- or three-dimensional function in the image coordinate system. In this study, we consider two unified frameworks to handle such multidimensional or functional output regressions, which are applicable to a wide range of predictive analyses in material science. The first approach employs generative adversarial networks, which are known to exhibit outstanding performance in various computer vision tasks such as image generation, style transfer, and video generation. We also present another type of statistical modeling inspired by a statistical methodology referred to as functional data analysis. This is an extension of kernel regression to deal with functional outputs, and its simple mathematical structure makes it effective in modeling even with small amounts of data. We demonstrate the proposed methods through several case studies in materials science.

Macroscopic Adhesion of Thermoreversible ABC Triblock Copolymer-Based Hydrogels Via Boronic Acid-Sugar Complexation.

Two complementary thermoreversible ABC triblock copolymers containing either phenylboronic acids with low pKa values or galactosyl groups in the hydrophilic B blocks are synthesized by sequential reversible addition-fragmentation chain transfer polymerization and subsequent modification of the functional groups. Both ABC triblock copolymers undergo reversible sol-to-gel transitions upon temperature change and form physically cross-linked hydrogels under physiological conditions. Furthermore, the spontaneous adhesion of these thermoreversible hydrogels via the formation of boronic esters between the phenylboronic acid and galactosyl groups under physiological conditions is realized for the first time.

Mesenchylmal Stem Cell Culture on Poly(N-isopropylacrylamide) Hydrogel with Repeated Thermo-Stimulation.

We prepared thermoresponsive hydrogels by mixing poly(N-isopropylacrylamide) (PNIPAAm) derivatives as the main chain components, octa-arm polyethylene glycol (PEG) as a crosslinker, and the Arg-Gly-Asp-Ser (RGDS) peptides as cell adhesion units. Human bone marrow-derived mesenchymal stem cells (hbmMSCs) were cultured on the hydrogels. The PNIPAAm gel prepared by the post-crosslinking gelation method was revealed to be cytocompatible and showed temperature-dependent changes in mechanical properties. Repeated changes in the swelling ratio of the PNIPAAm gel affected the shape of the hbmMSCs. With respect to both cytocompatibility and reversibility of changes in mechanical properties, the PNIPAAm gel system could be potentially useful for the analysis of cell mechanobiology.

Self-Assembly of Thermoreversible Hydrogels via Molecular Recognition toward a Spatially Organized Coculture System.

In this study, we present the spontaneous adhesion of two thermoreversible physically cross-linked hydrogels via molecular recognition under a physiological condition. We successfully prepared two types of hydrogels generated using two kinds of well-defined ABA type triblock copolymers: CAT-ABA and PBA-ABA, which contain catechol and phenylboronic acid groups as functional side chains, respectively. Both types of ABA triblock copolymers were able to undergo sol-to-gel transition with the increase in temperature resulting from the formation of physical cross-links at a physiological temperature, which enables easy cell encapsulation in the hydrogel. It was determined that the cell encapsulating hydrogels exhibited spontaneous macroscopic adhesion through the formation of boronic esters between phenylboronic acid and catechol at the hydrogel interface. This novel system likely represents a promising method to construct a precisely organized, three-dimensional coculture system to enable the reconstruction of complicated tissues such as the liver in vitro.

Design of Polymer Networks Involving a Photoinduced Electronic Transmission Circuit toward Artificial Photosynthesis.

Many strategies have been explored to achieve artificial photosynthesis utilizing mediums such as liposomes and supramolecules. Because the photochemical reaction is composed of multiple functional molecules, the surrounding microenvironment is expected to be rationally integrated as observed during photosynthesis in chloroplasts. In this study, photoinduced electronic transmission surrounding the microenvironment of Ru(bpy)3(2+) in a polymer network was investigated using poly(N-isopropylacrylamide-co-Ru(bpy)3), poly(acrylamide-co-Ru(bpy)3), and Ru(bpy)3-conjugated microtubules. Photoinduced energy conversion was evaluated by investigating the effects of (i) Ru(bpy)3(2+) immobilization, (ii) polymer type, (iii) thermal energy, and (iv) cross-linking. The microenvironment surrounding copolymerized Ru(bpy)3(2+) in poly(N-isopropylacrylamide) suppressed quenching and had a higher radiative process energy than others. This finding is related to the nonradiative process, i.e., photoinduced H2 generation with significantly higher overall quantum efficiency (13%) than for the bulk solution. We envision that useful molecules will be generated by photoinduced electronic transmission in polymer networks, resulting in the development of a wide range of biomimetic functions with applications for a sustainable society.

Evolved Colloidosomes Undergoing Cell-like Autonomous Shape Oscillations with Buckling.

In living systems, there are many autonomous and oscillatory phenomena to sustain life, such as heart contractions and breathing. At the microscopic level, oscillatory shape deformations of cells are often observed in dynamic behaviors during cell migration and morphogenesis. In many cases, oscillatory behaviors of cells are not simplistic but complex with diverse deformations. So far, we have succeeded in developing self-oscillating polymers and gels, but complex oscillatory behaviors mimicking those of living cells have yet to be reproduced. Herein, we report a cell-like hollow sphere composed of self-oscillating microgels, that is, a colloidosome, that exhibits drastic shape oscillation in addition to swelling/deswelling oscillations driven by an oscillatory reaction. The resulting oscillatory profile waveform becomes markedly more complex than a conventional one. Especially for larger colloidosomes, multiple buckling and moving buckling points are observed to be analogous to cells.

Preparation of molecule-responsive microsized hydrogels via photopolymerization for smart microchannel microvalves.

Microdevices designed for practical environmental pollution monitoring need to detect specific pollutants such as dioxins. Bisphenol A (BPA) has been widely used as a monomer for the synthesis of polycarbonate and epoxy resins. However, the recent discovery of its high potential ability to disrupt human endocrine systems has made the development of smart systems and microdevices for its detection and removal necessary. Molecule-responsive microsized hydrogels with ß-cycrodextrin (ß-CD) as ligands are prepared by photopolymerization using a fluorescence microscope. The molecule-responsive micro-hydrogels show ultra-quick shrinkage in response to target BPA. Furthermore, the flow rate of a microchannel is autonomously regulated by the molecule-responsive shrinking of their hydrogels as smart microvalves.

Periodic reciprocating motion of a polymer gel on an aqueous phase synchronized with the Belousov-Zhabotinsky reaction.

A self-oscillating gel induced by the Belousov-Zhabotinsky (BZ) reaction was investigated on an aqueous phase. When the Ru-catalyst in the gel was rapidly oxidized, the gel was accelerated in a direction opposite to the side of oxidation. The gel then returned to its original position while the Ru-catalyst in the gel was slowly reduced. To clarify the mechanism of this periodic reciprocation of the gel, the contact angle between a sessile bubble and the gel and the time-variation of the adhesive force of the gel on the aqueous phase were measured. The experimental results suggest that the periodic reciprocation of the gel is driven by the periodic change in the contact angle of the gel induced by the BZ reaction.

Self-oscillating vesicles: spontaneous cyclic structural changes of synthetic diblock copolymers.

A large variety of synthetic vesicles has been created for potential engineering applications and as model systems which mimic living organisms. In most cases, the structure is designed to be thermodynamically stable. However, mimicking dynamic behaviors of living vesicles still remains undeveloped. Herein, we present a synthetic vesicle which shows autonomous disintegration-reconstruction cycles without any external stimuli and which is similar to those in living organisms, such as in the nuclear envelope and synaptic vesicles. The vesicle is composed of a diblock copolymer which has a hydrophilic and a thermosensitive segment. The thermosensitive segment includes a redox moiety that acts as a catalyst for an oscillatory chemical reaction and also controls the aggregation temperature of vesicles. Furthermore, autonomous fusion of vesicles is also observed during the cycles.

Self-oscillating polymer brushes.

An autonomous functional surface has been designed by using self-oscillating polymers that convert the chemical energy of the Belousov-Zhabotinsky reaction into conformational changes of the polymer chains (see picture: red: hydrophobic/collapsed, green: hydrophilic/extended). Self-oscillating polymer brushes were grafted onto the inner surface of a glass capillary, and autonomous propagation of a chemical wave was observed.

Design of self-oscillating gels and application to biomimetic actuators.

As a novel biomimetic polymer, we have developed polymer gels with an autonomous self-oscillating function. This was achieved by utilizing oscillating chemical reactions, called the Belousov-Zhabotinsky (BZ) reaction, which is recognized as a chemical model for understanding several autonomous phenomena in biological systems. Under the coexistence of the reactants, the polymer gel undergoes spontaneous swelling-deswelling changes without any on-off switching by external stimuli. In this review, our recent studies on the self-oscillating polymer gels and application to biomimetic actuators are summarized.

Molecular design and functional control of novel self-oscillating polymers.

If we could realize an autonomous polymer system driven under biological conditions by a tailor-made molecular design, human beings could create unprecedented biomimetic functions and materials such as heartbeats, autonomous peristaltic pumps, etc. In order to achieve this objective, we have investigated the molecular design of such a polymer system. As a result, we were the first to demonstrate a self-oscillating polymer system driven in a solution where only malonic acid existed, which could convert the chemical energy of the Belousov-Zhabotinsky (BZ) reaction into a change in the conformation of the polymer chain. To cause the self-oscillation in solution, we have attempted to construct a built-in system where the required BZ system substrates other than the organic acid are incorporated into the polymer itself. That is, the novel polymer chain incorporated the metal catalyst of the BZ reaction, a pH-control site and an oxidant supply site at the same time. As a result of introducing the pH control and oxidant supply sites into the conventional-type self-oscillating polymer chain, the novel polymer chain caused aggregation-disaggregation self-oscillations in the solution. We clarified that the period of the self-oscillation of the novel self-oscillating polymer chain was proportional to the concentration of the malonic acid. Therefore, the concentration of the malonic acid can be determined by measuring the period of the novel self-oscillating polymer solution. In this review, we introduce the detailed molecular design of the novel self-oscillating polymer chain and its self-oscillating behavior. Moreover, we report an autonomous self-oscillating polymer gel actuator that causes a bending-stretching motion under the constant conditions.

Active polymer gel actuators.

Many kinds of stimuli-responsive polymer and gels have been developed and applied to biomimetic actuators or artificial muscles. Electroactive polymers that change shape when stimulated electrically seem to be particularly promising. In all cases, however, the mechanical motion is driven by external stimuli, for example, reversing the direction of electric field. On the other hand, many living organisms can generate an autonomous motion without external driving stimuli like self-beating of heart muscles. Here we show a novel biomimetic gel actuator that can walk spontaneously with a worm-like motion without switching of external stimuli. The self-oscillating motion is produced by dissipating chemical energy of oscillating reaction. Although the gel is completely composed of synthetic polymer, it shows autonomous motion as if it were alive.

iQSPR in XenonPy: A Bayesian Molecular Design Algorithm.

iQSPR is an inverse molecular design algorithm based on Bayesian inference that was developed in our previous study. Here, the algorithm is integrated in Python as a new module called iQSPR-X in the all-in-one materials informatics platform XenonPy. Our new software provides a flexible, easy-to-use, and extensible platform for users to build customized molecular design algorithms using pre-set modules and a pre-trained model library in XenonPy. In this paper, we describe key features of iQSPR-X and provide guidance on its use, illustrated by an application to a polymer design that targets a specific range of bandgap and dielectric constant.

Autonomously oscillating viscosity in microgel dispersions.

We present autonomously oscillating viscosity in microgel dispersions. The microgels were obtained by introducing the Ru catalyst for the Belousov-Zhabotinsky (BZ) reaction into a cross-linked copolymer. In this microgel system, the chemical energy of the BZ reaction is converted to rhythmic swelling/deswelling oscillation of the microgels. Moreover, self-flocculating/self-dispersing oscillation of the microgels occurs near its phase transition temperature. Through the use of these two oscillations of the microgels, a new function of colloidal dispersions has been discovered, namely, autonomously oscillating viscosity in a microgel dispersion. The viscosity in the dispersion oscillated autonomously, following the swelling/deswelling and self-flocculation/self-dispersion oscillations of the microgels. As a result, we can control the rhythm and amplitude of the oscillation using these two phenomena of the microgels.

Fabrication of micropatterned thermosensitive gel with highly-ordered honeycomb surface and inverse opal structure.

Thermosensitive poly(N-isopropylacrylamide) gels with highly-ordered honeycomb surface and inverse opal structure were successfully fabricated by several microfabrication methods using closely packed silica beads as a template. The gels are able to reversibly change the shapes and sizes of the pores with swelling-deswelling by temperature changes. In particular, regular buckling was induced due to compression with swelling. Such a thermoregulation of surface topography might be useful for design of functional surfaces with tunable physical properties.

Self-oscillating polymer fueled by organic acid.

Here we report the biomimetic polymer that causes self-oscillation driven by the addition of biorelated organic acid. We constructed the built-in system where all of the substrates of the BZ reaction other than biorelated organic substrates were incorporated into the polymer chain. The quarternary copolymer, which includes both of the pH-control and oxidant-supplying sites in the poly(N-isopropylacrylamide-co-Ru(bpy)3) chain was synthesized. By using the polymer, we first succeeded in causing the self-oscillation of the polymer only in the coexistence of organic acid.

Chemical and optical control of peristaltic actuator based on self-oscillating porous gel.

We demonstrate the chemical and optical control of the self-sustaining peristaltic motion of a structural colored porous hydrogel.