Stimuli‐Sensitive Polymers

Abstract

Stimuli-sensitive polymers can respond to certain external environmental changes (“Stimulus”) by altering properties such as shape, permeability, or color. The ability of a material to recognize a stimulus and respond to it is derived from stimuli- sensitive processes on the molecular and/or supramolecular level, as well as on the level of phase morphology, which are translated and amplified to the macroscopic level. The response to a stimulus often involves several processes, which take place at different hierarchical levels (e.g. photoisomerization reaction on the molecular level and phase transition on the morphology level in liquid crystalline elastomers). They can also occur on different time scales. In pH-responsive hydrogels the protonation/deprotonation of functional groups of the polymer network chains is a fast process compared to the diffusion of water molecules in the polymer network structure or the phase separation leading to the shrinkage of the gel. In some cases the material needs to be taught by physical processes to gain stimuli-responsiveness (e.g. shape-memory effect, (SME)). The field of stimuli-sensitive polymers is presently progressing rapidly. Current research topics involve extending the repertoire of suitable stimuli, realization of multifunctionality in one material, exploring concepts for materials, which can continuously adapt their (structural) properties to the requirements of their environment by implementing self- regulating processes, and investigating the influence of specimen dimensions on the shape changing behavior, e.g. on nano- and microparticles. On the other hand applications are being realized based on stimuli-sensitive polymers for various areas including aerospace, packaging, textiles, microfluidics, sensors and actuators as well as bioengineering. In this special issue three important classes of stimuli-sensitive polymers are comprehensively described in reviews and progress reports: shape-memory polymers (SMPs), stimuli-responsive gels, and liquid crystalline elastomers (LCE). In addition, advances in oscillating gels, and molecular modeling approaches as predictive tools for stimuli-responsive polymers are covered. Finally, exciting recent results in the field of stimuli- sensitive polymers are presented in selected communication articles such as multiphase polymer networks capable of a reversible triple shape effect (Zotzmann et al., DOI: 10.1002/adma.200904202) as well as LCE-based nanocomposites with partially aligned carbon nanotubes (CNT) having anisotropic and frequency dependent optical properties (Terentjev and co-workers, DOI: 10.1002/adma.200904103). The design principles for stimuli-sensitive polymers are elucidated exemplarily for photosensitive polymers. Rhodopsin, a sensory molecule for the visual perception, is an example of a photosensitive polymer from nature. It consists of the protein opsin and the photochromic molecule retinal, which can undergo a photoisomerization from 11-cis to all-trans retinal. This isomerization causes a conformational change in opsin, whereby the associated G-protein is activated. Photochromic molecules such as azobenzene or diarylethene (Figure 1a–b) are the starting point for Russew and Hecht (DOI: 10.1002/adma.200904102) to explain how responsive materials with switchable macroscopic properties can be created based on such stimuli-sensitive molecular processes. The photosensitive groups enabled photo-controllable self-assembly and self-organization of block copolymers as well as of low molecular weight gelator molecules in solution, switch assemblies at surfaces and photo-induced swelling and shrinkage of gels, e.g. functionalized poly(N-isopropylacrylamide). The incorporation of diazobenzene groups into LCE leads to photo-induced shape-changing materials, whereby the isomerization induces a liquid crystalline phase transition. It is notable that this field so far has been limited to only a few selected photochromic molecules most of which are already known for a long time. Therefore the design and synthesis of novel photosensitive molecules is a challenging area for future research. As the existing molecules require UV or visible light, the development of molecules sensitive to the NIR range would be desirable especially for biomedical applications, where a deep penetration of light without harming tissue is required. Schematic illustrations of reversible photoisomerization (a–b) and photochemical reactions (c–d). a) E/Z-photoisomerization of azobenzene groups. b) Ring-closure/ring-opening reaction of dithienylethene. c) Photo-induced ionic dissociation of triphenylmethane leuco derivatives. d) Photodimerization of cinnamic acid group. (a,c,d) reproduced with permission from.3 (b) adapted from Russew and Hecht, DOI: 10.1002/adma.200904102. Besides photochromic molecules, molecules containing thermolabile bonds are investigated as molecular switches in stimuli-sensitive polymers. Polyphthalaldehyde is an example of a self-amplified depolymerization molecule, in which the breaking of a single bond induces the spontaneous depolymerization of the entire polymer. This relatively fast chemical reaction can be performed in an impressively high spatial accuracy by application of a hot silicon tip, whereby 700 °C was determined to be a sufficient heater temperature corresponding to a polymer temperature of 300–400 °C. Arbitrary three-dimensional patterns with 40 nm lateral and 1 nm vertical resolution could be created and characterized. It is expected that this technology will be applied in printing optics on chips or the creation of nanoscale three- dimensional templates for shape matching self-assembly of nanorods or -cubes (Knoll et al., DOI: 10.1002/adma.200904386). The most prominent molecular architecture for stimuli-sensitive polymers is entropy-elastic polymer networks, consisting of chemical or physical crosslinks and highly flexible network chains (Figure 2). These networks serve as a molecular skeleton for the covalent attachment of functional groups (e.g. photochromic molecules) or as a matrix for particles (e.g. magnetic nanoparticles or CNT) or molecules (e.g. molecules forming liquid crystallines) acting as gates for translating the stimulating signal. The network segments may also act by themselves as a functional unit, whereby the chemical structure of their repeating units as well as the sequence structure in case of copolymer- based segments have to be tailored. Different molecular architectures for shape-memory polymers. a) Covalent network; b) multiblock copolymer; multimaterial systems: c) blend, and d) IPN. Gray and black lines: amorphous polymer chain segments, blue and red lines: crystalline polymer chain segments. Image adapted from Behl et al., DOI: 10.1002/adma.200904447. LCEs are polymer networks, which are loaded with a liquid crystalline material or contain covalently bound mesogenic groups (Ohm et al., DOI: 10.1002/adma.200904059). The mesogen can be part of the polymer backbone or be attached as a side chain via a flexible spacer (“end-on” or “side on”). Several synthetic pathways have been developed to crosslink the LCE in a way such that the materials can be oriented into liquid crystalline mono-domains. If the anisotropy of the liquid crystalline phase gets lost, e.g. because it is heated into the isotropic phase, a shape change of the LCE occurs, which is reversed on cooling when the anisotropic phase is regained. Photosensitive LCEs were obtained by incorporation of photoswitchable mesogens. Shape changes in electric fields were achieved by resistive heating. According to Ohm et al., a future potential for LCE might be in microscopically structured devices as they can be processed by soft molding, microfluidics or ink-jet printing. In general the long-term functionality/stability of LCEs needs to be improved. SMPs contain reversible crosslinks in addition to the netpoints determining the original permanent shape of the polymer network. Reversible crosslinks can be based on stimuli-depending physical interactions of functional groups or switching segments. In thermo-sensitive SMPs switching domains formed by such switching segments are able to temporarily fix a mechanical deformation by solidification caused by crystallization or vitrification. The fixation of the temporary shape as well as the recovery of the permanent shape is related to the thermal transition temperature associated with the switching domains. Reversible crosslinks can also be achieved by reversible chemical reactions, such as the photodimerization of cinnamate-groups (Figure 1d). In this way a light-induced shape-memory effect could be obtained. Different polymer architectures for polymers capable of undergoing a thermally-induced SME are displayed in Figure 2. Computational models for the thermally activated shape-memory effect are being developed as predictive tools facilitating the optimization of shape-memory properties (Nguyen and co-workers, DOI: 10.1002/adma.200904119). A prerequisite for the shape-memory effect is the creation of the temporary shape, which requires external manipulation. Once the original, permanent shape is recovered, a new temporary shape needs to be created to enable an additional SME. In this context the shape-memory effect is a one-way effect. A reversible shape change could be achieved for SMP containing a crystallizable switching segment kept under constant stress. During cooling under constant stress conditions a crystallization-induced elongation (CIE) occurred. This increased elongation is reversed by a melting-induced contraction (MIC) driven by entropy when the sample was reheated. Triple-shape polymers are able to perform two subsequent shape changes occurring at two different switching temperatures when heated. The triple-shape effect is in analogy to the classic shape-memory effect (dual-shape effect) an irreversible one-way effect. Zotzmann et al. (DOI: 10.1002/adma.200904202) report on a reversible triple-shape effect of polymer networks containing polypentadecalactone- and poly(ε-caprolactone)-segments, which was observed when a constant stress was applied. Suitable values for the constant stress level and the cooling rate were found to ensure two substantial CIEs and two MICs with similar contribution from both segments. Shape-memory polymers and gels as well as LCEs are able to self-sufficiently change their shape on demand and thus all belong to the class of actively moving polymers.1, 2 However the mechanisms for the shape changes are different, e.g. LCE change their shape as long as they are exposed to a suitable stimulus while the temporary shape of an SMP stays unchanged until exposed to the stimulus. Inspired by the complex and diverse requirements of potential applications, e.g. in biomedicine or in aerospace vehicles, multifunctional SMP are explored intensively. Here the shape-memory effect is combined with other functions (e.g. degradability, electrical conductivity, magnetic sensitivity, or radio-opacity), whereby the different functions shall be independent from each other. There are two different approaches to achieve multifunctionality (Behl et al. DOI: 10.1002/adma.200904447): multi-material systems, in which each material component contributes a certain function, and one-component materials, where several functions (e.g. SME and hydrolytic degradability) are integrated. An example of a multi-material approach are (nano)composites, in which a SMP matrix is combined with particulate fillers. Sellinger et al. (DOI: 10.1002/adma.200904107) report a fundamental study on the electromechanical effect of a nanocomposite from polyimide filled with CNT. The application of electrical current results in an increase in the temperature due to resistive heating. Thermal expansion of the polymer leads to a reversible shape change of the nanocomposite. Mechanical softening associated with the reversible phase transition at Tg can also be utilized to achieve substantial strain increases over a small ΔT. An impressive example of a multi-material system, composed of a main-chain thermotropic liquid crystalline copolymer (LCP) and CNT is described in the communication from Ji et. al. (DOI: 10.1002/adma.200904103). The LCP exhibits an enhanced compatibility with different pristine CNT, which was achieved by end group functionalization of the copolymer with pyrene- moieties. A particularly interesting result of this study is that a monodomain CNT-LCE composite could be prepared, in which LCP wrapped CNT were at least partially aligned. An anisotropy and frequency-dependency of its refractive index makes this material system useful for optical applications in the GHz-THz region. Stimuli-sensitive polymeric gels are able to swell and shrink in response to certain changes in their environmental conditions such as solvent composition, temperature, light, ionic strength, or pH. For example photosensitive gels were obtained by incorporation of triphenylmethane leuco derivatives, which dissociate into ion pairs upon exposure to UV light irradiation (Figure 1c). The back reaction recombining the ion pair occurs thermally in the dark. The reversible variation of electrostatic repulsion between photo-generated charges in gels results in expansion or shrinkage.4 For a general overview about this wide field looking back over more than 30 years of research, we refer the readership to references5 and.6. Although SME has been demonstrated in hydrogels as early as the mid 1990s,7 only few reports have been published about shape-memory gels since then. In this special issue four current research topics from the area of stimuli-responsive gels are addressed: microgels, porous hydrogels at interfaces, self-oscillating gels and finally enzymatically degradable hydrogels as temporary substitute of the extracellular matrix. Romeo et al. (DOI: 10.1002/adma.200904189) investigated suspensions of microgels from crosslinked poly(N-isopropylacry­lamide) having a lower critical solution temperature (LCST) at 33 °C. At temperatures higher than LCST, the gel particles shrink while at the same time the physical interaction between the particles increases, which can lead to the formation of a gel. For this reason concentrated suspensions of poly(N-isopropylacrylamide)-microgels behaved like a colloidal glass below LCST, like a liquid in the range of LCST, and exhibited properties like a colloidal gel above LCST. Structuring of stimuli-responsive gels lead to novel functions e.g. the capability to control the mass transport through intelligent membranes. Tokarev and Minko (DOI: 10.1002/adma.201000165) report on porous hydrogel films, where controlled closing and opening of pores can be achieved by external stimuli such as pH, ionic strength, or temperature. Such systems can be applied as plain films or capsules e.g. for filtration, separation, controlled release of drugs, sensors, or actuators. Self-oscillating gels perform swelling-shrinking cycles without requiring an external stimulus to control this process (Yoshida, DOI: 10.1002/adma.200904075). This effect is driven by an oscillating chemical reaction (Belousov-Zhabotinsky reaction). The catalyst of the reaction is covalently bound to a poly(N-isopropylacrylamide)-network, while the reactants are added to the solvent. Potential applications of these gels are actuators as well as active mass transport systems. Stimuli-responsive hydrogels have a high application potential in biomedical applications especially in regenerative therapies where they can act as a temporary substitute of the extracellular matrix. Two types of stimuli-sensitive functions are explored for hydrogels in this application area: volume changes and degradation. Hydrogels exhibiting volume changes on demand can be applied as coating in cell culture devices to detach cell layers without application of enzymes, e.g. by slightly increasing the temperature.8 Enzymatically degradable hydrogels (Kloxin et al., DOI: 10.1002/adma.200904179) can be used as implantable scaffolds for induced autoregeneration as well as miniscaffolds or injectable in-situ forming hydrogel systems for cell therapies. Cells experience these gels solely in their local microenvironment, e.g. via focal adhesion. Therefore the characterization of the local mechanical properties and the degradation behavior of the gels are of high importance. Atomic force microscopy under physiological conditions and tracer particle microrheology are modern methods to determine gel modulus and viscoelastic properties in spatial resolution. The insights obtained by such studies might contribute to a knowledge-based design of scaffolds, which will be capable of guiding e.g. cell differentiation and tissue formation. We wish to thank all authors for their contributions to this special issue and hope that the research on stimuli- sensitive polymers presented in this issue will inspire and stimulate the readership to further develop this fascinating field of materials science. Andreas Lendlein is Director of the Institute of Polymer Research at GKSS Research Center in Teltow, Germany and Member of the Board of Directors of the Berlin-Brandenburg Center for Regenerative Therapies. He is Professor at University of Potsdam and Honorary Professor at Freie Universität Berlin as well as Member of the Medical Faculty of Charité University Medicine Berlin. He completed his Habilitation in Macromolecular Chemistry in 2002 at RWTH Aachen University and received his doctoral degree in Materials Science from the Swiss Federal Institute of Technology (ETH) in Zürich in 1996. His current research interests include (multi)functional polymer-based materials and their interaction with physiological environments. V. Prasad Shastri is the Bioss Professor of Cell Signaling Environments and Professor of Biofunctional Macromolecular Chemistry, and director of the Institute for Macromolecular Chemistry. Shastri received his PhD degree from the Rensselaer Polytechnic Institute in 1995 and received his postdoctoral training at the Massachusetts Institute of Technology under Professor Robert Langer. Shastri has made seminal contributions in development of new degradable polymers, in vivo engineering of organs and tissue, and drug delivery. His research interests include biofunctional polymers, nanoscale engineering of surfaces, systems for controlling cell functions and imaging, in vivo engineering of tissues, and transdermal delivery.