Stimuli-responsive Polymers and Their Applications PDF

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Polymer Chemistry This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online REVIEW View Journal | View Issue Stimuli-responsive polymers and their applications Open Access Article. Published on 25 October 2016. Downloaded on 10/19/2024 12:24:17 AM. Cite this: Polym. Chem., 2017, 8, 127 Menglian Wei, Yongfeng Gao, Xue Li and Michael J. Serpe* Responsive polymer-based materials are capable of altering their chemical and/or physical properties upon exposure to external stimuli. These materials have been intensively studied over the years for a Received 9th September 2016, diverse range of applications, e.g., for on-demand drug delivery, tissue generation/repair, biosensing, Accepted 11th October 2016 smart coatings, and artificial muscles. Here, we review recent advances in the areas of sensing and bio- DOI: 10.1039/c6py01585a sensing, drug delivery, and actuators. Specific examples are given in each of these areas, and we highlight www.rsc.org/polymers our group’s work on poly(N-isopropylacrylamide)-based microgels and assemblies. 1. Introduction composed of many elementary units (monomers) covalently bound together. This theory was further supported by the Polymers are ubiquitous in the things we use in everyday life, experiments of Carothers, who first synthesized nylon.5,6 and are even responsible for life itself, e.g., due to the poly- Following the work of these pioneers, a number of other mers of DNA and proteins.1 For ages, polymers have been used researchers have made ground-breaking advances in the field, to improve the quality of life, although the true polymeric and the work has yielded many Nobel Prizes over the decades. nature of the substances (e.g., natural rubber) was not known.2 This combined knowledge has allowed the development of Likely driven by the economic impetus of the rubber industry polymers for nearly every application imaginable, and is in the 19th and 20th centuries more effort was spent on investi- single-handedly responsible for the high quality of life that gating why the materials (i.e., polymers) behave the way they many have become accustomed to. do. Hence, the intense debate about the nature and structure This foundational research also led to the development of a of polymers began, and eventually Staudinger’s macromolecu- new class of polymers, which respond to their environment by lar theory was accepted,3,4 which described polymers as being changing their physical and/or chemical properties.7–9 These polymers, referred to as stimuli-responsive polymers (or smart/ intelligent polymers), have been synthesized to be responsive Department of Chemistry, University of Alberta, Edmonton, AB, T6G 2G2, Canada. to a variety of stimuli, e.g., pH,10 temperature,11 mechanical E-mail: [email protected] force,12 the presence of various small molecules and Menglian Wei received her B.Sc. Yongfeng Gao received his B.Sc. degree from Wuhan University in degree in Chemistry from 2011. She joined Prof. Michael Tsinghua University, Beijing, J. Serpe’s group as a Ph.D. China, in 2009 and obtained his student in 2012 and her research M.Sc. degree in Chemical has focused on the development Engineering from Beijing of a novel surface plasmon reso- University of Chemical nance spectrometer for studying Technology, Beijing, China, in confined polymer brushes, and 2012. He is presently a Ph.D. for improved sensing and bio- candidate in the Department of sensing. Chemistry at the University of Alberta, under the supervision of Menglian Wei Yongfeng Gao Prof. Michael J. Serpe. His research interests focus on stimuli-responsive microgels and microgel-based systems for con- trolled drug delivery. This journal is © The Royal Society of Chemistry 2017 Polym. Chem., 2017, 8, 127–143 | 127  View Article Online Review Polymer Chemistry biomolecules,13 and electric/magnetic fields.14–16 Their devel- donating or accepting protons upon environmental pH opment is oftentimes driven by the desire to mimic changes could be used. Some common examples are, acrylic nature.17–19 Such intelligent polymers have found many appli- acid (AAc)10,45–47 and N,N-dimethylaminoethyl methacrylate cations in the fields of biology and medicine and can be used (DMAEMA).48–50 Light responsive monomers can also be used This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. as sensors and biosensors,20 for controlled and triggered drug to generate materials that exhibit both temperature and light delivery,21 environmental remediation,22 chemo-mechanical responsivity; a common example is azobenzene.51–53 In most actuators,23–25 and for many other applications.26–28 cases the response of these polymers is a result of light trig- Of the multitude of responses to stimuli (some specifically gered isomerization of light sensitive molecules incorporated mentioned above), by far the most well-studied and under- into the polymer, although other mechanisms are possible, stood response is to temperature. For example, some polymers including light triggered ionization. Finally, biologically Open Access Article. Published on 25 October 2016. Downloaded on 10/19/2024 12:24:17 AM. exhibit a lower critical solution temperature (LCST),29 which is responsive systems, e.g., enzyme responsive polymers,54–56 and the lowest temperature at which temperature induced demix- glucose responsive polymers57,58 can also be generated, which ing occurs. That is, below the LCST the polymer chains and have the ability to respond to stimuli that are inherently solvent molecules are in one homogeneous mixed phase and present in biological samples.59 Generally, the response is a above the LCST, phase separation occurs via an entropically result of capture biomolecules immobilized in the polymer driven process. Poly(N-isopropylacrylamide) ( pNIPAm)11,30–32 interacting with the target, which results in network cross- is one of the most extensively studied temperature responsive linking and/or ionization. polymers that exhibits a LCST at ∼32 °C, which is close to the In this review, we mainly discuss recent examples of the use physiological temperature. As the solution temperature rises of stimuli-responsive polymers for sensing and biosensing, above the LCST, pNIPAm chains undergo a transition from an controlled and triggered drug delivery, and artificial muscles. extended (solvated) random coil to a compact (desolvated) In these individual areas we will highlight recent work from globular conformation. For individual polymer chains, the coil our own group. We point out that this review will focus on to globule transition can be thermodynamically controlled by applications, while many other recent reviews have focused on adjusting the polymer composition,33 i.e., the LCST shifts to the synthesis and fundamental properties of stimuli respon- higher or lower temperature by copolymerization with a hydro- sive polymers, and those details will not be rehashed here.60–64 philic or hydrophobic monomer, respectively.34,35 There are a variety of polymers that exhibit LCSTs, such as poly[N-[2- (diethylamino)ethyl acrylamide]] (PDEAEAM),36 poly(N,N- 2. Applications of stimuli-responsive dimethylaminoethyl methacrylate) (PDMAEMA),37–39 poly(N,N- polymers diethylaminoethyl methacrylate) (PDEAEMA),40 poly(2-(N- morpholine)ethyl methacrylate) (PMEMA),40 poly[oligo(ethyl- 2.1 Sensing and biosensing ene glycol)methacrylate]41,42 and poly(N,N-diethylacrylamide) A sensor is a self-contained integrated device that is able to (PDEAAM).43,44 In addition, multi-responsive polymers can be receive an input from its surroundings and convert it into an synthesized by incorporating other functional groups into the output signal that can be processed and converted to a read- temperature responsive polymer. For example, pH responsive able result.65 Likewise, a biosensor is a device that is capable compounds that have ionizable functional groups capable of of detecting and quantifying biological species of interest. Xue Li received her B.S. degree Michael J. Serpe received his B.S. from Qufu Normal University in degree from the University of 2009, and M.Sc. degree from Central Florida in 2000, his Nanjing University in 2011 Ph.D. from the Georgia Institute where she studied analytical of Technology in 2004 and com- chemistry in the group of Prof. pleted his postdoctoral studies at Yu Qin. In the same year she Duke University in 2009. In the joined Prof. Michael J. Serpe’s same year he joined the group as a Ph.D. student at the Department of Chemistry at the University of Alberta and University of Alberta as an received her Ph.D. in 2016. Assistant Professor and was pro- While in the Serpe group, she moted to Associate Professor in Xue Li developed pNIPAm microgel- Michael J. Serpe 2014. His group’s research based etalons for biosensing program is focused on developing applications and polymer-based new technologies to solve problems associated with health and the materials for artificial muscles. environment using fundamental and applied polymers, colloids (nano and microparticles), surface and materials chemistry. 128 | Polym. Chem., 2017, 8, 127–143 This journal is © The Royal Society of Chemistry 2017  View Article Online Polymer Chemistry Review In general, a biosensor should be capable of detecting a species unique optical properties (e.g., bright emission with no photo- of interest (analyte) from a complex mixture containing a bleaching), which make them ideal candidates for reporters in variety of interfering species, and provide accurate results in a sensors. Furthermore, the conformational change of the short time. In some cases, biosensors should be able to detect surface bound stimuli responsive polymers can translate into This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. biological analytes in resource-limited settings and at the observable optical property changes, which can be used for point-of-care (POC) to increase efficiency of treating patients in sensing and biosensing. In one example, Hoogenboom and co- developing parts of the world. Accomplishing this will have workers developed a colorimetric temperature and salt sensor positive health outcomes for those people in developing parts by coating Au nanoparticles (AuNPs) with a thermoresponsive of the world. pNIPAm shell.68 The pNIPAm polymer was synthesized by Responsive polymer-based sensors have attracted consider- RAFT polymerization using methyl 2-(((butylthio)carbo- Open Access Article. Published on 25 October 2016. Downloaded on 10/19/2024 12:24:17 AM. able attention due to their ability to convert the presence of nothioyl)thio)propanoate (MBTTC) as a chain transfer agent analytes into a physical and/or chemical change that a user (CTA), and further grafted to the AuNP surface by a ligand can relate to the status of a system.66 In one example, Dostalek exchange process. When exposed to solutions of different salt and coworkers generated a poly(N-isopropylacrylamide)-co- concentrations, the pNIPAm modified AuNPs were able to methacrylic acid ( pNIPAm-co-MAAc) hydrogel on a surface change color from red to purple or blue at elevated tempera- plasmon resonance (SPR) sensor surface with indium tin oxide tures, as shown schematically in Fig. 2. This is due to AuNP microheaters embedded to allow for SPR signal tuning, as aggregation induced electronic coupling of the SPR leading to shown in Fig. 1.67 Using the microheaters, rapid thermal a visible color change. In this study, the authors also found responses of the pNIPAm-based material between swollen and that the range of temperature sensitivity increased in the pres- de-swollen could be triggered, yielding a thermo-optical coeffi- ence of NaSCN, compared to NaCl, due to charge screening cient of dn/dT = 2 × 10−2 RIU K−1. Further, the hydrogel layer and Hofmeister effects. can serve as a 3D binding matrix for biosensor applications by A conceptually similar approach was used to generate CO2 engineering bio-recognition elements in the polymer network. sensors. CO2 has physiological significance, and abnormal In this example, the authors modified the hydrogel with concentrations have been associated with metabolism-related mouse immunoglobulin G (mIgG) via 1-ethyl-3-(3-dimethyl- diseases. Ma et al. developed a CO2 sensor by coating AuNPs aminopropyl)carbodiimide (EDC) coupling, which was able to with the CO2 responsive polymer, poly(N-(3-amidino)-aniline) capture Alexa Fluor 647 dye-labeled goat antimouse IgG (PNAAN), as shown in Fig. 3c.69 The hybridized particles were (a-mIgG). Enhanced fluorescence intensity was observed at the synthesized by directly reducing HAuCl4 with the CO2 respon- SPR resonance angle, which was attributed to the enhanced sive monomer N-(3-amidino)-aniline (NAAN). As CO2 dissolves electric field by SPR. In addition, upon a temperature increase, in solution, the amidine group of PNAAN can be protonated the binding matrix collapsed and resulted in a resonance into hydrophilic amidinium, which induced PNAAN to swell angle shift as well as diminished fluorescence intensity. and detach from the AuNP surface, resulting in AuNP aggrega- Therefore, the fluorescence signal excited by SPR at the reso- tion and a color change, as shown in Fig. 3a and b. The CO2 nance angle can be virtually switched on and off by swelling sensor exhibited a linear range of 0.0132 to 0.1584 hPa and a and de-swelling of the hydrogel binding matrix. limit of detection (LOD) of 0.0024 hPa by monitoring the UV Stimuli-responsive polymer-modified nanoparticles have absorbance change of AuNPs. attracted significant attention in recent years for sensing and In a very interesting application of nanotechnology com- biosensing. Due to quantum effects, nanoparticles exhibit bined with stimuli responsive polymers, Paek et al. generated a colorimetric pH sensor by anchoring “blue” and “orange” light emitting quantum dots (BQDs and OQDs) to a single graphene oxide (GO) sheet (MQD-GO) through different pH responsive linkers, as shown in Fig. 4.70 The photoluminescence emis- sions of the BQDs and OQDs on MQD-GO can be controlled independently through the two types of pH-responsive linkers of poly(acrylic acid) (PAA) ( pKa = 4.5) and poly(2-vinylpyridine) (P2VP) ( pKa = 3.0). The polymer linkers were able to change their conformation at distinct pH ranges, which ultimately tuned the Förster resonance energy transfer efficiencies from the BQDs to the GO and from the OQDs to the GO. As a result, the color of MQD-GO transitions from orange to near-white to blue over a wide range of pH values. Furthermore, the MQD-GO sensor showed excellent reversibility and high dis- persion stability in pure water, all of which satisfy the critical Fig. 1 Schematic diagram of a pNIPAm-co-MAAc hydrogel modified SPR sensor device with embedded ITO microheaters enabling rapid requirements of a pH sensor. signal tuning. Reprinted with permission from ref. 67. Copyright 2013, Stimuli-responsive polymers can also be used as building American Chemical Society. blocks for generating photonic crystals (PCs), which exhibit This journal is © The Royal Society of Chemistry 2017 Polym. Chem., 2017, 8, 127–143 | 129  View Article Online Review Polymer Chemistry This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Open Access Article. Published on 25 October 2016. Downloaded on 10/19/2024 12:24:17 AM. Fig. 2 Schematic illustration of the synthesis of pNIPAm brush modified AuNPs and their thermoresponsive behavior in aqueous solution and their aggregation in the presence of various concentrations of NaCl. Reprinted with permission from ref. 68. Copyright 2016, The Royal Society of Chemistry. Fig. 3 TEM images of AuNPs (a) before and (b) after being purged with CO2 gas. (c) Schematic illustration of CO2 induced AuNP aggregation. Fig. 4 Structures of (a) P2VP-OQD and (b) PAA-BQD. (c) Schematic Insets of (a) and (b) show photographs of the AuNP solutions (a) before illustration of the conformation and behavior of MQD-GO at the indi- and (b) after being purged with CO2 gas. Reprinted with permission cated solution pH. (d) Photographs of MQD-GO in buffer solutions at from ref. 69. Copyright 2016, American Chemical Society. the indicated solution pH under irradiation with 365 nm light. Reprinted with permission from ref. 70. Copyright 2014, American Chemical Society. structural color due to light interaction with the periodic struc- ture of the material. These interactions ultimately lead to con- structive/destructive interference of specific wavelengths of sive polymer building blocks, then the lattice spacing (and light, which yield color. Generally, PCs can be classified as visual color) can also be tuned by applying external stimuli. one-dimensional (1-D), two-dimensional (2-D), and three- Perhaps the most well-known early examples of responsive PCs dimensional (3-D) depending on the number of dimensions come from the Asher group who pioneered the development of the order occurs, as shown in Fig. 5.71 The wavelength of light 3-D photonic crystal-based sensors. This was accomplished by “reflected” from the device is primarily determined by the embedding ordered crystalline colloidal arrays (CCA) in material’s lattice spacing, which also dictates the visual color analyte-responsive hydrogel matrices. These materials were of the material. If the photonic crystal is composed of respon- used to detect solution pH, ionic strength, temperature, and 130 | Polym. Chem., 2017, 8, 127–143 This journal is © The Royal Society of Chemistry 2017  View Article Online Polymer Chemistry Review temperature, the polymer stack exhibited a Bragg peak at 710 nm and an orange color. Upon heating, the pNIPAm-based polymer layer shrunk, resulting in the approach of the PpMS layers and a concomitant shift in the reflected light to lower This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. wavelengths. This also yielded a color change, as can be seen in Fig. 6a. Furthermore, the color tunability was fully reversible with temperature. The Serpe group has fabricated etalons (a basic 1D photo- nic material) that respond to a variety of stimuli, such as pH,80 light,81 electric field,82 temperature,46 nerve agents,83 and Open Access Article. Published on 25 October 2016. Downloaded on 10/19/2024 12:24:17 AM. Fig. 5 Schematic illustrating the different dimensions of order in photonic materials. Reprinted with permission from ref. 71. Copyright various biomolecules.84 As detailed in these publications, 2014, American Chemical Society. etalons were constructed by depositing a thin layer of Au (typi- cally 15 nm) on top of a glass substrate by thermal evaporation followed by “painting” a layer of microgels onto the Au, and the presence of biological or chemical targets.72–78 In one subsequent deposition of another Au layer (typically 15 nm) on example, a 3-D PC sensor for metal ions was developed by top of the microgel layer. This structure allows light to enter copolymerizing 4-acryloylaminobenzo-18-crown-6 (AAB18C6) the dielectric cavity and resonate between the two reflective Au into a hydrogel composed of an ordered array of polystyrene layers. This resonating light yields constructive and destructive spheres.72 As metal ions bound to the crown ether of interference, allowing certain wavelengths of light to be AAB18C6, the hydrogel swelled due to the charge density reflected. The wavelength of the reflected light can be pre- increase in the polymer network yielding an increase in dicted using eqn (1): osmotic pressure and network swelling. As a result of the swell- ing, the polystyrene spheres in the hydrogel network separated λm ¼ 2nd cos θ ð1Þ from one another resulting in a red shift of the “reflected” light. where the specific wavelength maximum of the reflected peak In another example, Hayward and coworkers developed a (λ) depends on the peak order (m), refractive index of the colorimetric temperature sensor by depositing alternating dielectric (n) and the spacing between the mirrors (d ), as well layers of high and low refractive index polymers on a surface to as the angle of incidence (θ). For etalons, the Au and pNIPAm- generate a one dimensional Bragg mirror as shown in based microgel layers serve as the mirrors and the dielectric Fig. 6b.79 The high refractive index polymer was non-respon- layer, respectively. These devices have been shown to be able sive poly( para-methyl styrene) (PpMS), while the low refractive to detect glucose,85 CO2,86 triacylglycerols (TAGs),87 proteins,88 index polymer was temperature responsive poly(N-isopropyl- and DNA.89 For example, Zhang et al.87 synthesized TAG- acrylamide)-co-acrylic acid. After immersion in water at room responsive microgels by conjugating lipase to poly(N-iso- propylacrylamide-co-4-vinylpyridine-co-N-acryloxysuccinimide) ( pNIPAm-4VP-NAS) microgels, as shown in Fig. 7. When trio- lein penetrated into the microgel layer, it was hydrolyzed into a long chain fatty acid (C18H37COOH) by the lipase inside the microgels. The long chain fatty acid could subsequently attach to the microgels via acid–base reactions between fatty acid and the microgel’s pyridine groups. The lipophilicity of long chain fatty acid increases the hydrophobicity of the microgels, hence water was expelled from the microgels, and they collapsed. This resulted in a blue shift of the etalon’s reflectance peaks, which corresponded to the concentration of triolein (Fig. 7). Such devices were able to detect the physiologically relevant range of triolein. Multi-responsive microgels and etalons could also be gener- ated by incorporating a multi-responsive moiety into the pNIPAm-based microgel at the time of polymerization.83,90 Serpe and coworkers synthesized spiropyran (SP)-modified pNIPAm-based microgels and investigated their responsivity to multiple stimuli including temperature, pH, Cu2+, UV, visible, Fig. 6 (a) Photographs of a sensor changing color as a function of and near-infrared radiation.90 The responses were a result of temperature—heating induces deswelling, while cooling induces swell- ing. (b) Schematic representation of sensor fabrication (red layers, PpMS; the SP groups undergoing a reversible isomerization/reaction blue layers, pNIPAm-co-AAc). Reprinted with permission from ref. 79. from a neutral to a charged form, as shown in Fig. 8. SP’s Copyright 2012, Wiley-VCH Verlag GmbH & Co. KGaA. C(spiro)–O bond can be cleaved by UV light exposure or at low This journal is © The Royal Society of Chemistry 2017 Polym. Chem., 2017, 8, 127–143 | 131  View Article Online Review Polymer Chemistry This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Open Access Article. Published on 25 October 2016. Downloaded on 10/19/2024 12:24:17 AM. Fig. 7 (a) Triacylglyceride responsive microgel synthesis scheme, and the resulting microgel chemical composition. (b) The magnitude of the reflec- tance peak blue-shift as a function of triglyceride concentration at 30 °C. Reprinted with permission from ref. 87. Copyright 2015, The Royal Society of Chemistry. Fig. 8 Spiropyran modified pNIPAm-based microgel response to multiple stimuli. Reprinted with permission from ref. 90. Copyright 2015, American Chemical Society. pH ( 450 nm irradiation) and zwitterionic merocyanine (MC, to be reduced into thiols, and have been proposed as a candi- λ1 < 420 nm irradiation) states. The microstructures of both SP date to develop smart responsive systems for controlled drug and MC polymersomes are synergistically stabilized due to delivery. Zhu and coworkers synthesized multiblock copoly- cooperative noncovalent interactions from hydrophobic, hydro- mers with multiple enes and disulfides in hydrophobic blocks gen bonding, π–π stacking, and paired electrostatic (zwitter- and then encapsulated modified doxorubicin (Dox) via conju- ionic) interactions, with the latter two types being exclusive for gation and core-crosslinking reactions.124 The obtained nano- Open Access Article. Published on 25 October 2016. Downloaded on 10/19/2024 12:24:17 AM. MC polymersomes. Moreover, reversible phototriggered SP/MC prodrug micelles presented stable nano-scaled spherical par- polymersome transition is accompanied by membrane per- ticles under physiological conditions, while quickly dissociat- meability switching from being impermeable to selectively per- ing in response to 10 mM D,L-dithiothreitol (DTT). The Oh meable towards non-charged, charged, and zwitterionic small group also recently reported a novel rosin-based block copoly- molecule species below critical molar masses, as shown in mer designed to self-assemble toward micellar nanocarriers Fig. 12. They further demonstrate photoswitchable spatiotem- with positioned disulfides at interfaces of hydrophobic rosin poral release of 4′,6-diamidino-2-phenylindole (DAPI, cell cores and hydrophilic poly(ethylene glycol) (PEG) coronas.125 nuclei staining dye) within living HeLa cells. UV-actuated MC This block copolymer-based self-assembled micellar nano- polymersomes possess two types of release modules: (1) sus- carrier exhibited glutathione (GSH)-responsivity that enhanced tained release upon short UV irradiation duration by taking release of encapsulated drugs. The resulting micelles with PEG advantage of the unexpectedly slow spontaneous MC-to-SP coronas had excellent colloidal stability in the presence of pro- transition kinetics (t1/2 > 20 h) in the dark; and (2) on-demand teins, suggesting prolonged blood circulation in vivo. In and switchable release under alternated UV-vis light response to 10 mM GSH as a biological reducing agent, the irradiation. In another example, the Huang group incorporated disulfides at the core/corona interfaces were effectively cleaved, azobenzene derivatives into supramolecular structures to causing the destabilization of micelles, thus leading to the create a supra-amphiphilic polypseudorotaxane, which can enhanced release of encapsulated Dox. Due to the hydrophobi- self-assemble to form vesicles in water.123 Due to the dual- city of rosin species in micellar cores, the Dox release appeared responsivity of the molecular recognition motif, the reversible to be slowed. These studies suggest that the designing of transformations between solid nanospheres based on the self- responsive block copolymers and their assembled nano- assembly of the polymer backbone and vesicles based on the structures with reduction-responsive properties offers great self-assembly of the supra-amphiphilic polypseudorotaxane versatility as intracellular drug-delivery nanocarriers for cancer was achieved by adjusting the solution temperature or UV- therapy. Fig. 12 Photochromic polymersomes exhibiting photoswitchable and reversible bilayer permeability. Reprinted with permission from ref. 122. Copyright 2015, American Chemical Society. 136 | Polym. Chem., 2017, 8, 127–143 This journal is © The Royal Society of Chemistry 2017  View Article Online Polymer Chemistry Review The wide range of stimuli that can be exploited to trigger room temperature without any extra additives. This convenient drug release at the right place and time, and the diversity of method allows for the facile preparation of asymmetric GO/ responsive materials and other functional materials that can prGO-PPy hybrid films which can be applied in advanced be assembled in different architectures, allow great flexibility actuation systems such as moisture or electrochemical actua- This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. in the design of stimuli-responsive drug delivery systems. As tors. PPy-based actuators and microactuators have many poss- we have shown in this section, building up novel structures ible applications, particularly in cell biology and biomedicine from stimuli-responsive polymers can yield materials with because they can operate under a variety of conditions includ- important applications to solve problems related to human ing various salt solutions, blood plasma, urine, and cell health. The next section will describe their utility as artificial culture medium.136–138 muscles and actuators. Serpe and coworkers139,140 have demonstrated novel humid- Open Access Article. Published on 25 October 2016. Downloaded on 10/19/2024 12:24:17 AM. ity responsive self-bending bilayer-based actuators made by 2.3 Artificial muscles and actuators depositing layers composed of poly(N-isopropylacrylamide)- Natural muscles are biological organs that transform chemical based microgels and the polyelectrolyte polydiallyldimethyl- energy into mechanical energy. The process is complex, and ammonium chloride ( pDADMAC) on a flexible substrate. The involves an electrical pulse from the brain that triggers the lib- responsive materials bend upon drying and the degree of eration of ions inside the sarcomere, chemical reactions (ATP bending depends on the atmospheric humidity. The dried hydrolysis), and eventual conformational changes along the PDADMAC layer is composed of both amorphous and crystal- natural muscle fibers. For years, groups have been attempting line phases. The amorphous layer can readily absorb water, to mimic this behavior, and Otero,126,127 Inganäs,128,129 and which results in actuation, while the crystalline phase tem- MacDiarmid130,131 have conducted numerous investigations plates the specific bending characteristics of the device. They on bilayers (the most common polymer-based actuator format) worked on applying them as artificial muscles and humidity composed of a single actuating conducting polymer film de- sensors based on their understanding of the bending mechan- posited on an electromechanically inert layer. In a few ism, which is shown in Fig. 14. To investigate the humidity examples, artificial muscles with tactile sensitivities were con- response, the author connected the assembly to a circuit com- structed from electrochemo-mechanical and macroscopic posed of a LED and battery and collected the LED light inten- devices using films of PPy electrogenerated on double-sided sity as a function of humidity; this is shown schematically in tape to generate bilayers and trilayers.132–134 Qu and co- Fig. 14b, left. They also connected the assembly to a multi- workers135 reported the spontaneous formation of a partially meter (attached onto the gold surface of the strain sensor) and reduced graphene oxide and PPy ( prGO-PPy) film via a self oxi- placed the setup in a humidity-controlled chamber. As can be dation–reduction strategy as shown in Fig. 13. This reaction seen in Fig. 14b, right, the light intensity likewise depended occurs by direct exposure of the GO film to pyrrole vapor at on humidity. That is, as the humidity decreased the LED light Fig. 13 (a) Schematic illustrating the fabrication process of the humidity responsive asymmetric GO/prGO-PPy film actuator. (b) Plot of the curva- ture of the GO/prGO-PPy film versus relative humidity (RH). The insets are photographs of the GO/prGO-PPy film at the indicated humidities. (c) The actuation mechanism of the asymmetric G/G-PPy film. (d) Photographs of the bending for the G/G-PPy film actuator driven by the electro- chemical potential within ±0.8 V. The G and G-PPy sides are placed on the left and right sides on the actuator, and the corresponding potentials of +0.8 V (1), 0 V (2), and −0.8 V (3). Reprinted with permission from ref. 135. Copyright 2016, American Chemical Society. This journal is © The Royal Society of Chemistry 2017 Polym. Chem., 2017, 8, 127–143 | 137  View Article Online Review Polymer Chemistry This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Open Access Article. Published on 25 October 2016. Downloaded on 10/19/2024 12:24:17 AM. Fig. 14 (a) A bent substrate (∼2 inches long) was hung from an arm and cycled between low and high humidity. (b, left) Schematic depiction of the experimental setup used to measure resistance and LED light intensity as a function of device bending. (b, right) Light intensity (left axis) and resist- ance (right axis) changes induced by the bending of the bilayers coupled to the strain sensors. Reprinted with permission from ref. 139. Copyright 2013, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim and ref. 140. Copyright 2016, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. intensity increased due to the decreased resistance. There was deformation of the polymer is dependent on the manner of nearly no hysteresis between multiple humidity increase and alignment of the LCP mesogens.141 The monodomain LCP decrease cycles. with in-plane alignment of mesogens bent along the align- Photoresponsive polymer-based materials can also be used ment direction towards the irradiation source. They further to generate shape memory polymers, polymer gels, and liquid fabricated light driven soft actuators from azobenzene LCP/ crystalline polymers (LCP).141,142 They are responsible for con- polyethylene laminated films.153 Recently, Bléger and co- verting light energy into mechanical work. Generally, polymers workers described a liquid crystalline polymer film doped with are modified with light responsive groups, which induce visible light responsive fluorinated azobenzene capable of con- photochemical reactions and visible macroscopic effects on tinuous “chaotic” oscillatory motion when exposed to ambient the polymer. In a specific example, photoresponsive units were sunlight in air,154 which is shown in Fig. 15. The presence of used to crosslink liquid crystalline polymers and used as simultaneous illumination by blue and green light is necessary actuators.143–147 Warner and coworkers introduced azobenzene for the oscillating behavior to occur, suggesting that the moieties into a monodomain nematic LCP as crosslinkers and dynamics of continuous forward and backward switching are generated films, which were shown to exhibit significant con- causing the observed effect. The motion is programmed by the traction upon exposure to 365 nm radiation.148 Terentjev and molecular organization in the polymer film and is indepen- coworkers also worked on incorporating various azobenzene dent of the position of the light source. The unique behavior derivatives into LCPs and examined the deformation of the makes this material potentially useful for outdoor applications system upon exposure to UV light.149 This was demonstrated including self-cleaning coatings and surfaces. Furthermore, in a study published by Ikeda and coworkers. They showed self-propelling/morphing soft actuators could be used to that light-driven bending of azobenzene LCPs could be harvest and convert solar energy. achieved by creating an asymmetric deformation between the Another very important class of actuators is composed of surface and the bulk of a film.150–152 They found that the hydrogels that change volume in response to stimuli. Stimuli 138 | Polym. Chem., 2017, 8, 127–143 This journal is © The Royal Society of Chemistry 2017  View Article Online Polymer Chemistry Review This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Open Access Article. Published on 25 October 2016. Downloaded on 10/19/2024 12:24:17 AM. Fig. 15 (a) Chemical structures of the components and their molar percentage used to prepare the nematic liquid crystalline network. (b) Photograph of the splay-oriented film after removal from the cell under ambient interior light (homeotropic side on top) and (c) schematic of the LC splay aligned film (grey) containing F-azo molecules (orange). Reprinted with permission from ref. 154. Copyright 2016, Nature Publication. responsive hydrogels are 3D networks that can absorb water and swell and shrink in response to various external stimuli including temperature, pH, ionic strength, chemicals, electri- city, and light.155,156 Hydrogel actuators produce macroscopic changes upon swelling and shrinking.157–160 In a recent example, Aida and coworkers developed a layered hydrogel consisting of cofacially oriented electrolyte nanosheets. This unusual geometry leads to significant anisotropic electrostatic repulsion in the hydrogel interior. They showed that the material could be operated by modulating its electrostatic anisotropy in response to changes of electrostatic permittivity. The electrostatic permittivity could be controlled by varying the material’s solvation state, which depended on solution temperature.161 Recently, Ding and co-workers developed a computational model to demonstrate a new reversible shape- Fig. 16 A self-folding–unfolding flower. (a) Schematic of two activated changing component design concept enabled by 3D printing shape memory petal-like structure. (b) The curvature change under of stimuli responsive polymers, shape memory polymers (SMP) thermal activation as a function of time. (c–f ) The sequence of reversible and hydrogels.162 This approach uses the swelling of a hydro- actuation. (g) The dried configuration is stiff and can carry a load of 25 g. The scale bar in (g) is 12.5 mm. Reprinted with permission from ref. gel as the driving force for the shape change, and the tempera- 162. Copyright 2016, Nature Publication. ture-dependent modulus of a shape memory polymer to regu- late the time of such shape changes. Controlling the tempera- ture and aqueous environment allows switching between two stable configurations. The structures are relatively stiff and can shown in Fig. 16b, which has the largest curvature and the carry cargo in each state without mechanical loading for fastest response speed with the thinner SMP layer. After device training. By applying the design principles, they created putting this structure into low temperature water for 12 h, the and demonstrated the behavior of several shape-changing inner layer bends a little bit as shown in Fig. 16d, and then on structures that exhibit reversible shape changes based on immersion into hot water, all layers bend and form the flower- folding, curling, and origami concepts. Fig. 16 shows one of like structure as shown in Fig. 16e. On taking the structure out the examples, self-folding and unfolding flowers. The three of the hot water and letting it dry, as shown in Fig. 16g, we can layers were designed with different thickness ratios of layers of see that it maintains the flower shape structure and can carry the elastomer, the hydrogel, and the SMP as shown in Fig. 16a. a load of 25 g. When the structure was put into hot water it The inner layer was designed with the thinnest SMP layer of became flat again as shown in Fig. 16f. The whole process can 0.3 mm, and the second layer with a 0.4 mm SMP layer, and be repeated many times. 0.5 mm of SMP layer for the outer layer, but the total thickness In summary, polymer-based actuators are materials capable of the elastomer, the hydrogel and the SMP layer were always of converting energy from external stimuli (e.g. heat, light, kept the same. The corresponding curvature change profile is and electricity) to mechanical forces, thus exhibiting shape This journal is © The Royal Society of Chemistry 2017 Polym. Chem., 2017, 8, 127–143 | 139  View Article Online Review Polymer Chemistry changes. Polymer-based actuators can be generated from a 3 H. Staudinger, From organic chemistry to macromolecules, variety of materials (hydrogels, liquid crystal polymers, and Wiley, New York, 1970. shape memory polymers). The material that is used depends 4 R. Mülhaupt, Angew. Chem., Int. Ed., 2004, 43, 1054–1063. on the intended application, e.g., soft hydrogels could be used 5 W. H. Carothers, US Pat, 2071251A, 1937. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. for delicate biological applications, while hard shape memory 6 W. H. Carothers, US Pat, 2130523A, 1938. polymers could be used for lifting/moving heavy masses. It is 7 P. Theato, J. Polym. Sci., Part A: Polym.