Introduction to Smart Polymers and Their Applications

C H A P T E R

1

Introduction to Smart Polymers and Their Applications María Rosa Aguilar⁎,†, Julio San Román⁎,† ⁎

Group of Biomaterials, Department of Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology, (ICTP-CSIC), Madrid, Spain, †Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain Living systems respond to environmental conditions to accommodate their structure and functionality to variations in nature via the action of complex sensing mechanisms, actuating and regulating functions, and feedback control systems. Therefore, nature can be considered the best example a scientist can have in mind when developing new materials and applications; the overall challenge is to create materials with dynamic and tunable properties that mimic the active microenvironment that occurs in nature. Smart polymers or stimuli-responsive polymers undergo reversible, large, physical or chemical changes in their properties as a consequence of small environmental variations. They can respond to a single or multiple stimuli such as temperature, pH, electric or magnetic fields, light intensity, biological molecules, etc. that induce macroscopic responses in the material, such as swelling, collapse, or solution-to-gel transitions, depending on the physical state of the chains (Aguilar et al., 2007). Linear and solubilized smart macromolecules will pass from monophasic to biphasic near the transition conditions giving rise to reversible sol-gel states. Smart cross-linked networks undergo chain reorganization at transition conditions where the network passes from a collapsed to an expanded state. Smart surfaces change its hydrophilicity as a function of a stimulus providing responsive interfaces. All these changes can be used in the design of smart devices for multiple applications, for example, minimally invasive injectable systems (Nguyen and Lee, 2010), pulsatile drug delivery systems (Tran et al., 2013; Arora et al., 2011), or new substrates for cell cultures or tissue engineering (Duarte et al., 2011).

Smart Polymers and Their Applications https://doi.org/10.1016/B978-0-08-102416-4.00001-6

1

© 2019 Elsevier Ltd. All rights reserved.

2

1.  Introduction to Smart Polymers and Their Applications

Moreover, most polymers can be easily functionalized by prepolymerization (Guillerm et al., 2012) or postpolymerization (Arnold et al., 2012) methods incorporating functional molecules to the structure, such as biological receptors (Shakya et al., 2010). Therefore, polymer scientists have a wide range of possibilities in terms of polymer chemical structures, polymer architectures, and polymer modifications to develop an infinite number of applications with these smart materials (Stuart et al., 2010). The aim of this new edition of Smart Polymers and Their Applications is not only to guide the reader through the state-of-the-art in this area but also shed some light on future research directions in this research field. The first part of the book (Chapters 2 to 11) gives the reader a wide overview about different stimuli-responsive polymers. Temperature, pH, light intensity, conductive and electroactive-responsive polymers, metabolite and enzyme-responsive polymers, and inflammation-responsive polymers are described. Moreover, due to their actual and future applications, special attention was paid to smart protein fibers, smart hydrogels, and self-healing polymers.

1.1  TYPES OF SMART POLYMERS Temperature-sensitive polymers present low critical solution temperature (LCST) or upper critical solution temperature (UCST) depending on their transition behavior from monophasic to biphasic when temperature is raised or, on the contrary, from biphasic to monophasic when temperature is raised, respectively. LSCT polymers have been widely investigated, whereas UCST polymers are quite rare. Most common LCST polymers are the poly(N-substituted acrylamide), poly(vinyl amide), and poly(oligoethylene glycol (meth)acrylate) families. However, many other polymers can present LCST if the proper hydrophilic-hydrophobic balance is present in the macromolecules. Poly(vinyl ether)s (Aoshima and Kanaoka, 2008), poly(2-oxazoline)s (Guillerm et al., 2012), and poly(phosphoester)s (Wang et al., 2009) also present temperature-responsive behavior and are specifically described in Chapter  2. Moreover, the three main classes of T-responsive polymers are also reviewed, that is, shape-memory materials (Löwenberg et al., 2017), liquid-crystaline materials (Ober and Weiss, 1990), and responsive polymer solutions (Hoffman, 2013). Polymers that respond to temperature changes and, more specifically, those that undergo a phase transition in water solution are gaining special attention due to their potential applications in the biomaterials field (Bajpai et al., 2010), architecture (Yang et  al., 2013; Rotzetter et  al., 2012), or water-­recovery strategies (Yang et al., 2013), among others. pH-sensitive polymers bear weak polyacidic (poly(acrylic acids) or poly(methacrylic acids)) or polybasic (poly(N-dimethylaminoethyl ­



1.1  Types of Smart Polymers

3

methacrylate), poly(N-diethylaminoethyl methacrylate), or poly(ethyl pyrrolidine methacrylate)) moieties in their structure that protonate or deprotonate as a function of the surrounding pH. Personal care, biomedical field (Yu et al., 2017), industrial processes (Kan et al., 2013), and water remediation (Wang et al., 2016) are some of the multiple areas of application described for this kind of smart polymer. Photosensitive polymers undergo a reversible or irreversible change in conformation, polarity, amphiphilicity, charge, optical chirality, or conjugation in response to a light stimulus. Reversible chromophores or reversible molecular switches (e.g., azobenzenes, spiropyran, diaryl ethane, or coumarin) undergo a reversible isomerization upon light irradiation (Wang and Wang, 2013) whereas irreversible chromophores are cleaved from the polymer chain upon light exposure (e.g., ο-nitrobenzyl photolabile protecting group) or induced reactivity resulting in the coupling of two species (e.g., 2-naphtoquinone-3-methides). Both molecular switches and irreversible chromophores have been applied in multiple applications such as drug delivery systems, functional micropatterns, responsive hydrogels, photodegradable materials, or photoswitchable liquid crystalline elastomers for remote actuation (Ohm et al., 2010). Intrinsically conductive polymers are organic polymers that conduct electricity. Chapter  7 focuses on conductive polymers for bioelectronics, that is, the interface between electronics and biology. Poly(3,4-ethylenedioxythiophene) (PEDOT) and its derivatives PEDOT:poly(styrene sulfate) (PEDOT:PSS), PEDOT:biopolymer, and poly(3,4-Propylenedioxythiophene) (ProDOT) and its derivatives are most successful in bioelectronics and have been used as electrodes for electrophysiology, organic chemical transistors (OECTs), organic electronic ionpump (OEIP), electronic textiles, and electronic skin (Simon et al., 2016). Peptides can be rationally designed by chemical or biotechnological procedures to assemble into different shapes (e.g., fibers, spheres, tubes) as a result of specific stimuli. Chapter 9 reviews stimuli-responsive protein fibers for their application as sensors (Liu et al., 1996). Moreover, their bioapplications as a drug and gene delivery system (Yucel et al., 2014), scaffolds for tissue engineering (Li et al., 2006), or wound dressing (Gil et al., 2013) of silk-based fibers are reviewed in depth. Polymer hydrogels play a key role in the development of new biomaterials due to their high levels of hydration and their 3D structure resembles natural tissue. However, despite the superior performance of hydrogels, they present several limitations mainly due to their poor controllability, actuation, and response polymers. Several advances have been made in this sense by the use of smart polymers in the preparation of hydrogels (Ravichandran et  al., 2012). For example, magnetically responsive polymer gels and elastomers are composites based on magnetic nanoparticles dispersed in a high elastic polymeric matrix. Magnetic field quickly deforms

4

1.  Introduction to Smart Polymers and Their Applications

the polymer matrix without noise, heat evolution, or exhaustion, which make these materials ideal for the preparation of sensors, micromachines, energy transducing devices, controlled delivery systems, or even artificial muscles (Li et al., 2013). One of the limiting steps in the development of these materials has been the precise coupling of magnetic nanoparticles to the gel; however, this problem has been overcome when magnetic nanoparticles form the cross-linking nodes of the hydrogel (Ilg, 2013). Macroscopic transitions of the smart polymers can also be triggered by “biology-to-material” interactions in the so-called biointeractive polymers. These materials incorporate receptors for biomolecules that, when stimulated, cause localized or bulk modifications in the material properties. Those polymers that respond to selective enzyme catalysis are called enzyme responsive polymers. These materials represent an important advance in the integration of artificial materials with biological entities as they link together the polymer properties with specific biological processes naturally controlled by either regulating enzyme expression levels or availability of cofactors (Hu et al., 2012). Enzyme responsive polymers can also display reversible and dynamic responses to a stimulus in the formulation of new biomaterials such as cell supports, injectable scaffolds, or drug delivery systems (De La Rica et al., 2012). Among all the systems that interact with the biological environment, those that respond to a pathological microenvironment and, more specifically, to the inflammatory microenvironment have aroused great interest in the medical community. Inflammation is a fundamental natural defense process during the body’s response to pathogens and in the triggering of tissue repair. However, when uncontrolled, it can be associated with a large number of chronic diseases and also plays a key role in the formation and progression of cancer. One or more of the specific characteristics of inflammation microenvironment, that is, the increased permeability of the blood vessels, upregulation of specific cell surface receptors, reduced pH, high oxidative stress, and overexpression of inflammatory and matrix-remodeling enzymes, have been exploited in the development of inflammation-responsive polymeric systems for more effective treatment of these diseases. These macromolecular systems can be selectively accumulated in the inflammatory area via passive targeting (due to the socalled ELVIS effect) (D'Arcy and Tirelli, 2014); cell-mediated targeting of inflammation-recruited phagocytic cells (e.g., macrophages) (Dong et al., 2017); or direct targeting to specific cell surface receptors overexpressed in the inflammatory areas (Coco et al., 2013). Due to the complexity of the inflammatory microenvironment, dual and multistimuli-responsive polymers have also been described for this application (Daniel et al., 2016). Shape-memory polymers represent one of the most active areas in material science due to their easier processability and lower cost when compared with shape-memory metals or ceramics. These kind of smart polymers



1.2  Applications of Smart Polymers

5

have the ability to recover their predefined shape (permanent) when stimulated by an external stimulus. A stable network and a reversible switching transition of the polymer are the two prerequisites for shape-memory effect. The stable network is responsible of the original shape and reversible switching transition fixes the temporary shape, which can be crystal­ lization/melting transition, liquid crystal anisotropic/isotropic transition, reversible molecule cross-linking (photodimerization, Deals-Alder reaction, and oxidation/redox reaction of mercapto groups), and supramolecular association/disassociation (hydrogen bonding, self-assembly metal-ligand coordination, and self-assembly of β-cyclodextrin). In addition to the mentioned reversible switches, other stimuli that change chain mobility can also trigger shape-memory effect, such as light, pH, moisture, electric field, magnetic field, pressure, etc. (Pretsch, 2010). Shape-memory polymers allow large recoverable strains; however, they normally present low mechanical properties and do not support great shape-recovery stresses. Therefore, great efforts are being made in the development of shape-memory composites with reinforced properties. Shape-memory polymers present numerous actual and potential applications in medicine, aerospace, textiles, engineering, microfluidics, lithography, and household products (Meng and Li, 2013). Self-healing or restoration of lost functionalities without external help is a dream come true when talking about self-healing polymers (Aïssa et  al., 2012). Extrinsic (the healing compound is isolated from the polymer matrix in capsules, fibers, or nanocarriers) or intrinsic (the polymer chains temporarily increase mobility and flow to the damaged area) healing mechanisms (Billiet et  al., 2013) are responsible for property restoration, such as structural integrity (White et al., 2001), surface aesthetics (Yao et al., 2011), electrical conductivity (Tee et al., 2012), hydrophobicity and hydrophilicity (Ionov and Synytska, 2012), and mechanical properties (Jones et al., 2013).

1.2  APPLICATIONS OF SMART POLYMERS The second part of the book (Chapters 12 to 18) compile relevant applications of smart polymers and their future trends according to the opinion of well-known researchers in the field. Most important developments were registered in the biomedical field by the use of smart polymers in the development of new therapies for the treatment of several diseases or sophisticated medical devices that react to the environment of the surrounding tissues (pH, temperature, enzymes, or analytes concentration) or external stimuli (light or magnetic radiation). Responsive polymeric substrates or instructive substrates regulate cell behavior in response to external factors and are of high importance in

6

1.  Introduction to Smart Polymers and Their Applications

t­issue engineering applications (Pérez et  al., 2013). Cell behavior (adhesion, migration, and proliferation) is conditioned to substrate surface properties (Alves et al., 2010). Tunable surface properties such as stiffness and wettability, surface functionalization with bioactive molecules, or the design of 3D patterns at the micro- or nanoscale in hydrogels are interesting strategies actually being developed to obtain specific cell response to smart surfaces for tissue engineering applications, e.g., cell sheet engineering (Haraguchi et  al., 2012), smart biomineralization (Huang et  al., 2008), heart valve and vascular graft tissue engineering (Fioretta et  al., 2012), drug delivery (Moroni et al., 2008), cell recruitment (Custódio et al., 2012), or the development of new and more effective medical devices. Temperature-sensitive polymers and more specifically shape-memory polymers have been used in the preparation of minimally invasive surgery medical devices (Yakacki and Gall, 2010). The unique properties of these materials allow the introduction of the medical device in a compressed form that expands once located in the desired place by minimally invasive surgery procedures. One of the most relevant applications using this kind of polymer is the development of stents for either vascular or urologic procedures. Polymeric stents are considered a promising option compared to the conventional metallic stents not only due to their mechanical properties but also the possibility of incorporating a drug to be eluted in the functional place [e.g., to reduce restenosis and/or thrombosis after implantation in vascular stents or to minimize infections in urinary stents (Xue et al., 2012)]. Smart polymers have played a key role in the fabrication of new medical devices for cancer diagnosis and therapy. In this sense, magnetic nanoparticles have been used in the development of hyperthermia treatments, magnetic separation, immunoassay, cellular labeling, and magnetic resonance imaging diagnosis (Karimi et  al., 2013). Biosensors based on smart polymers have been used in clinical diagnosis and forensic analysis because alterations in the concentration of certain analytes [e.g., glucose in diabetes (Thammakhet et al., 2011)] or in physical variables such as temperature or pH [e.g., pH sensor for the quantification of partial pressure of CO2 in the stomach for the diagnosis of gastrointestinal ischemia (Herber et al., 2005)] occur in several diseases. Biosensors and actuators have been also combined in unique medical devices, for example, glucose-sensing and insulin-delivery medical devices (Brahim et al., 2002) or cochlear implants (Laursen, 2006). Microfluidics-based medical devices or “Lab on a Chip” also combine biosensors to detect systemic levels of certain analytes and actuators to release bioactive components in response to excessive or insufficient concentrations of these analytes (Do et al., 2008). Smart polymer nanocarriers for drug delivery applications play an important role in the development of highly active and selective treatments,



1.2  Applications of Smart Polymers

7

­permitting a controlled delivery of the drug in the right place at the right moment (Fleige et  al., 2012). Better knowledge of the molecular biology and synthesis of new polymers with stimulus-sensitive moieties have given rise to more effective, specifically localized action and personalized therapies. This is the case for human neutrophil elastase degradable links that will be specifically degraded at inflammation sites where neutrophils act (Fleige et al., 2012; Aimetti et al., 2009) or cathepsin B-sensitive polyglutamates that will be better degraded in women than in men because the activity of lysosomal cysteine protease cathepsin B enzyme closely correlates with estrogen levels (Lammers et al., 2012). Smart polymers have also been used for bioseparation and other biotechnological applications such as purification techniques (Galaev et al., 2007). New smart polymers have benefited from progress in affinity precipitation (Gautam et al., 2012), aqueous polymer two-phase partitioning (Qu et  al., 2010), controlled permeation membranes (Wang and Chen, 2007), thermosensitive chromatography (Kanno et al., 2011), and modulation of catalytic processes (Zhang et al., 2010). Information and communication technologies, more specifically data storage devices, have improved amazingly in the last several years due to the fabrication of new smart materials. In this way, volume holographic storage will give rise to the next generation of data storage devices due to their much higher storage capacity and much higher transfer rate compared with actual 2D optical discs (Garan, 2013). In this sense, azobenzene chromophores stand by its capacity to induce optical anisotropy when incorporated in photoaddressable polymeric materials (Shishido, 2010). Smart polymers are also employed in the detection and quantification of specific ions and molecules by highly sensitive sensors for multiple applications, such as gas detection (Xue et al., 2013), heavy metal cations quantification (Tokuyama et al., 2016), and biological molecule detection (Shrivastava et  al., 2016). Conductive polymers, polymers with chiral motifs, molecularly imprinted polymers, and polymeric nanocomposites have been described with this purpose. Environmental purposes and more specifically climate change is moving the scientific community to develop more efficient rechargeable batteries for the electrification of the grid and automotive transportation. The polymeric binder is a key part of these batteries that provide mechanical stability to the electrode. Chapter 18 reviews the new strategies carried out to obtain advanced polymeric binders with hierarchical structures (Ling et  al., 2015), high elasticity (Wang et  al., 2017), and self-healing properties (Wang et al., 2013) to improve the cohesion between the active particles and buffer the dimensional changes occurring during the charge/ discharge process.

8

1.  Introduction to Smart Polymers and Their Applications

1.3 CONCLUSIONS Multidisciplinary research involving scientists of very different disciplines will be required to make future advances in smart polymers and their application. Organic chemists, polymer chemists, material engineers, physicists, biologists, pharmacists, and medical doctors will have to work together in a very close and fluid manner to respond to the necessities of society in developing new materials that improve the quality of life not only from a medical point of view but also for the architectural, food industry, data storage, and energy storage fields.

Acknowledgment The authors greatly acknowledge the financial support from MAT2017-84277-R project.

References Aguilar, M.R., Elvira, C., Gallardo, A., Vázquez, B., San Román, J., 2007. Smart polymers and their applications as biomaterials. In: Ashammakhi, N., Reis, R.L., Chiellini, E. (Eds.), Topics in Tissue Engineering. e-book, Expertissues. Aimetti, A.A., Machen, A.J., Anseth, K.S., 2009. Poly(ethylene glycol) hydrogels formed by thiol-ene photopolymerization for enzyme-responsive protein delivery. Biomaterials 30, 6048–6054. Aïssa, B., Therriault, D., Haddad, E., Jamroz, W., 2012. Self-healing materials systems: overview of major approaches and recent developed technologies. Adv. Mater. Sci. Eng. 2012, 17. Article ID 854203. Alves, N.M., Pashkuleva, I., Reis, R.L., Mano, J.F., 2010. Controlling cell behavior through the design of polymer surfaces. Small 6, 2208–2220. Aoshima, S., Kanaoka, S., 2008. Synthesis of stimuli-responsive polymers by living ­polymerization: poly(N-isopropylacrylamide) and poly(vinyl ether)s. Adv. Polym. Sci. 210, 169–208. Arnold, R.M., Huddleston, N.E., Locklin, J., 2012. Utilizing click chemistry to design functional interfaces through post-polymerization modification. J. Mater. Chem. 22, 19357–19365. Arora, G., Singh, I., Nagpal, M., Arora, S., 2011. Recent advances in stimuli induced pulsatile drug delivery system: a review. Res. J. Pharm. Technol. 4, 691–703. Bajpai, A., Shukla, S., Saini, R., Tiwari, A. (Eds.), 2010. Temperature sensitive release systems. Stimuli Responsive Drug Delivery Systems: From Introduction to Application UKSmithers Rapra Technologies, Shawbury. Billiet, S., Hillewaere, X.K.D., Teixeira, R.F.A., Du Prez, F.E., 2013. Chemistry of crosslinking processes for self-healing polymers. Macromol. Rapid Commun. 34, 290–309. Brahim, S., Narinesingh, D., Guiseppi-Elie, A., 2002. Bio-smart hydrogels: co-joined molecular recognition and signal transduction in biosensor fabrication and drug delivery. Biosens. Bioelectron. 17, 973–981. Coco, R., Plapied, L., Pourcelle, V., Jerome, C., Brayden, D.J., Schneider, Y.J., Preat, V., 2013. Drug delivery to inflamed colon by nanoparticles: comparison of different strategies. Int. J. Pharm. 440, 3–12. Custódio, C.A., Frias, A.M., Del Campo, A., Reis, R.L., Mano, J.F., 2012. Selective cell recruitment and spatially controlled cell attachment on instructive chitosan surfaces functionalized with antibodies. Biointerphases 7, 1–9.

REFERENCES 9

Daniel, K.B., Callmann, C.E., Gianneschi, N.C., Cohen, S.M., 2016. Dual-responsive nanoparticles release cargo upon exposure to matrix metalloproteinase and reactive oxygen species. Chem. Commun. 52, 2126–2128. D'Arcy, R., Tirelli, N., 2014. Fishing for fire: strategies for biological targeting and criteria for material design in anti-inflammatory therapies. Polym. Adv. Technol. 25, 478–498. De La Rica, R., Aili, D., Stevens, M.M., 2012. Enzyme-responsive nanoparticles for drug release and diagnostics. Adv. Drug Deliv. Rev. 64, 967–978. Do, J., Lee, S., Han, J., Kai, J., Hong, C.C., Gao, C., Nevin, J.H., Beaucage, G., Ahn, C.H., 2008. Development of functional lab-on-a-chip on polymer for point-of-care testing of metabolic parameters. Lab Chip 8, 2113–2120. Dong, X., Chu, D., Wang, Z., 2017. Leukocyte-mediated delivery of nanotherapeutics in inflammatory and tumor sites. Theranostics 7, 751–763. Duarte, A.R.C., Mano, J.F., Reis, R.L., 2011. Thermosensitive polymeric matrices for three-­ dimensional cell culture strategies. Acta Biomater. 7, 526–529. Fioretta, E.S., Fledderus, J.O., Burakowska-Meise, E.A., Baaijens, F.P.T., Verhaar, M.C., Bouten, C.V.C., 2012. Polymer-based scaffold designs for in situ vascular tissue engineering: controlling recruitment and differentiation behavior of endothelial colony forming cells. Macromol. Biosci. 12, 577–590. Fleige, E., Quadir, M.A., Haag, R., 2012. Stimuli-responsive polymeric nanocarriers for the controlled transport of active compounds: concepts and applications. Adv. Drug Deliv. Rev. 64, 866–884. Galaev, I. (Ed.), Mattiasson, B. (Ed.), Snowden, M., Okay, O., Starodubtsev, S., Khovhlov, A., Alvarez-Lorenzo, C., Concheiro, A., Chuang, J., Ivanov, A., Prieto, S., Borisov, O., Laukkanen, A., Moorthy, J., Alonso, M., Rodriguez-Cabello, J., Gomez, J., Peppas, N., Tenhu, H., Grosberg, A., Kazakov, S., 2007. Smart Polymers. Applications in Biotechnology and Biomedicine. CRC Press, Taylor & Francis Group, Boca Raton. Garan, S.S., 2013. Holographic imaging: information recording and retrieval. J. Indian Inst. Sci. 93, 35–45. Gautam, S., Dubey, P., Varadarajan, R., Gupta, M.N., 2012. Role of smart polymers in protein purification and refolding. Bioeng. Bugs 3, 286–288. Gil, E.S., Panilaitis, B., Bellas, E., Kaplan, D.L., 2013. Functionalized silk biomaterials for wound healing. Adv. Healthc. Mater. 2, 206–217. Guillerm, B., Monge, S., Lapinte, V., Robin, J.J., 2012. How to modulate the chemical structure of polyoxazolines by appropriate functionalization. Macromol. Rapid Commun. 33, 1600–1612. Haraguchi, Y., Shimizu, T., Yamato, M., Okano, T., 2012. Scaffold-free tissue engineering using cell sheet technology. RSC Adv. 2, 2184–2190. Herber, S., Bomer, J., Olthuis, W., Bergveld, P., Van Den Berg, A., 2005. A miniaturized carbon dioxide gas sensor based on sensing of pH-sensitive hydrogel swelling with a pressure sensor. Biomed. Microdevices 7, 197–204. Hoffman, A.S., 2013. Stimuli-responsive polymers: biomedical applications and challenges for clinical translation. Adv. Drug Deliv. Rev. 65, 10–16. Hu, J., Zhang, G., Liu, S., 2012. Enzyme-responsive polymeric assemblies, nanoparticles and hydrogels. Chem. Soc. Rev. 41, 5933–5949. Huang, Z., Sargeant, T.D., Hulvat, J.F., Mata, A., Bringas Jr., P., Koh, C.Y., Stupp, S.I., Snead, M.L., 2008. Bioactive nanofibers instruct cells to proliferate and differentiate during enamel regeneration. J. Bone Miner. Res. 23, 1995–2006. Ilg, P., 2013. Stimuli-responsive hydrogels cross-linked by magnetic nanoparticles. Soft Matter 9, 3465–3468. Ionov, L., Synytska, A., 2012. Self-healing superhydrophobic materials. Phys. Chem. Chem. Phys. 14, 10497–10502. Jones, A.R., Blaiszik, B.J., White, S.R., Sottos, N.R., 2013. Full recovery of fiber/matrix interfacial bond strength using a microencapsulated solvent-based healing system. Combust. Sci. Technol. 79, 1–7.

10

1.  Introduction to Smart Polymers and Their Applications

Kan, K.H.M., Li, J., Wijesekera, K., Cranston, E.D., 2013. Polymer-grafted cellulose nanocrystals as pH-responsive reversible flocculants. Biomacromolecules 14, 3130–3139. Kanno, S., Watanabe, K., Yamagishi, I., Hirano, S., Minakata, K., Gonmori, K., Suzuki, O., 2011. Simultaneous analysis of cardiac glycosides in blood and urine by thermoresponsive LC-MS-MS. Anal. Bioanal. Chem. 399, 1141–1149. Karimi, Z., Karimi, L., Shokrollahi, H., 2013. Nano-magnetic particles used in biomedicine: Core and coating materials. Mater. Sci. Eng. C 33, 2465–2475. Lammers, T., Kiessling, F., Hennink, W.E., Storm, G., 2012. Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. J. Control. Release 161, 175–187. Laursen, W., 2006. Breaking the sound barrier [cochlear implants]. Eng. Technol. 1, 38–41. Li, C., Vepari, C., Jin, H.J., Kim, H.J., Kaplan, D.L., 2006. Electrospun silk-BMP-2 scaffolds for bone tissue engineering. Biomaterials 27, 3115–3124. Li, Y., Huang, G., Zhang, X., Li, B., Chen, Y., Lu, T., Lu, T.J., Xu, F., 2013. Magnetic hydrogels and their potential biomedical applications. Adv. Funct. Mater. 23, 660–672. Ling, M., Zhao, H., Xiaoc, X., Shi, F., Wu, M., Qiu, J., Li, S., Song, X., Liu, G., Zhang, S., 2015. Low cost and environmentally benign crack-blocking structures for long life and high power Si electrodes in lithium ion batteries. J. Mater. Chem. A 3, 2036–2042. Liu, Y., Liu, H., Qian, J., Deng, J., Yu, T., 1996. Feature of an amperometric ferrocyanide-­ mediating H2O2 sensor for organic-phase assay based on regenerated silk fibroin as immobilization matrix for peroxidase. Electrochim. Acta 41, 77–82. Löwenberg, C., Balk, M., Wischke, C., Behl, M., Lendlein, A., 2017. Shape-memory hydrogels: evolution of structural principles to enable shape switching of hydrophilic polymer networks. Acc. Chem. Res. 50, 723–732. Meng, H., Li, G., 2013. A review of stimuli-responsive shape memory polymer composites. Polymer (United Kingdom) 54, 2199–2221. Moroni, L., De Wijn, J.R., Van Blitterswijk, C.A., 2008. Integrating novel technologies to fabricate smart scaffolds. J. Biomater. Sci. Polym. Ed. 19, 543–572. Nguyen, M.K., Lee, D.S., 2010. Injectable biodegradable hydrogels. Macromol. Biosci. 10, 563–579. Ober, C.K., Weiss, R.A., 1990. Current Topics in Liquid-Crystalline Polymers. LiquidCrystalline Polymers. American Chemical Society 435, 1–13. Ohm, C., Brehmer, M., Zentel, R., 2010. Liquid crystalline elastomers as actuators and sensors. Adv. Mater. 22, 3366–3387. Pérez, R.A., Won, J.E., Knowles, J.C., Kim, H.W., 2013. Naturally and synthetic smart composite biomaterials for tissue regeneration. Adv. Drug Deliv. Rev. 65, 471–496. Pretsch, T., 2010. Review on the functional determinants and durability of shape memory polymers. Polymers 2, 120–158. Qu, F., Lü, F., Zhang, H., 2010. Smart polymer based aqueous two-phase systems applied in bio-molecule separation and purification. Prog. Chem. 22, 125–132. Ravichandran, R., Sundarrajan, S., Venugopal, J.R., Mukherjee, S., Ramakrishna, S., 2012. Advances in polymeric systems for tissue engineering and biomedical applications. Macromol. Biosci. 12, 286–311. Rotzetter, A.C.C., Schumacher, C.M., Bubenhofer, S.B., Grass, R.N., Gerber, L.C., Zeltner, M., Stark, W.J., 2012. Thermoresponsive polymer induced sweating surfaces as an efficient way to passively cool buildings. Adv. Mater. 24, 5352–5356. Shakya, A.K., Sami, H., Srivastava, A., Kumar, A., 2010. Stability of responsive polymer-­ protein bioconjugates. Prog. Polym. Sci. (Oxford) 35, 459–486. Shishido, A., 2010. Rewritable holograms based on azobenzene-containing liquid-crystalline polymers. Polym. J. 42, 525–533. Shrivastava, S., Jadon, N., Jain, R., 2016. Next-generation polymer nanocomposite-based electrochemical sensors and biosensors: a review. TrAC, Trends Anal. Chem. 82, 55–67. Simon, D.T., Gabrielsson, E.O., Tybrandt, K., Berggren, M., 2016. Organic bioelectronics: bridging the signaling gap between biology and technology. Chem Rev. 116, 13009–13041.

REFERENCES 11

Stuart, M.A.C., Huck, W.T.S., Genzer, J., MÜller, M., Ober, C., Stamm, M., Sukhorukov, G.B., Szleifer, I., Tsukruk, V.V., Urban, M., Winnik, F., Zauscher, S., Luzinov, I., Minko, S., 2010. Emerging applications of stimuli-responsive polymer materials. Nat. Mater. 9, 101–113. Tee, B.C.K., Wang, C., Allen, R., Bao, Z., 2012. An electrically and mechanically self-healing composite with pressure- and flexion-sensitive properties for electronic skin applications. Nat. Nanotechnol. 7, 825–832. Thammakhet, C., Thavarungkul, P., Kanatharana, P., 2011. Development of an on-column affinity smart polymer gel glucose sensor. Anal. Chim. Acta 695, 105–112. Tokuyama, H., Kitamura, E., Seida, Y., 2016. Detection of Au(Iii) ions using a poly(N,N-­ dimethylacrylamide)-coated Qcm sensor. Talanta 146, 507–509. Tran, P.H.L., Tran, T.T.D., Vo, V.T., Lee, B.J., 2013. pH-sensitive polymeric systems for controlling drug release in nocturnal asthma treatment. In: IFMBE Proceedings. 4th International Conference on the Development of Biomedical Engineering in Vietnam, Ho Chi Minh City, Vietnam, 8–12 January 2012, Code 94545. IFMBE, vol. 40. pp. 304–308. Wang, W., Chen, L., 2007. "Smart" membrane materials: preparation and characterization of PVDF-g-PNIPAAm graft copolymer. J. Appl. Polym. Sci. 104, 1482–1486. Wang, D., Wang, X., 2013. Amphiphilic azo polymers: molecular engineering, self-assembly and photoresponsive properties. Prog. Polym. Sci. 38, 271–301. Wang, Y.C., Yuan, Y.Y., Du, J.Z., Yang, X.Z., Wang, J., 2009. Recent progress in polyphosphoesters: from controlled synthesis to biomedical applications. Macromol. Biosci. 9, 1154–1164. Wang, C., Wu, H., Chen, Z., McDowell, M.T., Cui, Y., Bao, Z., 2013. Self-healing chemistry enables the stable operation of silicon microparticle anodes for high-energy lithium-ion batteries. Nat. Chem. 5, 1042. Wang, Y., Shi, Y., Xu, M., Wu, L., Jia, X., Wei, T., Zhang, S., Guo, X., 2016. Smart flocculant with temperature and pH response derived from starch. RSC Adv. 6, 44383–44391. Wang, Y., Gozen, A., Chen, L., Zhong, W.-H., 2017. Gum-Like nanocomposites as conformable, conductive, and adhesive electrode matrix for energy storage devices. Adv. Energy Mater. 7, 1601767. White, S.R., Sottos, N.R., Geubelle, P.H., Moore, J.S., Kessler, M.R., Sriram, S.R., Brown, E.N., Viswanathan, S., 2001. Autonomic healing of polymer composites. Nature 409, 794–797. Xue, L., Dai, S., Li, Z., 2012. Synthesis and characterization of elastic star shape-memory polymers as self-expandable drug-eluting stents. J. Mater. Chem. 22, 7403–7411. Xue, M., Li, F., Wang, Y., Cai, X., Pan, F., Chen, J., 2013. Ultralow-limit gas detection in ­nano-dumbbell polymer sensor via electrospinning. Nanoscale 5, 1803–1805. Yakacki, C.M., Gall, K., 2010. Shape-memory polymers for biomedical applications. Adv. Polym. Sci 226, 147–175. Yang, H., Zhu, H., Hendrix, M.M.R.M., Lousberg, N.J.H.G.M., De With, G., Esteves, A.C.C., Xin, J.H., 2013. Temperature-triggered collection and release of water from fogs by a sponge-like cotton fabric. Adv. Mater. 25, 1150–1154. Yao, L., Yuan, Y.C., Rong, M.Z., Zhang, M.Q., 2011. Self-healing linear polymers based on RAFT polymerization. Polymer 52, 3137–3145. Yu, J., Zhang, Y., Kahkoska, A.R., Gu, Z., 2017. Bioresponsive transcutaneous patches. Curr. Opin. Biotechnol. 48, 28–32. Yucel, T., Lovett, M.L., Kaplan, D.L., 2014. Silk-based biomaterials for sustained drug delivery. J. Control. Release 190, 381–397. Zhang, Y., Xu, J., Yuan, Z., Xu, H., Yu, Q., 2010. Artificial neural network-genetic algorithm based optimization for the immobilization of cellulase on the smart polymer Eudragit L-100. Bioresour. Technol. 101, 3153–3158.