Smart polymer brushes and their emerging applications

Abstract

Polymer brushes with stimuli-responsive properties, also known as smart polymer brushes (SPBs), have attracted substantial research interest in the past few years because they offer a wealth of opportunities to design responsive materials triggered by external stimuli, and have a number of applications in many areas in science and technology. Changing the length, chemical composition, architecture, and topology of the chains allows a change in response mechanisms and rates. This review introduces some key strategies for preparing polymer brushes and discusses various smart polymer brush surfaces and the recent developments on route to application. Current and future challenges in this field of smart polymer brushes are addressed.

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1 Introduction

Polymer brushes can be defined as long-chain macromolecules that are attached with the anchor sites to a surface¹ or these graft copolymers in which multiple polymer chains are grafted to a linear polymer. They are ensembles of sufficiently densely packed polymer chains.^2–4 Smart macromolecular brushes are also called as stimuli-responsive polymer brushes in some literatures, whose physicochemical properties and shape usually show rapid and reversible changes in response to small changes of their environment (e.g., pH, temperature, salt concentration, electric potential, solvent and surrounding media).^5–7 Smart polymer brushes (SPBs) in the past few years have attracted substantial research interest because these responses can be changed or tuned in an accurate and predictable manner by using an external stimulus, and these smart polymer brush surfaces play an important role in a diverse range of applications to many areas in science and technology.^5,8–16 Smart polymeric-based devices and surfaces that reversibly alter their physico-chemical characteristics in response to their different environment are the center of many studies related to the development of materials and concepts in a broad-range of multi-disciplinary fields, which include responsive biointerfaces that are functionally similar to natural surfaces,^17,18 controlled drug-delivery and release systems,^12,19 anti-fog surfaces and sensor devices,^20,21 coatings that are capable of interacting and responding to their environment,^22,23 composite materials that actuate and mimic the action of muscles,²⁴ and thin films and particles that are capable of sensing very small concentrations of analytes.^25,26

This article concentrates on SPBs that are capable of conformational and chemical changes caused by the external stimuli signal from their environment. These changes are accompanied by variations in the physical properties of polymer. Here, we introduce the key strategies for preparing SPBs, discuss different smart polymer brush surfaces and review the recent developments on the route to application. Finally, challenges in making synthetic systems capable of responding to stimuli in a controllable and predictable manner and future prospectives are examined.

2 The classification and fabricating strategy of polymer brush

Polymer brushes can be defined as long-chain polymer molecules that are attached with one or with a few anchor sites to a surface or a linear polymer.^1,27–30 In polymer brushes, the distance between grafting points is smaller than the chain end-to-end distance. The main chain is commonly referred to as the backbone and the branches as the side chains. If the length of the backbone is significantly longer than that of the side chains, intramolecular excluded volume effects cause the polymer to adopt a cylindrical shape with the backbone polymer in the core, from which the side chains emanate radially.^31–40 Conversely, macromolecular brushes with backbones on the order of the length of the side chains generally adopt compact, spherical dimensions that resemble star polymers.⁴¹ Many synthetic surface-tethered smart polymers, known as SPBs, respond to small external changes in their environment with dramatic property variations.^12,42–46 These polymers can have different composition and architecture, including not only homo-polymers, but also statistical/block copolymers,⁴⁷ grafting copolymers and molecular brushes. Due to densely grafted side chains on a linear polymer main chain, they can be imaged as single molecules by atomic force microscopy (AFM) (Fig. 1a) similar to photographs that are found in a variety of places within the body (Fig. 1b). Molecular brushes have been proposed as synthetic substitutes in order to understand the architecture-property relationship.

Fig. 1 AFM images of molecular brushes: (a) molecular brushes with poly (n-butyl acrylate) (PBA) side chains, and (b) proteoglycans having a protein backbone with glucosaminoglycan side chains.^27,221

Fig. 2 Classification of molecular brushes by branching topologies and chemical composition of side chains.^65,66

2.1 The types of polymer brush

Based on the chemical compositions in the side chains, molecular brushes can be divided into two categories: (1) brushes with homopolymer side chains: linear brushes, gradient brushes with a gradient in grafting density along the copolymer backbone,^48–50 and brush–block–coil copolymers ^51,52 and (2) brushes with copolymer side chains: brushes with random/block copolymer side chains,^53–60 heterografted brushes,^61,62 and AB-type brush (block brush) copolymers^28,63,64etc. While the simplest molecular brushes with one type of homopolymer side chain have been extensively studied, copolymer side chain brushes have also been prepared. Besides the linear cylindrical shape of molecular brushes, special types of brushes with various branching topologies have been synthesized such as star-like multiarm structures.^65–67

2.2 The fabricating strategy of polymer brush

Fixing or anchoring one end of the polymer chain onto a surface, i.e. tethering of the polymer, is one popular method to obtain polymer brushes. Tethering of the polymer to the surface, known as polymer brushes, can be performed either by physical adsorption or covalent attachment. Covalent attachment is often preferred due to the inherent resistance to degradation by temperature or solvents. Atom transfer radical polymerization (ATRP),^68–73 stable free radical polymerization (SFRP),^74,75 and reversible addition fragmentation chain transfer (RAFT) polymerization techniques^76–80 have been the most successful methods. The tethering should be sufficiently dense so that the polymer chains can adopt a defined, stretched chain conformation, which significantly differs from the random-walk conformation of free polymer chains in solution or in conventional solution cast polymer coatings. Controlled/living radical polymerization (CRP) has also been employed for the preparation of molecular brushes,⁸¹ which has provided a versatile route for the synthesis of well-controlled polymers with predetermined molecular weight (MW), narrow molecular weight distribution (MWD), various architectures, and useful end-functionalities.^82–87 We can sum up the strategy to attach polymers to a substrate using the three approaches described below.

2.2.1 Surface grafting. Numerous SPBs were developed by chemical grafting. Generally, as shown schematically in Fig. 3, there are three methods for the synthesis of molecular brushes: “grafting to”, “grafting through” (polymerization of macromonomers), and “grafting from” (grafting the side chains from the backbone).^29,88–133

Fig. 3 Grafting methods for preparing molecular brushes by “grafting to”, “grafting through”, and “grafting from”. “Grafting to” involves the coupling of individual side chains to a common backbone polymer. “Grafting through” consists of the polymerization of macromonomers. “Grafting from” involves growth of the side chains from a well-defined backbone macroinitiator.²⁹⁹

In the “grafting-to” approach, both backbone and side chains are prepared separately, the reaction of end-functional polymers with a polymer backbone precursor containing complimentary functionality on each monomer unit forms covalently bonded layers. Therefore, functional macromolecular chain can tether to the surface or substrate with reactive groups by coupling reaction, radical addition, condensation reaction, etc. In addition, the end-functional polymer chain may attach to the active surface through physicochemical adsorption. However, slow diffusion of the bulky side chains hinders preparation of brushes with high grafting density. In the “grafting from” method, a macroinitiator with a predetermined number of initiation sites is prepared, followed by grafting the side chains from the macroinitiator, therefore this kind of polymerization belongs to surface-initiated polymerization (SIP). Growth of side chains has been mainly achieved via ATRP initiated by pendant bromoester groups on a polymer backbone or on a substrate. In ATRP and other CRP, initiator usually plays a key role for the growth of polymer brush. The popular initiator mainly includes transition metal solid/pyridine ligand; α-organic bromide (such as α-bromoketone, etc.). The “grafting from” or surface-initiated polymerization method usually produces polymer brushes with a higher grafting density and a greater thickness, but it requires the immobilization of an initiator on the surface first. These mechanisms are suitable for molecular brush synthesis via grafting from. The grafting through route involves the polymerization of macromonomers–polymers with polymerizable end groups—“through” their terminal functionality. This method can obtain polymer brushes with high grafting density, assuming a sufficient purity of the original macromonomer. It is difficult, however, to synthesize molecular brushes with a high degree of polymerization (DP) and low polydispersity because of the inherently low concentration of polymerizable groups and the steric hindrance of side chains.

2.2.2 Self-assembled monolayers (SAMs). In general, the attachment of surface-bound initiators onto the substrate needs to be performed prior to SIP studies. Particularly common is the attachment of surface-bound initiators via formation of SAMs,^134,135 which form spontaneously by the adsorption of an active material onto a surface, and possess important properties of self-organization and adaptability to a number of technologically relevant surface substrates. Molecular structures forming SAMs can be classified into three features: (1) a headgroup which strongly binds to the substrate; (2) an endgroup that allows the introduction of a variety of organic functionalities to be incorporated into a monomolecular film; (3) and a spacer unit that connects the headgroup and endgroup and strongly affects the intermolecular separation, molecular orientation and the degree of order in surface. As such the properties of a SAM (thickness, structure, surface energy, stability) can be easily controlled and specific functionalities can be introduced into the building blocks, monomers can be polymerized from surface-anchored initiators generally immobilized by the SAM technique.^17,136–138 Therefore, SAMs offer ease of preparation and versatile surface chemistry, polymer brushes can be produced by SIP techniques with a better control over surface coverage, thickness and composition.

2.2.3 The combined layer-by-layer (LbL) and SIP techniques. Surface tethered polymer chains by chemisorption method can overcome the weaker adhesion to the surface inherent with the physisorption method. In order to ensure that the surface tethered chains grow in the brush regime, a sufficiently high initiator density is required.¹³⁹ In a previous publication, Advincula's group demonstrated the fabrication of intelligent surfaces based on pH and temperature responsive polymer brushes utilizing the combined LbL and SI-ATRP techniques.¹⁴⁰ Relatively thick and dense poly (n-isopropylacrylamide) (PNIPAM) brushes were produced by having multiple layers of the ATRP macroinitiators deposited. The sole deposition of polyelectrolyte macroinitiators and the subsequent polymerization of dense poly (2-hydroxyethyl methacrylate) (PHEMA) polymer brushes have also been reported.¹⁴¹ They have utilized the LbL technique on flat substrates to electrostatically adsorb oppositely charged macroinitiators onto a functionalized substrate, achieving high initiator densities compared to SAMs. Novel films exhibiting properties of low surface energy were prepared with these LbL brush films (Fig. 4).

Fig. 4 Brush surface fabrication via the layer-by-layer (LbL) technique.²⁹⁷

3 Smart polymer brush surfaces

With the application of an external stimulus, smart polymer brush surfaces may be capable of physical and chemical changes. These changes are accompanied by variations in energy of the brush system owing to reconstruction of the polymer chains tethered to the surface.¹⁴²

3.1 The energetic requirements of smart polymer surface

Due to the anchoring of one end of the polymeric segment to the surface, restricted freedom of movement is “transmitted” along the chain. The energy required for the segments further away from the anchoring point to respond is a function of the distance from the surface.¹⁴³ Those segments close to the anchoring points of surface, the transitions from A to B needs relatively higher energy input (ΔE_SR(surface)) because more space and free volume are available further away from the anchoring points. Fig. 5 illustrates the relationship between the surface layer equilibrium energy (z axis), stimulus energy input (x axis), and a physical/chemical response to a stimulus (y axis). The free energy in a polymer brush system is used to evaluate polymer chain or segment transfers from one state to another state spontaneously. Generally, stimuli-responsiveness at polymeric surfaces is an entropy (ΔS) driven process,¹⁴⁴ in which the disorder of anchored chains (ΔS) has greater contributions to the free energy (ΔG) values than the conformational changes resulting from the enthapic component of the free energy (ΔH).

Fig. 5 The relationship between equilibrium energy, stimuli energy input, and physical/ chemical response.¹⁴³

3.2 The main stimuli-responsive types of smart polymer brush

The increasing need for “smartness” in biomedical and engineering materials has generated a growing interest for synthetic polymers that exhibit environmentally responsive behavior. One area of substantial research on stimuli-responsive systems contains the simplest homopolymers that undergo reversible conformational changes in response to external stimuli such as solvent, pH, temperature, and so on, leading to changes in physicochemical properties of both materials and single molecules.

3.2.1 Solvent-responsive polymer brushes. In scaling theory and self-consistent field theory¹⁴⁵ the thickness of the polymer brush is linearly proportional to the degree of polymerization N (but not obviously in a bad solvent). Experiments proved that this relationship retains unchanged for solvents of different quality.¹⁴⁶ However, the prefactor depends on solvent quality and grafting density of polymer chains. Besides the chain constitution, the grafting density is the parameter which affects conformational responsiveness of polymer brushes.

For most polymers, the macromolecular chain can stretch freely and become coil-like in good and bad solvents, respectively. This will lead to a separation tendency among different polymer segments, i.e. phase segregation of the polymer blend. The solvent quality is capable of affecting polymer chain conformation. Whichever, the mixed polymer brush or block polymer brush, they are capable of switching surface wettability due to a reversible, solvent-induced phase segregation of the brush. This solvent selectivity alters the brush morphology and enables control over which phase becomes exposed to the external environment.^147–151 For example, a mixed polymer brush prepared from polystyrene (PS) and poly (2-vinylpyridine) (P2VP)¹⁵² changed the surface composition and wetting behavior after treatment in different solvents. The contact-angle change was found to be strongly amplified on a rough surface where the wetting properties switched from complete wetting to ultrahydrophobic behaviour.¹⁵³ It was shown that a mixed brush made of polystyrene and poly (methylmethacrylate) can induce the local motion (in the range of a few nanometres) of adsorbed nanometre-scale objects through solvent-induced topographical variations of the brush surface.¹⁵⁴ A poly (ethyleneimine)–poly (dimethylsiloxane) mixed brush switched spontaneously from the hydrophilic state in water to the hydrophobic one in air.¹⁵⁵ This adaptive behaviour of mixed brushes was used to develop materials with poor adhesion in a changeable environment. The surface coatings that were fabricated from mixed poly ethylene oxide (PEO)–poly (dimethylsiloxane) brushes¹⁵⁶ were adaptive to liquid and vapour environments so that the surfaces were spontaneously transformed to non-sticky states in air and in water. This behavior was observed on several cycles of exposure of the samples to air and aqueous solutions.

Single molecular conformation transition of brushes by solvent treatments involves the preparation of core–shell molecular brushes in which side chains are composed of hydrophobic–hydrophilic block copolymers. Müller¹⁵⁷ synthesized molecular brushes with PS-b-PtBA, PtBA-b-PS and PtBA-b-PBA, PBA-b-PtBA side chains, followed by hydrolysis of the t-butyl groups, which led to acrylic acid units.^158,159 These brushes are interesting since they resemble a unimolecular micelle of cylindrical shape. As a result, they are not susceptible to dissociation on dilution while conventional multimolecular micelles dissociate below the critical micelle concentration (CMC). Due to the responsive nature of the PAA blocks toward different kinds of solvent, conformational transitions were observed as a function of solvent quality. Gallyamov et al.¹⁶⁰ studied solvent-induced length variation of molecular brushes. They found that the length of brushes varies with the solvent quality of the side chains: the lengths of the backbone and side chains become shorter in a poor solvent as compared to a good solvent.

Vyas et al.¹⁴⁸ used binary polystyrene (PS)–poly (2-vinylpyridine) (P2VP) brushes to switch between several phase-segregated morphologies and thus affect the chemical composition of the brush top layer (Fig. 6). The switching process can be controlled by treating the binary brushes with selective solvents, such as toluene for PS or acidic water for P2VP. When these brushes are treated with toluene, PS chains swell and stretch away from the surface to preferentially occupy the outer-most layer, turning the surface hydrophobic (CA ∼87°). Conversely, when the brushes are treated with acidic water, P2VP chains are solvated and able to stretch away from the surface, turning it hydrophilic (CA ∼18°). The chemical composition of these mixed polymer brushes after treatment with different solvents was confirmed by X-ray photoelectron spectroscopy (XPS) as the soluble polymer chains are preferentially enriched at the outermost layer after drying.¹⁴⁹

Fig. 6 Schematic diagram showing switching behavior of binary polymer brushes upon treatment with selective solvents.¹⁴⁸

At small grafting densities (so called “mushroom regime”) the response of grafted chains is very similar to that of the bulk polymer solution.¹⁴⁵ At high grafting densities the collapse is weak and the brush forms a homogeneous layer, which is slightly thinner in a poor solvent than in a good solvent or in the θ regime. That is because of the very crowded layer of strongly stretched polymer chains when there is no free space for conformational changes. In the grafting density regime, in which layers vary between very low and high surface coverage regimes, the brushes are unstable in poor solvents and form clusters (pinned micelles) on the surface to avoid unfavorable interactions with the poor solvents.^161,162 In a good solvent the brush is swollen and it forms a homogeneous layer of stretched tethered chains. In this grafting density regime (cross-over regime) the polymer brush demonstrates the most pronounced response to solvent quality.¹⁶³ Thus, we may conclude that the largest conformational response in a polymer brush is in the very beginning of the brush regime when chains start to overlap. Switching a range of the thin polymer film properties relevant to density and thickness of the film can be easily approached with the brushes of moderate grafting densities. It is noteworthy that the optimal grafting density may be affected by a concentration dependency of the x-parameter for some polymer–solvent systems. For example, the high responsiveness (collapse in water above a lower critical solution temperature) of both brush thickness and density profile is sensitive to grafting density and solvent quality. The responsive behavior of the homopolymer brush is referred to changes of free energy of the brush in its environment due to the change of solvent quality. Any application of the responsive homopolymer brushes will be grounded on this principle.

Unlike conformation transition of brushes in solution, solid state conformation changes driven by exposure to different kinds of solvent are particularly interesting due to the possibility of both in situ visualization by AFM and manipulation of the conformational properties of molecular brushes. Gallyamov and co-workers studied conformational transitions of PBPEM-g-PBA brushes induced by cyclic exposure of the wafers with the adsorbed brushes to water and alcohol vapors.^164,165 Exposure to saturated alcohol vapor induced collapse of the adsorbed individual polymer chains while exposure to saturated water vapor promoted their extension.¹⁶⁶ In the presence of the alcohol layer with the lower surface energy, these brushes tend to minimize the occupied surface area through partial desorption of the PBA side chains leading to a transition from an extended to a globular conformation. Upon condensation of water vapor, PBA side chains re-adsorb to the substrate and cause extension of the backbone.

3.2.2 pH-responsive polymer brushes. All pH responsive polymers contain pendant acidic (e.g. carboxylic and sulfonic acids) or basic (e.g. ammonium salts) groups that are capable of either accepting or releasing protons in response to environmental changes in pH.¹⁶⁷ Changes in the environmental pH thus lead to conformational changes of the soluble polymers and a change in the swelling behavior of the hydrogels when ionizable groups are linked to the polymer structure. Therefore pH is an important signal, which can be addressed through pH-responsive materials.^168–174 Ionizable polymers with a pK_a between 3 and 10 are candidates for pH-responsive systems. Weak acids and bases like carboxylic acids, phosphoric acid and amines exhibit a change in the ionization state upon variation of the pH. This leads to a conformational change for the soluble polymers when these ionizable groups are linked to the polymer structure. For example, the pK_a of poly (acrylic acid) (PAA) depends on molecular weight and ranges within 6.8–7 for molecular weights of order 100 kDa.¹⁷⁵ When the pH of the solution is below the pK_a value, the polymer is in a compact, collapsed form. As the pH increases above the pK_a, the polymer exhibits the fully stretched conformation due to the electrostatic repulsion between the segments.¹⁷⁶ Classical monomers are acrylic acid (AA), methacrylic acid (MAA), maleic anhydride (MA), and N,N-dimethylaminoethyl methacrylate (DMAEMA). The unique properties of pH-responsive polymers arise from the facile pH adjustment which induces the ionic interaction and hydrogen bonding, resulting in a reversible microphase separation or self-organization phenomenon. Thus, pH responsive polymeric systems provide the possibility for the preparation of smart functional materials which can be used for potential therapeutic applications, e.g., controlled drug delivery based on pH-triggered release.

A change in the ionization state caused by pH variation usually accompanies conformational changes of single molecular brushes. Atomic force microscopy was used to study the conformation of adsorbed brushes as a function of pH. The adsorbed molecules undergo a globule-to-extended conformational transition as the solution is changed from acidic to basic. This transition was monitored on a mica surface by imaging individual molecules with AFM.¹⁷⁷

Poly-2-(dimethylamino)-ethyl methacrylate (PDMAEMA) is a unique responsive polymer since it responds to temperature and also to pH in aqueous solution. It can also be permanently quaternized and converted to zwitterionic structures (via reaction with propanesultone), forming materials with upper critical solution temperature (UCST) properties, as described in the previous section. As expected, the structural changes were induced by variation of pH, ranging from 2 to 10.¹⁷⁸ At pH 7, the PDMAEMA brushes formed worm-like structures that can be quite curved. At pH 2, most of the brushes are protonated and ionized, showed more stretched morphologies. More remarkably, at pH 10, the brushes are strongly contracted with an average length around 110 nm, which is attributed to a collapse of the non-ionized PDMAEMA side chains. pH responsive PDMAEMA brushes were also synthesized from a conductive polythiophene (PT) backbone by Winnik et al.¹⁷⁹ They observed conformational transitions of PT-g-PDMAEMA with a change in pH that contributed to spectral shifts. As shown schematically in Fig. 7, the polymer brush forms a more extended conformation with a decrease in pH from 8 to 2.

Fig. 7 Proposed mechanism for the molecular conformational transition accompanying the change of solvent polarity or the change of pH in water.¹⁷⁹

3.2.3 Temperature-responsive polymer brushes. The effect of temperature on the temperature-responsive copolymer brushes focuses on the point of the critical solution temperature in a special medium. When the temperature of the medium nears to upper or lower the critical solution temperature of the polymer, the brushes will exhibit a sudden change in surface morphology. Such copolymers, which become insoluble upon heating, have a lower critical solution temperature (LCST). Conversely, systems which become soluble upon heating have an UCST. Thermodynamically, the LCST and UCST behavior of polymers can be explained as a balance between the entropic effects of the dissolution and the ordered state of water molecules in the vicinity of the polymer and the enthalpic effects due to hydrogen bonding and hydrophobic interactions. These transitions are observed as coil-to-globule transitions. The physical properties—for example shape, size, color, solubility, viscosity or wettability—of thermoresponsive materials vary in response to mild temperature fluctuations.¹⁸⁰ Thus, these types of materials have been shown to be useful for a wide range of applications such as biosensors, implants, scaffolds for tissue engineering or drug-delivery devices, selective bioseparation, phase separation immuno-assays, cell patterning, and DNA sequencing etc.^181–191. In particular, PNIPAM has been by far the most studied thermoresponsive polymer in materials science.¹⁹²

Reversible solubilization of thermoresponsive polymers upon a change in temperature leads to conformational change such as stimulated collapse by dehydration and expansion by rehydration. The resulting conformational changes can be unique for molecular brushes because these temperature driven changes occur on the single molecule level. Water-soluble polymers whose solubility depends on temperature result in materials with a LCST or UCST. While most synthetic water-soluble polymers become more soluble upon heating, some of them precipitate in solution. Polymers with tunable LCST are of increasing interest for biological applications, because they are soluble in aqueous solution below their LCST through hydrogen bonding with water molecules, but become dehydrated and insoluble when heated above the LCST, resulting in abrupt phase separation. For example, thermoresponsive linear polymers such as PNIPAm, exhibit sharp coil–globule transition in water at 32 °C, changing from a hydrophilic state below this temperature to a hydrophobic state above it.^193–195 The phase transition, as shown schematically in Fig. 8, and hence the origin of the ‘smart’ behavior, arises from the entropic gain as water molecules associated with the side-chain isopropyl moieties are released into the bulk aqueous phase as the temperature increases past a critical point.

Fig. 8 Schematic of ‘smart’ polymer response with temperature.⁴²

An interesting UCST polymer brush, poly [2-(methacryloyloxy)ethyl]-dimethyl(3-sulfopropyl) ammonium hydroxide (PMEDSAH), was synthesized and characterized by Azzaroni et al.¹⁹⁶ Zwitterionic PMEDSAH brushes exhibit a complex temperature behavior that depends on the PMEDSAH molecular weight and grafting density, and results in various inter- and intrachain associated states.¹⁹⁷ By lowering the surface graft density, the magnitude of the contact angle change could be increased from about 10° (100% initiator grafting density) to about 35° at 10% initiator graft density. Sun et al.¹⁹⁸ grafted thermally responsive PNIPAAM brushes on both a flat and a rough silicon substrate via surface initiated atom transfer radical polymerization. However, reversible, thermoresponsive switching between superhydrophilic (∼0°) and superhydropobic (∼150°) states was realized only on the microscopically rough surfaces (Fig. 9a). Similarly, Fu et al.¹⁹⁹ realized a dynamic superhydrophobic to superhydrophilic switch by synthesizing a PNIPAAM brush on a nanoporous anodic aluminum oxide surface²⁰⁰ (Fig. 9b).

Fig. 9 (a) Switching between superhydrophilicity and superhydrophobicity of a PNIPAAM-modified rough silica surface,²¹² and (b) representative topographical atomic force microscopy (AFM) images of PNIPAAM grafted of a PNIPAAM-modified nanoporous, structured anodic aluminum oxide membranes in water at 25 °C (left) and at 40 °C (right).¹⁹⁹

Another class of thermally responsive systems is based on oligo (ethylene glycol) methyl ether methacrylates (OEGMA).^201–204 These thermoresponsive polymers containing short oligo (ethylene glycol) side chains were recently proposed as an attractive alternative to PNIPAM. Poly (ethylene glycol) (PEG) is an uncharged, water-soluble, nontoxic polymer used to prepare biocompatible materials, such as biosensors and drug delivery systems.^{202,203,205–207} Recently, Lutz²⁰³ carried out the copolymerization of di (ethylene glycol) methyl ether methacrylate (MEO₂MA) with poly (ethylene glycol) methyl ether methacrylate (PEGMA, MW = 475) by ATRP and demonstrated that the LCST of obtained polymer increased with increasing composition of PEGMA. This concept has been applied to molecular brush systems by Matyjaszewski and co-workers.⁶⁵ Molecular brushes with statistical or block copolymers of di (ethylene glycol) methyl ether methacrylate (MEO₂MA) and tri (ethylene glycol) methyl ether methacrylate (MEO₃MA) have been prepared by grafting from a poly (2-(2-bromoisobutyroyloxy)ethyl methacrylate (PBIEMA) macroinitiator via ATRP.²⁰⁸ In the case of brushes with statistical copolymer side chains, the LCST increased with the mole fraction of MEO₃MA in the side chain, and the hysteresis between the heating and cooling cycles decreased with the length of the side chain. For brushes with block copolymer side chains, the cloud point of the block brushes solution displayed two stages of aggregation during heating, exhibiting the results of both intermolecular and intramolecular aggregation.

As many other methacrylate monomers, OEGMA can be polymerized under controlled radical polymerization methods yielding well-defined materials. Polymers constructed from these PEG macromonomers exhibit fascinating solution properties in aqueous media. Depending on the molecular structure of their monomer units (i.e., nature of the polymerizable moiety, length of the PEG side chain, end group of the PEG side chain), the polymers can be insoluble in water and readily soluble up to 100 °C or even show thermoresponsive behavior. It is worth noting that, while temperature-responsive behavior of polymers is predominantly monitored in solution, their solid state responsiveness has also been studied by differential scanning calorimeter (DSC) and dynamic mechanical analysis (DMA).²⁰⁹

3.2.4 Mechanically-responsive polymer brushes. As already discussed, changes in the surrounding environmental conditions can trigger chemical and conformational changes in stimulus-responsive polymer brush layers.^210–212 It is, however, also possible for a stimulus-responsive polymer system to change chemically in response to a mechanical stimulus. This is similar to the known phenomenon of mechanotransduction in biology, i.e., the ability of cells to convert a mechanical stimulus into an electrical signal.

Engineering new polymer surfaces involves designing complex architectures with features such as graded branching and composition that will lead to novel material properties in terms of mechanical behavior, adaptability, and functionality. Nanoscale devices and their operating environment require adaptive surfaces constructed with smart properties that can not only sense or respond to environmental stimuli but can also be robust and possess tailored, on-demand physical properties.^213–215 The polymer brush layers are chemically tethered to the surface at one end, virtually any chemistry can be designed into the layer depending on intended surface interactions, and the high grafting density combined with uniformity in composition, thickness, and structure allows the entire surface to respond to local environmental stimuli.²¹⁶ They inherently provide the ability to control and change surface composition, allow on-demand properties, and are becoming increasingly significant for practical application in the fields such as nanoscale lubrication, sensing, and biocompatibility.^217–220 Therefore, polymer brushes are considered as the ideal choices in such applications.

Molecular brushes change their shape upon variation of film pressure during either lateral compression^50,221–223 or spreading²²⁴ on a substrate. Similar to the effect of the vapor pressure discussed above, the transition between extended and globular conformations occurs due to the interplay of energetically favored adsorption and entropically disadvantaged stretching of the PBA side chains. AFM allows in situ tracing of the pressure-responsive macromolecules as they change their shape in response to the pressure gradient during spreading on a solid substrate. Unlike static films, which have the same conformation across the film, molecules in a flowing monolayer are unevenly compressed due to the pressure gradient in the flow direction. This system is particularly interesting since lubrication properties of thin layers in micromechanical joints depend on pressure, which controls the substrate coverage as well as conformation and orientation of the adsorbed molecules. In addition to the backbone extension, steric repulsion between the densely grafted side chains causes significant tension in the backbone covalent bonds. The bond tension depends on molecular architecture and interaction of macromolecules with the surrounding environment.²²⁵ The unique property of these miniature tensile machines is that the bond tension is self-generated without applying any external force. One can control the bond tension in a broad range from pico- to nano-Newtons through variation of temperature, solvent quality, and substrate composition. In solution, the highest tension, which is developed in maximally dense brushes in an athermal solvent, can be calculated as f = f₀N^3/8, where N-degree of polymerization of side chains and f₀ = kT/b ≅4 pN. For example, for a molecular brush with N = 100 and monomer length b = 1 nm, the backbone tension ranges from f = f₀ = 4 pN in a melt to f = f₀N^3/8 ≅20 pN in a good (athermal) solvent. This tension may be enough to break a weak hydrogen bond; however, it is too small to rupture a covalent bond. In order to achieve higher tensions, one should change the molecular design. Recently, Panyukov et al.²²⁶ have shown that bond tension in the order of 1 nN can be developed in a short space of pom-pom macromolecules.

The kinetics of backbone scission has been studied as a function of substrate surface energy.²²⁷ The scission rate revealed extremely high sensitivity to the surface energy of the substrate. Fig. 10 shows kinetics of the decrease of the average polymer chain length (L) on substrates with different surface tension γ. It shows that the rate constant of the scission reaction increases by almost 2 orders of magnitude when the surface tension of the underlying substrate increases by just 5%. Fig. 11 shows a series of AFM images obtained from each of the brushes exposed to aqueous substrates with different surface energies for a time interval of 62 min. One can see that the molecules are noticeably shorter on substrates with a higher surface energy. As such, these polymer architectures can be regarded as miniature tensile testing machines, wherein the brush section generates force of a desired magnitude and transmits it to covalent bonds in the backbone. These molecular devices can be used for mechanical activation of chemical reactions at specific chemical bonds within a macromolecule. For example, brushes with a disulfide (S–S) bond in the middle of the all-carbon polymethacrylate backbone have been synthesized to demonstrate that only one specific bond within a macromolecule can be broken while leaving other bonds intact.²²⁸

Fig. 10 Kinetics of the decrease of the average polymer chain length (L) on substrates with different surface tension.²²⁷

Fig. 11 AFM height images of molecular brushes taken up on mica surfaces after spending 62 min on aqueous substrates with different surface tensions.²²⁷

3.2.5 Electro- and magnetic-responsive polymer brushes. Comparing with the single pH-responsive system, an electrical field in the form of an external stimulus offers numerous advantages (e.g. availability of equipment). This form of an external stimulus also allows for precise control over the magnitude of the current, the duration of electrical pulses and the interval between pulses.²²⁹ These systems exploiting this external stimulus are prepared from polyelectrolytes, which are polymers that contain a relatively high concentration of ionizable groups along the backbone chain. This property renders these polymers pH-responsive as well as electro-responsive.^167,229 Under the influence of an electric field, electro-responsive hydrogels generally shrink or swell and this property has allowed its application in drug delivery systems, artificial muscle or biomimetic actuators.²³⁰

Molecular brushes with block copolymer side chains can also act as templates for the preparation of nanostructured hybrid materials by coordination with metal ions. Various metal, metal oxides, and semiconducting nanoparticles have been prepared in this way. Similarly, the cylindrical shape of brushes with diblock copolymer side chains composed of PAA-b-PBA has been used as a single molecular template for the preparation of magnetic nanoparticles, wherein PAA core blocks coordinate with Fe²⁺ or Fe³⁺ ions and the PBA shell provides the stability of nanoparticles.⁵³ Temperature-dependent magnetic properties of the hybrid nanocylinders have been investigated. In the temperature range of 25–295 K, the fabricated nanoparticles are superparamagnetic because no hysteresis is observed. The ferrimagnetic nature of the fabricated magnetic nanoparticles, however, was detected at very low temperatures, such as 2 K, showing symmetric hysteresis loop.⁵⁴

3.2.6 Ion-responsive polymer brushes. As discussed above, zwitterionic polymers such as poly (sulfobetaine)s have thermoresponsive UCST properties. Another way to achieve the water solubility of poly (sulfobetaine) is to add a simple salt. The site-binding ability of the cation and the anion allows polymer chains preferentially to complex the low molecular weight electrolyte and reduce the attractive inter-chain interaction, leading to chain expansion in aqueous solution. For cationic polyelectrolyte brushes, however, addition of salt was found to screen the electrostatic interactions within the polyelectrolyte, resulting in conformation changes from stretched to collapsed form. Indeed, the quaternized PDMAEMA brushes collapse in solution with high concentration of monovalent salt,¹⁷⁸ in the presence of a di- or trivalent salt, this collapse passes through an intermediate state in which the cylindrical polymer brushes assume a helical conformation. The formation of the helix is prompted by the contraction of the polymer molecules along the long axis by the presence of the multivalent ions.

3.2.7 Complex-responsive polymer brushes. Recently, the research interest of the stimuli-responsive behavior of smart polymers has been extended to multiple external stimuli from single stimuli. Of special importance seem to be polymers that are responsive to light and temperature, and accordingly, there have been several reports on temperature-responsive poly (N-alkylacrylamide) copolymers, for example, those containing light-responsive azobenzene in the side groups of the polymer chain.^231–235 Azobenzene groups are known to undergo a reversible isomerization from trans- to cis-configuration upon irradiation.²³⁶ In the excited cis-configuration, the higher dipole moment leads to an increase of local polarity of the polymer chain, which causes an increase of the LCST.^{234–235,237} As a result, these copolymers can be precipitated upon irradiation with UV light within a certain temperature range. The azobenzene chromophores were incorporated as side groups in the polymer backbone and not at the chain end. Upon increasing the number of azobenzene units, the photoinduced shift increased up to a certain value but decreased thereafter. These phenomena might be due to the variety in the number of azobenzene moieties and side-group effects of the photofunctional units. Akiyama and Tamaoki²³⁸ demonstrated that photoisomerization of a single terminal unit of a polymer could also trigger a phase transition of a polymer chain. They prepared an end-functionalized PNIPAM by atom transfer radical polymerization with an azobenzene derivative initiator. A linear increase of the LCST shifts with increasing amount of azobenzene located at the end group was found by this group, which was in contrast to the transition behavior of azobenzene-functionalized PNIPAM copolymers.

A growing trend in designing stimuli-responsive polymeric solutions is toward creating systems with multiple-responsive components, with covalently or physically bonded segments responsive to different stimuli. One example of the multi-responsive switchable copolymer is based on temperature responsive PNIPAM and pH- and photo-responsive spirobenzopyran which exhibits temperature, pH, and photo-responsiveness in aqueous solutions. In mixed brushes, two or more different polymers are attached to the same substrate and constitute the brush. Unlike unmixed brush polymer, different polymers in the mixed brush segregate into nanoscopic phases. The phase segregation is a lateral segregation process in a nonselective solvent in which different polymers form spherical or elongated clusters. Both the polymers are exposed on the top of the brush. In selective solvents, the mixed brush structure may be seen as a combination of lateral and layered segregation mechanisms. In the latter case, one polymer preferentially segregates to the top of the brush, while another polymer forms clusters segregated onto the grafting surface. The most important difference of the mixed brush compared to the homopolymer brush is that not only the height and density profile but also the composition profile depends on the solvent quality. In other words, the surface composition of the brush is switched by a change in its environment.

Much like AB diblock copolymers, when molecular weights are sufficiently high, the two immiscible homopolymers in mixed brushes will undergo microphase separation; the covalent fixation of one end of polymer chains on a solid surface prevents macroscopic phase segregation. The phase behavior of binary mixed homopolymer brushes on a planar solid substrate is dictated by a number of factors, including (i) degree of polymerization (DP) of each grafted polymer (N_A and N_B), (ii) Flory–Huggins interaction parameters between two components (χ_A–B), between each polymer and environment (χ_A-E and χ_B-E), and between each polymer and the grafting substrate (χ_A–S and χ_B–S), where A, B, E, and S represent respectively polymer A, polymer B, environment E (E could be a solvent or a polymer matrix, etc.), and substrate, (iii) grafting density of each polymer, and (iv) distribution of grafting sites of two polymers on the substrate.

When AB binary brushes, which consist of hydrophilic and hydrophobic homopolymers, contact with a hydrophilic solvent the hydrophilic constituent segregates to the surface, vice versa. Besides the segregation perpendicular to the surface the laterally structured phase might become stable, but forms dimples, i.e., small clusters on the surface which are separated by a distance of chain extension. If the solvent is bad for one component and good for the other component surface micelles form, i.e., the component with the low solvent affinity collapses into a dense core, which is shielded by other components. Theoretical research showed that for equal amounts of A and B chains grafted to the surface Φ = 1/2 as a function of overlap δ and incompatibility χ, the disordered phase which is neither laterally nor perpendicularly segregated, the layered phase (1D), where the symmetry between A and B is spontaneously broken and the two components segregated perpendicular to the surface, the “ripple” phase, in which the two components segregated laterally into symmetrical cylinders, and two “dimple” phases.

The phase diagrams are shown in Fig. 12. The incompatibility χ at which the “ripple” structure forms increases linearly with δ in the limit of strong overlap δ→0. Upon the increasing incompatibility, a second order transition from the disordered phase to the “ripple” phase to an hexagonal “dimple” phase. Fig. 12(b) is the phase diagram for δ = 1/2 as a function of the composition Φ. At high incompatibilities or extreme compositions the majority component forms a hexagonal array of clusters. At lower incompatibilities or more symmetrical composition, a hexagonal “dimple” phase was found, but the minority component forms the clusters.

Fig. 12 (a) Phase diagram for a symmetric polymer brush (Φ = 1/2): under good solvent conditions a transition between a disordered and a “ripple” phase can be found. In bad solvent conditions the disordered, the ripple and two “dimple” phases are stable. (b) Phase diagram for δ = 1/2 as a function of the composition Φ and the incompatibility χ , “dimple A” and “dimple B” denote the hexagonal arrangement of A rich and B rich clusters, respectively. The inset displays the variation of the lateral unit cell size L along the “dimple” “ripple” phase boundary. The solid line corresponds to the ripple phase the dashed line corresponds the dimple phase.¹⁵⁷

The complexity of the problem, however, substantially increases when the designs of complex responsive systems that mimic the functions of life systems are considered. Such artificially created systems will be capable of reporting on toxins, diagnosing cancer cells, monitoring important parameters of organs, and targeting the release of drugs. Currently, research is focused on how the interactions with polymer brushes may be precisely tuned and monitored in a controlled environment. This has potential benefits for biomaterials, sensors, microfluidic technologies, adhesive materials, micro-actuators, and so forth.

4 Emerging applications of SPBs

The major objective for the application of SPBs is to regulate, adjust, and switch interaction forces between the brush and its environment constituted of liquid, vapor, solid, another brush, particles, and so forth. The simplest formulation of the problem is switching between attraction and repulsion. For example, the polymer brush-like layer stabilizes colloidal dispersion. However, upon a stimulus (a change of its environment or medium, actually), the colloid coagulates because the repulsive forces of the brush have been “switched off.” This simple effect has numerous important applications in various technologies, and it has not yet been fully explored and engineered. The same simple problem is important if the friction coefficient and adhesion, or wetting could be rapidly changed to switch off and on for capillary flow,¹⁸⁹ cell adhesion, protein adsorption,⁴² cell growth,²³ membrane permeability²³⁹ and drug release.²⁴⁰ Therefore, polymer brushes with different stimuli-responsive properties may be applied to different fields.

4.1 Micro/nanomaterial system fabrication

The stimulus-response capability of polymer brushes could be used as a triggered “catch and release” surface for nanomaterial fabrication. These brush surfaces provide interesting substrates for making novel devices, the preferential chain orientation of brushes on the surface can also be used to template micro/nanoscale materials. For example, Comrie and Huck²¹⁰ harnessed this capability for the fabrication of polymer–metal micro-objects. They incorporated a hydrophobic functional group into poly (glycidyl methacrylate) (PGMA) brushes, as a means of creating a robust etch-resistant film on a chromium substrate. As shown in Fig. 13, Tugulu et al.²⁴¹ used poly(methacrylic acid) (PMAA) brushes as a novel template to form microstructured, crystalline calcite thin films. This strategy makes use of photo-lithographically patterned PMAA brushes grown by SI-ATRP and capitalizes on the film's ionic structure. When supersaturated calcium carbonate solution is passed over the PMAA brush, the brush templates the calcium carbonate through ionic interactions and, upon annealing, produces a crystalline calcite film that is an exact 3D reproduction of the patterned PMAA brush. The use of SPBs in this approach may bestow additional control over the template morphology by inducing compressive or lateral stresses that enable nanofilm porosity control or finely tuned fractal geometries. For structural patterning, it should be become an interesting development in the future to use SPBs and selective deposition techniques.

Fig. 13 A novel approach to form microstructured, crystalline calcite thin films. Photo-lithographically patterned poly (methacrylic acid) (PMAA) brushes are grown by SI-ATRP and capitalize on the film's ionic structure, and the preferential chain orientation of brush thin films can be used to template micro/nanoscale for novel device fabrication.²⁴¹

4.2 Lubrication of surfaces

Polymer brush lubrication mainly stems from the desire for reducing or controlling the friction forces between surfaces in relative sliding motion.^{139,242–246} While the observation of extremely small kinetic friction coefficients has stimulated first interesting applications, as, for example, in the design of artificial joints,²⁴³ the theoretical understanding is still incomplete.²⁴⁷ Since most of the investigations have been devoted to (quasi-) stationary processes, such as for instance steady or oscillatory shear motion, little is known about nonstationary polymer-brush lubrication. The same applies to polymer-brush lubricated surfaces with embedded macromolecules, as they appear in nature, e.g., in mammalian synovial joints.²⁴⁸

Apart from synovial joints, many other biological systems contain brush-like structures and most of them also contain macromolecular inclusions, e.g., capillaries in plants or bloodstream. Such inclusions increase the frictional loss within the bilayer, but bear the distinct advantage of stabilizing nonstationary processes. This should be very important for the understanding of biological transport processes.

4.3 Novel biological sensors

Smart polymer brush films have been designed by using a variety of approaches, including reversible photoisomerisation reactions, reversible swelling/collapsing of grafted polymers, and phase separation in mixed grafted brushes or diblock copolymers.^15,249 These surfaces are capable of responding to very subtle changes in the surrounding environment such as light, temperature, salt concentration and pH.²⁵⁰ The macroscopic responses are caused by the reorganization of the internal or external surface structure of the deposited polymer layers. Chemically- and biochemically-responsive surfaces offer intriguing possibilities for the development of novel biological sensors,

4.3.1 Electrochemical DNA (E-DNA) sensors. Indeed, smart polymer brush surfaces that respond to specific chemical and biological species have been the basis for the fabrication of highly sensitive, reagentless, re-usable biosensors. One recent development is the electrochemical DNA (E-DNA) sensor,^251–253 which is the electrochemical equivalent of an optical molecular beacon-oligonucleotide²⁵⁴ probe that becomes fluorescent upon hybridization with target DNA molecules. The detection method in the E-DNA sensor is based on the alteration of the electron transfer dynamics as a consequence of a structural rearrangement induced by target hybridization. An E-DNA sensor is comprised of a surface-confined DNA stem-loop labeled with an electroactive reporter as the hybridization sensing element²⁵⁵ (Fig. 14a). In the absence of a target, the stem-loop holds the redox moiety (e.g. ferrocene, Fc) in proximity to the electrode, producing a large Faradaic current. Other directly related sensors based on binding-induced folding of aptamers have been developed.^256,257

Fig. 14 (a) Signal-off E-DNA sensor based on a surface-confined stem-loop oligonucleotide that holds the ferrocene (Fc) group into close proximity with the gold electrode surface, thus allowing facile electron transfer from the redox group to the electrode. On hybridization with the target sequence, the distance between the Fc group and the electrode is altered, decreasing the electron transfer efficiency,²²⁵ (b) and (c) signal-on E-DNA sensors, wherein a large detection signal arises upon hybridization with target DNA.^253,256

4.3.2 Electrochemical aptamer-based (E-AB) sensors and cell-based sensors. E-AB sensors and cell-based sensors based on binding-induced folding of aptamers have been developed.²⁵⁷ Aptamers are DNA or RNA sequences selected in vitro from combinatorial libraries by systematic evolution of ligands by exponential enrichment (SELEX). Aptamers can be selected against diverse targets, such as dyes, proteins, peptides, aromatic small molecules, antibiotics and other biomolecules, with high specificity and affinity,²⁵⁸ and thus they are particularly useful as the basic sensing element for biosensor applications. A series of novel electrochemical aptamer-based (E-AB) sensors (Fig. 14b, c), an analogous version to the E-DNA sensor, have been reported for such diverse targets as the blood-clotting enzyme thrombin,^256,257 the small molecule cocaine²⁵⁹ and adenosine triphosphate (ATP).²⁶⁰ Cell-based sensors have also been exploited. An elegant approach to establish molecular communication between cells and material surfaces based on enzyme-responsive SAMs was introduced by Mrksich et al.²⁶¹ The authors demonstrated²⁶² first that 4-hydroxyphenyl valerate-terminated SAMs on gold electrodes could be switched enzymatically by cutinase from a redox inactive molecular brush surface to a redox active molecular brush surface.

4.4 Drug delivery

Conventional drug delivery methods physically entrap molecules within a polymer lattice; the drug is released slowly by diffusion or upon degradation of the network. These methods typically result in an early peak in plasma drug concentration followed by a steady, linear release. This is far from ideal because the local drug concentration and location of delivery is not precisely controlled. Below the therapeutic dose, the drug is ineffective whereas high concentrations of drug may be toxic or lead to undesirable side effects. Polymers have been used to tailor drug release, which maintains the drug concentration within the desired therapeutic range. However, such controlled release systems are insensitive to metabolic changes in the body and are able to neither modulate drug release nor target the drug to diseased tissue. This lack of control has motivated the exploitation of bioresponsive polymers as drug carriers. More recently, drug carriers that respond to magnetic fields,²⁶³ light,²⁶⁴ radiation,²⁶⁵ and ultrasound²⁴⁰ have also been developed. These external stimuli allow for greater control over when and where the drug is released. By tuning the formulation or chemical moieties of the polymer, the sensitivity to the stimuli can be precisely controlled.

Externally regulated drug delivery systems allow for pulsatile drug delivery, which may be defined as the rapid and transient release of a certain amount of drug within a short time period immediately after a predetermined off-release period.²⁶⁶ Targeted drug delivery systems allow for drug delivery to specific sites, organs, tissues or cells in the body where drug therapy is required, e.g. the specific targeting of drugs to cancer cells.²⁶⁷ A very effective way of achieving site-specific drug targeting is by employing stimuli-responsive polymers. In the field of drug delivery it is the LCST of polymers and systems that is generally more relevant. In terms of thermodynamics, the phenomenon of polymer aggregation at the LCST is owed to the entropy (S) of the two-phase polymer and water system.²⁶⁸ A positive ΔS allows the increase in temperature to contribute to the system aggregation. This is also encouraged by the positive enthalpy ΔH (which is smaller than the entropy term). Under these circumstances, association is favorable as the free energy of association (ΔG = ΔH − TΔS) is negative.²⁶⁹ Theoretically, a negative excess entropy of mixing is required for an LCST; however, the nature of the polymer–water interactions may also be responsible.^{193,270–274}

Electroactive functionalized surfaces based on the hydroquinone–quinine redox couple have been shown to give real-time control over the molecular interactions that mediate peptide attachment (Fig. 15). The electroactive monolayers were able to directly switch peptide ligand activities on and off, and subsequently to influence the behavior of attached cells in situ and in real time.²⁷⁵ This dynamic property was based on the use of the electroactive O-silyl hydroquinone moiety to tether the arginine–glycine–aspartic acid (RGD) peptide ligand to the monolayer. Upon electrochemical oxidation of the O-silyl hydroquinone to the corresponding benzoquinone moiety, the silyl ether was hydrolyzed and the RGD peptides were selectively released from the surface.

Fig. 15 Selective release of the RGD peptide from a monolayer presenting the O-silyl hydroquinone by electrochemical oxidation and subsequent immobilisation of a second RGD peptide by a Diels–Alder reaction.²⁶²

4.5 Electrically-controlled switchable biological surfaces

The molecular brush surfaces with a number of different electroactive groups have been successfully employed to switch on functionalities in situ, offering an unprecedented ability to manipulate the interactions of DNA, proteins, and cells with brush surfaces.²⁶² Electrically conducting polymers are of considerable interest for a variety of biomedical applications.²⁷⁶ Conducting polymer is generally comprised of a conjugated polymer chain with π electrons delocalised along the backbone, yielding a semiconducting polymer that can be reversibly tuned through doping, an oxidation–reduction process where charge carriers are introduced to the polymeric backbone either chemically or electrochemically.

Polypyrrole is a particularly interesting candidate for biomedical applications, by virtue of its chemical and thermal stability, and low cytotoxicity. Apart from being exploited in drug-delivery systems,^277,278 polypyrrole polymers may be especially useful as advanced substrates for cell cultures since they provide a non-invasive way to regulate cell form and function (e.g. DNA synthesis). By reversibly changing their oxidation state and, consequently, their properties and surface binding characteristics, polypyrrole polymer films on indium tin oxide (ITO) coated glass substrates have been shown to act as dynamic cell culture substrates.²⁷⁹In vitro studies demonstrated that extracellular matrix molecules, such as fibronectin, adsorb efficiently onto the oxidised (polycation) polypyrrole thin films, and support cell attachment under serum-free conditions.

Low density polymer brushes on gold have attracted interest for controlling protein adsorption and release under electrical modulation.^280,281 These surfaces display increased interchain distances, enabling the reversible conformational transition of surface-confined molecules. Amino-terminated monolayer polymer brushes induced a neutral and hydrophobic surface under a negative potential and a positively charged and hydrophilic surface under a positive potential. These low density SAMs have been successfully integrated in microfluid chips to reversibly control the assembly of two proteins with different isoelectric points²⁸¹ (Fig. 16).

Fig. 16 Amino-terminated monolayer brushes show reversible and different conformational reorientation behavior under negative and positive potentials.²⁸¹

4.6 Thermo-responsive culture dishes for cells

A class of thermally-responsive polymer surfaces that regulate molecular recognition events and control cell attachment and detachment without cell damage has been studied during the past few years. The most widely studied system is PNIPAM, which has a LCST of 32 °C in aqueous solution. Below its LCST, PNIPAM polymer is in an extended, solvent-swelled conformation, but when heated up above the LCST, the polymer undergoes a phase transition to yield a collapsed morphology that excludes solvent. This behavior is based on a widespread hydrogen bond network between the amide groups and water molecules at lower temperatures, whereas at higher temperatures the stabilizing H-bonds break up and the hydrophobic interactions become predominant²²² (Fig. 17).The fact that PNIPAM undergoes a sharp property change in response to a moderate thermal stimulus near physiological temperatures has been utilized to develop thermo-responsive culture dishes for cells.

Fig. 17 Diagram illustrating the temperature-induced switching of a PNIPAM-modified surface.²⁹⁸

4.7 Permeability switching in micro/nanoporous membranes

The possibility of dynamic control of the permeation of chemicals through nanoporous membrances^26,282,283 or the interaction of molecules and ions with a responsive surface^284,285 offers a unique opportunity for bioseparation.^286,287 Surface-grafted SPBs provide an exciting means for controlling permeation through nano- and microporous membranes. The application of smart polymer surface to filtration systems can possibly improve filter life, streamline cleaning cycles, or provide antimicrobial properties to the surface. An advancement of this, however, can be envisioned with the application of SPBs within a filter pore, providing mechanical control over head loss, permeation flow rates, or particle size distribution.^288–290 These pore-mediated transport structures include polymer micro/nanoporous membranes,^291,292 porous silica materials,²⁹³ carbon fibers,²⁹⁴ porous alumina membranes,²⁹⁵ with potential applications in separation science.²³⁹

Lokuge et al.²³⁹ reported that grafting SPBs to membrane surfaces is an effective route to obtaining controllable, active filtration capabilities. Their nanocapillary arrays, made of Au-coated track-etched polycarbonate, consisted of 80–200 nm regularly arranged pores (Fig. 18). In their approach, physical changes in a surface-grafted PNIPAAM film can be triggered by heating the polymer above its LCST; this causes the membrane permeability for dextran molecules to be switched on because the effective membrane pore diameter increases with decreasing film swelling above the LCST. By tuning the molecular weight and graft density so that brush height is on the order of the pore diameter, control over hydraulic permeability can thus be exerted.

Fig. 18 Reversible switching capability of a PNIPAAM-grafted NCAM membrane. Permeation of 77 kDa dextran through an ID200/Au50/PNIPAAm 10 nanocapillary array membrane (NCAM) over several heating–cooling cycles.²³⁹

4.8 Tunable catalysts

The possibility of exposing or hiding functional group or nanoparticles in the reconstructable surfaces has opened new directions in chemical and biochemical catalysis. These surfaces can be created by attaching some smart polymers. Since the polymer brushes dictate how hairy particles interact with environment, the conformation changes of individual polymer chains could cause the particles to exhibit different behavior. A representative example of such polymers is thermosensitive hydrophilic polymers that can undergo coil-to-globule or hydration-to-dehydration transitions in water at lower critical solution temperatures (LCSTs). Just like what is shown in Fig. 19, temperature-dependent swelling and shrinking of shell were used to alternatively expose and hide the silver nanoparticles on the surface of the colloids. The reagents at low temperature can diffuse freely to the nanoparticles that act as catalysts. However, the network shrinks and the catalytic activity of the nanoparticles is strongly diminished at higher temperatures (T > 30 °C). Conjugation of stimuli-responsive polymeric systems with catalytic nanoparticles and enzymes could thus create new opportunities for bio- and chemical technologies.²⁹⁶

Fig. 19 PS-NIPA-Ag composite particles consisting of thermosensitive core–shell particles in which Ag nanoparticles are embedded.²⁹⁶

5 Conclusion and outlook

SPBs can be used for a variety of applications, such as switching surfaces and adhesive, protective coatings that adapt to the environment, artificial muscles, sensors and controllable drug delivery. The field of SPBs is a continuously expanding area of research. The expansion is not very fast because of the complexity of the systems for the fabrication as well as for investigations.

Although nature serves as the model for smart polymers and provides many inspirations for designing and developing new materials, making synthetic systems capable of responding to stimuli in a controllable and predictable manner represents significant challenges to create materials that interact with, or respond to, biological environments, especially in mimicking biological systems where structural and compositional gradients at various length scales are necessary for precise and orderly responsive behavior.

There remain, however, challenges ahead in developing more sophisticated stimuli-responsive systems. For example, how might we reach the complexity of stimuli-response that we observe in nature? This goal requires engineered materials with features such as reversible stimuli-response, so that the response can be turned on and off in a controlled fashion. In addition, some particular applications, such as materials for drug release, may require a graded response depending on the intensity of the stimulus. Another challenge that is inherent to almost all organic systems pertains to long-term stability (to temperature, ultraviolet light, solvent vapors) and durability (such as mechanical stability, abrasion). Finally, is it possible to create a stimuli-responsive system wherein a single stimulus produces a cascade of responses in a manner similar to biological systems? The search for smart materials challenges researchers to create fast response, increased sensitivity and robust behavior smart polymers at the molecular level to address our future needs.

Nomenclature

AA	acrylic acid

AFM	atomic force microscopy

ATP	adenosine triphosphate

ATRP	atomic transfer radical polymerization

CA	contact angle

CMC	critical micelle concentration

CRP	controlled/living radical polymerization

DMA	dynamic mechanical analysis

DMAEMA

N,N-dimethylaminoethyl methacrylate

DP	degree of polymerization

E

energy

G	free energy

H

enthapic

ITO	indium tin oxide

LbL	layer-by-layer

LCST	lower critical solution temperature

MA	maleic anhydride

MAA	methacrylic acid

MW	molecular weight

MEO2MA

di(ethylene glyene glycol) methyl ethermethacrylate

MEO3MA

tri(ethylene glyene glycol) methyl ether methacrylate

MWD	molecular weight distribution

OEG	oligo (ethylene glycol)

OEGMA

oligo [(ethylene glycol) methacrylate]

PAA	poly (acrylic acid)

PBA	poly (butyl acrylate)

PBA-b- PtBA

poly (butyl acrylate)-block-poly (tert-butyl acrylate)

PBIEMA

poly-2-bromoisobutyloxyethyl methacrylate

PEG	poly (ethylene glycol)

PEGMA

poly [(ethylene glycol) methacrylate]

PGMA	poly (glycidyl methacrylate)

PHEMA

poly (2-hydroxyethyl methacrylate)

PMAA	poly (methacrylic acid)

PMEDSAH

poly [2-(methacryloyloxy)ethyl dimethyl-(3-sulfopropyl)ammonium hydroxide]

PNIPAM

poly (n-isopropylacrylamide)

P2VP	poly (2-vinylpyridine)

PS	polystyrene

PS-b-PtBA

polystyrene-block-poly(tert-butyl acrylate)

PT	poly (thiophene)

PtBA-b-PS

poly (tert-butyl acrylate)-block-polystyrene

PtBA-b-PBA

poly (tert-butyl acrylate)-block-poly (butyl acrylate)

PT-g- PDMAEMA

poly (thiophene)-graft-poly(N,N-dimethylaminoethyl methacrylate)

RAFT	reversible addition fragmentation chain transfer

RGD	arginine–glycine–aspartic

S

entropy

SIP	surface-initiated polymerization

SAMs	self-assembled monolayers

SPBs	smart polymer brushes

SELEX

systematic evolution of ligands by experimental enrichment

SFRP	stable free radical polymerization

UCST	upper critical solution temperature

XPS	X-ray photoelectron spectroscopy

Acknowledgements

The authors would like to thank Dr Manuel Palacio for reading the manuscript.

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