Synthesis and Properties of pH‐ and Temperature‐Sensitive Poly[(N‐isopropylacrylamide)‐co‐(2‐methylenebutane‐1,4‐dioic acid)] Hydrogels

Summary: Hydrogels of NIPA and MBDA were synthesized by free‐radical crosslinking copolymerization with different monomer ratios and with two concentrations of the crosslinking agent. The aim of this work was to study the swelling behavior of these gels that are both temperature and pH sensitive. PNIPA hydrogels are typical examples of thermo‐shrinking hydrogels with a LCST, T_C, around 31–34 °C. MBDA is a weakly ionizable monomer which imparts a pH sensitiveness to the copolymer hydrogels. The pH influence on the swelling behavior of the studied hydrogels was analyzed using deionized water and aqueous HCl and NaOH as swelling media. According to the results found in deionized water, the swelling processes of P(NIPA‐MBDA) hydrogels follow second‐order kinetics at 22 and 37 °C. The equilibrium water content, W_∞, and the rate constant, K, increased at greater concentrations of MBDA and decreased as the crosslinking agent concentration increased. As the MBDA content in the hydrogel increased, the collapsing of the hydrogels at higher temperatures than the LCST became of less importance. The degree of swelling of pure PNIPA hydrogels was not influenced by the pH of the swelling medium. However, this influence increased as the MBDA content increased. This was due to the fact that at low pH most of the MBDA units are in the protonated (neutral) form and at high pH in the ionized one.

Swelling isotherms of hydrogels with different copolymer compositions and with 1.5 wt.‐% of BIS at 22 °C in deionized water.     

pH‐ and Temperature‐Sensitive Chitosan Hydrogels: Swelling and MRI Studies

MRI and swelling experiments are used to probe the state of water and infer the microstructure of chitosan hydrogels. SEM reveals a porous open scaffold‐type structure for hydrogels that were equilibrated at 2 °C before freezing as compared to those equilibrated at 37 °C. ADC MRI measurements reveal an anisotropy in the microstructure of these gels. T₁ relaxation MRI values were larger as the pH increased from 7.6 to 12.0, the result of a lower rate of exchange between protons of the hydration sphere of the polymer and bulk water. The thermosensitive and pH‐sensitive properties of these hydrogels can be utilized in the development of innovative materials for biotechnological and biomedical applications, including criobiocatalysis and bioremediation as well as in programmed drug delivery.

     

Temperature‐Responsiveness and Antimicrobial Properties of CNT–PNIPAM Hybrid Brush Films

Temperature‐responsive carbon nanotube (CNT)/poly(N‐isopropylacrylamide) (PNIPAM) hybrid brush films were prepared by combining the layer‐by‐layer and surface‐initiated polymerization (LbL‐SIP) techniques. Atom transfer radical polymerization (ATRP) is employed for the preparation of PNIPAM polymer brushes. Antibacterial activity of the CNT/PNIPAM films are investigated against Exiguobacterium sp. AT1b and Exiguobacterium sibiricum strains. Dead assay results show high microbial inactivation on coated surfaces with CNT films, while very low microbial inactivation is observed in PNIPAM films at all temperatures tested. The CNT–PNIPAM films, on the other hand, have antibacterial properties below 32 °C, which is below the lower critical solution temperature (LCST), but allows biofilm formation above the LCST.     

Mechanical Properties and UV Curing Behavior of Poly(N‐Isopropylacrylamide) in Phosphonium‐Based Ionic Liquids

N‐isopropylacrylamide (NIPAM) is photopolymerized in a range of phosphonium‐based ionic liquids (ILs). The curing behaviour of polymer‐IL solutions (linear pNIPAM) and ionogels (crosslinked pNIPAM) is studied using rheometry, DSC, and GPC. It is found that the IL influences the mechanical properties, the rate of polymerization, and the LCST of the resulting pNIPAM ionogels. Ionogels made in trihexyl‐tetradecyl phosphonium dicyanamide show an order of magnitude smaller ratio of loss/storage moduli compared to that of trihexyl‐tetradecyl phosphonium chloride, and a doubling of the UV polymerization rate. Temperature‐ramp rheology scans of the water‐swollen ionogels show that upon LCST transition the moduli of the polymer network exhibit anion dependent increases.

     

Versatile Mechanical and Thermoresponsive Properties of Macroporous Copolymer Gels

Random copolymer gels of N‐isopropylacrylamide (NIPAM) and N‐ethylacrylamide (NEAM) are synthesized using different monomer compositions in 1:1 methanol–water mixtures. The samples are characterized by scanning electron microscopy, atomic force microscopy (AFM), and rheological studies. It is observed that with the variation of the monomer compositions in the reaction mixture, the thermoresponsive, morphological, AFM, and rheological properties varied significantly. Porosity and roughness of the gels gradually increase with the gradual increase in NIPAM loading in the gels, lower critical solution temperature, mechanical strength (Young's modulus, storage modulus) significantly decreases with the increase in poly(N‐isopropylacrylamide) loading in the gels. All results can be explained on the basis of the differences in thermoresponsive character of homo‐ and copolymer gels of NIPAM and NEAM in water, their composition in the reaction mixtures, and their different kind of interactions with solvents.

     

Conductive and Tough Smart Poly(N‐isopropylacrylamide) Hydrogels Hybridized by Green Deep Eutectic Solvent

Conductive smart hydrogels with several virtues such as similar characters to biological tissues, sensitive response to ambient variations, have shown their excellent talents in the field of flexible electrical sensors, biomedical devices and directional transportation. However, complex preparing approaches or the instable inner structures have not only been time‐consuming, but also broken up the performance and reliability of the smart hydrogel‐based devices. In this work, a facile one‐step method is put forward to synthesize a kind of conductive poly(N‐isopropylacrylamide) (PNIPAM) hydrogel doped by a new green solvent of deep eutectic solvent (DES) containing choline chloride (ChCl) and acrylic acid (AA). Through the copolymerization of AA and NIPAM, the mechanical strength of the DES‐doped PNIPAM hydrogels is drastically improved compared to the pure PNIPAM gels, and some doped hydrogels lost the typical phase transition temperature of PNIPAM. Moreover, due to the ionic property of DES, the hybrid hydrogels also present the thermal‐depending conductivity as well as sensitive deformation response, which can be used as a smart switch in a circuit or a sensing element with environmental response ability. The cost‐effective preparation and the attractive performance of the DES‐doped hydrogels offer a new avenue to construct multi‐functional materials.     

Asymmetric Behavior of Temperature‐Responsive Poly(N‐isopropylacrylamide) Ultrathin Layers Observed by Atomic Force Microscopy

During characterization of a temperature‐responsive poly(N‐isopropylacrylamide) (PIPAAm) layer grafted onto a Si(100) substrate, atomic force microscopy (AFM) is able to probe the interactions between the microscope tip and the polymer. The modification of the AFM tip surface with octadecyltrichlorosilane (OTS) changes the interaction between the PIPAAm surface and the tip. Although a repulsive interaction is observed between a commercially available Si tip and the PIPAAm surface, a strong attractive interaction between the OTS‐modified Si tip and the surface is observed. Adhesion‐force analysis shows changes in the hydrophilic/hydrophobic character of ultrathin PIPAAm surfaces immediately after a change in temperature. The PIPAAm surface becomes hydrophobic less than 30 min after temperature increase, but requires 120 min to become hydrophilic after temperature reduction.

     

Thermo‐ and pH‐Sensitivities of Thiosemicarbazone‐Incorporated,Fluorescent and Amphiphilic Poly(N‐isopropylacrylamide)

Summary: Novel hydrophobic comonomer (p‐methacrylamido)acetophenone thiosemicarbazone was synthesized and polymerized with N‐isopropylacrylamide to get a series of amphiphilic copolymers. The self‐aggregation behavior and thermo‐sensitive character of the (co)polymers were confirmed by TEM observation, fluorescence spectra, and cloud point measurement. Fluorescence emission of copolymer was significantly strengthened or switched off at an excitation wavelength of 320 nm upon the addition of acid or base, respectively. Thermo‐sensitivity, pH‐sensitivity, and pharmacologically versatile thiosemicarbazone groups were integrated into these novel fluorescent and amphiphilic copolymers, which will develop the novel applications of amphiphilic copolymer and environment‐responsive materials.

Fluorescence intensity at 393 nm of polymer 2 in water at 18 °C excited at 320 nm upon addition of acid and base.     

A Stimuli‐Responsive Hydrogel with Reversible Three‐State Transition Controlled by Redox Stimulation

A great extent of past work has focused on the development of stimuli‐responsive hydrogels that can primarily achieve a two‐state transition, such as sol‐gel translation. In the current work, a reversible hydrogel with three‐state transition is designed. The three transformations between original, oxidized, and reduced states are achieved via controlling the external stimuli conditions. Hydrogels in their original state possess a weak self‐healing property and negligible fluidity. The oxidized state hydrogel can keep molding, however, losing the self‐healing property. In contrast, the reduced state hydrogels exhibit strong self‐healing property. Moreover, the hydrogel becomes injectable subsequent to dithiothreitol addition. Thereafter, under UV‐light irradiation or NaClO immersion, the hydrogels can be remolded to any desired shapes. These properties provide novel designing strategies and potential applications for smart and reusable materials.

     

Temperature‐ and pH‐Sensitive Nanocomposite Gels with Semi‐Interpenetrating Organic/Inorganic Networks

An intelligent nanocomposite hydrogel with a semi‐interpenetrating organic/inorganic network was synthesized through in situ free‐radical polymerization of NIPA in the presence of an inorganic clay and linear PAA. The resulting semi‐interpenetrating nanocomposite gels (sI‐NC gels) showed mechanical and swelling/deswelling properties greatly superior to those of other PNIPA/PAA hydrogels. The sI‐NC gels repeatedly changed their swelling behavior in response to both temperature and pH while retaining their remarkable mechanical properties. The structure and homogeneity of these networks were studied and related to the properties of sI‐NC gels and the hydrogen bonding interactions among the constituents.

     

A Novel Double‐Network,Self‐Healing Hydrogel Based on Hydrogen Bonding and Hydrophobic Effect

In this paper, acrylamide is used as a hydrophilic monomer, and octadecyl methacrylate (C18) and polyurethane (PU) monomers are used as hydrophobic monomers. In an aqueous solution containing mixed surfactants of cetyl trimethylammonium bromide and sodium dodecyl sulfate, a series of composite physical hydrogels with dual network structures are synthesized using these three monomers through in situ micelle copolymerization. The results indicate that, with the increase in PU content (<0.08 g), the thermal stability and mechanical properties (stretching and compressive) of the composite gel are enhanced, while the swelling performance becomes poorer. Furthermore, it can heal at room temperature and the self‐healing property approaches 88% of that of the original sample after 60 min. Additionally, the self‐healing efficiency shows a downward trend with the increase in the amount of PU, which is mainly related to the recovery efficiency of the network chain (polyacrylamide (PAAM) chain and PU chain) and the decrease in the mobility of C18. By constructing the double‐crosslinked network, the design and preparation of polymer hydrogels with high stretching capability, good elasticity and self‐healing performance provides a new approach to preparing hydrogels with excellent properties.     

Effects of Cross‐Link Density on Structures and Properties of Dual‐Sensitive Semi‐Interpenetrating Polymer Networks Hydrogel Microspheres

Semi‐interpenetrating polymer network (semi‐IPN) strategy is employed to fabricate uniform microspheres with temperature and pH dual‐responsive behavior, which is composed of poly(N‐isopropylacrylamide) and poly(acrylic acid) in the presence of N ,N ′‐methylenebisacrylamide (MBA) as the cross‐linker. The influences of MBA amount (M _m) on the structures and properties of the microspheres are investigated in terms of particle size, surface morphology, pH sensitivity, and thermo‐sensitivity with low critical solution temperature in the range M _m = 2.5–15%. Additionally, functional group distributions in the microspheres are probed by titration and employing the Henderson–Hasselbalch equation. The results show that all the properties strongly change depending on M _m. Based on transmission electron microscopy and confocal laser scanning microscopy measurements, and these properties, the M_m‐induced changes in the structures of the semi‐IPN microspheres are discussed.

     

Preparation and Characterization of Novel Temperature Sensitive Poly(N‐isopropylacrylamide‐co‐acryloyl beta‐cyclodextrin) Hydrogels with Fast Shrinking Kinetics

Summary: Novel temperature sensitive poly(N‐isopropylacrylamide‐co‐acryloyl beta‐cyclodextrin) (P(NIPA‐co‐A‐CD)) hydrogels with fast shrinking rates were prepared by radical polymerization of NIPA, A‐CD and crosslinker in a mixture of water/1,4‐dioxane as solvent. Because the mixed solvent was a poor solvent for the copolymers, phase separation occurred during the polymerization, which resulted in a heterogeneous, porous structure of the hydrogels. In contrast to the normal PNIPA hydrogel and the homo P(NIPA‐co‐A‐CD) gel prepared in water, the P(NIPA‐co‐A‐CD) hydrogels synthesized in water/1,4‐dioxane as solvent exhibited higher swelling ratios at the temperature below the lower critical solution temperature (LCST) and shrunk rapidly to equilibrium within shorter time when the temperature was increased above LCST. Increasing the acryloyl beta‐cyclodextrin content in the gels led to a slight decrease of the swelling ratio at lower temperature and had no marked influence on the shrinking kinetics. The gels prepared in water/1,4‐dioxane, at different v/v ratios of 1.0/0.2, 0.8/0.4 and 0.6/0.6, showed similar properties.

SEM photos of the heterogeneous P(NIPA‐co‐A‐CD) hydrogel prepared in water/1,4‐dioxane.     

Amphiphilic Poly(N‐vinyl acetamide) Gels Strengthened with Swelling Solvent

Improving fragility is important for the practical application of gels. In this study, the mechanical strength of gels composed of poly(N‐vinyl acetamide) (PNVA) and glycols is investigated focusing on the retained solvent in the gels. The solvent for the PNVA hydrogel is adequately replaced by various glycols. Using poly(ethylene glycol) (PEG) with molecular weights of 400 or 600 g mol^?1, the compressive strength of the gel is dramatically enhanced to approximately 10 MPa while that of hydrogel is 0.2 MPa. This is because of solvent viscosity, interaction between PEG and PNVA, and the favorable aggregation of the PNVA. From FTIR spectroscopy investigations, the absorption bands of the carbonyl and amino groups of PNVA gels with PEG400 are shifted as compared with PNVA gels in water, suggesting hydrogen bond formation.

     

Temperature‐Induced Phase Transition Characterization of Responsive Polymer Brushes Grafted onto Nanoparticles

Temperature‐induced phase transition parameters of responsive free polymer and brushes onto nanoparticles are measured using high‐resolution magic‐angle sample spinning (HRMAS) NMR spectroscopy. To this purpose, a two‐state statistical model of temperature dependence of thermodynamic observables is developed and applied to obtain parameters which characterize the process of temperature‐induced phase transition of stimuli‐sensitive polymers. In this investigation the thermodynamic observable is the integral intensity of the ¹H HRMAS NMR spectrum peaks and the derived thermodynamic parameters are transition temperature and transition entropy. This approach is applied to investigate the dependence of temperature‐induced coil‐to‐globule transition of poly(N‐isopropylacrylamide), (PNIPAm), asymmetric end functionalized with benzyl and thiol groups (Bn–PNIPAm–SH) on molecular weight in the range 3600–30 000 g mol^–1 in aqueous solutions. The characteristics of the phase transition represented by transition temperature, and transition entropy are compared to that of Bn–PNIPAm–SH brushes onto gold nanorods in the same range of molecular weight. The method used for measuring the characteristics of phase transition is based on transverse magnetization relaxation (T ₂) spin‐echo enhance editing of the integral intensities of the ¹H HRMAS NMR spectra. This NMR observable reflects changes in transverse relaxation times as an indicative of the polymer chains conformations and dynamics reached in the process of temperature‐induced phase transition.

     

Porous Semi‐Interpenetrating Hydrogel Networks Based on Dextran and Polyacrylamide With Superfast Responsiveness

AAm was free‐radical polymerized at various temperatures in the presence of N,N'‐methylenebisacrylamide as a cross‐linker and dextran resulting in novel Dx/PAAm semi‐IPNs. The structure and morphology of networks were investigated by means of FTIR, DSC, and ESEM. In comparison to the PAAm network, the interior network structures of the novel semi‐IPNs prepared at ?18 °C exhibit a heterogeneous morphology consisting of pores of sizes about 80 µm, while those formed at +5 and +25 °C have pores with sizes about 3 µm. The Dx/PAAm semi‐IPNs exhibited higher swelling ratios, than those without Dx, irrespective of the gel preparation temperature. Moreover, Dx/PAAm semi‐IPN hydrogels formed at ?18 °C attain the equilibrium state in water within 15 s.

     

Temperature‐Responsive Electrophoretic Deposition of Sulfone‐Containing Nonionic Poly(N‐isopropylacrylamide)

Recently, it has been found that nonionic aliphatic and aromatic poly(ester sulfone)s show anode selective electrophoretic behavior, and it is shown that the electrophoresis is induced by a partial charge separation of the protic solvent at the dispersion interface. In this paper, the first example of temperature‐responsive electrophoretic deposition (EPD) is reported. Electrophoresis of a nonionic sulfone‐containing poly(N‐isopropylacrylamide) [poly(NIPAM)] is performed above the lower critical solution temperature. The poly(NIPAM) is prepared via reversible addition–fragmentation chain transfer radical copolymerization of NIPAM with a sulfone‐containing methacrylate. After EPD, adhesion of human umbilical vein endothelial cells on the deposited surfaces is also demonstrated, aiming at the subsequent temperature‐sensitive detachment.     

Thermoresponsive Properties of Sugar Sensitive Copolymer of N‐Isopropylacrylamide and 3‐(Acrylamido)phenylboronic Acid

Summary: The copolymer of N‐isopropylacrylamide and 3‐(acrylamido)phenylboronic acid (82:18, = 47 000 g · mol^?1) was prepared by free radical polymerization. The copolymer showed typical thermal precipitation behavior in aqueous solutions, its precipitation temperature (T_P) being increased from 23 to 32 °C by increasing the pH from 6.5 to 9.7, because of ionization of the phenylboronate units. The pK_a was evaluated as 8.9 ± 0.1 from the effect of pH on T_P. At pH > 9, i.e., in the anionic form of the copolymer, T_P was affected by a very low concentration of glucose (5.6 μM , ΔT_P = 1–1.5 °C), because of complex formation with a high binding constant. At a higher concentration of polyols (560 μM , pH > 8) the increase of T_P was maximal for the copolymer complexes with fructose (7–10 °C) and decreased in the order: fructose > glucose ≈ mannitol > pentaerythritol > galactose > Tris >glycerol. Di‐ and oligosaccharides (lactose, sucrose, and dextran) caused a slight increase of T_P at pH 7.5–8.7 while no effect was observed at pH > 9. Isothermal dissolution of the copolymer suspension in water (27 °C, pH 8.5) was possible in the presence of fructose or mannitol but required higher concentrations (1.4–3.6 × 10³ μM ) as compared to those which enabled the shift of T_P in the soluble copolymer. The dissolution rate increased with fructose concentrations.

Effect of pH on T_P of poly(NIPAAM‐co‐AAPBA) in the presence of various monosaccharides.     

Biodegradable pH‐Dependent Thermo‐Sensitive Hydrogels for Oral Insulin Delivery

A series of pH‐dependent thermo‐sensitive hydrogels for oral insulin delivery is designed and synthesized. In contrast to normal pH‐ and thermo‐sensitive hydrogels, the release of oral insulin from them is mainly controlled by the adjustable swelling ratios in gastric and intestinal juice with their variable pH sensitivity. The release behavior of loaded insulin depends on the swelling/shrinking transition because of the changing LCST at different pH values. The hydrogels presented are composed of PNIPAAm chains and PMAA segments and are prepared with the biodegradable acryloyl‐poly(?‐caprolactone)‐2‐hydroxylethyl methacrylate as a crosslinker. The biodegradation rates of the hydrogels are directly related to their PMAA content. In vitro release of insulin from the hydrogels is investigated and the release profiles indicate that the smart hydrogels are of great promise in pH–temperature oral insulin delivery systems.