Polysaccharide-Based Polymers for Designing Thermoresponsive Hydrogels for Treating Wound Healing.

Novel dual thermoresponsive block copolymers displaying lower critical solution temperature (LCST) and upper critical solution temperature (UCST) were synthesized by reversible addition−fragmentation chain transfer (RAFT) polymerization of two proline-based monomers. Poly(N-acryloyl-l-proline methyl ester), poly(A-Pro-OMe), was selected as a thermoresponsive segment, whereas poly(N-acryloyl-4-trans-hydroxy-l-proline), poly(A-Hyp-OH), could be regarded as a water-soluble polymer. The block copolymer having suitable comonomer composition (A-Pro-OMe/A-Hyp-OH = 27/73) exhibited soluble−insoluble−soluble transition with lower (LCST = 19−21 °C) and upper (UCST = 39−45 °C) critical solution temperatures in acidic water. The comonomer composition of poly(A-Pro-OMe)-b-poly(A-Hyp-OH) and pH value in the aqueous solution were found to affect characteristic thermoresponsive behaviors. The temperature-dependent assembled structures and chiroptical properties were evaluated by dynamic light scattering (DLS) and circula...

Nonionic double thermoresponsive diblock copolymers with both upper critical solution temperature (UCST) and lower critical solution temperature (LCST) phase transitions are synthesized via eco-friendly photoiniferter reversible addition-fragmentation chain transfer polymerization. While the biocompatible random copolymer of di(ethylene glycol) methyl ether methacrylate and oligo(ethylene glycol) methacrylate accounts for the LCST transition, the block of polymethacrylamide from an easily accessible monomer with low health hazard is responsible for the UCST transition. Temperature-dependent dynamic light scattering measurements confirm the formation of micellar aggregates in water at the temperatures below UCST- and above LCST-type cloud points. Additionally, the temperature interval between UCST and LCST, where both blocks are dissolved, can be tailored by varying the comonomer ratio in the random copolymer block. With these unique advantages, the presented work introduces a new polymer system for the design of schizophrenic polymers.

Self-assembly of thermally responsive polypeptides into unique nanostructures offers intriguing attributes including dynamic physical dimensions, biocompatibility, and biodegradability for the smart bio-nanomaterials. As elastin-based polypeptide (EBP) fusion proteins with lower critical solution temperature (LCST) are studied as drug delivery systems, EBP block copolypeptides with the resilin-based polypeptide (RBP) displaying an upper critical solution temperature (UCST) have been of great interest. In this study, we report thermally triggered, dynamic self-assembly of EBP- and RBP-based diblock copolypeptides into switched nanostructures with reversibility under physiological conditions. Molecular DNA clones encoding for the EBP-RBP diblocks at different block length ratios were biosynthesized via recursive directional ligation and overexpressed, followed by nonchromatographic purification by inverse transition cycling. Genetically engineered diblock copolypeptides composed of the EBP with an LCST and the RBP with a UCST showed converse phase transition behaviors with both a distinct LCST and a distinct UCST (LCST < UCST). As temperature increased, three phases of these EBP-RBP diblocks were observed: (1) self-assembled micelles or vesicles below both LCST and UCST, (2) whole aggregates above LCST and below UCST, and (3) reversed micelles above both LCST and UCST. In conclusion, these stimuli-triggered, dynamic protein-based nanostructures are promising for advanced drug delivery systems, regenerative medicine, and biomedical nanotechnology.

A QSPR study for predicting θ(LCST) and θ(UCST) in binary polymer solutions

Self-healing hydrogels have drawngreat attention in the past decade since the self-healing property is one of the characteristics of living creatures. In this study, poly(acrylamide-stat-diacetone acrylamide) P(AM-stat-DAA) with a pendant ketone group was synthesized from easy accessible monomers, and thermo-responsive self-healing hydrogels were prepared through a series of diacylhydrazide compounds cross-linking without any additional stimulus. Although the copolymers do not show thermo-response, the hydrogels became thermo-responsive andboth the lower critical solution temperature (LCST) and upper critical solution temperature (UCST) varied with the composition of the copolymer and structure of cross-linkers. With a dynamic covalent bond connection, the hydrogel showed gel-sol-gel transition triggered by acidity, redox, and ketone to acylhydrazide group ratios. This is another interesting cross-linking induced thermo-responsive (CIT) hydrogel with different properties compared to PNIPAM-based thermo-responsive hydrogels. The self-healing hydrogel with CIT properties could have great potential for application in areas related to bioscience, life simulation, and temperature switching.

Rational design of thermoresponsive polymers in aqueous solutions: A thermodynamics map

Expansion microscopy (ExM) is a technique in which swellable hydrogel-embedded biological samples are physically expanded to effectively increase imaging resolution. Here, we develop thermoresponsive reversible ExM (T-RevExM), in which the expansion factor can be thermally adjusted in a reversible manner. In this method, samples are embedded in thermoresponsive hydrogels and partially digested to allow for reversible swelling of the sample-gel hybrid in a temperature-dependent manner. We first synthesized hydrogels exhibiting lower critical solution temperature (LCST)- and upper critical solution temperature (UCST)-phase transition properties with N-alkyl acrylamide or sulfobetaine monomers, respectively. We then formed covalent hybrids between the LCST or UCST hydrogel and biomolecules across the cultured cells and tissues. The resulting hybrid could be reversibly swelled or deswelled in a temperature-dependent manner, with LCST- and UCST-based hybrids negatively and positively responding to the increase in temperature (termed thermonegative RevExM and thermopositive RevExM, respectively). We further showed reliable imaging of both unexpanded and expanded cells and tissues and demonstrated minimal distortions from the original sample using conventional confocal microscopy. Thus, T-RevExM enables easy adjustment of the size of biological samples and therefore the effective magnification and resolution of the sample, simply by changing the sample temperature.

A dual thermoresponsive block copolymer of poly[2-(dimethylamino)ethyl methacrylate]-block-poly(sulfobetaine methacrylate) (PDMAEMA-b-PSBMA) exhibited reversible schizophrenic aggregation behavior in water because of the upper critical solution temperature (UCST) of the PSBMA block and the lower critical solution temperature (LCST) of the PDMAEMA block. Both the UCST and LCST shifted to lower values with increasing DMAEMA/SBMA block ratios, which was ascribed to the hydrophobic/hydrophilic balance of both blocks. Because of the salt-sensitive PSBMA and pH-responsive PDMAEMA, the UCST and LCST values of PDMAEMA-b-PSBMA were codetermined by varying the salt concentrations and pH. Specifically, increasing the salt concentration resulted in a notable decrease in the UCST and a slight increase in the LCST due to the salt-induced screening of the electrostatic attractions of the PSBMA and salt-enhanced solubility of the PSBMA blocks, respectively. The LCST decreased with increasing pH because of the deprotonation of PDMAEMA, and the UCST first increased and then decreased with increasing pH. Besides, the copolymer with larger PDMAEMA content was more sensitive to pH. For the repetitive adjustment to thermoresponsive aggregation, repeated addition of acids and bases induced salt accumulation and diminished the switchability of pH, whereas repeated switching cycles were achieved by CO2/N2 bubbling without introducing salt enrichment. The difference in HCl/NaOH titration and CO2/N2 bubbling also existed in the switching cycles when PDMAEMA-b-PSBMA served as a stimulus-responsive emulsifier.

Summary: Thermosensitive association of a diblock copolymer consisting of poly(3‐dimethyl(methacryloyloxyethyl) ammonium propane sulfonate) (PdMMAEAPS), as an upper critical solution temperature (UCST) block, and poly(N,N‐diethylacrylamide) (PdEA), as a lower critical solution temperature (LCST) block, has been investigated by using IR spectroscopy. The ν(CO) and ν(SO) bands of the PdMMAEAPS block and the amide I band of PdEA block critically changed at the UCST and LCST, respectively, indicating that the segmental interaction of each block is altered at each transition.The double temperature responsiveness of a UCST block and LCST block containing diblock copolymer. Micelles form at temperatures both below the UCST and above the LCST of the blocks.magnified imageThe double temperature responsiveness of a UCST block and LCST block containing diblock copolymer. Micelles form at temperatures both below the UCST and above the LCST of the blocks.

Tunable UCST thermoresponsive copolymers based on natural glycyrrhetinic acid

The multi-thermo-responsive block copolymer of poly[2-(2-methoxyethoxy)ethyl methacrylate]-block-poly[N-(4-vinylbenzyl)-N,N-diethylamine] (PMEO2MA-b-PVEA) displaying phase transition at both the lower critical solution temperature (LCST) and the upper critical solution temperature (UCST) in the alcohol/water mixture is synthesized by reversible addition-fragmentation chain transfer polymerization. The poly[2-(2-methoxyethoxy)ethyl methacrylate] (PMEO2MA) block exhibits the UCST phase transition in alcohol and the LCST phase transition in water, while the poly[N-(4-vinylbenzyl)-N,N-diethylamine] (PVEA) block shows the UCST phase transition in isopropanol and the LCST phase transition in the alcohol/water mixture. Both the polymer molecular weight and the co-solvent/nonsolvent exert great influence on the LCST or UCST of the block copolymer. By adjusting the solvent character including the water content and the temperature, the block copolymer undergoes multiphase transition at LCST or UCST, and various block copolymer morphologies including inverted micelles, core-corona micelles, and corona-collapsed micelles are prepared. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4399–4412

A thermoresponsive polymer poly(diethylene glycol methyl ether methacrylate) (PMeO2MA) is grafted from poly(vinylidene fluoride) (PVDF) backbone by using a combined ATRC and ATRP technique with a high conversion (69%) of the monomer to produce the graft copolymer (PD). It is highly soluble polymer and its solution property is studied by varying polarity in pure solvents (water, methanol, isopropanol) and also in mixed solvents (water-methanol and water-isopropanol) by measuring the hydrodynamic size (Z-average) of the particles by dynamic light scattering (DLS). The variation of Z-average size with temperature of the PD solution (0.2%, w/v) indicates a lower critical solution temperature (LCST)-type phase transition (T(PL)) in aqueous medium, an upper critical solution temperature (UCST)-type phase transition (T(PU)) in isopropanol medium, and no such phase transition for methanol solution. In the mixed solvent (water + isopropanol) at 0-20% (v/v) isopropanol the TPL increases, whereas the T(PU) decreases at 92-100% with isopropanol content. For the mixture 20-90% isopropanol, PD particles having larger sizes (400-750 nm) exhibit neither any break in Z-average size-temperature plot nor any cloudiness, indicating their dispersed swelled state in the medium. In the methanol + water mixture with methanol content of 0-30%, T(PL) increases, and at 40-60% both UCST- and LCST-type phase separations occur simultaneously, but at 70-90% methanol the swelled state of the particles (size 250-375 nm) is noticed. For 50 vol % methanol by varying polymer concentration (0.07-0.2% w/v) we have drawn a quasibinary phase diagram that indicates an approximate inverted hourglass phase diagram where a swelled state exists between two single phase boundary produced from LCST- and UCST-type phase transitions. An attempt is made to understand the phase separation process by temperature-dependent (1)H NMR spectroscopy along with transmission electron microscopy.

Polymers with upper critical solution temperature behavior in alcohol/water solvent mixtures

Many intrinsically disordered proteins (IDPs) can undergo a liquid-liquid phase separation (LLPS) in water, depending on solution conditions (temperature, pH, and ionic strength). There are two types of LLPS that are controlled by temperature: those occurring above a lower critical solution temperature (LCST) and those occurring below an upper critical solution temperature (UCST). IDP coarse-grained (CG) models are particularly appropriate for investigating the physical and chemical factors that govern their LLPS and supramolecular organization. However, the development of CG models allowing simulations of both LCST and UCST behavior of temperature-sensitive IDPs is still in its infancy. In this context, we present here a novel temperature-dependent (TD) CG model for IDP simulations based on the MARTINI 3 force field. The model was developed by modifying the Lennard-Jones potentials between apolar or charged solute beads and water with a TD rescaling factor. It was parametrized to fit the TD potentials of mean force (PMF) between two apolar or two charged molecules computed using all-atom (AA) simulations. We show that the TD CG model is able to reproduce the experimentally known LLPS of both LCST and UCST low-complexity sequences and to estimate phase transition temperatures comparable to experimental measurements.

Core-shell microgels were synthesized via a free radical emulsion polymerization of thermoresponsive poly-(N-isopropyl acrylamide), pNipam, on the surface of silica nanoparticles. Pure pNipam microgels have a lower critical solution temperature (LCST) of about 32 °C. The LCST varies slightly with the crosslinker density used to stabilize the gel network. Including a silica core enhances the mechanical robustness. Here we show that by varying the concentration gradient of the crosslinker, the thermoresponsive behaviour of the core-shell microgels can be tuned. Three different temperature scenarios have been detected. First, the usual behaviour with a decrease in microgel size with increasing temperature exhibiting an LCST; second, an increase in microgel size with increasing temperature that resembles an upper critical solution temperature (UCST), and; third, a decrease with a subsequent increase of size reminiscent of the presence of both an LCST, and a UCST. However, since the chemical structure has not been changed, the LCST should only change slightly. Therefore we demonstrate how to tune the particle size independently of the LCST.