Thermoresponsive Graft Copolymers Research Articles

Phase behavior of P(NIPAM-g-PLA) films for cell sheet technology assessed with atomic force microscopy

Thermoresponsive graft copolymers of N-isopropylacrylamide with polylactide (P(NIPAM-g-PLA)) are promising materials for the preparation of cell supports in cell sheet technology. Here, we studied the thermal behavior of thin and thick films prepared by spin-coating from P(NIPAM-g-PLA) (fresh and stored for 1 year), using atomic force microscopy. P(NIPAM-g-PLA) copolymers of different molecular weights were synthesized. The films’ swelling, Young’s moduli and roughness were tracked when lowering the temperature to that of the phase transition. The obtained thermal dependencies demonstrated that, in contrast to neat PNIPAM films, the prepared films efficiently dissolved at the temperature corresponding to the LCST of the copolymer in a solution. After a year of storage in ambient conditions, certain signs of polymer deterioration due to water uptake were observed. The obtained data on the phase transition in thin films of P(NIPAM-g-PLA) are of importance for their potential use as cell supports in the cell sheet technology.

Synthesis of Thermoresponsive Chitosan-graft-Poly(N-isopropylacrylamide) Hybrid Copolymer and Its Complexation with DNA.

A hybrid synthetic-natural, thermoresponsive graft copolymer composed of poly(N-isopropyl acrylamide) (PNIPAM) side chains, prepared via RAFT polymerization, and a chitosan (Chit) polysaccharide backbone, was synthesized via radical addition-fragmentation reactions using the "grafting to" technique, in aqueous solution. ATR-FTIR, TGA, polyelectrolyte titrations and 1H NMR spectroscopy were employed in order to validate the Chit-g-PNIPAM copolymer chemical structure. Additionally, 1H NMR spectra and back conductometric titration were utilized to quantify the content of grafted PNIPAM side chains. The resulting graft copolymer contains dual functionality, namely both pH responsive free amino groups, with electrostatic complexation/coordination properties, and thermoresponsive PNIPAM side chains. Particle size measurements via dynamic light scattering (DLS) were used to study the thermoresponsive behavior of the Chit-g-PNIPAM copolymer. Thermal properties examined by TGA showed that, by the grafting modification with PNIPAM, the Chit structure became more thermally stable. The lower critical solution temperature (LCST) of the copolymer solution was determined by DLS measurements at 25-45 °C. Furthermore, dynamic and electrophoretic light scattering measurements demonstrated that the Chit-g-PNIPAM thermoresponsive copolymer is suitable of binding DNA molecules and forms nanosized polyplexes at different amino to phosphate groups ratios, with potential application as gene delivery systems.

One‐Pot/Simultaneous Synthesis of PHPMA‐G‐PLA Copolymers via Metal‐Free Rop/Raft Polymerization and their Self‐Assembly from Micelles to Thermoresponsive Vesicles

AbstractThe present article reports a simple and straightforward approach to access thermoresponsive graft copolymers based on lactide (LA) and a methacrylic monomer, 2‐hydroxypropyl methacrylate (HPMA), using a synthesized carboxy‐functionalized trithiocarbonate‐based chain transfer agent. One protocol involves a metal‐free simultaneous synthesis through a combination of reversible addition‐fragmentation chain transfer polymerization and organic acid‐catalyzed ring‐opening polymerization, which follows first‐order kinetics. The resulting copolymers with a controlled structure exhibit remarkably narrow molecular weight distributions (Ð < 1.10). Within this framework, the self‐assembly of PHPMA‐g‐PLA graft copolymers (GCs) into nanoparticles (NPs) is demonstrated at concentrations of 0.2 and 0.5 wt.%, respectively. The displacement method, based on the rapid injection of the organic solvent (acetone) into an aqueous medium under vigorous stirring, produces spherical NPs such as micelles, vesicles, or non‐spherical “lumpy rods”. The presence of a pseudo‐thermoresponsive segment (PHPMA) in GCs facilitates stimulus‐responsive self‐assembly behavior. Well‐defined spherical NPs—primarily vesicles of substantial size—develop upon heating above the glass transition temperature (Tg ≈35–36 °C) of the GCs in an acetone–water (80/20 wt.%) mixture. Last, specific interactions between the obtained PHPMA‐g‐PLA nano‐objects and blood proteins in human plasma are studied using isothermal calorimetry.

Double thermoresponsive graft copolymers with different chain ends: feasible precursors for covalently crosslinked hydrogels.

The tailored synthesis of graft copolymers from acrylic and methacrylic monomers can be accomplished solely through photoiniferter reversible addition-fragmentation chain transfer (RAFT) polymerization. Samples with poly[oligo(ethylene glycol) methacrylate] (POEGMA) backbones synthesized under green light irradiation and poly(N-isopropylacrylamide) (PNIPAM) side chains growing under blue light irradiation are presented. As monitored by temperature-dependent dynamic light scattering (DLS) measurements and temperature-variable nuclear magnetic resonance (NMR) spectroscopy, the architecture of the graft copolymers allows unique two-step lower critical solution temperature (LCST) transitions in aqueous solutions. Meanwhile, different end-groups introduced by the corresponding RAFT agents affect the detailed thermoresponsive behavior remarkably. This RAFT strategy shows more advantages when the multiple trithiocarbonate groups are converted into thiol reactive pyridyl disulfide (PDS) groups via a facile post-polymerization modification. The PDS-terminated graft copolymer can then be regarded as a usable precursor for various applications, such as thermoresponsive hydrogels.

Thermoresponsive poly(di(ethylene glycol) methyl ether methacrylate)-ran-(polyethylene glycol methacrylate) graft copolymers exhibiting temperature-dependent rheology and self-assembly

Graft copolymers with brush-type architectures are explored containing poly(ethylene glycol) methacrylates copolymerized with “thermoresponsive” monomers which impart lower critical solution temperatures to the polymer. Initially, the chemical structure of the thermoresponsive polymer is explored, synthesizing materials containing N-isopropyl acrylamide, N,N-diethyl acrylamide and diethylene glycol methyl ether methacrylate. Thermoresponsive graft-copolymers containing di(ethylene glycol) methyl ether methacrylate (DEGMA) exhibited phase transition temperature close to physiological conditions (ca 30 °C). The effect of polymer composition was explored, including molecular weight, PEG-methacrylate (PEGMA) terminal functionality and PEGMA/DEGMA ratios. Molecular weight exhibited complex relationships with phase behavior, where lower molecular weight systems appeared more stable above lower critical solution temperatures (LCST), but a lower limit was identified. PEGMA/DEGMA feed was able to control transition temperature, with higher PEGMA ratios elevating thermal transition. It was found that PEGMA terminated with methoxy functionality formed stable colloidal structures above LCST, whereas those the hydroxy termini generally formed two-phase sedimented systems when heated. Two thermoresponsive DEGMA-based graft polymers, poly(PEGMA7-ran-DEGMA170) and poly(PEGMA1-ran-DEGMA38), gave interesting temperature-dependent rheology, transitioning to a viscous state upon heating. These materials may find application in forming thermothickening systems which modify rheology upon exposure to the body’s heat.

Synthesis and Self-Assembly of Thermoresponsive Biohybrid Graft Copolymers Based on a Combination of Passerini Multicomponent Reaction and Molecular Recognition.

Amphiphilic graft copolymers exhibit fascinating self-assembly behaviors. Their molecular architectures significantly affect the morphology and functionality of the self-assemblies. Considering the potential application of amphiphilic graft copolymers in the fabrication of nanocarriers, it is essential to synthesize well-defined graft copolymers with desired functional groups. Herein, the Passerini reaction and molecular recognition are introduced to the synthesis of functional thermoresponsive graft copolymers. A bifunctional monomer 2-((adamantan-1-yl)amino)-1-(4-((2-bromo-2-methylpropanoyl)oxy)phenyl)-2-oxoethyl methacrylate (ABMA) with a bromo group for atom transfer radical polymerization (ATRP) and an adamantyl group for molecular recognition is synthesized through the Passerini reaction. The graft copolymers are prepared by reversible addition-fragmentation transfer (RAFT) copolymerization of ABMA and oligo(ethylene glycol) methyl ether methacrylate (OEGMA) followed by RAFT end group removal and ATRP of di(ethylene glycol)methyl ether methacrylate (DEGMA) initiated by the ABMA units. The graft copolymer P(OEGMA-co-ABMA)-g-PDEGMA can be functionalized with β-cyclodextrin modified peptides, affording a thermoresponsive biohybrid graft copolymer. At a temperature above its lower critical solution temperature, the biohybrid graft copolymer self-assembles into peptide-modified polymersomes.

Synthesis, Structure, Hydrodynamics and Thermoresponsiveness of Graft Copolymer with Aromatic Polyester Backbone at Poly(2-isopropyl-2-oxazoline) Side Chains.

New thermoresponsive graft copolymers with an aromatic polyester backbone and poly(2-isopropyl-2-oxazoline) (PiPrOx) side chains are synthesized and characterized by NMR and GPC. The grafting density of side chains is 0.49. The molar masses of the graft-copolymer, its backbone, side chains, and the modeling poly-2-isopropyl-2-oxaziline are 74,000, 19,000, 4300, and 16,600 g·mol−1, respectively. Their conformational properties in nitropropane as well as thermoresponsiveness in aqueous solutions are studied and compared with that of free side chains, i.e., linear PiPrOx with a hydrophobic terminal group. In nitropropane, the graft-copolymer adopts conformation of a 13-arm star with a core of a collapsed main chain and a PiPrOx corona. Similarly, a linear PiPrOx chain protects its bulky terminal group by wrapping around it in a selective solvent. In aqueous solutions at low temperatures, graft copolymers form aggregates due to interaction of hydrophobic backbones, which contrasts to molecular solutions of the model linear PiPrOx. The lower critical solution temperature (LCST) for the graft copolymer is around 20 °C. The phase separation temperatures of the copolymer solution were lower than that of the linear chain counterpart, decreasing with concentration for both polymers.

Quantitative Grafting for Structure-Function Establishment: Thermoresponsive Poly(alkylene oxide) Graft Copolymers Based on Hyaluronic Acid and Carboxymethylcellulose.

A series of thermoresponsive graft copolymers, gelling at physiological conditions in aqueous solution and cell growth media, have been synthesized using quantitative coupling between a small set of amino-functionalized poly(alkylene oxide) copolymers (PAO) and the carboxylate of the biologically important polysaccharides (PSa) carboxymethylcellulose and the less reactive hyaluronate. Quantitative grafting enables the establishment of structure-function relationship which is imperative for controlling the properties of in situ gelling hydrogels. The EDC/NHS-mediated reaction was monitored using SEC-MALLS, which revealed that all PAOs were grafted onto the PSa backbone. Aqueous solutions of the graft copolymers were Newtonian fluids at room temperatures and formed reversible physical gels at elevated temperatures which were noncytotoxic toward chondrocytes. The established structure-function relationship was most clearly demonstrated by inspecting the thermogelling strength and the onset of thermogelling in a phase diagram. The onset of the thermogelling function could be controlled by the global PAO concentration, independent of graft ratio.

Thermoresponsive behavior of graft copolymers based on poly(N,N‐dimethylacrylamide‐co‐diacetoneacrylamide) side chains

ABSTRACTA thermoresponsive graft copolymer was synthesized through free radical copolymerization and a “graft onto” method in aqueous solution. The primary structure of the graft copolymer is constituted of a partially hydrolyzed polyacrylamide (HPAM) backbone and thermosensitive side chains [amino‐terminated poly(N,N‐dimethylacrylamide‐co‐diacetone acrylamide) or P(DMA‐co‐DAAM)] with molecular weight around 105 g/mol. The 1H‐NMR spectra at various temperatures showed the temperature of thermoassociation (Tass) in the copolymer. At the same time, the pyrene fluorescence measurements demonstrated the formation of hydrophobic microdomains of P(DMA‐co‐DAAM) above Tass. The thermothickening behavior of the graft copolymers was studied by viscosity measurements, and the results suggested that in semidilute solutions, the Tass and the magnitude of thermothickening could be regulated by varying the hydrolysis degree of the backbone, the composition of side chains, and the addition of NaCl. The oscillatory shear experiments demonstrated that the copolymer can present a remarkable elasticity increase as the temerature increased to Tass. These thermoassociating copolymers with temperature‐tunable properties can have potential applications as smart materials in enhanced oil recovery. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 135, 47051.

Thermoresponsive behavior of sodium alginate grafted with poly(N-isopropylacrylamide) in aqueous media

Thermoresponsive graft copolymers were synthesized. Thermally induced properties were introduced by grafting poly (N-isopropylacrylamide) (PNIPAM) side chains onto a sodium alginate backbone. The resulting graft copolymers cover a broad range in PNIPAM composition and molecular weight. Remarkable thermothickening behavior in water and 0.1 M NaCl is observed by viscometry when the temperature, concentration, weight ratio of PNIPAM side chains to backbone, and PNIPAM molecular weight are higher than certain critical values. This behavior is reversible and could have applications in oil rigs and drug delivery systems.

Synthesis, Characterization and Application of Thermoresponsive Polyhydroxyalkanoate-graft-Poly(N-isopropylacrylamide)

A thermoresponsive graft copolymer polyhydroxyalkanoate-g-poly(N-isopropylacrylamide) or short as PHA-g-PNIPAm, was successfully synthesized via a three-step reaction. First, PNIPAm oligomer with a trithiocarbonate-based chain transfer agent (CTA), short as PNIPAm-CTA, with designed polymerization degree was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Subsequently, the PNIPAm-CTA was treated with n-butylamine for aminolysis in order to obtain a pendant thiol group at the end of the chain (PNIPAm-SH). Finally, the PNIPAm-SH was grafted onto unsaturated P(3HDD-co-3H10U), a random copolymer of 3-hydroxydodecanoate (3HDD) and 3-hydroxy-10-undecylenate (3H10U), via a thiol-ene click reaction. Enhanced hydrophilicity and thermoresponsive property of the resulted PHA-g-PNIPAm were confirmed by water contact angle studies. The biocompatibility of PHA-g-PNIPAm was comparable to poly-3-hydroxybutyrate (PHB). The graft copolymer PHA-g-PNIPAm based on biopolyester PHA could be a promising material for biomedical applications.

Preparation of thermo-responsive graft copolymer by using a novel macro-RAFT agent and its application for drug delivery

A methodology to prepare thermo-responsive graft copolymer by using a novel macro-RAFT agent was proposed. The macro-RAFT agent with pendant dithioester (ZC(S)SR) was facilely prepared via the combination of RAFT polymerization and esterification reaction. By means of ZC(S)SR-initiated RAFT polymerization, the thermo-responsive graft copolymer consisting of poly(methyl methacrylate-co-hydroxylethyl methacrylate) (P(MMA-co-HEMA)) backbone and hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) side chains was constructed through the “grafting from” approach. The chemical compositions and molecular weight distributions of the synthesized polymers were respectively characterized by 1H nuclear magnetic resonance (1H NMR) and gel permeation chromatography (GPC). Self-assembly behavior of the amphiphilic graft copolymers (P(MMA-co-HEMA)-g-PNIPAAm) was studied by transmission electron microscopy (TEM), dynamic light scattering (DLS) and spectrofluorimeter. The critical micelle concentration (CMC) value was 0.052mgmL−1. These micelles have thermo-responsibility and a low critical solution temperature (LCST) of 33.5°C. Further investigation indicated that the guest molecule release property of these micelles, which can be well described by a first-order kinetic model, was significantly affected by temperature. Besides, the micelles exhibited excellent biocompatibility and cellular uptake property. Hence, these micelles are considered to have potential application in controlled drug delivery.

Synthesis and characterization of poly (N-isopropylacrylamide)-g-carboxymethyl chitosan copolymer-based doxorubicin-loaded polymeric nanoparticles for thermoresponsive drug release

Thermoresponsive graft copolymer (PNIPAm-g-OCMC) with PNIPAm and chitosan was prepared by conjugation of amine-terminated PNIPAm with O-carboxymethylchitosan through graft-onto method. The results of FTIR and proton NMR confirmed the synthesis of a copolymer. Furthermore, XRD analysis revealed conjugation reaction of polymeric materials. Doxorubicin-loaded polymeric nanoparticles (D-PNPs) were fabricated using copolymer by gelation method. Morphology illustration through TEM showed the spherical shape of D-PNPs. Particles size measurement study indicates thermoresponsive properties of D-PNPs at various temperatures. Lower critical solution temperature (LCST) of D-PNPs was obtained at 38 °C predicted by turbidimetry analysis. Release studies at three different temperatures notified that thermoresponsive doxorubicin release of D-PNPs. The release of doxorubicin was slower at 25 °C, moderately released at 37 °C, and faster released at 42 °C due to adjustment of the framework of the D-PNPs. Based on the results such as transmittance measurement, particle size observation, and release studies, we declare that the D-PNPs exhibit temperature-responsive behavior, which could make them appropriate for a thermoresponsive drug delivery.

Thermoresponsive N-vinyl caprolactam grafted sodium alginate hydrogel beads for the controlled release of an anticancer drug

A series of thermoresponsive sodium alginate-g-poly(vinyl caprolactam) (NaAlg-g-PNVCL) beads were prepared as drug delivery matrices of 5-flurouracil (5-FU) crosslinked by glutaraldehyde (GA) in the hydrochloric acid catalyst. Graft copolymers of sodium alginate with vinyl caprolactam were synthesized using azobisisobutyronitrile as an initiator, and characterized by Fourier infrared spectroscopy, differential scanning calrimetry and X-ray diffraction for analysis of the amorphous nature drug in the beads, and by scanning electron microscopy for the spherical nature of the beads. Preparation condition of the beads was optimized by considering the percentage of encapsulation efficiency, swelling behavior of beads and their release data. Effects of variables such as GA concentration, drug/polymer ratio and catalyst concentration on the release of 5-FU were carried out at two different temperatures (25 and 37 °C) in simulated intestinal fluid for 12 h. It was observed that, drug release from the beads decreased with increasing drug/polymer (d/p) ratio, extent of crosslinking agent and catalyst concentration. The swelling degree of graft copolymer beads was found to be increased with decreasing of environmental temperature. In vitro release studies were performed at 25 and 37 °C for 12 h, and showed that thermoresponsive graft copolymer beads had higher drug release behavior at 25 °C than that at 37 °C, following Fickian diffusion transport mechanism with slight deviation.

Synthesis of Ethyl Cellulose Grafted Poly(N-isopropylacrylamide) Copolymer and Its Micellization

Thermo-responsive graft copolymers, ethyl cellulose grafting poly(N-isopropylacrylamide) (EC-g-PNIPAm), were synthesized by single-electron transfer living radical polymerization (SET-LRP) in THF/methanol mixed solvent. Ethyl cellulose macro-initiators (EC-Br) for SET-LRP were synthesized by the esterification between the hydroxyl groups on EC backbones and 2-bromoisobutyryl bromides. The degree of substitution of the EC-Br macro-initiator was tailored by varying the feeding mole ratio of 2-bromoisobutyryl bromide to the hydroxyl group on ethyl cellulose. Three EC-Br macro-initiators with different Br substitutions were used as the macro-initiators and it was found that the converting degree of the initiator sites was efficient and the graft density of graft copolymer was controllable. The SET-LRP of NIPAm was efficient that the monomer conversion was above 60% within 25 h. The linear plot of ln((M)0/(M)t) versus the conversion indicated that the reaction was living and controllable. The graft copolymers were characterized by means of gel permeation chromatography (GPC), 1 H NMR and FTIR spectroscopy. GPC peak of the graft copolymer became narrower and shifted to the low elution time with the increase of reactive time. The molecular weight of the side-chain linearly increased with the reaction time. EC-g-PNIPAm copolymers were typical amphiphilic graft copolymers, having the hydrophobic EC backbone and the hydro- philic PNIPAm side chains. They could be self-assembled and form stable micelles in a selective solvent, water. The micelles were in spherical shape with typical diameter around 100 nm. Rod-like and flower shaped particles were also observed, which was probably due to the fusion of the spherical shaped micelles. The structure of the spherical shaped micelles was that the EC backbone collapsed to form the core of the micelles and the hydrophilic PNIPAm chains stayed in the outside of the micelles to stabilize the micelles. Due to the thermoresponsive branch chains of PNIPAm, the micelles could shrink with rising temperature due to the collapses of the PNIPAm side chains. Keywords ethyl cellulose; poly(N-isopropylacrylamide); single-electron transfer living radical polymerization (SET-LRP), graft polymerization; thermoresponsive

Temperature-sensitive hydrogel prepared by graft polymerization of N-isopropylacrylamide onto macroradical Pluronic

A new series of thermo-responsive graft copolymers were prepared via consecutive Pluronic backbone-initiated by t-butylperoxybenzoate with N-isopropylacrylamide (NIPAAm) onto Pluronic by a radical-induced graft polymerization technique. The thermal characterizations of the graft copolymers were investigated by differential scanning calorimetry (DSC). The Pluronic- g-poly(NIPAAm) copolymers exhibited sol-to-gel transitions depending on chain length of the grafted poly(NIPAAm) onto Pluronic. The graft copolymers indicated that the hydrophobic–hydrophilic balance achieved by varying contents of NIPAAm was an important parameter in controlling the transition temperature of the graft copolymers in solution and stability of the resultant gels. The data suggest that graft copolymers may be attractive substrates for tissue engineering and drug delivery applications as the combination of mechanistically independent gelation techniques with regard to gelation kinetics.

Hyperbranched homo and thermoresponsive graft copolymers by using ATRP‐macromonomer initiators

AbstractMacromonomer initiators behave as macro cross‐linkers, macro initiators, and macromonomers to obtain branched and cross‐linked block/graft copolymers. A series of new macromonomer initiators for atom transfer radical polymerization (MIM‐ATRP) based on polyethylene glycol (Mn = 495D, 2203D, and 4203D) (PEG) were synthesized by the reaction of the hydroxyl end of mono‐methacryloyl polyethylene glycol with 2‐bromo propanoyl chloride, leading to methacryloyl polyethylene glycol 2‐bromo propanoyl ester. Poly (ethylene glycol) functionalized with methacrylate at one end was reacted with 2‐bromopropionyl chloride to form a macromonomeric initiator for ATRP. ATRP was found to be a more controllable polymerization method than conventional free radical polymerization in view of fewer cross‐linked polymers and highly branched polymers produced from macromonomer initiators as well. In another scenario, ATRP of N‐isopropylacrylamide (NIPAM) was initiated by MIM‐ATRP to obtain PEG‐b‐PNIPAM branched block/graft copolymers. Thermal analysis, FTIR, 1H NMR, TEM, and SEM techniques were used in the characterization of the products. They had a thermo‐responsive character and exhibited volume phase transition at ∼ 36°C. A plasticizer effect of PEG in graft copolymers was also observed, indicating a lower glass transition temperature than that of pure PNIPAM. Homo and copolymerization kinetics were also evaluated. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Synthesis and characterization of thermo-sensitive graft copolymer of carboxymethyl guar and poly( N-isopropylacrylamide)

Thermo-responsive graft copolymers of carboxymethyl guar [CMG] and semitelechelic poly( N-isopropylacrylamide) [PNIPAm] were synthesized by coupling reaction between them using a water-soluble coupling agent namely, 1-(3-(dimethylamino) propyl)-3-ethyl carbodiimide hydrochloride [EDC]. The incorporation of PNIPAm into CMG was confirmed by FT-IR and NMR spectroscopy. The graft copolymers, CMG-g-PNIPAm showed enhanced viscosity as compared to the unmodified CMG in the semi-dilute regime. Due to the presence of a LCST side chains [PNIPAm], the graft copolymers exhibited thermo-responsive nature with respect to temperature which was investigated using pyrene fluorescence probe studies. Although the thermo-responsive property was observed, the thermo-thickening behavior was not seen in these polymers. The graft copolymers in the semi-dilute regime ( C p ≈ 10–20 g/L) showed viscoelastic properties and the relaxation time, τ, could be obtained from the crossover of frequency ( ω c) of storage modulus ( G′) and loss modulus ( G″) in the oscillatory experiments. The activation energy ‘ E a’ of associations was investigated using the time temperature superpsition (TTS). These thermo-responsive polymers along with the biodegradability of CMG can have potential application as industrial thickening agent.

A novel thermoresponsive graft copolymer containing phosphorylated HEMA for generating detachable cell layers

AbstractA novel polymeric formulation based on N‐isopropylacrylamide (NIPAAm), methylmethacrylate (MMA), and phosphorylated hydroxylethyl methacrylate (Phosp‐HEMA) was synthesized and characterized. NIPAAm was copolymerized with a known quantity of MMA to form a poly(NIPAAm–MMA) copolymer and was subsequently grafted with Phosp‐HEMA by gamma irradiation to a total dose of 0.5 kGy. The thermoresponsive graft copolymer was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, contact angle measurements, and energy dispersive X‐ray analysis. The cytotoxicity of the graft copolymer analyzed using L‐929 fibroblast cells showed noncytotoxic response. The cell adhesion on the graft copolymer was studied using rabbit corneal cells (SIRC) and human osteoblasts (HOS). The adhered cells were found to spread leading to the formation of cell layers. The cell layers with intact cell–cell and cell–extra cellular matrix contact were detached by lowering temperature below the lower critical solution temperature (29°C) of the graft copolymer. The viability and morphology of the cells in detached cell sheets were assessed by live dead staining and environmental scanning electron microscopy, respectively. This interesting feature of cell adhesion to form cell layers and cell sheet retrieval is implicit to be due to the properties of phosphate moieties on thermoresponsive copolymer. To the authors knowledge there is no previous report on phosphate moiety containing thermo responsive polymeric formulations which can modulate cell adhesion and cell sheet retrieval. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Synthesis and Characterization of Thermoresponsive Graft Copolymers of NIPAAm and 2-Alkyl-2-oxazolines by the “Grafting from” Method

New thermoresponsive graft copolymers were synthesized by the cationic ring-opening polymerization of 2-methyl-2-oxazoline (MeOxa) or 2-ethyl-2-oxazoline (EtOxa), initiated by the random copolymers of chloromethylstyrene (CMS) and N-isopropylacrylamide (NIPAAm) using the “grafting from” method with a yield of 66−94%. The polymers were characterized by NMR, GPC, and DSC, and the conformational transition (lower critical solution temperature, LCST) of macroinitiators and graft copolymers was determined by the turbidity and DSC measurements. The transition temperature of the graft copolymers could be fine-tuned through the composition of the macroinitiator and the graft copolymer. An increasing quantity of the hydrophobic comonomer chloromethylstyrene in the macroinitiator lowered its LCST, while in the graft copolymer an increasing content of the hydrophilic segment of poly(2-methyl-2-oxazoline) or poly(2-ethyl-2-oxazoline) raised the transition temperature. For graft copolymers with a high content of long poly(2-alkyl-2-oxazoline) grafts, stabilized aggregates with a thermoresponsive core can be formed at the LCST instead of precipitation of the material.