Multifunctional temperature-responsive polymers as advanced biomaterials and beyond

The versatility and applicability of thermoresponsive polymeric systems have led to great interest and a multitude of publications. Of particular significance, multifunctional poly(N-isopropylacrylamide) (PNIPAAm) systems based on PNIPAAm copolymerized with various functional comonomers or based on PNIPAAm combined with nanomaterials exhibiting unique properties. These multifunctional PNIPAAm systems have revolutionized several biomedical fields such as controlled drug delivery, tissue engineering, self-healing materials, and beyond (e.g., environmental treatment applications). Here, we review these multifunctional PNIPAAm-based systems with various cofunctionalities, as well as highlight their unique applications. For instance, addition of hydrophilic or hydrophobic comonomers can allow for polymer lower critical solution temperature modification, which is especially helpful for physiological applications. Natural comonomers with desirable functionalities have also drawn significant attention as pressure surmounts to develop greener, more sustainable materials. Typically, these systems also tend to be more biocompatible and biodegradable and can be advantageous for use in biopharmaceutical and environmental applications. PNIPAAm-based polymeric nanocomposites are reviewed as well, where incorporation of inorganic or carbon nanomaterials creates synergistic systems that tend to be more robust and widely applicable than the individual components. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48770.     

PVA hydrogels loaded with a Brazilian propolis for burn wound healing applications

PVA hydrogels offer many suitable characteristics for burn wound dressings. However, unmodified PVA gels do not act against infection. Propolis is a natural antimicrobial agent suitable for incorporation into PVA gels. PVA–propolis gels were produced by freeze–thawing method, and their microstructure, mechanical, and swelling properties (in standard PBS and a PBS‐based solution with pH 4.0) were characterized. The propolis release profiles and the gel's antibacterial and cytotoxicity properties were also investigated. The presence of propolis in the gels interfered with the PVA crystallization profile and with the mechanical properties. All samples swelled at least 400% in both media. The propolis was mostly released to the media in the first day of immersion. PVA–propolis gels with concentrations of 15% propolis or more were active against the gram‐positive bacterium Staphylococcus aureus, which is associated with initial colonization of the wound. All PVA–propolis samples acted as barriers to microbial penetration. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42129.     

The effect of curvature on chondrocytes migration and bone mesenchymal stem cells differentiation

Numerous cells grow in columnar tissues and organs with different curvatures and curvature gradients. Therefore, it is necessary to study the effect of curvature on cell behavior to control and promote cell development. Herein, we prepared polydimethylsiloxane (PDMS) with different micro-nano patterns using ultraviolet soft lithography. Hydrophilic polydopamine (PDA) was modified on the PDMS surface to prepare PDMS/PDA to improve its biocompatibility. The PDMS/PDA was characterized by contact angle tester and scanning electron microscopy (SEM). The effect of curvature on bone cell migration and differentiation was studied through SEM, inverted phase contrast microscope and fluorescence microscopy. We found that different curvatures had different effects on the bone cell migration and differentiation. Chondrocytes migrated rapidly in grooves with a curvature range of 1/575–1/875 μm⁻¹. Bone mesenchymal stem cells (BMSCs) had high efficiency of differentiation into chondrocytes in the grooves with a curvature range of 1/775–1/1375 μm⁻¹. Furthermore, BMSCs showed high efficiency of differentiation into chondrocytes at the edges of micro-nano patterns with different perimeter curvatures, and the differentiation efficiency was the highest at 120° convex curvature. This work shows that curvature is a principle to be considered in bone tissue regeneration engineering and provides inspiration for future biomaterials design.     

Recent biomedical advances with polyampholyte polymers

Polyampholyte polymer systems are composed of varying mixtures of charged monomer subunits. These polymeric systems have gained increasing attention because it is possible to design the final material properties through careful selection of the charged monomer subunits and controlling the polymer architecture. Characteristics that have been manipulated include the hydration, mechanical properties, pH responsive swelling, temperature responsive swelling, resistance to nonspecific protein adsorption, and protein conjugation capability. This had led researchers to propose the use of polyampholyte polymers as biosensor platforms, fouling release membranes, drug delivery vehicles, and tissue engineering scaffolds. This review is focused on advances that have been made over the last 5 years to develop polyampholyte polymers for these biomedical applications. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014 , 131, 40069.     

Materials selection and residual solvent retention in biodegradable electrospun fibers

Electrospun tissue engineering scaffolds provide mechanical support to seeded cells that populate the structure while depositing specific extracellular matrix components. The potent sterilizing agent 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) is often used in electrospinning investigations involving biologically‐derived polymers. Surprisingly, there has been no study of solvent retention versus composition even though materials selection should influence organic solvent content. We developed a method quantifying HFIP retention following electrospinning of gelatin, polycaprolactone (PCL), and PCL‐gelatin blends using electro‐spray mass spectroscopy. The acetone content of acetone‐spun PCL was also established. Pure gelatin fiber contained as much as 1600 ppm of HFIP. In contrast, little acetone or HFIP was detected in 100% PCL. Gelatin clearly has a greater affinity for HFIP than PCL and materials selection has a strong influence on the amount of retained solvent. Vacuum + heat treatment at 37 and 45ºC reduced [HFIP] to 10 and 5.6 ppm, respectively, levels having no demonstrated effects on mammalian cell viability. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Conjugated polymers with anionic dyes: Synthesis,properties, and sensing ability for nucleosides,DNA, and BSA

The reaction of N-(2,4-dinitrophenyl)pyridinium chloride (salt[Cl⁻]) with sodium salts of anionic dyes, such as acid red 52 (AR52), acid violet 49 (AV49), and coomassie brilliant blue G-250 (CBBG250) involves an anion exchange between the chloride anion of salt(Cl⁻) and sulfonium anion of the dyes, resulting in the generation of novel Zincke salts, namely, salt(AR52), salt(AV49), and salt(CBBG250), respectively. Reactions of salt(AR52), salt(AV49), and salt(CBBG250) with piperazine in the absence of catalysts resulted in the opening of the pyridinium ring to yield ionic polymers comprising units of 5-piperazinium-2,4-dienylideneammonium and the corresponding dye anion, namely polymer(AR52), polymer(AV49), and polymer(SBBG250), respectively. The corresponding model compounds for the polymers were also synthesized by reacting salt(AR52), salt(AV49), and salt(CBBG250) with piperidine. Polymer(AV49) and polymer(SBBG250) were found to be suitable for the detection of nucleosides, DNA, and proteins, realized by monitoring the changes in their UV–vis absorption spectra, arising from the anionic dyes within the polymers. The polymers and the model compounds were electrochemically oxidized in solution.     

Biodegradable and temperature‐responsive thermoset polyesters with renewable monomers

A series of biodegradable thermoset polyesters, poly(1,8‐octanediol–glycerol–dodecanediaote)s (POGDAs), were synthesized with the polycondensation polymerization method without a catalyst and with different monomer molar ratios. Synthesis was confirmed with structural analysis via Fourier transform infrared spectroscopy. The effect of varying the monomer molar ratio on the material properties was illustrated in the gel content and swelling analysis, ultraviolet–visible spectroscopy, differential scanning calorimetry, X‐ray diffraction, and degradation tests. Degradation tests were performed in phosphate‐buffered solution at 37 °C for 60 days. Temperature‐responsive behavior was revealed with POGDA (0.5 glycerol), and bending tests were performed to study the shape‐memory effect. In vitro cytotoxicity tests and cell proliferation tests suggested that these POGDAs have potential applications in biomedical fields such as tissue engineering. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44007.     

Synthesis of novel antibacterial monomers (UDMQA) and their potential application in dental resin

To prepare antibacterial dental resin, a series of novel urethane dimethacrylates quaternary ammonium methacrylate monomers (UDMQAs) with different substituted alkyl chain length were synthesized, and their structures were confirmed by FTIR and ¹H‐NMR spectra. The obtained UDMQAs were used to replace 2,2‐Bis[4‐(2‐hydroxy‐3‐methacryloyloxypropyl)‐phenyl]propane (Bis‐GMA) totally as base monomers of dental resin and mixed with Tri‐ethyleneglycol dimethacrylate (TEGDMA) at the mass ratio of 50/50. The properties of these prepared resins like antibacterial activity, double bond conversion (DC), polymerization shrinkage, flexural strength (FS), and modulus (FM), water sorption and sol fraction were investigated. The most commonly used dental resin Bis‐GMA/TEGDMA (50wt/50wt) was chosen as a reference. The results showed that UDMQAs could endow dental resin with antibacterial activity. Compared with Bis‐GMA‐based dental resin, UDMQAs‐based resin had the same or higher DC, lower polymerization shrinkage, lower flexural strength and modulus, and higher water sorption and sol fraction. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Photosensitive polymers containing pendent chalcone moieties via oxyethylene group

Vinylchalcone derivatives were prepared by the reaction of the sodium salt of 4-hydroxychalcone with 2-chloroethanol, followed by esterfication of the hydroxy groups with methacryloyl chloride in the presence of triethylamine as a base. The photosensitive monomers, 4-(methacryloyloxyethoxy)chalcone and its 4′-methyl and 4′-chloro-derivatives, have been homo- and copolymerized with p-nitrophenylmethacrylate under free radical conditions to give the copolymers containing different ratios of photosensitizer group. The photosensitivities of the polymeric chalcone derivatives were investigated through their photochemical reactions on exposure to UV light and measuring the changes in UV spectra before and after irradiation. The results of these measurements indicate that the insolubilization percentage, i.e. the rate of the double bond disappearance depends on the effects of (i) the time of exposure to UV light, (ii) the position of the substituent in the phenyl ring of the chalcone, (iii) the spacer between the active moiety and the polymer backbone, and (iv) the ratio of the photosensitizer group.     

Vinyl monomers bearing chromophore moieties and their polymers. VII. Synthesis,photochemical, and initiation behavior of acrylic monomers bearing phenothiazine oxide moieties and their polymers

Four acrylic monomers bearing phenothiazine oxide moieties, that is, N-acryloyl-phenothiazine-5-oxide (APTO), N-acryloyl-2-chlorophenothiazine-5-oxide (ACPTO), N-acryloyl-phenothiazine-5,5-dioxide (APTDO), and N-acryloyl-2-chlorophenothiazine-5,5-dioxide (ACPTDO) were synthesized by oxidation of corresponding N-acryloyl-phenothiazine (APT) and N-acryloyl-2-chlorophenothiazine (ACPT) using sodium perborate as an oxidant. These monomers could easily be polymerized by initiation of AIBN. The emission fluorescence spectra of the monomers and their polymers were recorded, and the results indicated that these 4 new monomers possess a fluorescence structural self-quenching effect (SSQE), as we have reported previously. Moreover, with the change of the electronic structure of sulfur atom in the phenothiazine chromophore, that is, from sulfide to sulfoxide and sulfone groups, the tendency of SSQE of these monomers is in the order of APT > APTO > APTDO. This would be ascribed mainly to the decrease of electron-donating abilities of monomers in a sequence of sulfide, sulfoxide, and sulfone groups; that is, at the sulfur atom of these monomers, APT has 2 lone-pair electrons, APTO has 1 lone-pair electrons, and APTDO completely loses its lone-pair electrons. Based on the exciplex formation, the monomers APTO, APTDO, ACPO, and ACPTDO could act as sensitizers for the photopolymerization of acrylonitrile (AN). The combination of APTO or ACPTO with organic peroxides such as BPO could also initiate the polymerization of vinyl monomers, such as AN, by redox nature. © 1998 John Wiley & Sons, Inc. J. Appl. Polym. Sci. 70: 1191–1199, 1998     

Synthesis of new metal-containing side-chain monomers and polymers

New metal-containing vinyl monomers, hexyl-6-oxy-{4-[4-(4-carboxy cyclopentadienyl manganese tricarbonyl phenyl)phenyl]benzoyloxy}methacrylate and hexyl-6-oxy-{4-[4-(4-ferrocenoyl phenyl)phenyl]benzoyloxy}methacrylate, and the corresponding homopolymers and random copolymers with hydroxy monomer hexyl-6-oxy-{4-[4-(4-hydroxyphenyl)phenyl]benzoyloxy}methacrylate were synthesized. The compounds were characterized by¹H NMR; their thermal behavior was investigated by means of differential scanning calorimetry. Monomers and polymers containing the ferrocene unit melt at lower temperatures than those derived from the cyclopentadienyl managanese tricarbonyl moiety. The melting temperatures of the monomers and polymers ranged from 399 to about 515 K, Both monomers and polymers failed to exhibit mesogenic behavior. Values ofM _n,M _w,M _w/M _n, and degree of polymerization were obtained by gel permeation chromatography. TheM _n ranged from 16,500 for the copolymer containing hexyl-6-oxy-{4-[4-(4-ferrocenoyl phenyl)phenyl] benzoyloxy}methacrylate and hydroxy monomer hexyl-6-oxy-{4-[4-(4-hydroxyphenyl)phenyl]benzoyloxy}methacrylate at a 1:3 ratio to 26,000 for the copolymer containing hexyl-6-oxy-{4-[4-(4-carboxy cyclopentadienyl manganese tricarbonyl phenyl)phenyl]benzoyloxy}methacrylate and hydroxy monomer hexyl-6-oxy-{4-[4-(4-hydroxyphenyl)phenyl]benzoyloxy}methacrylate at a 1:3 ratio.M _w/M _n ranged from 1.6 in the case of the copolymer containing hexyl-6-oxy-{4-[4-(4-carboxy cyclopentadienyl manganese tricarbonyl phenyl)phenyl]benzoyloxy}methacrylate and hydroxy monomer hexyl-6-oxy-{4-[4-(4-hydroxyphenyl)phenyl]benzoyloxy}methacrylate at a 1:3 ratio to 2.2 in the case of poly(hexyl-6-oxy{4-[4-(4-carboxy cyclopentadienyl manganese tricarbonyl phenyl)phenyl]benzoyloxy}methacrylate).     

Preparation and properties of a novel bio‐based and non‐crystalline engineering elastomer with high low‐temperature and oil resistance

A series of poly(succinic acid/sebacic acid/itaconic acid/butanediol/propanediol) bio‐based and non‐crystalline engineering elastomers (BEE) were obtained by changing the molar ratio of succinic acid (SA) to sebacic acid (SeA) from 5:5 (BEE‐5) to 8:2 (BEE‐8). We prepared bio‐based engineering elastomer composites (BEE/CB) by mixing BEE with carbon black N330. The low‐temperature and oil resistance properties of the BEE/CB composites were investigated in terms of low‐temperature brittleness, coefficient of cold resistance under compression, oil resistance test at different temperatures, and tensile properties. The results showed that the low‐temperature brittleness temperature of the BEE/CB composites ranged from ?50 to ?60°C and the coefficient of cold resistance under compression was 0.18 high at ?60°C for BEE‐7/CB and 0.23 high at ?40°C for BEE‐8/CB. The oil resistance properties of BEE‐7/CB were higher than those of nitrile‐butadiene rubber N240S (NBR N240S), and the oil resistance properties of BEE‐8/CB were even as high as those of nitrile‐butadiene rubber N220S (NBR N220S). © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 132, 42855.     

Antimicrobial polyester

Two N‐halamine siloxane precursors, 5,5‐dimethyl‐3‐(3′‐triethoxysilylpropyl)hydantoin and 3‐(3′‐triethoxysilylpropyl)‐7,7,9,9‐tetramethyl‐1,3,8‐triazaspiro[4.5]decane‐2,4‐dione, have been synthesized and coated onto polyester fiber surfaces. The coated polyester was rendered biocidal after exposure to household bleach solution by converting the heterocyclic precursors to N‐halamine moieties. The thermal properties of these coated polyester samples were determined with differential scanning calorimetry. The chlorinated polyester swatches were challenged with Staphylococcus aureus (ATCC 6538) and Escherichia coli O157 : H7 (ATCC 43895) with contact times ranging from 1 to 30 min. The biocidal testing showed that the chlorinated samples inactivated S. aureus and E. coli O157 : H7 within 5 and 30 min of contact, respectively. Standard washing tests indicated that the chlorinated coated fibers were very resistant to loss of the coating through hydrolyses. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Antimicrobial silica and sand particles functionalized with an N‐halamine acrylamidesiloxane copolymer

The monomer 2‐acrylamido‐2‐methyl‐1‐(5‐methylhydantoinyl)propane (HA) was copolymerized with 3‐(trimethoxysilyl)propyl methacrylate (SL) and covalently attached onto silica gel and sand particles. As a result HASL copolymer‐grafted silica gel and sand particles (HASL SGPs and SPs) were obtained. These two types of HASL SGPs and SPs provided excellent biocidal efficacy against Gram positive S. aureus and Gram negative E. coli O157:H7 bacteria when the copolymer‐grafted particles were exposed to dilute sodium hypochlorite (household bleach) solution. In a flowing water application, seven logs of bacteria were inactivated within 10 s of contact time with the particles packed into a column. The treated particles also exhibited good washing and storage stabilities. The chlorine loss during extensive flow could be recovered by further exposure to dilute bleach solution. The antimicrobial particles have potential application for use in inexpensive disinfecting water filters for slow water flows. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43413.     

Synergistic effect of graphene oxide and sodium carboxymethylcellulose on the properties of poly(vinyl alcohol) hydrogels

Hydrogels are a promising candidate for applications in biomedicine and bioengineering, but their mechanical properties often restrict their applications. To improve the mechanical performance of poly(vinyl alcohol) (PVA) hydrogels, we introduced sodium carboxymethylcellulose (CMC), and graphene oxide (GO) into them. We prepared a series of composite hydrogels composed of PVA, CMC, and GO with epichlorohydrin as a chemical crosslinker. We used Fourier transform infrared spectroscopy and X-ray diffraction to characterize the chemical structures of GO and the hydrogel. The dynamic mechanical analysis results show the synergistic enhancement effects of CMC and GO on the PVA hydrogel. The swelling process of the hydrogels also fit well with the second-order kinetic equation. Scanning electron microscopy results suggest that the neat mesh structure facilitated superior mechanical properties in the hydrogels. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47644.     

Physicochemical modification of hydroxylated polymers to develop thermosensitive double network hydrogels

Due to the unique biophysicochemical characteristics of synthesized superhydrophilic poly[N-[tris(hydroxymethyl)methyl] acrylamide] (PTHMMA) and poly(vinyl alcohol) (PVA), in this study, we investigated the preparation of physically and chemically crosslinked thermosensitive double network (DN) hydrogels with superior mechanical properties. The effect of the combination of PTHMMA with PVA was further explored experimentally and theoretically. Moreover, adjusting the lower critical solution temperature (LCST) of PTHMMA/PVA DN hydrogels in the phosphate buffer was achieved by chemical alteration and crosslinking of water-soluble polymers. Changing the composition and the extent of ether/acetal linkages altered the LCST based on hydrophilic/hydrophobic composition, which decreased the complexity of adjusting hydrogels' temperature sensitivity. PTHMMA-comprising hydrogels were found to have non-Fickian and super case ΙΙ transport characters. Moreover, the construction of shrunken PVA at high temperature was tailored by introducing PTHMMA into the network to permit a relaxed drug release of indomethacin (IND) at 37°C and pH 7.4. Finally, the tensile strength, the equilibrium water content, thermo-sensitivity, and cell viability behaviors suggest that these materials can be tailored for potential applications as biomaterials.     

Novel π-conjugated cyclophane polymers containing phenylamine moieties with strong blue-light emission

Novel through-space conjugated polymers based on poly(p-phenylene-ethynylene) (PPE) containing alternate [2.2]paracyclophane and phenylamine moieties in the main chain were synthesized by the Sonogashira coupling reaction. Polymers were soluble in common organic solvents, and transparent and uniform thin films of the polymers were obtained easily by casting or spin-coating from toluene solution. According to the UV-vis absorption spectra, π-electrons of the polymer were delocalized via the through-space interaction between the two benzene rings in the cyclophane unit. The polymer exhibited strong blue emission in solution and in the solid state.     

Studies on chain extension of a novel bio‐based engineering elastomer using 4,4‐diphenyl methane diisocyanate as a chain extender

A novel hydroxyl‐terminated bio‐based engineering elastomer (BEE) was synthesized from four bio‐based monomers by adding excess diol. Then the BEE was chain extended in Haake torque rheometer with 4,4‐diphenyl methane diisocyanate (MDI) as chain extender. The molar ratio of NCO/OH, reaction temperature and reaction time of the chain‐extension reaction were studied, and the optimum condition was determined by the gel permeation chromatography (GPC), soxhlet extraction, and fourier transform infrared spectroscopy (FTIR) results. After chain extension, (i) the number‐average molecular weight of BEE became about 3.5 times of the original BEE, (ii) the thermal stability was improved and the crystallization rate was lower, (iii) and the mechanical properties were significantly improved with nano‐SiO₂ as reinforcing filler. The chain‐extended BEE would have potential wide applications in engineering field. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40756.     

Modifying and managing the surface properties of polymers

An ongoing challenge in polymer science is the preparation of materials with bespoke surface properties which differ from that of the bulk, for example hydrophobicity, wettability, chemical resistance, adhesion or biocompatibility. We highlight here recent efforts in the design, development and application of (multi)end‐functionalized polymers as additives for the efficient modification of polymer surface properties. Aryl‐ether moieties bearing up to eight functional groups have been used as initiators for the controlled polymerization of both styrene and methyl methacrylate by atom transfer radical polymerization (ATRP) and of lactide by ring opening polymerization (ROP). The resulting polymers have been used as additives to modify the surfaces of the corresponding bulk polymers. Fluorinated polymer surfaces are particularly appealing in terms of their liquid repellence, chemical inertness and low coefficient of friction. When an additive consisting of a low molecular weight polystyrene chain, end‐capped with four C₈F₁₇ groups, is present in a matrix of polystyrene at levels as low as 0.1%, near polytetrafluoroethylene‐like surface properties result. Copyright © 2007 Society of Chemical Industry     

Synthesis and characterization of poly{N‐[3‐(dimethylamino) propyl] methacrylamide‐co‐itaconic acid} hydrogels for drug delivery

A novel pH‐sensitive hydrogel system composed of itaconic acid (IA) and N‐[3‐(dimethylamino) propyl] methacrylamide was designed. This system was prepared by aqueous copolymerization with N,N‐methylene bisacrylamide as a chemical crosslinker. The chemical structure of the hydrogels was characterized by Fourier transform infrared (FTIR) spectroscopy. The microstructure and morphology of the hydrogels were evaluated by X‐ray diffraction (XRD) and scanning electron microscopy (SEM). The SEM study of hydrogels on higher magnification revealed a highly porous morphology with uniformly arranged pores ranging from 40 to 200 μm in size. XRD analysis revealed the amorphous nature of the hydrogels, and it was found that an increase in the IA content in the monomer feed greatly reduced the crystallinity of the hydrogels. Swelling experiments were carried out in buffer solutions at different pH values (1.2–10) at 37°C ± 1°C to investigate their pH‐dependent swelling behavior and dimensional stability. An increase in the acid part (IA) increased the swelling ratio of the hydrogels. Temperature‐sensitive swelling of the hydrogels was investigated at 20–70°C in simulated intestinal fluid. The hydrogels swelled at higher temperatures and shrank at lower temperatures. 5‐Aminosalicylic acid (5‐ASA) was selected as a model drug, and release experiments were carried out under simulated intestinal and gastric conditions. 5‐ASA release from the poly N‐[3‐(dimethylamino) propyl] methacrylamide‐co‐itaconic acid‐80 (PDMAPMAIA‐80) hydrogel was found to follow non‐Fickian diffusion mechanism under gastric conditions, and a super case II transport mechanism was found under intestinal conditions. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011