PNIPAAm Polymer Research Articles

Intelligent solar-driven “switch” photothermal hydrogel for clean water harvesting

Water shortage is becoming a huge challenge to mankind. Inspired by pufferfish, we developed an intelligent solar-driven “switch” hydrogel system PEG-PNIPAAm/Fe3O4 hydrogel (PPFH). This hydrogel system is characterized by a uniform porous network structure formed by the integration of hydrophilic PEG, temperature-responsive PNIPAAm polymer and Fe3O4 photothermal nanoparticles. The three-dimensional porous structure provides a higher surface area, offering more adsorption sites for water molecules. The interaction between PPFH and water primarily relies on the hydrogen bonding between the amide groups in PNIPAAm and water molecules, which enhances the hydration of the hydrogel network for rapidly water harvesting. However, when exposed to sunlight, the presence of Fe3O4 nanoparticles causes the ambient temperature to rise rapidly above the LCST, the hydrogen bonding between molecules gradually weakens, while the hydrophobic interactions among the hydrophobic groups in PNIPAAm become stronger, causing the polymer chains to contract and water releasing. The fog capture performance of PPFH can reach up to 3.2 g g−1, and under the irradiation of a sunlight (1 kW m−2), the captured water can be released within 8 min, and the water release efficiency reaches 94 %. This design concept provides the possibility for promoting the widespread implementation of hydrogels-based solar evaporators in practical purification systems in the future, alleviating water shortages issues.

Smart Thermoresponsive Electrospun Nanofibers with On-Demand Release of Carbon Quantum Dots for Cellular Uptake.

Developing a smart responsive surface for on-demand delivery of organic, inorganic, and biological cargo in vitro cellular uptake is always in constant demand. Herein, we present carbon quantum dot (CQD)-loaded (poly(N-isopropylacrylamide) (PNIPAAm)/poly(methyl methacrylate (PMMA)) blend nanofiber sheets having a thermoresponsive nature. As a model cargo, fluorescent CQDs are used for the demonstration of the on-demand delivery mechanism. In addition, a thermoresponsive nature is produced by the PNIPAAm polymer in the nanofiber matrix while the PMMA polymer provides extra stability and firmness to the nanofibers against the sudden dissolution of the nanofibers in aqueous media. The synthesis of CQDs and their loading into a blend nanofiber matrix are confirmed using fluorescence spectrophotometry, transmission electron microscopy, and fluorescence microscopy. The morphologies and diameters of the nanofibers are analyzed by scanning electron microscopy. Burst effect analysis proves that 30% (w/w) PNIPAAm-containing nanofibers possess the highest stability with the least dissolution in aqueous media. Thermoresponsiveness of the nanofibers is further confirmed through water contact angle measurements. Quantitative fluorescence results show that more than 80% of loaded CQDs can be released upon thermal stimulation. The fluorescence micrographs reveal that the blend nanofiber sheets can effectively improve the cellular uptake of CQDs by simply increasing the local concentrations via applying thermal stimulation as the released mechanism.

Improved antifouling and drug delivery properties of polyvinyl alcohol hydrogel by grafting with N‐isopropylacrylamide via organic dye photocatalyzed PET‐RAFT polymerization

AbstractPolyvinyl alcohol (PVA) hydrogel was modified with NIPAAm via a green, efficient, and industrially applicable photo induced electron transfer‐reversible addition‐fragmentation chain transfer (PET‐RAFT) polymerization catalyzed by organic dye. The hydrophilicity of PVA‐g‐pNIPAAm became temperature sensitive due to the introduction of pNIPAAm polymer brushes. It was surprising that PVA‐g‐pNIPAAm became superhydrophilic (WCA = 4.3°) at 25°C while the grafting yield was 39.3%. In addition, no cytotoxic for primary human eyelid fibroblast cells was observed according to ISO 10993.5:2009. Antifouling properties of PVA‐g‐pNIPAAm were significantly improved due to the increase of surface steric repulsion effect. Drug release property of PVA‐g‐pNIPAAm was more controllable than PVA hydrogel. Thus, organic dye catalyzed PET‐RAFT polymerization could be applied to construct functional surface on biomaterials, and PVA‐g‐pNIPAAm hydrogel with lower cytotoxic, higher antifouling, and drug release properties had great potential in drug delivery.

The Combined Thermoresponsive Cell-Imprinted Substrate, Induced Differentiation, and "KLC Sheet" Formation

Purpose: Stem cells can exhibit restorative effects with the commitment to functional cells.Cell-imprinted topographies provide adaptable templates and certain dimensions for thedifferentiation and bioactivity of stem cells. Cell sheet technology using the thermo-responsivepolymers detaches the "cell sheets" easier with less destructive effects on the extracellularmatrix (ECM). Here, we aim to dictate keratinocyte-like differentiation of mesenchymal stemcells (MSCs) by using combined cell imprinting and sheet technology. Methods: We developed the poly dimethyl siloxane (PDMS) substrate having keratinocytecell-imprinted topography grafted with the PNIPAAm polymer. Adipose tissue-derived MSCs(AT-MSCs) were cultured on PDMS substrate for 14 days and keratinocyte-like differentiationmonitored via the expression of involucrin, P63, and cytokeratin 14. Results: Data showed the efficiency of the current protocol in the fabrication of PDMSmolds. The culture of AT-MSCs induced typical keratinocyte morphology and up-regulatedthe expression of cytokeratin-14, Involucrin, and P63 compared to AT-MSCs cultured on theplastic surface (P < 0.05). Besides, KLC sheets were generated once slight changes occur in theenvironment temperature. Conclusion: These data showed the hypothesis that keratinocyte cell imprinted substrate canorient AT-MSCs toward KLCs by providing a specific niche and topography.

Study of poly (N-isopropyl acrylamide) electrospinning magnetic fiber as a cell attach/detach substrate

In this study, we used electrospinning technology to develop a novel composite material with temperature and magnetic responsive characteristics which physical and chemical parameters were verified. Poly(N-isopropylacrylamide), PNIPAAm polymer was chosen as the main material for the spinning process, to prepare the temperature-responsive material with a hydrophobic/hydrophilic fiber structure. The fibers prepared by the electrospinning method resulted in high pores and high volume-surface area that can serve as substrates for cell tissue engineering applications. The material was then integrated with magnetic nanoparticles which led to composite materials of magnetic temperature-responsive spinning fibers and can further be used as a substrate material in the biomedical engineering field. Field-scanning emission electron microscopy (FSEM) and transmission electron microscopy (TEM) were used to characterize the spinning fibers diameter and surface morphology. The superconducting quantum interference device (SQUID) and thermogravimetric analyzer (TGA) were used to analyze the amount of magnetic nanoparticles confined in the magnetic temperature-responsive spinning fiber. The proportion of magnetic particles in magnetic temperature-responsive spinning fiber from SQUID and TGA analysis was 3.44% and 4.07%, respectively. This study successfully established the preparation of temperature-responsive spinning fiber with extracellular matrix structure through an electrospinning technique. In the future, this composite material with the advantage of switchable hydrophilic/hydrophobic temperature-responsive and magnetic induction properties can further be used in the field of biomedical engineering applications, such as drug-carrier, drug release, skin wound healing, and magnetic high-frequency heat treatment.

Thermo-responsive nanofibrous composite membranes for efficient self-cleaning of protein foulants

This study developed a self-clean thermo-responsive nanofibrous poly(vinylidene fluoride) (PVDF)/nylon-6,6/poly(N-isopropylacrylamide) (PNIPAAm) composite ultrafiltration membrane consisting of a nylon-6,6/PNIPAAm functional nanofibre layer integrated into a PVDF substrate. The morphological analysis showed the presence of electrospun nano-nets branching out from the main nanofibres as PNIPAAm concentration increased, affecting the pore size distribution and solute rejection. The PVDF/nylon-6,6/PNIPAAm membranes showed improved surface hydrophilicity below the low critical solution temperature (LCST) and strong thermo-switchability. With bovine serum albumin (BSA) as the model foulant, the rejection of the 4 wt% PNIPAAm membranes was greatly improved to above 96%. Through a two-cycle ultrafiltration study using feed solution containing BSA and CaCl2, the membrane with 4 wt% PNIPAAm showed superior recovery of water permeance up to 97% assisted with temperature-change cleaning, compared to the control membrane that only recovered 56%. Filtration experiments with and without intermediate temperature-change cleaning proved that the anti-fouling mechanism of the PNIPAAm membranes was strongly associated with surface wettability and rapid conformation of PNIPAAm polymer chains induced by volume-phase transition, resulting in reduced protein adsorption and ‘shaking-off’ of the absorbed proteins from the membrane surface. Such smart responsive membranes have great potential for the development of easy-to-clean membranes for food and wastewater treatment.

Selective adsorption of oppositely charged PNIPAAM on halloysite surfaces: a route to thermo-responsive nanocarriers

Halloysite nanotubes were functionalized with stimuli-responsive macromolecules to generate smart nanohybrids. Poly(N-isopropylacrylamide)-co-methacrylic acid (PNIPAAM-co-MA) was selectively adsorbed into halloysite lumen by exploiting electrostatic interactions. Amine-terminated PNIPAAM polymer was also investigated that selectively interacts with the outer surface of the nanotubes. The adsorption site has a profound effect on the thermodynamic behavior and therefore temperature responsive features of the hybrid material. The drug release kinetics was investigated by using diclofenac as a non-steroidal anti-inflammatory drug model. The release kinetics depends on the nanoarchitecture of the PNIPAAM/halloysite based material. In particular, diclofenac release was slowed down above the LCST for PNIPAAM-co-MA/halloysite. Opposite trends occurred for halloysite functionalized with PNIPAAM at the outer surface. This work represents a further step toward the opportunity to extend and control the delivery conditions of active species, which represent a key point in technological applications.

Thermo-Controlled in Situ Phase Transition of Polymer-Peptides on Cell Surfaces for High-Performance Proliferative Inhibition.

We herein report a thermocontrolled strategy for realizing in situ conformational transition of polymer-peptide conjugates at cell surfaces to manipulate and monitor HER2 receptor clustering, which finally result in effective breast cancer cell proliferation inhibition. Functional paring motifs (HBP) are covalently linked to a synthetic thermoresponsive polymer PNIPAAm to incorporate temperature control properties to HER2 targeting peptide. At 40 °C, the PNIPAAm polymers collapse and act as a "shield" to block the aggregation of HBP. Upon cooling to 35 °C, polymers are in their extended state and HBP are expose in aqueous and aggregate subsequently with enhanced fluorescence, allowing for promoting and in situ monitoring of receptor clustering. Ultimately, HER2 receptor clustering leads to cytoplasmic domain phosphorylation, which further results in effective cancer cell proliferation inhibition. We envision that this useful approach has the potential to be applied for molecule-targeted tumor therapy.

SPG 막유화 및 UV 광중합법에 의해 제조된 PNIPAAm 하이드로젤 입자의 형태학에 관한 연구

Abstract: W/O emulsions were prepared from the aqueous solution containing NIPAAm, MBA, and APS in the continuous phase of toluene and mineral oil mixture with HMP and Span80 by using SPG membrane emul-sification, and followed by the formation of PNIPAAm hydrogel microspheres through UV photopolymerization. As the ratio of mineral oil to toluene increased in the continuous phase, both particle size of the hydrogel in-creased and density of PNIPAAm polymer in the hydrogel particle increased, and which significantly affected swelling/deswelling ratio (V/V o ) with temperature change around VPTT. When the polymerization temperature was below LCST (20°C), PNIPAAm hydrogel showed filled particle morphology; however, it was turned out to hollow particle morphology with thick shell layer with 40°C. Both density of PNIPAAm and gel content of the hydrogel increased with the increase in MBA concentration. Keywords: SPG membrane emulsification, hydrogel, PNIPAAm, LCST 1. 서 론 1) 균일한 입도를 가지는 고분자 입자의 제조방법으로는 분산중합(dispersion polymerization) 및 무유화 에멀젼중합(soap-free emulsion polymerization) 등이 널리 알려져 있으나, 5 µm 이상의 균일한 입도를 가지는 고

Nanostructured Biointerfaces: Nanoarchitectonics of Thermoresponsive Polymer Brushes Impact Protein Adsorption and Cell Adhesion.

Controlling the reversibility, quantity, and extent of biomolecule interaction at interfaces has a significant relevance for biomedical and biotechnological applications, because protein adsorption is always the first step when a solid surface gets in contact with a biological fluid. Polymer brushes, composed of end-tethered linear polymers with sufficient grafting density, are very promising to control and alter interactions with biological systems because of their unique structure and distinct collaborative response to environmental changes. We studied protein adsorption and cell adhesion at polymer brush substrates which consisted of poly(N-isopropylacrylamide) (PNIPAAm), having a lower critical solution temperature (LCST), to control bioadsorptive processes by changing the environmental temperature. Preparing the PNIPAAm brushes by the "grafting-to"-method two differently synthesized PNIPAAm polymers were used, at which one possessed an additional hydrophobic terminal headgroup. It is known that hydrophobic moieties can influence protein adsorption significantly. The films were comprehensively analyzed by in situ spectroscopic ellipsometry, contact angle measurements, streaming potential, and atomic force microscopy. Our study was mainly focused on the investigation of the fibrinogen (FGN) adsorption responsiveness both on homo polymer PNIPAAm brushes with and without the hydrophobic terminal functionalization, and further on binary brushes made of the polyelectrolyte poly(acrylic acid) (PAA) and one of the prior described two PNIPAAm species. The results show that the terminal hydrophobic modification of PNIPAAm has a considerable impact on wettability, LCST, and morphology of the homo and the binary brush systems, which consequently led to an alteration of FGN adsorption. By using binary PNIPAAm-PAA brushes with different composition it was possible to induce stimuli dependent FGN adsorption with a considerable amplified switching effect by introducing a hydrophobic terminal residue to PNIPAAm. Cell adhesion studies with human mesenchymal stem cells reflected the results of the FGN adsorption.

A modular construction kit for supramolecular polymer gels

Supramolecular polymer gels are swollen networks of macromolecules interconnected by transient, non-covalent bonds; they form an extraordinarily useful class of soft, stimuli-sensitive materials. To optimize the use of supramolecular polymer gels in applications, their physical and chemical properties must be understood. This understanding is ideally achieved using model systems that allow the type and strength of supramolecular chain crosslinking to be varied to a great extent without concurrent alteration of the properties of the covalent polymer backbones. We introduce a system that provides these requirements. We use linear chains of electrophilic methacryl-succinimidyl (MASI) modified poly(N-isopropylacrylamide) (pNIPAAm). These polymers can be modified in a modular fashion by replacing their electrophilic MASI units by nucleophilic amine-functionalized derivatives of custom, supramolecular crosslinkable functionalities. We follow this approach and prepare a set of pNIPAAm polymers that consist of exactly the same polymer backbone functionalized with different types of crosslinkable sidegroups. These polymers are then crosslinked by addition of low molecular weight linkers that are complementary to the motifs on the polymer. We use multiple hydrogen bonding based on diaminotriazine and maleimide, cyanuric acid and Hamilton wedges, and diaminotriazine and cyanuric acid; we also use metal complexation based on terpyridine and different metal salts. This approach creates supramolecular networks of greatly varying rheological properties, from low viscous liquids to elastic gels, each showing consistent and quantitative correlation between the gel mechanical properties and the binding strength of the respective constituent supramolecular crosslinking motifs. Exploiting the good solubility of the common pNIPAAm backbone polymer in a variety of solvents allows these networks to be prepared and studied in different media with unprecedented consistency and flexibility.

Surface functionalized polymer particles and thereby generation of PNIPAAM grafted monoliths by shear aggregation and ATRP

Surface functionalization of the materials to achieve functionalities like thermal responsiveness has found increasing interest. In the current study, such a functionalization with poly(N-isopropylacrylamide) (PNIPAAM) polymer has been reported by controlled grafting from the surface of aggregated particles to form macroporous monoliths. The particles were first modified with a thin polymer shell of a functional monomer 2-(2-bromopropionyloxy) ethyl acrylate, BPOEA (or copolymer with styrene), which also contained a terminal atom transfer radical polymerization (ATRP) moiety. Surfactant free emulsion polymerization was carried out to generate polystyrene seed particles as well as the shell around them. Due to the colloidal unstability of BPOEA polymer chains, stable particles were formed only in presence of excess molar amount of styrene (styrene to BPOEA mole ratio of 3:1) or seed particles. Collapse of the BPOEA polymer chains on the seed particles was also enhanced by the addition of salt in the shell forming monomer batch, which did not allow the formation of stable secondary particles. The surface morphology of the particles was affected both by the kinetic collapse of the BPOEA chains on surface of the particles and subsequent polymerization as well as efficient stirring of the contents. The emulsifier free particles could not be gelated by the addition of salt and were destabilized by shear. The resulting aggregates were stable and porous which allowed simultaneous grafting of PNIPAAM polymer from the surface as well as imparted dimensional stability to the structure during the grafting process. It was also required to optimize the extent of grafting as the excess grafting could reduce the porosity of the structure.

Star polymers with random number of temperature sensitive arms and crosslinked poly(EGDMA)-core and their application to drug delivery

A simple methodology is described for the preparation of temperature sensitive star polymers with random number of arms and crosslinked core. In the first step, well defined, monodisperse poly( N-isopropylacrylamide) PNIPAAm polymers were prepared by reversible addition–fragmentation chain transfer polymerization (RAFT-polymerization) by using 4-cyanopentanoic acid dithiobenzoate as chain transfer agent (CTA). In the second step, the PNIPAAm polymers were used as macro-CTA’s for copolymerization with ethylene glycol dimethacrylate (EGDMA) by the RAFT-technique. Adjusting the macro-CTA to EGDMA ratio, nanometric star polymers with small or big core could be prepared as revealed by gel permeation chromatography (GPC), dynamic light scattering (DLS) and viscometry. The same methodology was applied for the preparation of star polymers with poly(NIPAAm)- b-poly(hexyl acrylate) arms. The so prepared temperature sensitive multiarm materials are a stable alternative to polymeric micelles as nano-carriers for drug-delivery applications.

Temperature sensitivity and drug encapsulation of star‐shaped amphiphilic block copolymer based on dendritic poly(ether‐amide)

The star-shaped amphiphilic block copolymer (DPEA-PCL-PNIPAAms) with different PCL block lengths was prepared through ring opening polymerization of epsilon-caprolactone (CL) initiated by hydroxyl end-capped dendritic poly(ether-amide) (DPEA-OH), and then coupling with carboxyl end-capped linear poly(N-isopropylacrylamide) (PNIPAAm-COOH) via an esterification process. The molecular structure was characterized by FT-IR, (1)H NMR, and GPC analysis. As the copolymer dissolved in water, the core-shell structural nanoparticle was formed as a micelle. The fluorescence, (1)H NMR, and dynamic light scattering (DLS) techniques were utilized to confirm the formation of micelles. The optical transmittance and US-DSC measurements demonstrated that the micelles performed the reversible dispersion/aggregation behavior in response to temperature through the outer PNIPAAm polymer shell. The micelles loaded with daidzein showed a very rapid drug release speed at temperatures above the lower critical solution temperature (LCST) due to the temperature-induced structural change of the polymeric micelles.

Drug permeation modeling through the thermo-sensitive membranes of poly( N-isopropylacrylamide) brushes grafted onto micro-porous films

Temperature-sensitive N-isopropylacrylamide (NIPAAm) polymer brushes of known molecular weight (20k–25k) were grafted onto micro-porous polycarbonate (PC) films (pore size 0.4 μm) using argon plasma treatment. The resulting composite membranes were tested for controlled drug release at various grafted chain density, which was controlled using 1–3% polymer concentrations. The composites were also characterized in terms of graft yield, membrane thickness, Fourier transform infrared (FTIR) spectra and scanning electron micrography (SEM). The drug permeabilities of 4-acetamidophenol and ranitidine HCl in the resulting membranes were determined at temperatures between 30 and 40 °C. The drug permeability changed remarkably at 34 °C, near the lower critical solution temperature (LCST). The drug passage was regulated by swelling (which occurs at a temperature lower than the LCST) or shrinkage (occurring at an elevated temperature) of the PNIPAAm polymer brushes. These membranes demonstrated on–off ratios of drug permeabilities up to 11 and 14 for the model drugs, respectively. These values are higher than most literature data with similar-size model molecules. The excellent on–off valve mechanism was discussed in terms of the suitable molecular weight and grafted chain density in relation to the pore size and porosity of the PC support. A mathematical model was proposed to predict the drug permeation flux based on the gel conformation data, graft density, characteristics of the micro-porous support, and drug concentrations and diffusivities in water and in the PNIPAAm gel. The model can successfully estimate the drug permeation flux through the composite with higher (0.42 mg cm −2) graft density with a coefficient of determination of 0.95. The discrepancy between the predicted and experimental data at the lower graft density (0.12 mg cm −2) was ascribed to pore channel narrowing resulting from the uneven polymer chain distribution.

Temperature-Controlled Flow Switching in Nanocapillary Array Membranes Mediated by Poly(N-isopropylacrylamide) Polymer Brushes Grafted by Atom Transfer Radical Polymerization

We report actively controlled transport that is thermally switchable and size-selective in a nanocapillary array membrane (NCAM) prepared by grafting poly(N-isopropylacrylamide) (PNIPAAm) brushes onto the exterior surface of a Au-coated polycarbonate track-etched membrane. A smooth Au layer on the membrane surface, which is key to obtaining a uniform polymer film, was prepared by thermal evaporation of approximately 50 nm Au on both exterior surfaces. After evaporation, the inner diameter of the pore is reduced slightly, but the NCAM retains a narrow pore size distribution. PNIPPAm brushes with 10-30 nm (dry film) thickness were grafted onto the Au surface through surface-initiated atom transfer radical polymerization (ATRP) using a disulfide initiator, (BrC(CH3)2COO(CH2)11S)2. Molecular transport through the PNIPAAm polymer brush-modified NCAMs was investigated by real-time fluorescence measurements using fluorescein isothiocyanate (FITC)-labeled dextrans ranging from 4.4 to 282 kDa in membranes with variable initial pore diameters (80, 100, and 200 nm) and different PNIPAAm thicknesses. Manipulating the temperature of the NCAM through the PNIPAAm lower critical solution temperature (LCST) causes large, size-dependent changes in the transport rates. Over specific ranges of probe size, transport is completely blocked below the LCST but strongly allowed above the LCST. The combination of the highly uniform PNIPAAm brush and the monodisperse pore size distribution is critical in producing highly reproducible switching behavior. Furthermore, the reversible nature of the switching raises the possibility of using them as actively controlled filtration devices.

Collagen-poly(N-isopropylacrylamide)-based membranes for corneal stroma scaffolds.

To investigate the feasibility of using the biocompatibility of collagen-based blended biomaterials as cell-delivery systems in ocular surface reconstruction in vivo. Collagen-based composites that were blended with synthetic acrylamide-based polymers [poly(N-isopropylacrylamide), pNIPAAm] were transplanted into corneal pockets of white rabbits, with a 3-mm epithelial window. Epithelial cells were allowed to migrate onto the polymer. Transplanted eyes were examined daily for up to 30 days, after which animals were killed for histologic examination. Immunohistochemistry was performed for vimentin, alpha-smooth muscle actin (alpha-SMA), CD4, and CD8. Gold-chloride staining was performed to observe neuronal regrowth. Human amniotic membranes (AMs) and sham-operated corneas served as controls. All animals received topical antibiotics (levofloxacin) without the use of steroids or other immunosuppressive agents. The pNIPAAm polymer allowed smooth epithelialization of the cornea, which was similar to the epithelialization observed in sham controls and AM-transplanted eyes. Histology revealed that epithelium overlying the polymer was bundled into several layers, without the orientation observed with AM and sham controls. The polymer gradually thinned and was gradually replaced by host tissue. Vimentin- and alpha-SMA-positive cells were found in stromal pockets up to 1 month following polymer transplantation. These cells were responsible for slight subepithelial haze near the wound edge. CD4- and CD8-positive lymphocytes were also observed in the vicinity of the polymer. Gold-chloride staining showed nerve regrowth in the wound edge after 1 month and subepithelial branches after 3 months. Collagen-pNIPAAm blended polymers may be effective as biomaterials to be used in the early stages of lamellar stromal replacement