Co-reporter:Xudong Zhang;Xin Liang;Jianjun Gu;Danfeng Chang;Jinxie Zhang;Zhaowei Chen;Yanqi Ye;Chao Wang;Wei Tao;Xiaowei Zeng;Gan Liu;Lin Mei;Zhen Gu
Nanoscale (2009-Present) 2017 vol. 9(Issue 1) pp:150-163
Publication Date(Web):2016/12/22
DOI:10.1039/C6NR07866D
Cancer cells use autophagy to resist poor survival environmental conditions such as low PH, poor nutrients as well as chemical therapy. Nanogels have been used as efficient chemical drug carriers for cancer treatment. However, the effect of nanogels on autophagy is still unknown. Here, we used Rab proteins as the marker of multiple trafficking vesicles in endocytosis and LC3 as the marker of autophagy to investigate the intracellular trafficking network of Rhodamine B (Rho)-labeled nanogels. The nanogels were internalized by the cells through multiple protein dependent endocytosis and micropinocytosis. After inception by the cells, the nanogels were transported into multiple Rab positive vesicles including early endosomes (EEs), late endosomes (LEs), recycling endosomes (REs) and lipid droplets. Finally, these Rab positive vesicles were transported to lysosome. In addition, GLUT4 exocytosis vesicles could transport the nanogels out of the cells. Moreover, nanogels could induce autophagy and be sequestered in autophagosomes. The crosstalk between autophagosomes and Rab positive vesicles were investigated, we found that autophagosomes may receive nanogels through multiple Rab positive vesicles. Co-delivery of autophagy inhibitors such as chloroquine (CQ) and the chemotherapeutic drug doxorubicin (DOX) by nanogels blocked the autophagy induced by DOX greatly decreasing both of the volume and weight of the tumors in mice tumor models. Investigation and intervention of the autophagy pathway could provide a new method to improve the therapeutic effect of anticancer nanogels.
Co-reporter:Jun-ying Weng;Zhuo Tang;Ying Guan 关英;X. X. Zhu
Chinese Journal of Polymer Science 2017 Volume 35( Issue 10) pp:1212-1221
Publication Date(Web):31 August 2017
DOI:10.1007/s10118-017-1962-1
A strategy was developed for the synthesis of highly ordered 2D arrays of Ag-PNIPAM hybrid microgel. The highly ordered 2D arrays of PNIPAM microgel were prepared by dispersing PNIPAM microgel on a charge-reversible substrate. The microgel spheres self-assembled into a 3D colloidal crystal, and the first 111 plane was fixed in situ onto the substrate as a result of spontaneous charge reversal of the substrate, leaving a high-quality 2D array of PNIPAM microgel. Ag nanoparticles were then synthesized in situ inside the microgel spheres by introduction of Ag+ ions into the microgel spheres and reduction with sodium borohydride. The resulting 2D arrays are highly ordered. The inter-particle distance in the array can be tuned. In addition, the method allows the synthesis of large size arrays and the use of nonplanar substrate.
Co-reporter:Jianjun Gu, Xiaoyun Li, Hancheng Ma, Ying Guan, Yongjun Zhang
Polymer 2017 Volume 110(Volume 110) pp:
Publication Date(Web):10 February 2017
DOI:10.1016/j.polymer.2016.12.076
•Smooth poly(2-hydroxyethyl methacrylate) (PHEMA) films were successfully synthesized by a simple one-step UV curing.•The resulting films generate various swelling-induced wrinkling patterns.•Large area, highly ordered, honeycomb-like wrinkling patterns were obtained from the resulting films.•The regular wrinkling patterns were successfully used for the fabrication of uniform multicellular spheroids.Poly(2-hydroxyethyl methacrylate) (PHEMA) films with gradient crosslinking density are the only hydrogel films capable of generating regular wrinkling patterns upon swelling, however, they were synthesized via a complicated two-stage photopolymerization. In an effort to develop a simple synthesis method, we found that one-step UV-curing of HEMA liquid always results in films with corrugated surface, which is a common issue when curing liquid prepolymers. We further found that the introduction of a physical network in the prepolymer solution could prevent the surface from corrugating during UV curing. For this purpose, linear PHEMA was added into the prepolymer solutions, and PHEMA films with a smooth surface were successfully synthesized by a simple one-step UV curing. The resulting films generate various swelling-induced wrinkling patterns, including random worms, peanuts and long-range ordered hexagons, depending on the contents of crosslinker and linear PHEMA in the prepolymer solution. Particularly, large area, highly ordered, honeycomb-like wrinkling patterns were obtained from films with proper content of crosslinker and linear PHEMA. These regular patterns are expected to find applications such as the fabrication of uniform multicellular spheroids.Download high-res image (184KB)Download full-size image
Co-reporter:Ya-Nan Zhao, Jianjun Gu, Siyu Jia, Ying Guan and Yongjun Zhang
Soft Matter 2016 vol. 12(Issue 4) pp:1085-1092
Publication Date(Web):04 Nov 2015
DOI:10.1039/C5SM02186C
Drug carriers capable of releasing drugs at a constant rate, or following zero-order kinetics, can lead to the best control of plasma drug concentration. Here we demonstrated that zero-order release of polyphenolic drugs, including tannic acid, epigallocatechin gallate, proanthocyanidins, and theaflavin-3′-gallate, could be achieved using hydrogen-bonded layer-by-layer films as the drug carrier. The films were fabricated using the polyphenolic drugs as hydrogen donors and polyethylene glycol (PEG) as the hydrogen acceptor. Because the drugs and PEG are bonded with reversible, dynamic hydrogen bonds, the films disintegrate gradually in aqueous solutions, and thus release the drugs into the media. Furthermore, because the PEG polymers have a narrow molecular weight distribution, the films disintegrate and release the polyphenolic drugs at a constant rate. Besides allowing for zero-order release, the drug carrier developed here also provides various ways to tune the drug release rate. The drug release rate increases with decreasing molecular weight of PEG. More importantly, the release rate could be tuned using external stimuli. Increasing the pH or temperature results in accelerated drug release, while the addition of salt retards the drug release.
Co-reporter:Xiaoyun Li, Junying Weng, Ying Guan, and Yongjun Zhang
Langmuir 2016 Volume 32(Issue 16) pp:3977-3982
Publication Date(Web):March 31, 2016
DOI:10.1021/acs.langmuir.6b00835
A method for the fabrication of high quality, large area 2D colloidal crystals (CCs) using poly(N-isopropylacrylamide) (PNIPAM) microgel sphere, an extremely soft colloid, as building block was proposed. First the microgel spheres were assembled into 3D colloidal crystals. The first 111 plane of the 3D crystal close to the substrate was then fixed in situ onto the substrate. Highly efficient photoinitiated thiol–ene coupling was chosen for the fixing purpose. Thanks to the high quality of 3D microgel CCs, the resulting 2D CCs exhibit a high degree of ordering. Large area 2D CCs were fabricated because large area 3D microgel CCs can be facilely fabricated. Besides planar substrates, the method allows the fabrication of 2D CCs on curved surface, too. In addition, the interpartical distance in the 2D CCs can be tuned by the concentration of the microgel dispersion.
Co-reporter:Junying Weng, Xiaoyun Li, Ying Guan, X. X. Zhu, and Yongjun Zhang
Langmuir 2016 Volume 32(Issue 48) pp:12876-12884
Publication Date(Web):November 4, 2016
DOI:10.1021/acs.langmuir.6b03359
2D colloidal crystals (CCs) have important applications; however, the fabrication of large-area, high-quality 2D CCs is still far from being trivial, and the fabrication of 2D microgel CCs is even harder. Here, we have demonstrated that they can be facilely fabricated using charge-reversible substrates. The charge-reversible substrates were prepared by modification with amino groups. The amino groups were then protected by amidation with 2,2-dimethylsuccinic anhydride. At acidic pH, the surface charge of the modified substrate will change from negative to positive as a result of the hydrolysis of the amide bonds and the regeneration of the amino groups. 2D microgel CCs can be simply fabricated by applying a concentrated microgel dispersion on the modified substrate. The negatively charged surface of the substrate allows the negatively charged microgel spheres, especially those close to the substrate, to self-assemble into 3D CCs. With the gradual hydrolysis of the amide bonds and the charge reversal of the substrate, the first 111 plane of the 3D assembly is fixed in situ on the substrate. The resulting 2D CC has a high degree of ordering because of the high quality of the parent 3D microgel CC. Because large-area 3D microgel CCs can be facilely fabricated, this method allows for the fabrication of 2D CCs of any size. Nonplanar substrates can also be used. In addition, the interparticle distance of the 2D array can be tuned by the concentration of the microgel dispersion. Besides rigid substrates (such as glass slides, quartz slides, and silicon wafers), flexible polymer films, including polyethylene terephthalate and poly(vinyl chloride) films, were also successfully used as substrates for the fabrication of 2D microgel CCs.
Co-reporter:Qing Du, Ying Guan, X. X. Zhu and Yongjun Zhang
Soft Matter 2015 vol. 11(Issue 10) pp:1937-1944
Publication Date(Web):16 Jan 2015
DOI:10.1039/C4SM02584A
Swelling-induced, spontaneously generated surface instability patterns in substrate-attached hydrogel films can be harnessed for advanced applications, however, methods to control their formation and morphology are missing. Here we propose that their generation may be guided by intentionally pre-introduced line structures. While uniform gel films produce irregular polygonal instability patterns, instability patterns generated in pre-patterned films with hexagonal line structures are regular hexagons with long-range order. The pre-introduced line structures act as defects in the generation of the surface instability patterns, which determine the position of the creases, regulate their rearrangement and determine their final morphology. The contrast between the pre-introduced structures and the surrounding area should be high enough for the pre-introduced structures to act as defects. Only when the characteristic wavelength of the pre-introduced pattern matches with the one of the gel film, perfect hexagonal patterns can be obtained. The gel films with uniform topographic features may find various advanced applications.
Co-reporter:Chong Li, Junxia Hou, Jianjun Gu, Qiuyan Han, Ying Guan and Yongjun Zhang
RSC Advances 2015 vol. 5(Issue 50) pp:39677-39685
Publication Date(Web):24 Apr 2015
DOI:10.1039/C5RA03967C
Fully water-soluble hydroxypropyl chitin (HPCh) was synthesized by the modification of chitin with propylene oxide in aqueous NaOH solution, a green and good solvent to chitin. HPChs with different degrees of substitution (DS) were obtained by varying the feeding ratio of propylene oxide to chitin. The HPCh solutions undergo a sol-to-gel transition upon heating. The transition was reversible, although an apparent hysteresis occurs in the cooling process. The gelation temperature (Tgel) decreases with increasing DS and concentration of the polymer. The thermal gelation could occur even at a concentration as low as 0.25 wt%. By adjusting the DS of the polymer, Tgel could be tuned from ∼20 °C to ∼80 °C. Meanwhile NaCl concentration and pH only slightly influence the Tgel. Preliminary tests show that the polymer is non-toxic to cells and it degrades in the presence of lysozyme. The ability to gel at temperatures below the body temperature, at relatively low polymer concentration, and biocompatibility and biodegradability of HPCh make the new thermal gelling materials quite suitable for biomedical applications.
Co-reporter:Lin Zhou, Mao Chen, Ying Guan and Yongjun Zhang
RSC Advances 2015 vol. 5(Issue 102) pp:83914-83921
Publication Date(Web):25 Sep 2015
DOI:10.1039/C5RA17684K
Dynamic layer-by-layer films were fabricated from a dextran–doxorubicin conjugate, PO-Dex–DOX, and glycol chitosan (GC), via the in situ Schiff base reaction between the aldehyde groups on PO-Dex–DOX and the amino groups on GC. Because of the reversible, dynamic nature of Schiff base bonds in the films, the films disintegrate gradually when soaked in aqueous solutions, and thus release DOX into the media. The release mechanism is different from ordinary drug carriers, in which the drug is usually released via diffusion or polymer degradation. The drug release rate decreases with increasing molecular weight of dextran. More importantly, because of the stimuli-responsivity of Schiff base bonds, the drug release rate can be tuned via external stimuli. Faster hydrolysis of Schiff base bonds at a lower pH and/or a higher temperature results in accelerated film disintegration and thus faster drug release. In vitro cytotoxicity test suggests that the released DOX retains its antitumor activity.
Co-reporter:Ya-nan Zhao, Qingping Yuan, Chong Li, Ying Guan, and Yongjun Zhang
Biomacromolecules 2015 Volume 16(Issue 7) pp:
Publication Date(Web):June 2, 2015
DOI:10.1021/acs.biomac.5b00438
Zero-order release is the ultimate goal of controlled drug release systems, however, it still remains a big challenge despite of numerous previous efforts. Here we show that the release of P(AAm-3-AAPBA) from P(AAm-3-AAPBA)/PVA film, a dynamic layer-by-layer (LBL) film, follows a perfect zero-order kinetics, provided that both polymers in the film have a narrow molecular weight distribution. Instead of releasing via diffusion or degradation, P(AAm-3-AAPBA) is released from the film via the dissociation of the interpolymer complex. The release rate is determined by molecular weight of the polymers. One could also tune the release rate via various external environmental stimuli, including pH, temperature, and glucose. The results suggest dynamic LBL film could serve as a new drug release platform that allows for not only zero-order release, but also intelligent release.
Co-reporter:Mao Chen;Yapeng Zhang;Siyu Jia;Lin Zhou;Dr. Ying Guan ;Dr. Yongjun Zhang
Angewandte Chemie International Edition 2015 Volume 54( Issue 32) pp:9257-9261
Publication Date(Web):
DOI:10.1002/anie.201503004
Abstract
The controlled introduction of artificial extrinsic defects is critical to achieve the functions of photonic crystals. Smart defects capable of responding to external stimuli lead to more advanced applications. Here we report a microgel colloidal crystal with a defect state which could be induced and erased reversibly by external stimuli. The crystal was assembled from PNIPAM microgel and P(NIPAM-AAc) microgel of the same size. The resulting doped crystal does not exhibit a defect state in its stop band because of the similar optical properties of the dopant and the host. By increasing the pH value, however, the dopant P(NIPAM-AAc) spheres swell to a larger size and turn into real defects in the crystal, resulting in the appearance of defect state. Adjusting the pH value back restores the size of the dopant spheres, and thus erases the defect state. Temperature, a second external stimulus, could also be used to induce and erase defect states of the crystal.
Co-reporter:Yang Liu, Ying Guan, Yongjun Zhang
Polymer 2015 Volume 77() pp:366-376
Publication Date(Web):23 October 2015
DOI:10.1016/j.polymer.2015.09.073
•Chitosan-AA was developed as a new inter-cellular linker to aggregate NaIO4-treated cells.•The new inter-cellular linker is of natural origin, degradable and biocompatible.•Generation of multicellular spheroids was accelerated by chemical pre-aggregation of cells with the new inter-cellular linker.Multicellular spheroids (MCSs) are in vitro tissue models having important biomedical applications. The MCS generation is usually time-consuming because most MCS fabrication methods exploit the inherent ability of cells to self-assemble to form spheroids. Here we tried to accelerate the MCS generation by chemical pre-aggregation of the cells. We first developed a method to chemically aggregate cells, which involves a first treatment of cells with NaIO4 to produce surface aldehyde functionalities, and then incubation with acrylic acid-modified chitosan (chitosan-AA), a new inter-cellular linker. Biocompatibility test indicates chitosan-AA is non-toxic to cells, even at a high concentration. When incubated in the presence of chitosan-AA, the NaIO4-treated cells aggregate quickly, because of the reaction between the amino groups on chitosan-AA and the aldehyde groups on cell surface. In addition, the cells in the resulting aggregates remain a high viability. The pre-aggregated cells were then seeded into an in situ-formed hydrogel to generate MCSs. While it takes several days to form MCSs in the control groups, it takes only 1 day for the cells to form compact spheroids in the pre-aggregation group. The spheroids formed in the pre-aggregation group (231 ± 74 μm at Day 4) are bigger than those obtained in the control groups (70 ± 17 μm at Day 4). In addition, the cells in the pre-aggregation group grow and proliferate faster (P < 0.05), because of the improved cell–cell interaction in the aggregates.
Co-reporter:Jia Song, Junxia Hou, Lili Tian, Ying Guan, Yongjun Zhang, X.X. Zhu
Polymer 2015 Volume 63() pp:237-243
Publication Date(Web):20 April 2015
DOI:10.1016/j.polymer.2015.03.009
•Silver dendrites were synthesized by first loading Ag+ ions in LBL films and then reducing them using p-hydroquinine.•They are two orders of magnitude larger than those synthesized in homogenous solutions.•They are 2D structures grown on the film surface.Ag dendrites were previously synthesized, with limited success, via the chemical reduction of Ag+ ions with a soluble reducing agent in homogeneous solutions. Here Ag+ ions were first loaded in hydrogen-bonded layer-by-layer (LBL) films fabricated from poly(vinyl pyrrolidone) (PVPON) and poly(acrylic acid) (PAA), then reduced chemically using p-hydroquinone (HQ) as a reducing agent to afford Ag dendritic structures. The dendrites were characterized by SEM, TEM, XRD and optical microscope. Compared with the Ag dendrites synthesized in homogenous solutions, the dendrites obtained here are much larger. The fully developed ones can reach a size over 600 μm, ca. 2 orders of magnitude larger than those synthesized in homogenous solutions (∼1–5 μm). In addition, the dendrites obtained here are 2 dimensional which grow along the surface of the LBL film, instead of 3 dimensional as those obtained in homogenous solutions. A possible 3-step growth mechanism, which involves the rapid reduction of the Ag+ ions in the film, formation of Ag seed particles on the film surface, and fractal dendritic structure formation as described by the diffusion-limited aggregation (DLA) model, was proposed.
Co-reporter:Chong Li;Qiuyan Han;Ying Guan
Polymer Bulletin 2015 Volume 72( Issue 8) pp:2075-2087
Publication Date(Web):2015 August
DOI:10.1007/s00289-015-1390-8
Michael reaction of chitosan with acryl reagents in acidic media is a facile method to introduce functional groups; however, when acrylamide (AAm) is used only a low degree of substitution was achieved. Here, the reaction was carried out in a new solvent, aqueous LiOH/urea solution. In the alkaline media, hydroxyl groups at the C-6 position, instead of amino groups at the C-2 position, act as Michael donor. The introduced amide groups continue to hydrolyze to give carboxylate groups. The reaction is faster, and the total degree of substitution is higher than the one achieved in acidic media, despite that the reaction temperature is lower and the reaction time is shorter. The total degree of substitution and hydrolysis percentage increases with increasing reaction time and elevated temperature. Increasing the feeding molar ratio of AAm to chitosan increases the total degree of substitution, but reduces hydrolysis percentage.
Co-reporter:Mao Chen;Yapeng Zhang;Siyu Jia;Lin Zhou;Dr. Ying Guan ;Dr. Yongjun Zhang
Angewandte Chemie 2015 Volume 127( Issue 32) pp:9389-9393
Publication Date(Web):
DOI:10.1002/ange.201503004
Abstract
The controlled introduction of artificial extrinsic defects is critical to achieve the functions of photonic crystals. Smart defects capable of responding to external stimuli lead to more advanced applications. Here we report a microgel colloidal crystal with a defect state which could be induced and erased reversibly by external stimuli. The crystal was assembled from PNIPAM microgel and P(NIPAM-AAc) microgel of the same size. The resulting doped crystal does not exhibit a defect state in its stop band because of the similar optical properties of the dopant and the host. By increasing the pH value, however, the dopant P(NIPAM-AAc) spheres swell to a larger size and turn into real defects in the crystal, resulting in the appearance of defect state. Adjusting the pH value back restores the size of the dopant spheres, and thus erases the defect state. Temperature, a second external stimulus, could also be used to induce and erase defect states of the crystal.
Co-reporter:Yuhan Wu, Ziqi Zhao, Ying Guan, Yongjun Zhang
Acta Biomaterialia 2014 Volume 10(Issue 5) pp:1965-1974
Publication Date(Web):May 2014
DOI:10.1016/j.actbio.2013.12.044
Abstract
Various galactosylated scaffolds have been developed for hepatocyte culture because galactose ligands help maintain cell viability, facilitate the formation of multicellular spheroids and help maintain a high level of liver-specific functions. However, it is difficult to harvest the cell spheroids generated inside the three-dimensional scaffolds for their further biological analysis and applications. Here we developed a new galactosylated hydrogel scaffold which solidifies in situ upon heating to physiological temperature, but liquefies again upon cooling back to room temperature. The new scaffold is composed of poly(N-isopropylacrylamide) (PNIPAM) microgel and poly(ethylene glycol) (PEG). Because of the thermosensitivity of PNIPAM microgel, the mixed dispersions gel upon heating and liquefy upon cooling. PEG was added to reduce the shrinkage of the gels. Part of the PNIPAM microgel was replaced with a galactosylated one to provide a series of blend gels with various galactose ligand contents. HepG2 cells, a human hepatocarcinoma cell line, were encapsulated in the in situ-formed gels. As expected, the cell viability increases with increasing content of galactose ligands. In addition, compact multicellular spheroids were obtained in gels containing galactose ligands, while loose spheroids formed in gel without galactose ligands. The cells cultured in galactose-containing gels also exhibit a higher level of liver-specific functions, in terms of both albumin secretion and urea synthesis, than those cultured in gel without these ligands. The new galactosylated scaffold not only promotes the formation of hepatocyte spheroids, but also allows for their harvest. By cooling back to room temperature to liquefy the gel, the hepatocyte spheroids can be facilely harvested from the scaffold. The reversible galactosylated scaffold developed here may be used for large scale fabrication of hepatocyte spheroids.
Co-reporter:Lin Zhou, Mao Chen, Ying Guan and Yongjun Zhang
Polymer Chemistry 2014 vol. 5(Issue 24) pp:7081-7089
Publication Date(Web):28 Aug 2014
DOI:10.1039/C4PY00868E
Stimuli-responsive hydrogels whose swelling degree changes in response to certain external stimulus are usually constructed by the introduction of a functional group. Here we show that they can also be constructed using dynamic bonds as crosslinks because the equilibrium of their formation and breakage can be shifted by external stimuli. As an example, hydrogel films were fabricated from partially oxidized dextran (PO-Dex) and chitosan (Chi) using the layer-by-layer assembly technique. The driving force for the film buildup is the in situ formation of Schiff base bonds between the aldehyde groups on PO-Dex and amino groups on Chi. The swelling of the film was studied using the Fabry–Perot fringes on the reflection spectra. Like ordinary hydrogels, the PO-Dex/Chi hydrogel films swell in water. Their swelling degree decreases with increasing oxidation degree of PO-Dex. The films swell to a larger degree when the pH is lowered. The pH-sensitivity was attributed to amino groups on chitosan and also the dynamic Schiff base linkages, because pH change shifts the equilibrium of the Schiff base reaction in the films, resulting in a change in the crosslink density and therefore a change in swelling degree. When the transient linkages were fixed by NaBH4 reduction, the pH-sensitivity of the films was significantly reduced. The films were found to be sensitive to other external stimuli, including temperature, L-lysine and pyridoxal. These stimuli-responsivities were also attributed to the dynamic Schiff base linkages in the film.
Co-reporter:Zhuo Tang, Ying Guan and Yongjun Zhang
Polymer Chemistry 2014 vol. 5(Issue 5) pp:1782-1790
Publication Date(Web):08 Nov 2013
DOI:10.1039/C3PY01190A
A new glucose-sensitive microgel, the poly(N-isopropylacrylamide-co-2-acrylamidophenylboronic acid) (P(NIPAM-2-AAPBA)) microgel, which contracts instead of expanding in the presence of glucose, was synthesized. The configuration of 2-AAPBA allows for the occurrence of an intramolecular B–O coordinated interaction, which stabilizes the tetrahedral form of the phenylboronic acid (PBA) group and makes it the dominant form in the microgel. Upon addition of glucose, with the formation of a 1:2 glucose–phenylboronate complex, the microgel size shrinks monotonously with increasing glucose concentrations. Addition of glucose also shifts the volume phase transition temperature of the microgel to lower temperatures. The glucose sensitivity of the microgel can be influenced by temperature, ionic strength and PBA content, but pH variation within the physiological range shows no influence. The P(NIPAM-2-AAPBA) microgel displays good glucose sensitivity at physiological pH and ionic strength. In addition, interference from fructose, galactose, and lactate is negligible. The new contraction-type glucose-sensitive microgel is expected to find applications in self-regulated insulin release and glucose sensing.
Co-reporter:Yang Liu;Ying Guan
Macromolecular Rapid Communications 2014 Volume 35( Issue 6) pp:630-634
Publication Date(Web):
DOI:10.1002/marc.201300893
Co-reporter:Chong Li, Qiuyan Han, Ying Guan and Yongjun Zhang
Soft Matter 2014 vol. 10(Issue 41) pp:8245-8253
Publication Date(Web):11 Aug 2014
DOI:10.1039/C4SM01336K
Chitosan can readily dissolve in a precooled aqueous alkali–urea solution, a solvent that has previously been developed to dissolve cellulose. Upon heating, the resulting solutions quickly become a gel. The thermal gelling of the chitosan solutions was studied by rheology. Initially, a temperature ramp test was used to determine the gelation temperatures (Tgel). It was found that Tgel does not significantly change with chitosan concentration. The in situ formed gels liquefy on cooling, but the liquefication temperature (Tliq) is considerably lower than Tgel, indicating a large hysteresis in the cooling process. In addition, Tliq decreases with increasing polymer concentration. The kinetics of thermal gelation was then studied by isothermal curing. The solution gels were cured not only at temperatures above the Tgel, which was determined in the temperature ramp test, but also at temperatures far below the Tgel, provided that the solution is cured at the temperature for a long enough time. The solutions become gel faster when cured at higher temperatures. When cured at the same temperature, higher concentration solutions become gel faster. The apparent activation energy for the thermal gelation of the chitosan solutions was determined to be ∼200 kJ mol−1. Physical gels of pure chitosan were obtained by repeated soaking the in situ formed gels in water. Preliminary test shows that new gels are highly biocompatible.
Co-reporter:Ying Guan
Journal of Applied Polymer Science 2014 Volume 131( Issue 19) pp:
Publication Date(Web):
DOI:10.1002/app.40918
ABSTRACT
Layer-by-layer (LBL) assembly, a simple but versatile method for thin film fabrication, has been widely employed to fabricate nanoengineered films with controlled composition and thickness. Dynamically bonded LBL films are films fabricated using dynamic bonds, that is, chemical bonds which can undergo reversible breaking and reformation usually under equilibrium conditions, as driving forces. Because of the reversible, dynamic nature of the dynamic bonds, these films exhibit various dynamic properties, ranging from a small scale movement of the polymer chains within the films (chain rearrangement), to a large scale movement of the chains, which results in film disintegration. Usually an external stimulus is used to trigger the response of a dynamic film. Novel applications have been proposed by exploiting the dynamic properties of these films. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40918.
Co-reporter:Na Huang; Dr. Ying Guan; Dr. X. X. Zhu; Dr. Yongjun Zhang
ChemPhysChem 2014 Volume 15( Issue 9) pp:1785-1792
Publication Date(Web):
DOI:10.1002/cphc.201400027
Abstract
Composite hydrogels—macroscopic hydrogels with embedded microgel particles—are expected to respond to external stimuli quickly because microgels swell much faster than bulky gels. In this work, the kinetics of the pH-induced swelling of a composite hydrogel are studied using turbidity measurements. The embedded microgel is a pH- and thermosensitive poly(N-isopropylacrylamide-co-acrylic acid) microgel and the hydrogel matrix is polyacrylamide. A rapid pH-induced swelling of the embedded microgel particles is observed, confirming that composite hydrogels respond faster than ordinary hydrogels. However, compared with the free microgels, the swelling of the embedded microgel is much slower. Diffusion of OH− into the composite hydrogel film is identified as the main reason for the slow swelling of the embedded microgel particles, as the time of the pH-induced swelling of this film is comparable to that of OH− diffusion into the film. The composition of the hydrogel matrix does not significantly change the characteristic swelling time of the composite hydrogel film. However, the swelling pattern of the film changes with composition of the hydrogel matrix.
Co-reporter:Ziqi Zhao, Jianjun Gu, Yening Zhao, Ying Guan, X. X. Zhu, and Yongjun Zhang
Biomacromolecules 2014 Volume 15(Issue 9) pp:
Publication Date(Web):July 29, 2014
DOI:10.1021/bm500722g
Three-dimensional (3D) multicellular spheroids (MCSs) mimic the structure and function of real tissue much better than the conventional 2D cell monolayers, however, their application was severely hindered by difficulties in their generation. An ideal method for MCS fabrication should produce spheroids with narrow size distribution and allow for control over their size. The method should also be simple, cheap, and scalable. Here, we use patterned nonadhesive poly(2-hydroxyethyl methacrylate) hydrogel films to guide the self-assembly of cells. The films were fabricated directly in the wells of cell culture plates. They were patterned spontaneously by swelling in water, without the use of any template or specialized facilities. When cell suspension is added, the cells settle down by gravity to the bottom. Because of the presence of the wrinkling pattern composed of uniformed microcaves, the cells accumulate to the center of the microcaves and gradually self-assemble into MCSs. Using this method, monodisperse MCSs were generated. The size of the spheroids can be facilely controlled by the number of cells seeded. The method is compatible with the conventional monolayer cell culture method. Thousands of spheroids can be generated in a single well. We expect this method will pave the way for the application of MCSs in various biomedical areas.
Co-reporter:Qiuyan Han, Chong Li, Ying Guan, X.X. Zhu, Yongjun Zhang
Polymer 2014 Volume 55(Issue 9) pp:2197-2204
Publication Date(Web):25 April 2014
DOI:10.1016/j.polymer.2014.03.015
Thin hydrogel films attached to a rigid substrate can only swell along the direction perpendicular to the substrate, which generates compressive stress within the gel. When the stress is sufficiently large, the free surface of the gel will locally buckle and fold against itself to form various wrinkling patterns. Here we show that hydrogen-bonded layer-by-layer (LBL) films of poly(vinyl pyrrolidone) (PVPON) and poly(acrylic acid) (PAA) also swell in ethanol/water mixtures. Like ordinary hydrogel films attached to a substrate, the LBL films also undergo mechanical instability when their swelling degree is large enough. By adjusting the composition and pH of the ethanol/water mixture, the swelling degree of the film can be adjusted, which further decides whether the mechanical instability occurs or not. Like ordinary hydrogel films, the surface wrinkling of the PVPON/PAA films occurs via a nucleation-growth process. Unlike ordinary hydrogels, the critical swelling degree for the onset of wrinkling for PVPON/PAA films increases with increasing film thickness. More importantly, the wrinkling patterns can be healed automatically, because the transient network of PVPON/PAA films allows for the relief of compressive stress via its rearrangement. The phenomenon observed here may provide a possible way to erase the undesired wrinkling patterns on constrained hydrogel films.
Co-reporter:Ying Guan and Yongjun Zhang
Chemical Society Reviews 2013 vol. 42(Issue 20) pp:8106-8121
Publication Date(Web):16 Jul 2013
DOI:10.1039/C3CS60152H
Boronic acid-containing hydrogels are important intelligent materials. With the introduction of boronic acid functionality, these hydrogels exhibit a lot of interesting properties, such as glucose-sensitivity, reversibility and self-healing. These materials have found important applications in many areas, especially in biomedical areas. This paper aims to provide an overview of the current state of the art of the study in this area. We review the synthesis and properties of various boronic acid-containing hydrogels, including macroscopic hydrogels, microgels and layer-by-layer self-assembled films. Their applications were described, with an emphasis on the design of various glucose sensors and self-regulated insulin delivery devices. New development in this area was highlighted. Problems and the new directions were discussed.
Co-reporter:Wenjing Zhang, Jia Song, Wang Liao, Ying Guan, Yongjun Zhang and X. X. Zhu
Journal of Materials Chemistry A 2013 vol. 1(Issue 10) pp:2036-2043
Publication Date(Web):21 Jan 2013
DOI:10.1039/C3TC00415E
Fluorescent Ag nanoclusters have been easily generated in layer-by-layer (LBL) films of poly(vinyl pyrrolidone) (PVPON) and poly(acrylic acid) (PAA) by photo-reduction of Ag+ ions, which were previously loaded via an ion exchange mechanism. Under UV irradiation, Ag+ ions were reduced to Ag atoms by the photo-generated radicals and then aggregate to form fluorescent nanoclusters. The Ag+ concentration plays a key role in the determination of the growth rate of Ag particles. Careful tuning of the Ag loading in the film prevented the growth of the fluorescent nanoclusters into larger non-fluorescent nanoparticles. Fluorescent Ag nanoclusters can be generated in both wet and dry films. However, the fluorescence intensity achieved in dry films is lower than that in wet films because the tight confinement of the polymer network retards the diffusion and aggregation of the photo-generated Ag atoms. Interestingly the fluorescence intensity can be enhanced significantly by a post-treatment in water, as it allows the Ag atoms to diffuse and aggregate to form more fluorescent nanoclusters. This work shows that the PVPON/PAA LBL films can serve as nanoreactors that allow the in situ generation of fluorescent Ag nanoclusters, yielding fluorescent Ag nanoclusters in a technically important form, in addition to providing a simple way to control the growth of the nanoparticles.
Co-reporter:Lin Zhou, Mao Chen, Lili Tian, Ying Guan, and Yongjun Zhang
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 9) pp:3541
Publication Date(Web):April 2, 2013
DOI:10.1021/am4008787
Layer-by-layer (LbL) assembled films have been exploited for surface-mediated drug delivery. The drugs loaded in the films were usually released via diffusion or the degradation of one of the film components. Here we demonstrate that drug release can also be achieved by exploiting the dynamic nature of hydrogen-bonded LbL films. The films were fabricated from tannic acid (TA), a model polyphenolic drug, and poly(vinyl pyrrolidone) (PVPON). The driving force for the film buildup is the hydrogen bonding between the two components, which was confirmed by Fourier transform infrared (FTIR) spectra. The film growth is linear, and the growth rate of the film decreases with increasing assembly temperature. Because of the reversible/dynamic nature of hydrogen bonding, when soaked in aqueous solutions, the PVPON/TA films disassemble gradually and thus release TA to the media. The release rate of TA increases with increasing pH and temperature but decreases with increasing ionic strength. Scanning electron microscopy (SEM) studies on the surface morphology of the film during TA release reveal that the film surface becomes smoother and then rougher again because of the dewetting of the film. The released TA can scavenge ABTS+• cation radicals, indicating it retains its antioxidant activity, a major biological activity of polyphenols.Keywords: antioxidant acitivity; drug release; dynamic bonds; hydrogen bonds; layer-by-layer assembly; polyphenolic drug;
Co-reporter:Wei Song, Ying Guan, Yongjun Zhang and X. X. Zhu
Soft Matter 2013 vol. 9(Issue 9) pp:2629-2636
Publication Date(Web):18 Jan 2013
DOI:10.1039/C2SM27534A
Polymerized crystalline colloidal array (PCCA) films, i.e., a highly ordered crystalline colloidal array of poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAM-AAc)) microgel particles embedded in a polyacrylamide (PAAm) hydrogel matrix, were prepared. The interaction between the embedded thermosensitive microgel particles and the non-thermosensitive hydrogel matrix was studied, using the Bragg diffraction of the films as a tool. The intensity and position of the diffraction peak change with temperature, from which important information on the interaction between the microgel particles and the hydrogel matrix was deduced. Our results indicate that the non-thermosensitive, hydrophilic PAAm hydrogel matrix significantly influences the thermosensitive phase transition of the embedded P(NIPAM-AAc) microgel particles. Compared with the freely dispersed microgel particles in solution, only a small change in the volume phase transition temperature of the embedded microgel particles was observed; however, the phase transition becomes less sharp. More importantly, the extent of size change is reduced significantly. On the other hand, the temperature-induced swelling/deswelling of the embedded microgel particles induces a swelling/deswelling of the surrounding hydrogel matrix, revealing that the interaction between the two components is mutual. The temperature-induced swelling/deswelling of the microgel particles is fast; in contrast, the swelling/deswelling of the hydrogel matrix is much slower. The stiffness of the hydrogel matrix affects the interaction between the two components. As the hydrogel matrix becomes stiffer, its influence on the swelling of the microgel particles becomes more prominent. On the other hand, the influence of the microgel particles on the swelling of the hydrogel matrix becomes less prominent.
Co-reporter:Mao Chen;Lin Zhou;Dr. Ying Guan ;Dr. Yongjun Zhang
Angewandte Chemie International Edition 2013 Volume 52( Issue 38) pp:9961-9965
Publication Date(Web):
DOI:10.1002/anie.201302466
Co-reporter:Mao Chen;Lin Zhou;Dr. Ying Guan ;Dr. Yongjun Zhang
Angewandte Chemie 2013 Volume 125( Issue 38) pp:10145-10149
Publication Date(Web):
DOI:10.1002/ange.201302466
Co-reporter:Xi Zhang, Ying Guan and Yongjun Zhang
Journal of Materials Chemistry A 2012 vol. 22(Issue 32) pp:16299-16305
Publication Date(Web):03 Jul 2012
DOI:10.1039/C2JM33413E
Layer-by-layer assembled films using reversible/dynamic bonds between the polymer pairs as driving forces are dynamic in nature. They may disintegrate under certain conditions as a result of the breakage of the dynamic bonds. More importantly they disintegrate gradually under conditions of equilibrium control, making them suitable for sustained drug release. Here insulin release from dynamic LbL films was demonstrated as an example. The films were fabricated from a fluorescently-labeled insulin–PVA (PVA: polyvinyl alcohol) conjugate and poly[acrylamide-co-3-(acrylamido)-phenylboronic acid], using a reversible covalent bond, i.e., phenylboronate ester bond, as the driving force. Film fabrication was followed by UV-vis and fluorescence spectroscopy. In all cases linear film growth was observed. The film growth rate increases with decreasing pH and increasing ionic strength of the assembly solutions. Successful integration of insulin into the films was achieved by covalent conjugation of insulin with PVA. When immersed in an aqueous solution, the films disintegrate gradually, thus releasing insulin into the media. Insulin release rate increases with increasing pH and decreasing ionic strength of the media. More importantly, it increases with increasing glucose concentration in the media. The glucose response of the film was attributed to the conversion of PBA (PBA: phenylboronic acid) groups in the film from a neutral form to a negatively charged one as a result of the formation of glucose–PBA complexes, thus increasing the rate of the film disintegration.
Co-reporter:Yapeng Zhang, Kun Liu, Ying Guan and Yongjun Zhang
RSC Advances 2012 vol. 2(Issue 11) pp:4768-4776
Publication Date(Web):22 Mar 2012
DOI:10.1039/C2RA20466E
Amine modified gold nanorods (GNR) were assembled onto the surface of poly(N-isopropylacrylamide-co-3-acrylamidophenylboronic acid) (P(NIPAM–AAPBA)) microgel particles via electrostatic interactions. The effects of pH and GNR/microgel ratio on the self-assembly were studied. It was revealed that GNRs can be sequestered more effectively at a higher pH because the surface charge density of the microgel particles increases with increasing pH. In addition, the surface coverage of the GNRs increases with increasing GNR/microgel ratio. Based on these observations hybrid microgels were prepared at pH 8.5 and 9.0 using a high GNR/microgel ratio. Upon heating these hybrid microgels exhibit a redshift of over 100 nm in their plasmon band, which is much larger than those reported in the literature. At the same time, the color of the microgel dispersion gradually changes from blue to grey. The hybrid microgel can be regarded to have a core/shell-like structure, as the radius increase of the hybrid microgel, either at a fully swollen state or a fully collapsed state, is comparable to the diameter of the GNRs. The thermal phase transition of the hybrid microgel starts at the same temperature as that of the bare microgel, but ends at a much higher temperature. The widened phase transition is attributed to the restriction of the non-thermosensitive GNR shell on the deswelling of the core. Similarly glucose-induced swelling is also retarded, resulting in a reduced glucose-sensitivity. The glucose-induced swelling also results in the blueshift of the plasmon band and color change of the sample. The new hybrid microgel can be used as a dual colorimetric sensor for temperature and glucose.
Co-reporter:Xi Zhang, Ying Guan, and Yongjun Zhang
Biomacromolecules 2012 Volume 13(Issue 1) pp:
Publication Date(Web):December 4, 2011
DOI:10.1021/bm2012696
Novel biosensors have been designed by reporting an analyte-induced (de)swelling of a stimuli-responsive hydrogel (usually in a form of thin film) with a suitable optical transducer. These simple, inexpensive hydrogel biosensors are highly desirable, however, their practical applications have been hindered, largely because of their slow response. Here we show that quick response hydrogel sensors can be designed from ultrathin hydrogel films. By the adoption of layer-by-layer assembly, a simple but versatile approach, glucose-sensitive hydrogel films with thickness on submicrometer or micrometer scale, which is 2 orders of magnitude thinner than films used in ordinary hydrogel sensors, can be facilely fabricated. The hydrogel films can not only respond to the variation in glucose concentration, but also report the event via the shift of Fabry–Perot fringes using the thin film itself as Fabry–Perot cavity. The response is linear and reversible. More importantly, the response is quite fast, making it possible to be used for continuous glucose monitoring.
Co-reporter:Dan Cheng, Yuhan Wu, Ying Guan, Yongjun Zhang
Polymer 2012 Volume 53(Issue 22) pp:5124-5131
Publication Date(Web):12 October 2012
DOI:10.1016/j.polymer.2012.08.054
We previously showed that poly(N-isopropylacrylamide) (PNIPAM) microgel dispersions thermally gel under proper conditions and the in situ-formed hydrogels can be used for 3D cell culture. To further improve their performance, here we tailor the properties of the hydrogels by blending with poly(ethylene glycol) (PEG). The microgel/PEG mixtures containing no salt do not gel upon heating, however, they gel at physiological pH and ionic strength. The gelation temperature decreases with increasing PEG content, which was attributed to the decreased volume phase transition temperature of the microgel, and also depletion attraction because of the presence of PEG chains. Compared with the pure PNIPAM hydrogel, the blend hydrogels exhibit a lower mechanical strength (one-way ANOVA, P < 0.05), however, the syneresis of the hydrogel is reduced or even totally prevented by PEG blending. HepG2 cells were seeded and cultured in the blend hydrogels. While the cells do not grow in pure PNIPAM hydrogels, they grow very well in the blend hydrogel containing 0.75 wt% PEG (one-way ANOVA, P < 0.05), because of its reduced syneresis. Further increasing PEG content results in reduced cell–scaffold interaction, which in turn results in decreased cell growth rate. PEG content also influence the morphology of the multicellular spheroids formed inside the scaffold. Compact spheroids form in hydrogel containing 0.75 wt% PEG, while looser and smaller spheroids form in hydrogels with higher PEG content. Our results indicate physical blending can be a simple but effective method to finely tune the properties of injectable hydrogel scaffolds.Graphical abstract
Co-reporter:Wang Liao, Yongjun Zhang, Ying Guan, and X. X. Zhu
Langmuir 2012 Volume 28(Issue 29) pp:10873-10880
Publication Date(Web):July 6, 2012
DOI:10.1021/la3016386
Dispersions of poly(N-isopropylacrylamide) (PNIPAM) microgel thermally gel in the presence of inorganic salts. The in situ-formed hydrogels, with a network of soft particles, represent a new type of colloidal gels. Here, their fractal structures were determined by rheological measurements, using the models of both Shih et al. and Wu and Morbidelli. According to the definition of Shih et al., the colloidal PNIPAM gels fall into the strong-link regime. Yet the calculated fractal dimension of the floc backbone, x, yielded unrealistic negative values, suggesting this model is inapplicable for the present system. The Wu–Morbidelli model gives physically sounder results. According to this model, the strengths of the inter- and intrafloc links are comparable, and the in situ-formed gels are in the transition regime. The fractal dimension, df, of the hydrogel decreases from ∼2.5 to ∼1.8 when the heating temperature increases from 34 to 40 °C. The df values suggest different aggregation mechanisms at different temperatures, that is, a reaction-limited one accompanied by rearrangement at low temperature, a typical reaction-limited one at the intermediate temperature, and a diffusion-limited one at high temperature. With increasing salt concentration, the df of the hydrogel decreases from ∼2.1 to ∼1.7, suggesting the aggregation mechanism changes from reaction-limited to diffusion-limited. The effects of both temperature and salt concentration can be explained by the changes in the interactions among the microgel particles. The thermogellable PNIPAM microgel dispersions may serve as a model system for the study of heat-induced gelation of globular proteins.
Co-reporter:Wenjing Zhang, Aijuan Zhang, Ying Guan, Yongjun Zhang and X. X. Zhu
Journal of Materials Chemistry A 2011 vol. 21(Issue 2) pp:548-555
Publication Date(Web):27 Oct 2010
DOI:10.1039/C0JM02369H
As nanoreactor for the synthesis of metal nanoparticles, hydrogen-bonded layer-by-layer assembled (LBL) films may be a better choice than the electrostatic ones, because more carboxylic acid groups are available for metal ion binding. However, these films should be crosslinked before metal ion loading because of their instability (Chem. Mater., 2005, 17, 1099–1105). Here we report that the uncrosslinked hydrogen-bonded poly(vinyl pyrrolidone)/poly(acrylic acid) (PVPON/PAA) LBL films remain stable during Ag+ loading. FTIR and XPS studies indicate that Ag+ binds with PVPONvia coordination interaction, while it simultaneously binds with PAAvia electrostatic interaction. Therefore the films do not disintegrate upon the disruption of hydrogen bonds between PVPON and PAA. After Ag+ loading, the erosion rate of the film in water decreases, indicating that the long-term stability of the film is actually improved. The loaded Ag+ can be easily unloaded by immersing the film in acidic solutions. The loading and unloading of Ag+ are reversible and can be repeated many times. Silver nanoparticles were synthesized in situ by UV irradiation. The nanoparticles are spherical in shape and present a surface plasmon absorption peak at 434 nm.
Co-reporter:Ying Guan and Yongjun Zhang
Soft Matter 2011 vol. 7(Issue 14) pp:6375-6384
Publication Date(Web):05 May 2011
DOI:10.1039/C0SM01541E
Poly(N-isopropylacrylamide) (PNIPAM) microgel is perhaps the most well-known intelligent soft nanomaterial. Combining the strengths of hydrogel and nanoparticles, with unique stimuli-responsivity, PNIPAM microgels have found numerous biomedical applications, such as drug delivery, biosensing, and so on. Usually they were used as dispersed particles, however, they can also be used as building blocks to fabricate 2D films and 3D aggregates. These nanostructured assemblies exhibit new properties which the dispersed particles do not have, and new biomedical applications have been found for these assemblies. In this paper, the biomedical applications of PNIPAM microgels in the form of dispersed particles, 2D films and 3D aggregates were reviewed and some recent progress in this area was highlighted.
Co-reporter:Wang Liao;Ying Guan;X. X. Zhu
Macromolecular Chemistry and Physics 2011 Volume 212( Issue 18) pp:2052-2060
Publication Date(Web):
DOI:10.1002/macp.201100137
Co-reporter:Jian He, Aijuan Zhang, Yongjun Zhang, and Ying Guan
Macromolecules 2011 Volume 44(Issue 7) pp:2245-2252
Publication Date(Web):March 4, 2011
DOI:10.1021/ma1029532
A new redox hydrogel using poly(hydroquinone) (PHQ) as polymeric redox couple and chitosan as matrix was synthesized by simple exposing an acidic chitosan/hydroquinone (HQ) solution to the air. PHQ was synthesized in situ by oxidative polymerization of HQ using oxygen as an oxidant. The presence of chitosan increases the reaction rate significantly, suggesting chitosan works as a template for the polymerization of HQ. The reaction rate increases linearly with chitosan concentration when molar ratio of chitosan/HQ is less than 0.96 but keeps constant beyond that point. These results suggest a pick-up mechanism for the template polymerization of HQ. The polymerization of HQ further results in the gelation of the aqueous solution, as physical cross-links forms between PHQ and chitosan. The gelation time decreases with increasing chitosan and HQ concentration and also increasing temperature. The resultant hydrogel are redox-active. Cyclic voltammogram of the hydrogel presents two oxidation peaks at 0.62 and 1.23 V and two reduction peaks at −0.79 and −1.66 V (vs Ag/AgCl). The in situ-formed redox hydrogel may find applications in biomedical areas.
Co-reporter:Dongdong Wang, Dan Cheng, Ying Guan, and Yongjun Zhang
Biomacromolecules 2011 Volume 12(Issue 3) pp:
Publication Date(Web):January 19, 2011
DOI:10.1021/bm101187b
Organ printing is an alternative to the classic scaffold-based tissue engineering approach in which functional living macrotissues and organ constructs are fabricated by assembly of the building blocks: microtissue spheroids. However, the method for scalable fabrication of cell spheroids does not exist yet. We propose here that it may be a suitable one to generate cell spheroids in thermoreversible hydrogel scaffold, followed by liquefying the scaffold and releasing the generated spheroids. We show that concentrated poly(N-isopropylacrylamide-co-acrylic acid) microgel dispersions solidify upon heating and liquefy upon cooling. A hysteresis in the cooling process was observed and explained by the slow kinetics of the dissolution of the aggregated polymer chains in the cooling process due to additional intra- and interchain interactions. Hep G2 cells are seeded by simple mixing the cells with the microgel dispersions at room temperature. Cell/scaffold constructs form in situ when heated to 37 °C. The cells proliferate and form multicellular spheroids. When brought back to room temperature, the hydrogel scaffolds liquefy, thus, releasing the generated cell spheroids. The released spheroids can attach on the cell culture plate, disassemble, and spread on the substrate, confirming the cell viability. The whole process is carried out under mild conditions and does not involve any toxic additives, which may introduce injury to the cells or DNA. It is scalable and may meet the need for large scale fabrication of cell spheroids for organ printing.
Co-reporter:Shuying Xing, Ying Guan, and Yongjun Zhang
Macromolecules 2011 Volume 44(Issue 11) pp:4479-4486
Publication Date(Web):May 9, 2011
DOI:10.1021/ma200586w
Rapid swelling is a major advantage of microgels over bulky gels, and chemical-induced swelling has been expected to occur on the same time scale as physically induced swelling. As an example, the kinetics of the glucose-induced swelling of poly(N-isopropylacrylamide-co-3-acrylamidophenylboronic acid) (P(NIPAM-AAPBA)) microgel was studied by turbidity. This process occurs on a time scale of 102 s, while the temperature-induced (de)swelling of PNIPAM microgels was reported to occur in time regime from 100 ns to tens of milliseconds. The slow glucose-induced swelling was attributed to the slow reaction between glucose and phenylboronic acid (PBA) groups, which was identified as the rate-determining step for microgel swelling. The rate constant of this reaction was further determined under various conditions and compared with that obtained in solution, using 3-aminophylboronic acid as low molecular weight analogue. The reaction is accelerated when the microgels are in a swollen state, while it is retarded when the microgels are shrunken, revealing different effects of the polymer network on the reaction kinetics. Although the swelling rate of P(NIPAM-AAPBA) microgel is limited by the slow reaction between glucose and PBA groups, it is still much faster than the macroscopic hydrogel beads with same components (∼several hours).
Co-reporter:Tiantian Gan, Ying Guan and Yongjun Zhang
Journal of Materials Chemistry A 2010 vol. 20(Issue 28) pp:5937-5944
Publication Date(Web):14 Jun 2010
DOI:10.1039/C0JM00338G
Using poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (P(NIPAM-HEMA)) microgel as an example, we proposed that thermogelable microgel dispersions can be used as a new type of injectable cell scaffolds. However, these in situ formed hydrogels shrink with time, which is undesirable for their use as cell scaffolds. In this work, the syneresis of hydrogels from poly(N-isopropylacrylamide) (PNIPAM) microgel dispersions with various acrylic acid (AA) contents were measured. These concentrated microgel dispersions can all thermally gelate at physiological pH and ionic strength. With increasing AA content in the microgels, the gelation temperature of the dispersion increases, but the degree of syneresis of the resulting hydrogels decreases. The kinetics of shrinkage can be well described by the Tanaka-Fillmore equation, indicating that the deswelling of the hydrogels is governed by the cooperative diffusion of the gel network. These hydrogels present an interconnected porous structure with pore size decreases with an increasing degree of syneresis. HepG2 cells were seeded in these hydrogels. While the cells proliferate and form spheroid-like aggregates in hydrogels with a low degree of syneresis, their growth is inhibited in the one with a high degree of syneresis. These results indicate that the syneresis of the hydrogel has an adverse effect on cell culturing. This effect can be alleviated by adjusting AA content in the microgels. However, cells do not grow either if AA content is too high which results in a lack of cell-substrate interaction.
Co-reporter:Qiaofang Luo, Pengxiao Liu, Ying Guan and Yongjun Zhang
ACS Applied Materials & Interfaces 2010 Volume 2(Issue 3) pp:760
Publication Date(Web):February 12, 2010
DOI:10.1021/am900779a
Four series of poly(N-isopropylacrylamide) (PNIPAM) (core)/poly(N-isopropylacrylamide-co-3-acrylamidophenylboronic acid) (P(NIPAM-AAPBA)) (shell) microgels were synthesized by the modification of PNIPAM (core)/poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAM-AA)) (shell) microgels with 3-aminophenylboronic acid (APBA). Their thermosensitive behaviors were studied by dynamic light scattering. Two or three phase transitions were detected depending on the shell thickness. These transitions were confirmed by the first derivative plot of the turbidity data. The first transition occurring at about 17 °C was assigned to that of the P(NIPAM-AAPBA) shell, whereas the second and third ones, which occur at about 22 and 28 °C, respectively, were assigned to that of the PNIPAM core. These results indicate that the influences of a shrunk P(NIPAM-AAPBA) shell on the different parts of the PNIPAM core are different. As the outer part, or the “shell” part of the PNIPAM core, directly connects with the P(NIPAM-AAPBA) shell, its phase transition temperature is reduced to a larger degree as compared with that of the inner part, or the “core” part. Glucose-induced swelling was observed for all the microgels, indicating their glucose-sensitivity. However, the degree of glucose-induced swelling is much smaller than that of the pure P(NIPAM-AAPBA) microgels.Keywords: core/shell structure; glucose sensitive; microgel; poly(N-isopropylacrylamide); thermosensitive; volume phase transition
Co-reporter:Qiaofang Luo;Ying Guan;Muhammad Siddiq
Journal of Polymer Science Part A: Polymer Chemistry 2010 Volume 48( Issue 18) pp:4120-4127
Publication Date(Web):
DOI:10.1002/pola.24205
Abstract
A series of lead-sensitive poly(N-isopropylacrylamide) microgels with pendant crown ether groups were prepared. Their cation-sensitive behaviors were studied by dynamic light scattering. When ionic strength is not controlled, adding salts causes the microgel particles to deswell. However, when the salt effect is ruled out by keeping a constant ionic strength, adding Pb2+ results in much larger swelling. The Pb2+-induced swelling was explained by the formation of host–guest complex between Pb2+ and the pendant crown ether groups, which increases the hydrophilicity of the polymer and accordingly the degree of swelling. The lead sensitivity of the microgels increases with increasing crown ether content. For the modified microgel with the highest crown ether content, it swells to ∼430% of its original volume at [Pb2+] = 10 mM. Other cations also increase the swelling degree of the modified microgels. The extent of the cation-induced swelling mainly depends on their affinity to the pendant crown ether groups. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 4120–4127, 2010
Co-reporter:Pengxiao Liu, Qiaofang Luo, Ying Guan, Yongjun Zhang
Polymer 2010 Volume 51(Issue 12) pp:2668-2675
Publication Date(Web):28 May 2010
DOI:10.1016/j.polymer.2010.04.011
To study the drug release behaviors of glucose-sensitive poly(N-isopropylacrylamide-co-3-acrylamidophenylboronic acid) (P(NIPAM-PBA)) microgels, P(NIPAM-PBA) microgel monolayers were prepared by the modification of poly(N-isopropylacrylamide-co-acrylic acid) microgel monolayers with 3-aminophenylboronic acid under EDC catalysis. Alizarin Red S (ARS) and FITC-labeled insulin (FITC-insulin) were loaded in the monolayers respectively. Their release kinetics under various conditions were measured. For both drugs, at low temperature, the drug release can be described as passive diffusion of the drugs. At temperature higher than the phase transition temperature, however, the drugs are released via a “squeeze-out” mechanism. Glucose-regulated release for both drugs was observed. At all temperatures glucose enhances the release of ARS because it competes with ARS for binding with PBA groups. For FITC-insulin, glucose enhances its release at 4 °C, but retards at 37 °C. These results will guide the design of self-regulated insulin release systems based on P(NIPAM-PBA) microgels.
Co-reporter:Yun Liu, Yongjun Zhang and Ying Guan
Chemical Communications 2009 (Issue 14) pp:1867-1869
Publication Date(Web):20 Feb 2009
DOI:10.1039/B821706H
A new principle for PCCA sensing is proposed, in which the analyte-induced swelling of the CCA sphere, rather than that of the hydrogel matrix, is explored for sensing.
Co-reporter:Zhibo Ding, Ying Guan, Yongjun Zhang and X. X. Zhu
Soft Matter 2009 vol. 5(Issue 11) pp:2302-2309
Publication Date(Web):06 May 2009
DOI:10.1039/B901910C
Layer-by-layer (LBL) multilayer films were fabricated from poly(vinylalcohol) (PVA) and poly[acrylamide-co-3-(acrylamido)phenylboronic acid] [P(AAm-AAPBA)] by the use of covalent phenylboronate ester bonding as the driving force. The film thickness increases with decreasing pH and increasing ionic strength of the assembly solutions. Phenylboronate ester bonds in the film were confirmed from the IR marker mode at 1730 cm−1. Because the phenylboronate ester bonding is reversible, the PVA/P(AAm-AAPBA) films disassemble gradually when immersed in aqueous solutions. The disassembly rate increases with increasing pH and decreasing ionic strength of the aqueous solutions. Furthermore, the disassembly of the film is accelerated by the addition of glucose, which competes with PVA for phenylboronic acid groups and weakens the interaction between the two polymers. Interestingly, the PVA/P(AAm-AAPBA) film presents glucose-sensitive behavior even under physiological conditions. The enhanced glucose-sensitive behavior at physiological pH may originate from the stabilization of phenylboronate ester by the adjacent amide group. These glucose-sensitive LBL films hold promise for self-regulated insulin release.
Co-reporter:Wang Lin, Ying Guan, Yongjun Zhang, Jian Xu and X. X. Zhu
Soft Matter 2009 vol. 5(Issue 4) pp:860-867
Publication Date(Web):15 Dec 2008
DOI:10.1039/B813614A
Hydrogen-bonded layer-by-layer assembled films from poly(vinyl pyrrolidone) (PVPON) and poly(acrylic acid) (PAA) were fabricated. Fabry–Perot fringes were used as a simple but efficient method for studying the structure changes in the films during salt treatment. Results indicate that these films are very sensitive to salt when incubated in water. A brief treatment in salt solution of low concentration results in microphase separation in the films, the extent of which increases with increasing pH and salt concentration. The microphase separation in PVPON–PAA films is explained by the enhanced dissociation of PAA, which partially breaks the hydrogen bonds in the films. More importantly, the erosion of the PVPON–PAA films accelerates greatly in salt solution. Morphology changes during the erosion suggest a dewetting process of the films, which facilitates their dissolution. Finally, salt-triggered, rapid release of ibuprofen was achieved by the quick, salt-induced erosion of the hydrogen-bonded films.
Co-reporter:Zhibo Ding, Ying Guan, Yongjun Zhang, X.X. Zhu
Polymer 2009 50(17) pp: 4205-4211
Publication Date(Web):
DOI:10.1016/j.polymer.2009.07.001
Co-reporter:Tiantian Gan, Yongjun Zhang and Ying Guan
Biomacromolecules 2009 Volume 10(Issue 6) pp:
Publication Date(Web):April 14, 2009
DOI:10.1021/bm900022m
In this work we try to develop a new thermal gelling injectable scaffold for three-dimensional cell culture. Instead of using linear, branched, or grafted macromolecules, thermosensitive microgel particles or microspheres are used as building blocks for the construction of the macroscopic hydrogel scaffold. As a proof of concept, thermosensitive poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (P(NIPAM-HEMA)) microgel particles were synthesized, which present a volume phase transition temperature (VPTT) at about 29 °C. Rheological test shows that the concentrated P(NIPAM-HEMA) microgel dispersion is colloidally stable when heated above its VPTT, indicating hydrophobic interaction alone can not induce thermal gelation of the dispersion. In the presence of a low concentration of CaCl2, however, with the introduction of additional ionic cross-linking, the microgel dispersion gelates and forms macroscopic hydrogel. Gelation temperature of the microgel dispersion decreases with increasing ionic strength. SEM observation reveals that the resultant bulky gel has an interconnected porous microstructure. 293T cells, a human cell line, were encapsulated inside the hydrogel by simple mixing with the microgel dispersion at room temperature and heating to 37 °C. MTT (3-[4,5-dimethylthiazol-2-yl]-3,5-diphenyl tetrazolium bromide) assays reveal that the cells are viable and proliferate inside the 3D scaffold.
Co-reporter:Xiaoxiao Wang, Qian Li, Ying Guan, Yongjun Zhang
Materials Today Chemistry (October–December 2016) Volumes 1–2() pp:7-14
Publication Date(Web):1 October 2016
DOI:10.1016/j.mtchem.2016.10.005
•An optical glucose sensor was designed using GOD-containing hydrogel films as both sensing material and Fabry-Perot cavity.•The new sensor works well under physiological conditions.•Potential interferents for PBA-based sensors and GOD-based electrochemical sensors, do not influence the new sensor.•The new sensor responds linearly within the clinically relevant glucose range.•The response of the new sensor to glucose is quick.Hydrogel biosensors usually suffer from a slow response, which severely hinders their practical applications. Here a new optical glucose biosensor was designed, using glucose-sensitive hydrogel films as both glucose-sensing material and Fabry-Perot cavity. The film was fabricated by layer-by-layer assembly from partially oxidized dextran (PO-Dex), chitosan, and glucose oxidase (GOD). The film responds to glucose because the incorporated GOD converts glucose to gluconic acid, and thus lowers the local pH in the film, and, in turn, triggers the pH-sensitive film to swell. The glucose-induced swelling causes a shift of Fabry−Perot fringes on the reflection spectra of the film, from which the glucose concentration can be reported. The new sensor works well under physiological conditions. Potential interferents, such as diols for phenylboronic acid-based sensors and electroactive compounds for electrochemical sensors, do not influence the new sensor. The sensor can respond reversibly over a wide range of glucose concentration. Particularly, it responds linearly within the clinically relevant glucose range (0–20 mM). More importantly, because the film is very thin, the new sensor can respond quickly, making it potential for real-time, continuous glucose monitoring.Download high-res image (360KB)Download full-size image
Co-reporter:Yun Liu, Yongjun Zhang and Ying Guan
Chemical Communications 2009(Issue 14) pp:NaN1869-1869
Publication Date(Web):2009/02/20
DOI:10.1039/B821706H
A new principle for PCCA sensing is proposed, in which the analyte-induced swelling of the CCA sphere, rather than that of the hydrogel matrix, is explored for sensing.
Co-reporter:Tiantian Gan, Ying Guan and Yongjun Zhang
Journal of Materials Chemistry A 2010 - vol. 20(Issue 28) pp:NaN5944-5944
Publication Date(Web):2010/06/14
DOI:10.1039/C0JM00338G
Using poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) (P(NIPAM-HEMA)) microgel as an example, we proposed that thermogelable microgel dispersions can be used as a new type of injectable cell scaffolds. However, these in situ formed hydrogels shrink with time, which is undesirable for their use as cell scaffolds. In this work, the syneresis of hydrogels from poly(N-isopropylacrylamide) (PNIPAM) microgel dispersions with various acrylic acid (AA) contents were measured. These concentrated microgel dispersions can all thermally gelate at physiological pH and ionic strength. With increasing AA content in the microgels, the gelation temperature of the dispersion increases, but the degree of syneresis of the resulting hydrogels decreases. The kinetics of shrinkage can be well described by the Tanaka-Fillmore equation, indicating that the deswelling of the hydrogels is governed by the cooperative diffusion of the gel network. These hydrogels present an interconnected porous structure with pore size decreases with an increasing degree of syneresis. HepG2 cells were seeded in these hydrogels. While the cells proliferate and form spheroid-like aggregates in hydrogels with a low degree of syneresis, their growth is inhibited in the one with a high degree of syneresis. These results indicate that the syneresis of the hydrogel has an adverse effect on cell culturing. This effect can be alleviated by adjusting AA content in the microgels. However, cells do not grow either if AA content is too high which results in a lack of cell-substrate interaction.
Co-reporter:Wenjing Zhang, Aijuan Zhang, Ying Guan, Yongjun Zhang and X. X. Zhu
Journal of Materials Chemistry A 2011 - vol. 21(Issue 2) pp:NaN555-555
Publication Date(Web):2010/10/27
DOI:10.1039/C0JM02369H
As nanoreactor for the synthesis of metal nanoparticles, hydrogen-bonded layer-by-layer assembled (LBL) films may be a better choice than the electrostatic ones, because more carboxylic acid groups are available for metal ion binding. However, these films should be crosslinked before metal ion loading because of their instability (Chem. Mater., 2005, 17, 1099–1105). Here we report that the uncrosslinked hydrogen-bonded poly(vinyl pyrrolidone)/poly(acrylic acid) (PVPON/PAA) LBL films remain stable during Ag+ loading. FTIR and XPS studies indicate that Ag+ binds with PVPONvia coordination interaction, while it simultaneously binds with PAAvia electrostatic interaction. Therefore the films do not disintegrate upon the disruption of hydrogen bonds between PVPON and PAA. After Ag+ loading, the erosion rate of the film in water decreases, indicating that the long-term stability of the film is actually improved. The loaded Ag+ can be easily unloaded by immersing the film in acidic solutions. The loading and unloading of Ag+ are reversible and can be repeated many times. Silver nanoparticles were synthesized in situ by UV irradiation. The nanoparticles are spherical in shape and present a surface plasmon absorption peak at 434 nm.
Co-reporter:Xi Zhang, Ying Guan and Yongjun Zhang
Journal of Materials Chemistry A 2012 - vol. 22(Issue 32) pp:NaN16305-16305
Publication Date(Web):2012/07/03
DOI:10.1039/C2JM33413E
Layer-by-layer assembled films using reversible/dynamic bonds between the polymer pairs as driving forces are dynamic in nature. They may disintegrate under certain conditions as a result of the breakage of the dynamic bonds. More importantly they disintegrate gradually under conditions of equilibrium control, making them suitable for sustained drug release. Here insulin release from dynamic LbL films was demonstrated as an example. The films were fabricated from a fluorescently-labeled insulin–PVA (PVA: polyvinyl alcohol) conjugate and poly[acrylamide-co-3-(acrylamido)-phenylboronic acid], using a reversible covalent bond, i.e., phenylboronate ester bond, as the driving force. Film fabrication was followed by UV-vis and fluorescence spectroscopy. In all cases linear film growth was observed. The film growth rate increases with decreasing pH and increasing ionic strength of the assembly solutions. Successful integration of insulin into the films was achieved by covalent conjugation of insulin with PVA. When immersed in an aqueous solution, the films disintegrate gradually, thus releasing insulin into the media. Insulin release rate increases with increasing pH and decreasing ionic strength of the media. More importantly, it increases with increasing glucose concentration in the media. The glucose response of the film was attributed to the conversion of PBA (PBA: phenylboronic acid) groups in the film from a neutral form to a negatively charged one as a result of the formation of glucose–PBA complexes, thus increasing the rate of the film disintegration.
Co-reporter:Wenjing Zhang, Jia Song, Wang Liao, Ying Guan, Yongjun Zhang and X. X. Zhu
Journal of Materials Chemistry A 2013 - vol. 1(Issue 10) pp:NaN2043-2043
Publication Date(Web):2013/01/21
DOI:10.1039/C3TC00415E
Fluorescent Ag nanoclusters have been easily generated in layer-by-layer (LBL) films of poly(vinyl pyrrolidone) (PVPON) and poly(acrylic acid) (PAA) by photo-reduction of Ag+ ions, which were previously loaded via an ion exchange mechanism. Under UV irradiation, Ag+ ions were reduced to Ag atoms by the photo-generated radicals and then aggregate to form fluorescent nanoclusters. The Ag+ concentration plays a key role in the determination of the growth rate of Ag particles. Careful tuning of the Ag loading in the film prevented the growth of the fluorescent nanoclusters into larger non-fluorescent nanoparticles. Fluorescent Ag nanoclusters can be generated in both wet and dry films. However, the fluorescence intensity achieved in dry films is lower than that in wet films because the tight confinement of the polymer network retards the diffusion and aggregation of the photo-generated Ag atoms. Interestingly the fluorescence intensity can be enhanced significantly by a post-treatment in water, as it allows the Ag atoms to diffuse and aggregate to form more fluorescent nanoclusters. This work shows that the PVPON/PAA LBL films can serve as nanoreactors that allow the in situ generation of fluorescent Ag nanoclusters, yielding fluorescent Ag nanoclusters in a technically important form, in addition to providing a simple way to control the growth of the nanoparticles.
Co-reporter:Ying Guan and Yongjun Zhang
Chemical Society Reviews 2013 - vol. 42(Issue 20) pp:NaN8121-8121
Publication Date(Web):2013/07/16
DOI:10.1039/C3CS60152H
Boronic acid-containing hydrogels are important intelligent materials. With the introduction of boronic acid functionality, these hydrogels exhibit a lot of interesting properties, such as glucose-sensitivity, reversibility and self-healing. These materials have found important applications in many areas, especially in biomedical areas. This paper aims to provide an overview of the current state of the art of the study in this area. We review the synthesis and properties of various boronic acid-containing hydrogels, including macroscopic hydrogels, microgels and layer-by-layer self-assembled films. Their applications were described, with an emphasis on the design of various glucose sensors and self-regulated insulin delivery devices. New development in this area was highlighted. Problems and the new directions were discussed.
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