Co-reporter:Ning Wang, Yongmao Li, Yinyu Zhang, Yue Liao, and Wenguang Liu
Langmuir October 7, 2014 Volume 30(Issue 39) pp:11823-11832
Publication Date(Web):September 8, 2014
DOI:10.1021/la502916j
In the present study, high-strength photoresponsive hydrogels were prepared by the photoinitiated copolymerization of acrylamide (AAm, hydrophilic hydrogen bonding monomer), 2-vinyl-4,6-diamino-1,3,5-triazine (VDT, hydrophobic hydrogen bonding monomer), and spiropyran-containing monomer (SPAA) in the presence of cross-linker poly(ethylene glycol) diacrylate (PEG575DA, Mn = 575). The double hydrogen bondings from AAm–AAm and diaminotriazine–diaminotriazine contributed to the considerable enhancement in tensile and compressive properties of the hydrogels, which showed an excellent ability to resist a variety of external forces. Fifteen minutes of UV (365 nm) irradiation led to the detachment of adhered cells due to the increased surface hydrophilicity caused by the isomerization of spiropyran moieties. Furthermore, repeated attachment/detachment of cells was realized by the alternate illumination of visible and UV light. Reverse gene transfection was carried out successfully by anchoring the PVDT/pDNA complex nanoparticles on the gel surface through hydrogen bonding between diaminotriazine motifs prior to cell seeding. Importantly, fibronectin (FN) modification combined with supplementing PVDT/pDNA complex nanoparticles after the first cycle of reverse gene transfection, so-called sandwich gene transfection, further increased the gene transfection level. A short time of UV light exposure could result in the nonharmful detachment of gene-modified cells from the gel surface. This high-strength photosensitive hydrogel holds potential as a reusable soft–wet platform for cell harvesting as well as gene transfection operation at higher efficiency.
Co-reporter:Xinyun Zhai, Yufei Ma, Chunyong Hou, Fei Gao, Yinyu Zhang, Changshun Ruan, Haobo Pan, William Weijia Lu, and Wenguang Liu
ACS Biomaterials Science & Engineering June 12, 2017 Volume 3(Issue 6) pp:1109-1109
Publication Date(Web):May 17, 2017
DOI:10.1021/acsbiomaterials.7b00224
The emerging 3D bioprinting technique that is strongly dependent on the development of bioinks offers a promising opportunity to customize personalized bioscaffolds for precision and individualized therapy of bone defects. Hydrogels are one sort of attractive scaffolding materials due to their resemblance to extracellular matrices. Although much progress has been made in designing and fabricating high strength hydrogels, very few of them have been extended to the treatment of bone defects. In this work, we developed a hybrid bioink composed of a hydrogen bonding monomer (N-acryloyl glycinamide) (NAGA) and nanoclay. The hybrid ink could be conveniently tailored as a high strength PNAGA-Clay composite scaffold under UV light illumination of printed prehydrogel. The hydrogen bonding combined with physical cross-linking of nanoclay contributed to the superior mechanical performances as well as swelling stability of the hydrogels and bioscaffols. The sustainable release of intrinsic Mg2+ and Si4+ from the PNAGA-Clay scaffold was shown to promote the osteogenic differentiation of primary rat osteoblast (ROB) cells. Importantly, this implantable PNAGA-Clay scaffold highly efficiently facilitated the regeneration of new bone in tibia defects of rats. We anticipate that hybridization of the hydrogen bonding monomer with a variety of bioactive inorganic nanoparticles will offer new possibilities to develop numerous bioinks for 3D-printing of desired bioscaffolds to realize individualized repair of degenerated load-bearing tissues.Keywords: 3D-printing; bioactive; bone regeneration; high strength; nancomposite hydrogel scaffold;
Co-reporter:Wei Wang;Shuang Liang
Science China Technological Sciences 2017 Volume 60( Issue 8) pp:1278-1280
Publication Date(Web):15 June 2017
DOI:10.1007/s11431-017-9064-7
Co-reporter:Wei Wang, Yinyu Zhang, Wenguang Liu
Progress in Polymer Science 2017 Volume 71(Volume 71) pp:
Publication Date(Web):1 August 2017
DOI:10.1016/j.progpolymsci.2017.04.001
In nature, many soft supporting tissues capable of withstanding multiform external forces during various activities consist of high strength hydrogels (HSHGs) in their delicately organized structures, in which non-covalent interactions play an irreplaceable role in the formation of these HSHGs systems. Inspired by this, researchers have attempted to develop many strategies to construct HSHGs by introducing dynamic and reversible non-covalent interactions in polymer networks. In the last decade, various non-covalent interactions were employed as the enhancing factors to produce a series of multifunctional HSHGs in our lab. By incorporating dynamic non-covalent interactions into hydrogel systems, a myriad of intriguing properties have been unraveled, such as fatigue resistance, self-healing, thermoresponsiveness and/or pH responsiveness, self-recovery, shape memory, and remoldability/recyclability/reusability, and their encouraging applications have been explored as well. However, achieving functionalized HSHGs and extending them to a broad range of applications is still in its infancy. This article provides an overview of bioinspired construction of HSHGs by utilizing a variety of non-covalent interactions; their applications in diverse fields are also presented. Meanwhile, we point out the future development of non-covalent interaction-reinforced HSHGs and potential challenges.
Co-reporter:Yalei Ren, Yinyu Zhang, Wenhui Sun, Fei Gao, Weigui Fu, Peiyi Wu, Wenguang Liu
Polymer 2017 Volume 126(Volume 126) pp:
Publication Date(Web):22 September 2017
DOI:10.1016/j.polymer.2017.08.016
•Methyl influences dramatically the hydrogen bonding interactions•An automatic rapid healing is achieved in PMNAGA hydrogel•The mechanical properties of hydrogel can be tuned by methylPoly(N-acryloyl glycinamide) (PNAGA) with a protein-like thermoresponsive gelation behavior in water has been developed as a high strength self-healable supramolecular polymer(SP) hydrogels recently. However, harsh conditions, such as high temperature treatment and long waiting time, were required for achieving the complete healing due to strong dual amide hydrogen bonding interactions. In this study, to create an autonomic rapid self-healing SP hydrogel, we deliberately introduced a methyl into the opposite side to dual amide to synthesize N-methacryloyl glycinamide (MNAGA) monomer. Rheological analysis, dynamic light scattering(DLS), Fourier transform infrared (FTIR) spectroscopy, and Gaussian calculation revealed that one substitution methyl caused a considerable perturbation to the hydrogen bonding interaction, thus leading to the increased starting gelling concentration and pronounced decrease in mechanical properties of PMNAGA hydrogel compared to PNAGA hydrogel. The PMNAGA hydrogel was shown to exhibit rapid autonomic reparability without any external intervention, and dynamic swelling measurement indicated this PMNAGA hydrogel could evolve from permanent to transient network due to the metastable hydrogen bonding crosslinkage, depending on its environmental temperature. This intriguing robust, autonomous healing and autolytic PMNAGA hydrogel holds great potential as a short-term embolic agent for blocking blood vessel and artificial tears for moistening eyes.Download high-res image (287KB)Download full-size image
Co-reporter:Xuran Zhang;Bing Xu;Fei Gao;Pengbin Zheng
Journal of Materials Chemistry B 2017 vol. 5(Issue 28) pp:5588-5596
Publication Date(Web):2017/07/19
DOI:10.1039/C7TB01279A
Efficient repair of critical-size volumetric bone defects remains a challenge due to the additional complicated surgery required for fixation. In this work, we first synthesized hydrogen bonding crosslinked supramolecular polymer (SP) hydrogels termed as P(NAGA-VPA) by copolymerizing two carefully selected monomers, N-acryloyl glycinamide (hydrogen bonding monomer) and vinylphosphonic acid (mineralization active monomer) directly in a concentrated aqueous solution. The P(NAGA-VPA) hydrogels were then subjected to in situ precipitation mineralization to generate novel high strength mineralized SP hydrogels. The concerted dual physical crosslinkages of NAGA H-bonds and nanocrystal–polymer interaction led to the best comprehensive mechanical performances with a tensile strength of over 1 MPa and a compressive strength of 5 MPa in an equilibrium swelling state. The mineralized SP hydrogel tubular scaffold was fabricated and encapsulated with bone morphogenetic protein-2 (BMP-2). The BMP-2-loaded mineralized SP hydrogel tube was finely sleeved over the murine radial defect without resorting to any additional surgical fixation. The outcome of 8-weeks implantation demonstrated that this hybrid tubular scaffold contributed to an efficient repair of volumetric bone defect by accelerating new bone formation and seamlessly bonding to the bone surface.
Co-reporter:Qian Wu;Bing Xu;Jun-jie Wei;Qing Wang
Chinese Journal of Polymer Science 2017 Volume 35( Issue 10) pp:1222-1230
Publication Date(Web):31 August 2017
DOI:10.1007/s10118-017-1960-3
Over the past decades, the urgent need for high strength conductive hydrogels in diverse applications has motivated an unremitting effort to combine the improved mechanical properties of hydrogels with conductive performances. In this work, high strength conductive hydrogels intensified with intermolecular hydrogen bonding are fabricated by in situ mixing poly(2-vinyl-4,6-diamino-1,3,5-triazine-co-polyethylene glycol diacrylates) (PVDT-PEGDA) hydrogels with poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT/PSS). The conductive hydrogels in deionized water exhibit high mechanical performances with compressive strength and tensile strength in the range of 7.58−9.52 MPa and 0.48−1.20 MPa respectively, which are ascribed to the intermolecular hydrogen bonding interactions of diaminotriazine-diaminotriazine (DAT-DAT) in the network. Meanwhile, adding PEDOT/PSS can significantly increase both the specific conductivities and equilibrium water contents of the hydrogels. These cytocompatible conductive hydrogels may have a great potential to be used as electrical stimuli responsive soft biomaterials.
Co-reporter:Qing Wang;YinYu Zhang;XiYang Dai;XiaoHuan Shi
Science China Technological Sciences 2017 Volume 60( Issue 1) pp:78-83
Publication Date(Web):2017 January
DOI:10.1007/s11431-016-0698-0
Constructing high strength pH sensitive supramolecular polymer hydrogel remains very challenging due to the unavoidable network swelling caused by ionization of acid or basic groups at a specified pH. In this work, we proposed a simple and very convenient approach to fabricate high strength pH responsive supramolecular polymer (SP) hydrogels by one-pot copolymerization of N-acryloyl glycinamide (NAGA) and 2-vinyl-4,6-diamino-1,3,5-triazine (VDT), two feature hydrogen bonding monomers. In these PNAGA-PVDT SP hydrogels obtained, the hydrogen bonding of NAGA was shown to play a dominant role in reinforcing strength, while the hydrogen bonding of diaminotriazine served as a pH sensitive moiety. At pH 3, the mechanical properties of PNAGA-PVDT hydrogels decreased to a different extent due to the breakup of hydrogen bonding; in contrast, the hydrogel resumed the original strength while pH was raised to 7.4 because of reconstruction of hydrogen bonding. Over the selected pH range, the PNAGA-PVDT hydrogels exhibited up to 1.25 MPa tensile strength, 845% breaking strain, 69 kPa Young’s modulus and 21 MPa compressive strength. This novel high strength pH-responsive SP hydrogels may find applications in biomedical and industrial fields.
Co-reporter:Fei Gao, Yinyu Zhang, Yongmao Li, Bing Xu, Zhiqiang Cao, and Wenguang Liu
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 14) pp:8956
Publication Date(Web):March 25, 2016
DOI:10.1021/acsami.6b00912
Inspired by stimuli-responsive remarkable changes in consistency (hardening, softening, autolysis) of sea cucumbers, we synthesized a supramolecular polymer(SP) hydrogel directly by photoinitiated aqueous polymerization of N-acryloyl 2-glycine monomer bearing one amide and one carboxyl group on the side chain. The SP hydrogels doped with Ca2+ demonstrated excellent mechanical properties–high tensile strength (∼1.3 MPa), large stretchability (up to 2300%), high compressive strength (∼10.8 MPa), and good toughness (∼1000 J m–2) due to cooperative hydrogen bonding interactions from amide and carboxyl together with Ca2+ cross-linking. Responding to the change in pH and Ca2+ concentration, the hydrogels could modulate their network stability and mechanical properties: at pH3.0 and higher Ca2+ content, the hydrogel formed low swelling network which was stiff and stable; in alkaline or neutral buffer with lower content of or without Ca2+, the hydrogel formed a highly swollen transient network, which was soft and eventually autolyzed. The reversible multiple noncovalent bonds enabled the hydrogels to achieve thermoplasticity, self-healability, and reusability. Notably, distinct formulations of hydrogels could be welded together under heating to form a gradient hydrogel. In vitro cytotoxicity assay and subcutaneous implantation indicated that the SP hydrogels were biocompatible and autolytic in vivo. The SP hydrogels may find applications as temporary biodevices for intestinal drug delivery or for injectable filling in assisting suturing small vessels.Keywords: autolysis; calcium ion; high strength; hydrogel; hydrogen-bonding;
Co-reporter:Xiyang Dai;Yinyu Zhang;Lina Gao;Tao Bai;Wei Wang;Yuanlu Cui
Advanced Materials 2015 Volume 27( Issue 23) pp:3566-3571
Publication Date(Web):
DOI:10.1002/adma.201500534
Co-reporter:Yinyu Zhang;Yongmao Li
Advanced Functional Materials 2015 Volume 25( Issue 3) pp:471-480
Publication Date(Web):
DOI:10.1002/adfm.201401989
High strength hydrogels were previously constructed based on dipole–dipole and hydrogen bonding reinforcement. In spite of the high tensile and compressive strengths achieved, the fracture energy of the hydrogels strengthened with sole noncovalent bondings was rather low due to the lack in energy dissipating mechanism. In this study, combined dipole–dipole and hydrogen bonding interactions reinforced (DHIR) hydrogels are synthesized by one-step copolymerization of three feature monomers, namely acrylonitrile (AN, dipole monomer), acrylamide (AAm, H-bonding monomer), and 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS, anionic monomer) in the presence of PEGDA575, a hydrophilic crosslinker. The electrostatic repulsion from PAMPS allows the gel network to absorb water readily, and meanwhile the synergistic effect of dipole–dipole and H-bonding interactions enable the DHIR hydrogel to withstand up to 8.3 MPa tensile stress, 4.8 MPa compressive stress and 140–716% elongation at break with the fracture energy reaching as high as 5500 J/m2. In addition, this DHIR hydrogel exhibits reversible mechanical properties after undergoing cyclic loading and unloading. Interestingly, the DHIR hydrogels with appropriate compositions demonstrate temperature-tunable mechanical properties as well as accompanied shape memory effect. The dual noncovalent bonding strengthening mechanism reported here offers a universal strategy for significantly enhancing the comprehensive mechanical properties of hydrogels.
Co-reporter:Zongqing Ren, Yinyu Zhang, Yongmao Li, Bing Xu and Wenguang Liu
Journal of Materials Chemistry A 2015 vol. 3(Issue 30) pp:6347-6354
Publication Date(Web):02 Jul 2015
DOI:10.1039/C5TB00781J
A hydrogen bonded and calcium ion crosslinked hydrogel, termed PVDT-PAA, was synthesized by one-step photo-polymerization of 2-vinyl-4,6-diamino-1,3,5-triazine (VDT), acrylic acid (AA), and polyethylene glycol diacrylate (PEGDA, Mn = 4000). Combined physical crosslinking from inter-diaminotriazine and coordination of Ca2+ with carboxyls contributed to a significant enhancement in the mechanical properties of the PVDT-PAA hydrogels. Furthermore, reversible Ca2+ crosslinking imparted shape memory properties to the hydrogel allowing it to firmly memorize multiform shapes and return to its initial state in response to Ca2+. Interestingly, PVDT-PAA hydrogels with weaker H-bonding interactions demonstrated a sharp volume change phenomenon induced by Ca2+. This volume change could be utilized to trigger unharmful cell detachment from the hydrogel surface, which was thought to be due to Ca2+-induced marked variation in mechanotransduction between the cells and the substrate interface. This H-bonding and ionic crosslinking strategy opens up a new opportunity for designing and constructing multifunctional high strength hydrogels for biomedical applications.
Co-reporter:Wei Wang, Yongmao Li, Lu Cheng, Zhiqiang Cao and Wenguang Liu
Journal of Materials Chemistry A 2015 vol. 3(Issue 16) pp:3392-3392
Publication Date(Web):23 Mar 2015
DOI:10.1039/C5TB90055G
Correction for ‘Water-soluble and phosphorus-containing carbon dots with strong green fluorescence for cell labeling' by Wei Wang et al., J. Mater. Chem. B, 2014, 2, 46–48.
Co-reporter:Junfei Song, Pengfei Zhang, Lu Cheng, Yue Liao, Bing Xu, Rui Bao, Wei Wang and Wenguang Liu
Journal of Materials Chemistry A 2015 vol. 3(Issue 20) pp:4231-4241
Publication Date(Web):20 Apr 2015
DOI:10.1039/C5TB00205B
Nano hybrid materials have attracted extensive attention in the biomedical field. However, it is still a challenge to make biofunctional nanoparticles homogenously distributed in 3D scaffolds. In this research, histidine (His) was covalently cross-linked into collagen (Coll) scaffolds and the imidazole derived from His was employed as a template to chelate silver ions which were then reduced in situ to form silver nanoparticle (Ag NP)–hybridized Coll scaffolds. The resultant nanocomposite demonstrated an increased mechanical strength and the Ag NPs showed a narrow size distribution and were dispersed homogeneously in the 3D Coll/His scaffolds. Moreover, these hybrid scaffolds exhibited better biocompatibility and antibacterial properties against both Gram positive and Gram negative bacteria than Coll scaffolds. The Coll/His/Ag NPs scaffolds were transplanted to the infected full-thickness burn skin of the SD rat model; the results revealed excellent regeneration effects after three weeks compared with the groups not treated with Ag NPs. This study has offered a facile method to construct functional nanoparticle hybridized scaffolds for efficiently healing infected wounds.
Co-reporter:Yongmao Li, Jianhai Yang, Bing Xu, Fei Gao, Wei Wang, and Wenguang Liu
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 15) pp:8114
Publication Date(Web):April 2, 2015
DOI:10.1021/acsami.5b00851
Charge-conversional naturally occurring chitosan–agmatine bioconjugates are prepared by dimethylmaleic anhydride (DMA) modification and the nucleophilic reaction between tosyl of tosylated chitosan and primary amine of agmatine. These bioconjugates (CS-DM-Agm) are shown to condense siRNA into nanocomplexes, which are stable in the presence of serum at physical pH values. Furthermore, the surface charge of complexes can tune from negative to positive while pH is changed to weak acid tumor micromilieu, thus facilitating the target cancer cell internalization in resisting serum adsorption. More importantly, this smart biogenic system shows remarkable gene silencing efficiency and a high apoptotic rate of tumor cells both in vitro and in vivo, indicating its great potential for cancer therapy.Keywords: agmatine; cancer therapy; charge conversion; chitosan; gene silencing;
Co-reporter:Bing Xu, Yongmao Li, Fei Gao, Xinyun Zhai, Mengge Sun, William Lu, Zhiqiang Cao, and Wenguang Liu
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 30) pp:16865
Publication Date(Web):July 15, 2015
DOI:10.1021/acsami.5b05074
In this study, ion-responsive hydrogen bonding strengthened hydrogels (termed as PVV) were synthesized by one-pot copolymerization of 2-vinyl-4,6-diamino-1,3,5-triazine (VDT), 1-vinylimidazole (VI), and polyethylene glycol diacrylate. The diaminotriazine–diaminotriazine (DAT–DAT) H-bonding interaction and copolymerization of VI contributed to a notable increase in comprehensive performances including tensile/compressive strength, elasticity, modulus, and fracture energy. In addition, introducing mM levels of zinc ions could further increase the mechanical properties of PVV hydrogels and fix a variety of temporary shapes due to the strong coordination of zinc with imidazole. The release of zinc ions from the hydrogel contributed to an antibacterial effect, without compromising the shape memory effect. Remarkably, a multiwalled hydrogel tube (MWHT) fixed with Zn2+ demonstrated much higher flexural strengths and a more sustainable release of zinc ions than the solid hydrogel cylinder (SHC). A Zn2+-fixed MWHT was implanted subcutaneously in rats, and it was found that the Zn2+-fixed MWHT exhibited anti-inflammatory and wound healing efficacies. The reported high strength hydrogel with integrated functions holds potential as a tissue engineering scaffold.Keywords: high strength; implantable; ion-responsive; multifunctional; multiwalled hydrogel tubes
Co-reporter:Bing Xu;Yinyu Zhang
Macromolecular Rapid Communications 2015 Volume 36( Issue 17) pp:1585-1591
Publication Date(Web):
DOI:10.1002/marc.201500256
A double hydrogen bonding (DHB) hydrogel is constructed by copolymerization of 2-vinyl-4,6-diamino-1,3,5-triazine (hydrophobic hydrogen bonding monomer) and N,N-dimethylacrylamide (hydrophilic hydrogen bonding monomer) with polyethylene glycol diacrylates. The DHB hydrogels demonstrate tunable robust mechanical properties by varying the ratio of hydrogen bonding monomer or crosslinker. Importantly, because of synergistic energy dissipating mechanism of strong diaminotriazine (DAT) hydrogen bonding and weak amide hydrogen bonding, the DHB hydrogels exhibit high toughness (up to 2.32 kJ m−2), meanwhile maintaining 0.7 MPa tensile strength, 130% elongation at break, and 8.3 MPa compressive strength. Moreover, rehydration can help to recover the mechanical properties of the cyclic loaded–unloaded gels. Attractively, the DHB hydrogels are responsive to CO2 in water, and demonstrate unprecedented CO2-triggered shape memory behavior owing to the reversible destruction and reconstruction of DAT hydrogen bonding upon passing and degassing CO2 without introducing external acid. The CO2 triggering mechanism may point out a new approach to fabricate shape memory hydrogels.
Co-reporter:Yue Liao;Ning An;Ning Wang;Yinyu Zhang;Junfei Song;Jinxiong Zhou
Macromolecular Rapid Communications 2015 Volume 36( Issue 24) pp:2129-2136
Publication Date(Web):
DOI:10.1002/marc.201500390
Co-reporter:Pengyan Wang;Yinyu Zhang;Lu Cheng
Macromolecular Chemistry and Physics 2015 Volume 216( Issue 2) pp:164-171
Publication Date(Web):
DOI:10.1002/macp.201400456
Co-reporter:Pengyan Wang, Jinlong Zhang, Yongmao Li, Ning Wang, Wenguang Liu
Materials Letters 2015 Volume 142() pp:71-74
Publication Date(Web):1 March 2015
DOI:10.1016/j.matlet.2014.11.150
•Diaminotriazine-diaminotriazine hydrogen bonding strengthened hydrogels have been achieved through one step of copolymerization.•The hydrogel is uniquely responsive to thymidine.•The specific nucleoside responsive characteristic is harnessed to control drug permeation.Controlled or targeted release system responding to a specific biomolecular signal is an ideal goal in drug delivery. Herein, we fabricated diaminotriazine-diaminotriazine (DAT-DAT) hydrogen bonding strengthened functional hydrogels by one step of photo-initiated copolymerization which demonstrated unprecedented nucleoside responsive behavior. The hydrogen bonded hydrogels became increasingly swollen in response to thymidine due to much stronger competition of DAT-thymidine with DAT-DAT hydrogen bonding. Interestingly, thymidine was shown to facilitate drug release from the gels. This proof of concept study offers a new avenue to design and construct smart biomaterials capable of delivering target drug by virtue of nucleosides potentially from endogenously synthesized or indigested diet.
Co-reporter:Yongmao Li, Bing Xu, Tao Bai, Wenguang Liu
Biomaterials 2015 55() pp: 12-23
Publication Date(Web):
DOI:10.1016/j.biomaterials.2015.03.034
Co-reporter:Yongmao Li, Jianhai Yang, Liang Sun, Wei Wang and Wenguang Liu
Journal of Materials Chemistry A 2014 vol. 2(Issue 24) pp:3868-3878
Publication Date(Web):15 Apr 2014
DOI:10.1039/C4TB00294F
This study demonstrates a strategy to enhance gene delivery via photoregulated gene unpacking from its vector. Photoresponsive polycationic vectors composed of a middle azobenzene moiety and two terminal blocks of poly[2-(dimethylamino)ethyl methacrylate], termed as Azo-PDMAEMA, are synthesized using a difunctional azobenzene-based initiator via atomic transfer radiator polymerization (ATRP). The Azo-PDMAEMA exhibits trans to cis isomerization under alternate Vis-UV irradiation, and is capable of condensing plasmid DNA into nanocomplexes. Hydrophobic azobenzene groups in the cationic polymers are shown to enhance the interaction of complexes with the cell membrane, thus improving cell uptake and transfection efficiency. Increased gene expression in COS-7 cells, HepG-2 cells and CHO-K1 cells is achieved after UV irradiation due to UV-triggered intracellular gene unpacking. Time-resolved fluorescence assays further indicate that the trans to cis photoisomerization of Azo-PDMAEMA induces less compacted complexes, contributing to more exposure of genes for transcription.
Co-reporter:Wei Wang, Yongmao Li, Lu Cheng, Zhiqiang Cao and Wenguang Liu
Journal of Materials Chemistry A 2014 vol. 2(Issue 1) pp:46-48
Publication Date(Web):30 Oct 2013
DOI:10.1039/C3TB21370F
Water-soluble phosphorus-containing carbon dots (PCDs) with strong green fluorescence were synthesized through a facile one-step microwave assisted approach using phosphorus-rich phytic acid as a carbon source. Owing to their strong green fluorescence and low cytotoxicity, the PCDs are promising as bio-imaging agents.
Co-reporter:Lu Cheng, Yongmao Li, Xinyun Zhai, Bing Xu, Zhiqiang Cao, and Wenguang Liu
ACS Applied Materials & Interfaces 2014 Volume 6(Issue 22) pp:20487
Publication Date(Web):October 6, 2014
DOI:10.1021/am506076r
Nanomaterials that integrate functions of imaging and gene delivery have been of great interest due to their potential use in simultaneous diagnosis and therapy. Herein, polycation-b-polysulfobetaine block copolymer, poly[2-(dimethylamino) ethyl methacrylate]-b-poly[N-(3-(methacryloylamino) propyl)-N,N-dimethyl-N-(3-sulfopropyl) ammonium hydroxide] (PDMAEMA-b-PMPDSAH) grafted luminescent carbon dots (CDs) were prepared via surface-initiated atom transfer radical polymerization (ATRP) and investigated as a multifunctional gene delivery system (denoted as CD-PDMA-PMPD) in which the CD cores acted as good multicolor cell imaging probes, the cationic PDMAEMA acted as a DNA condensing agent, and the outer shell of zwitterionic PMPDSAH block protected the vector against nonspecific interactions with serum components. As revealed by the fluorescent spectrum study, the photoluminescent attributes, especially the tunable emission property, were well inherited from the parent CDs. The CD-PDMA-PMPD could condense plasmid DNA into nanospheres with sizes of approximate 50 nm at a proper complex ratio, posing little cytotoxicity at higher ratios. It was shown that the hybrid vector exhibited significantly suppressed BSA protein adsorption and superior hemocompatibility compared to those of the widely used PEI25k. In the in vitro transfection assay, an increased serum concentration from 10 to 50% caused a dramatic drop in PEI25k transfection performance, whereas the transfection efficiency of CD-PDMA-PMPD was well maintained; CD-PDMA80-PMPD40 showed 13 and 28 times higher transfection efficiencies than PEI25k at 30 and 50% serum concentration, respectively. Intriguingly, the carbon dots in the transfected cells displayed excitation-dependent fluorescent emissions, portending that this polycation-polyzwitterion modified CD will be a promising theranostic vector with excellent stealth performance.Keywords: bioimaging; carbon dots; gene delivery; polysulfobetaine; serum resistance
Co-reporter:Ning Wang, Jinlong Zhang, Liang Sun, Pengyan Wang, Wenguang Liu
Acta Biomaterialia 2014 Volume 10(Issue 6) pp:2529-2538
Publication Date(Web):June 2014
DOI:10.1016/j.actbio.2014.02.017
Abstract
Photoresponsive hydrogels are potentially useful as drug delivery and cell culture media, but there has been no report on manipulation of cell attachment/detachment and gene transfection simultaneously on the surface of this single gel. In the present study, strong light sensitive hydrogels were prepared mechanically by photoinitiated copolymerization of spiropyran-containing monomer, 2-vinyl-4,6-diamino-1,3,5-triazine, hydrogen bonding monomer, oligo(ethylene glycol) methacrylate and polyethylene glycol diacrylate (PEGDA, Mn = 575). The multiple hydrogen bondings of diaminotriazine residues could contribute to the increase in compressive strengths of the photosensitive hydrogels up to 5.1 MPa. UV (365 nm) irradiation led to detachment of adhered cells as a result of the increased surface hydrophilicity caused by a switch from hydrophobic spiropyran to hydrophilic merocyanine form. Furthermore, selective detachment of cells could also be achieved by UV light illumination on the specified gel surface. Hydrogen bonding between diaminotriazines were shown to tightly anchor the PVDT/pDNA complex particles on the gel surface, where reverse gene transfection was achieved. Following up with UV irradiation triggered the unharmful detachment of gene-modified cells from the gel surface. It is envisioned that this photosensitive hydrogel holds potential as a versatile platform for operating gene delivery and controlled harvest of desired cells for tissue engineering.
Co-reporter:Lu Liu;Ning Wang;Yanjiao Han;Yongmao Li
Macromolecular Rapid Communications 2014 Volume 35( Issue 3) pp:344-349
Publication Date(Web):
DOI:10.1002/marc.201300784
Co-reporter:Xiufeng Hu, Lu Cheng, Ning Wang, Liang Sun, Wei Wang and Wenguang Liu
RSC Advances 2014 vol. 4(Issue 36) pp:18818-18826
Publication Date(Web):08 Apr 2014
DOI:10.1039/C4RA01817F
Carbon nanodots (CDs) have become one of the hottest topics in the fluorescent nanoparticle family. During the preparation of CDs, two necessary materials are involved, namely, a carbon source and a passivator. Both of them greatly affect the photoluminescence (PL) and quantum yield (QY) of the CDs. We hypothesized that the interaction of carbon sources with passivation agents would make a great difference to the PL properties of CDs. 2-Hydroxyisobutyric acid (HBA), malic acid (MA) and citric acid (CA) with similar chemical structures and different numbers of carboxyl groups for dehydration and carbonization were selected as the carbon sources to investigate the effect of carboxyl groups on the PL properties of CDs. The three kinds of CDs were synthesized by one-step microwave-assisted pyrolysis in the presence of 1,2-ethylenediamine as a passivator. The maximum QYs of the as-prepared CDs from HBA, MA and CA were 11.81%, 24.52% and 56.42%, respectively. In addition, the fluorescence lifetime and nitrogen content increased with the number of carboxyl groups in the carbon source molecule. The different number of carboxyl groups was shown to influence the PL of CDs due to the different ability to conjugate amino groups. Moreover, the results of cell co-culture indicated that the resultant CDs were highly biocompatible and bright, holding great potential for biomedical applications.
Co-reporter:Xiufeng Hu;Hongbo Wang;Jianhai Yang;Wei Wang
Journal of Applied Polymer Science 2014 Volume 131( Issue 13) pp:
Publication Date(Web):
DOI:10.1002/app.40468
Abstract
In this work, a brushed polycationic polymer with primary and tertiary amino groups was designed and synthesized for gene delivery. The backbone polymer was poly(N-hydroxyethylacrylamide) (PHEAA) by the atom transfer radical polymerization (ATRP), and then 3,3′-diaminodipropylamine (DPA) was grafted onto the PHEAA by the reaction between hydroxyl and the secondary amine. A brushed PHEAA-DPA cationic polymer was achieved with primary and tertiary amino groups and the ratio was 2 : 1. The PHEAA100-DPA and PHEAA200-DPA could effectively condense plasmid DNA (pDNA) at the weight ratio of vector/DNA of 0.6 and 0.4, respectively. The cytotoxicity of PHEAA-DPA/pDNA to COS-7 cells and HepG-2 cells within the weight ratio of vector/DNA of 16 : 1 was lower than that of PEI25k, and cell viability decreased with the increment of the weight ratio. Although the cytotoxicity of PHEAA100-DPA/pDNA was lower than PHEAA200-DPA/pDNA, the latter possessed higher transfection efficiency at the same weight ratio both in COS-7 cells and HepG-2 cells, compared with PEI25k, the transfection efficiency of PHEAA200-DPA/pDNA was better in COS-7 cells and HepG-2 cells with the weight ratio of 12 : 1 and 10 : 1, respectively. These results showed that the PHEAA-DPA with less cytotoxicity and higher gene transfection efficiency has a broad perspective in gene therapy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40468.
Co-reporter:Wei Wang, Liang Sun, Pengfei Zhang, Junfei Song, Wenguang Liu
Acta Biomaterialia 2014 10(12) pp: 4983-4995
Publication Date(Web):
DOI:10.1016/j.actbio.2014.08.022
Co-reporter:Ning Wang, Yongmao Li, Yinyu Zhang, Yue Liao, and Wenguang Liu
Langmuir 2014 Volume 30(Issue 39) pp:11823-11832
Publication Date(Web):September 8, 2014
DOI:10.1021/la502916j
In the present study, high-strength photoresponsive hydrogels were prepared by the photoinitiated copolymerization of acrylamide (AAm, hydrophilic hydrogen bonding monomer), 2-vinyl-4,6-diamino-1,3,5-triazine (VDT, hydrophobic hydrogen bonding monomer), and spiropyran-containing monomer (SPAA) in the presence of cross-linker poly(ethylene glycol) diacrylate (PEG575DA, Mn = 575). The double hydrogen bondings from AAm–AAm and diaminotriazine–diaminotriazine contributed to the considerable enhancement in tensile and compressive properties of the hydrogels, which showed an excellent ability to resist a variety of external forces. Fifteen minutes of UV (365 nm) irradiation led to the detachment of adhered cells due to the increased surface hydrophilicity caused by the isomerization of spiropyran moieties. Furthermore, repeated attachment/detachment of cells was realized by the alternate illumination of visible and UV light. Reverse gene transfection was carried out successfully by anchoring the PVDT/pDNA complex nanoparticles on the gel surface through hydrogen bonding between diaminotriazine motifs prior to cell seeding. Importantly, fibronectin (FN) modification combined with supplementing PVDT/pDNA complex nanoparticles after the first cycle of reverse gene transfection, so-called sandwich gene transfection, further increased the gene transfection level. A short time of UV light exposure could result in the nonharmful detachment of gene-modified cells from the gel surface. This high-strength photosensitive hydrogel holds potential as a reusable soft–wet platform for cell harvesting as well as gene transfection operation at higher efficiency.
Co-reporter:Wei Wang;Lu Cheng
Science China Chemistry 2014 Volume 57( Issue 4) pp:522-539
Publication Date(Web):2014 April
DOI:10.1007/s11426-014-5064-4
Carbon dots (C-dots), since their first discovery in 2004 by Scrivens et al. during purification of single-walled carbon nanotubes, have gradually become a rising star in the fluorescent nanoparticles family, due to their strong fluorescence, resistance to photobleaching, low toxicity, along with their abundant and inexpensive nature. In the past decade, the procedures for preparing C-dots have become increasingly versatile and facile, and their applications are being extended to a growing number of fields. In this review, we focused on introducing the biological applications of C-dots, hoping to expedite their translation to the clinic.
Co-reporter:Liang Sun, Sijie Zhang, Jinlong Zhang, Ning Wang, Wenguang Liu and Wei Wang
Journal of Materials Chemistry A 2013 vol. 1(Issue 32) pp:3932-3939
Publication Date(Web):04 Jun 2013
DOI:10.1039/C3TB20553C
A chemical-crosslinked, biocompatible and injectable hydrogel was formed by Fenton reaction initiated polymerization. The gelation time of N-(2-hydroxyethyl)acrylamide and PEG-diacrylate, which are two representative monomers, was shown to be tunable from instant to 15 min at an H2O2 concentration below several mmol L−1 in neutral medium. The strength of the hydrogel could be regulated by the concentration of the monomer and the Fenton's reagent. The hydrogels prepared by H2O2/Fe2+ initiation showed low cytotoxicity. The bone marrow mesenchymal stem cells and L929 cells encapsulated in the gels exhibited high viability even after 7 days of co-culture. Both the L929 cells encapsulated in situ into the hydrogels and those co-cultured with the hydrogel showed negligible cell death and apoptosis. It is anticipated that the familiar Fenton reaction may act as a new initiator system to fabricate biocompatible injectable hydrogels.
Co-reporter:Hongbo Wang, Jianhai Yang, Yongmao Li, Liang Sun and Wenguang Liu
Journal of Materials Chemistry A 2013 vol. 1(Issue 1) pp:43-51
Publication Date(Web):2012/10/24
DOI:10.1039/C2TB00203E
Monodisperse magnetic nanoparticles (MNPs) were prepared through an organic phase process, and the obtained MNPs were capped with poly[2-(2-methoxyethoxy)ethyl methacrylate]-b-poly[2-(dimethylamino)ethyl methacrylate] synthesized by surface-initiated atom transfer radical polymerization (ATRP). The MNPs-polymer brushes exhibited both superparamagnetic and thermoresponsive behaviors, and could condense plasmid DNA into nanocomplexes with a size of 100–120 nm at appropriate complexing ratios. Enhanced gene expression in COS-7 cells and HepG-2 cells was achieved under a magnetic field and variable temperature conditions due to magnetic force-facilitated internalization of nanocomplexes, and temporary cooling-triggered intracellular gene unpacking. Amazingly, combining magnetic field and temperature dual stimuli contributed to a 50–100- and 25–45-fold increase of the transfection efficiency in HepG-2 cells compared to conventional protocol and PEI25k, respectively.
Co-reporter:Han Gao;Ning Wang;Xiufeng Hu;Wenjing Nan;Yanjiao Han
Macromolecular Rapid Communications 2013 Volume 34( Issue 1) pp:63-68
Publication Date(Web):
DOI:10.1002/marc.201200548
Abstract
Traditional pH-sensitive hydrogels inevitably suffer strength deterioration while the responsive weak acid or base groups are in the ionized state. In this study, we report on a facile approach to fabricate a novel pH-sensitive high-strength hydrogel from copolymerization of two hydrogen-bonding motif-containing monomers, 3-acrylamidophenylboronic acid and 2-vinyl-4,6-diamino-1,3,5-triazine with a crosslinker N,N-methylenebisacrylamide through hydrophilic optimization of the comonomer oligo(ethylene glycol) methacrylate. The double hydrogen bonding hydrogel exhibits both high tensile and compressive strengths over a broad pH range due to the unique ability to maintain at least one type of hydrogen-bonding crosslink over the whole course of pH change.
Co-reporter:Jinlong Zhang, Ning Wang, Wenguang Liu, Xiaoli Zhao and William Lu
Soft Matter 2013 vol. 9(Issue 27) pp:6331-6337
Publication Date(Web):11 Jun 2013
DOI:10.1039/C3SM50866H
The need for high strength hydrogels in load bearing applications has motivated an effort to improve the mechanical properties of these soft and wet materials. However, hydrogels with high strength, excellent elasticity and fatigue resistance are rarely reported. In this study, we fabricated hydrogels with excellent comprehensive mechanical performances by copolymerization of 2-vinyl-4,6-diamino-1,3,5-triazine (VDT) and chain length modulable polyethylene glycol diacrylates (PEGDA). The intermolecular hydrogen bonding effects from diaminotriazine were shown to increase both the tensile and compressive strengths of the gels up to MPa levels, and longer PEG chains could increase the gel's elongation to over 700%. The stress-softening phenomenon did not appear until the VDT content in all the hydrogels was above 50 wt%. PEG35K-PVDT gel containing 93 wt% water was able to resist car pressing and retain excellent fatigue resistance during 20000 cycles of compression due to hydrogen bonding reinforcing effect and effective energy dissipation of flexible polyethylene glycol chains. These high strength and elastic hydrogels with antifatigue ability may serve as soft tissue engineering scaffolds.
Co-reporter:Wenjing Nan, Wei Wang, Han Gao and Wenguang Liu
Soft Matter 2013 vol. 9(Issue 1) pp:132-137
Publication Date(Web):15 Oct 2012
DOI:10.1039/C2SM26918J
A dipole–dipole reinforced copolymer hydrogel was synthesized by the one-step photopolymerization of vinylimidazole (VI) and acrylonitrile (AN) comonomer in the presence of a polyethylene glycol-based crosslinker. The mechanical properties of PVI–AN gels were tremendously increased by only chelating several mmol L−1 zinc ions, which was shown to firmly lock the temporary shape of the gel. Extraction of zinc ions by a complexing agent could facilitate the recovery of a permanent shape, and the memory behavior was reversible. The PVI–AN hydrogels supported the growth of L929 cells. The cell-seeded flat hydrogel sheet was folded into a temporary tubular scaffold and fixed in a culture medium containing 5 mmol L−1 zinc ions. After unfolding the tube, the exposed L929 cells were shown to adhere well on the surface of the gel. It is anticipated that this cell-loaded SM hydrogel could be fixed to a desired shape in vitro by small numbers of zinc ions for a potential implantable tissue engineering scaffold.
Co-reporter:Wei Wang, Wenjing Nan, Liang Sun, Wenguang Liu
Reactive and Functional Polymers 2013 73(8) pp: 993-1000
Publication Date(Web):August 2013
DOI:10.1016/j.reactfunctpolym.2013.05.003
Co-reporter:Xinyun Zhai, Wei Wang, Chuandong Wang, Qin Wang and Wenguang Liu
Journal of Materials Chemistry A 2012 vol. 22(Issue 44) pp:23576-23586
Publication Date(Web):27 Sep 2012
DOI:10.1039/C2JM35502G
Serum stability is one of the key factors influencing the transfection efficiency of cationic vector-mediated gene delivery in vivo. In this work, we used an atomic transfer radical polymerization (ATRP) method to construct p(2-(dimethylamino) ethyl methacrylate)-b-p(N-(3-(methacryloylamino) propyl)-N,N-dimethyl-N-(3-sulfopropyl) ammonium hydroxide) (PDMAEMA-b-PMPDSAH) diblock copolymer brushes-modified ε-polylysine (ε-Ply-DMA-MPD) non-viral vectors. The agarose gel electrophoresis assay indicated that conjugation of sulfobetaine only slightly decreased the DNA condensation ability of PDMAEMA homopolymer brushes-modified ε-polylysine (ε-Ply-DMA70), but increased the stability of complexes in heparin sodium due to the anti-polyelectrolyte effect of polysulfobetaine. The transfection efficiencies of PEI25K and ε-Ply-DMA70 vectors under the serum conditions from 0% to 50% were shown to decrease dramatically; while ε-Ply-DMA70-MPDp vectors remained more stable for gene transfection in concentrated serum, and the efficiency of ε-Ply-DMA70-MPD20 is more than 10-fold higher than that of PEI25K. PDMAEMA-r-PMPDSAH random copolymer brushes-modified ε-polylysine (ε-Ply-DMA70-r-MPD20) showed no improved serum tolerant gene transfection. The MTT assays revealed that the cytotoxicity of ε-Ply-DMA70-MPDp vectors was much lower than that of ε-Ply-DMA70 due to the shielding of positive charges by polysulfobetaine. The expression of red fluorescence protein (RFP) was evaluated by a small animal in vivo fluorescence imaging system and the results showed that the expression of RFP was much higher in the mice injected with ε-Ply-DMA70-MPD20/pDNA-RFP than with ε-Ply-DMA70/pDNA-RFP.
Co-reporter:Yuan Liu, Jianhai Yang, Peng Zhang, Changjun Liu, Wei Wang and Wenguang Liu
Journal of Materials Chemistry A 2012 vol. 22(Issue 2) pp:512-519
Publication Date(Web):2011/10/31
DOI:10.1039/C1JM13063C
A collagen/poly(2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt) (collagen/PNaAMPS) interpenetrating polymer network (IPN) hydrogel was prepared by simultaneous reaction of EDC/NHS-mediated crosslinking of concentrated collagen solution and poly(ethylene glycol) diacrylate crosslinking NaAMPS in a sealed syringe. The collagen/PNaAMPS hydrogels were freeze-dried and immersed in an aqueous solution of PDMAEMA-capped ZnO quantum dots (QDs) to construct a ZnO QDs-laden collagen/PNaAMPS IPN hydrogel. The composite hydrogel containing nearly 90% water exhibited light transmission from 85% to 96%. Introducing the PNaAMPS network considerably improved the mechanical strength of the pristine collagen gel, whereas loading ZnO QDs only slightly affected the optical properties, mechanical properties and water absorption. Strikingly, the loaded ZnO QDs were found to serve dual roles – tracking the degradation of collagen by observing directly the reduction of fluorescence intensity in hydrogels; and as a collagenase inhibitor by the proposed interaction with metalloenzyme, an important characteristic which could be used to prolong the degradation time of pure collagen without physical screening of the IPN network. We also demonstrated that anionic PNaAMPS was able to dampen the cytotoxicity of composite hydrogels by neutralizing positive charges of ZnO QDs. The composite hydrogels carrying rabbit corneal anterior stromal fibroblasts and PolyJet™/DNA complexes could achieve the efficient expression of luciferase and EGFP genes. The model composite hydrogels offer an approach to design a novel corneal substitute with integrated functions of real-time degradation tracking, degradation inhibition and gene delivery for the specific treatment of ophthalmic diseases.
Co-reporter:Xinyun Zhai, Peng Zhang, Changjun Liu, Tao Bai, Wenchen Li, Liming Dai and Wenguang Liu
Chemical Communications 2012 vol. 48(Issue 64) pp:7955-7957
Publication Date(Web):21 Jun 2012
DOI:10.1039/C2CC33869F
Carbon nanodots (CDs) with a low cytotoxicity have been synthesized by one-step microwave-assisted pyrolysis of citric acid in the presence of various amine molecules. The primary amine molecules have been confirmed to serve dual roles as N-doping precursors and surface passivation agents, both of which considerably enhanced the fluorescence of the CDs.
Co-reporter:Peng Zhang, Wenchen Li, Xinyun Zhai, Changjun Liu, Liming Dai and Wenguang Liu
Chemical Communications 2012 vol. 48(Issue 84) pp:10431-10433
Publication Date(Web):04 Sep 2012
DOI:10.1039/C2CC35966A
Highly fluorescent polymerizable carbon nanodots (PCNDs), synthesized by microwave assisted pyrolysis and subsequent surface vinylation, were copolymerized with several model monomers to form different functional fluorescent polymeric materials in solution or the solid-state, indicating a simple and versatile approach to novel fluorescent polymer materials.
Co-reporter:Yongfeng Luo, Xinyun Zhai, Chaonan Ma, Peng Sun, Zhiping Fu, Wenguang Liu, Jun Xu
Journal of Controlled Release 2012 Volume 162(Issue 1) pp:28-36
Publication Date(Web):20 August 2012
DOI:10.1016/j.jconrel.2012.06.005
SiRNA-based strategies appear to be an exciting new approach for the treatment of respiratory diseases. To extrapolate siRNA-mediated interventions from bench to bedside in this area, several aspects have to be jointly considered, including a safe and efficient gene carrier with pulmonary deposition efficiency, as well as in vivo method for siRNA/nanoparticles delivery. Accordingly, in this work, (i) a non-viral DNA vector, guanidinylated chitosan (GCS) that has been developed in our previous study [X.Y. Zhai, P. Sun, Y.F. Luo, C.N. Ma, J. Xu, W.G. Liu, 2011], was tested for siRNA delivery. We demonstrated that GCS was able to completely condense siRNA at weight ratio 40:1, forming nanosize particles of diameter ~ 100 nm, 15 mV in surface potential. Guanidinylation of chitosan not only decreased the cytotoxicity but also facilitated cellular internalization of siRNA nanoparticles, leading to an enhanced gene-silencing efficiency compared to the pristine chitosan (CS). (ii) We chemically coupled salbutamol, a β2-adrenoceptor agonist, to GCS (SGCS), which successfully improved targeting specificity of the green fluorescent protein (GFP)-siRNA carrier to lung cells harbored with β2-adrenergic receptor, and remarkably enhanced the efficacy of gene silence in vitro and in the lung of enhanced green fluorescent protein (EGFP)-transgenic mice in vivo. (iii) It was proved that this chitosan-based polymer was able to provide both the pDNA and siRNA with the protection against destructive shear forces generated by the mesh-based nebulizers. Aerosol treatment improved the nanoparticle size distribution, which should be in favor of enhancing the transfection efficiency. We suggest a potential application of the chitosan-derived nanodelivery vehicle (SGCS) in RNA interference therapy for lung diseases via aerosol inhalation.
Co-reporter:Yanjiao Han;Tao Bai;Yuan Liu;Xinyun Zhai
Macromolecular Rapid Communications 2012 Volume 33( Issue 3) pp:225-231
Publication Date(Web):
DOI:10.1002/marc.201100683
Abstract
In this study, we demonstrate that dipole–dipole interaction can be employed to not only tremendously enhance the mechanical properties of hydrogel, but also impart the gel to an amazing ability to memorize two temporary shapes. Cross-linked hydrogels synthesized by copolymerization of acrylonitrile, a dipole–dipole containing monomer and hydrophilic comonomer are shown to exhibit triple shape memory (SM) triggered by the dynamic association and dissociation of dipole–dipole pairing between cynao groups uniquely responding to zinc ion species and concentration. This approach contributes to design and fabrication of novel SM hydrogels in a distinct way from conventional SM materials.
Co-reporter:Tao Bai, Yanjiao Han, Peng Zhang, Wei Wang and Wenguang Liu
Soft Matter 2012 vol. 8(Issue 25) pp:6846-6852
Publication Date(Web):31 May 2012
DOI:10.1039/C2SM07364A
We demonstrate that dipole–dipole reinforced (DDR) high-strength hydrogels with pre-programmed unilateral patterned surfaces exhibit a two-way reversible shape-changing and memory effect caused by dynamic association and dissociation of CN–CN dipole–dipole pairings uniquely responding to zinc ions. The curling geometry of the gel can be controlled by the direction of the stripes on the surface of the DDR hydrogel. Interestingly, annealing is shown to facilitate folding of hydrogel; especially annealing at selective regions of one single gel leads to a more complex shape changing effect. More strikingly, surface wrinkling can be conveniently generated by heat treatment of bilayer DDR hydrogels composed of a hierarchical structure, with the micropatterns exhibiting reversible “shape-memorizing” behavior driven by zinc ions. This strategy offers a facile approach to fabricating a promising mechanically strong soft-wet actuator and rewritable hydrogel surface.
Co-reporter:Ye Li, Jianhai Yang, Jingqing Li, Yuan Liu and Wenguang Liu
RSC Advances 2012 vol. 2(Issue 6) pp:2422-2426
Publication Date(Web):01 Feb 2012
DOI:10.1039/C2RA01208A
In this work, we synthesized PNIPAAm and poly[2-(2-methoxyethoxy)ethyl methacrylate] (PEG analogue) with a similar degree of polymerization by ATRP. Their thermoresponsive behaviors in aqueous solution were inspected with phase diagrams, rheological properties and static/time resolved fluorescence analyses. We found that the gelation capability of the PNIPAAm solution was far superior to the PMEO2MA solution due to more pronounced physical interactions between PNIPAAm chains, whereas for PMEO2MA, weak intermolecular interactions fail to result in gelling in the selected concentration range during heating. This distinct property suggests that the PNIPAAm solution will be more suitable for use as an injectable embolic or drug loading material; while thermoresponsive PEG analogues can be a beneficial supplement or even alternative to PNIPAAm in non-thermogelling applications.
Co-reporter:Changjun Liu, Peng Zhang, Xinyun Zhai, Feng Tian, Wenchen Li, Jianhai Yang, Yuan Liu, Hongbo Wang, Wei Wang, Wenguang Liu
Biomaterials 2012 33(13) pp: 3604-3613
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.01.052
Co-reporter:Jianhai Yang, Yuan Liu, Hongbo Wang, Lu Liu, Wei Wang, Chuandong Wang, Qin Wang, Wenguang Liu
Biomaterials 2012 33(2) pp: 604-613
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.09.067
Co-reporter:Changjun Liu, Peng Zhang, Feng Tian, Wenchen Li, Fan Li and Wenguang Liu
Journal of Materials Chemistry A 2011 vol. 21(Issue 35) pp:13163-13167
Publication Date(Web):08 Aug 2011
DOI:10.1039/C1JM12744F
Strong photoluminescent carbon nanodots (C-dots) were synthesized by one-step microwave assisted pyrolysis of glycerol in the presence of 4,7,10-trioxa-1,13-tridecanediamine (TTDDA). The formation and surface passivation of C-dots were accomplished simultaneously. The obtained C-dots exhibited excellent biocompatibility and preeminent multicolor photoluminescent properties for bioimaging.
Co-reporter:Peng Zhang, Jianhai Yang, Wenchen Li, Wei Wang, Changjun Liu, May Griffith and Wenguang Liu
Journal of Materials Chemistry A 2011 vol. 21(Issue 21) pp:7755-7764
Publication Date(Web):20 Apr 2011
DOI:10.1039/C1JM10813A
A novel cationic nanodiamond-polymer brush was synthesized by 2-bromoisobutyrate-modified nanodiamond (ND) surface-initiated atomic transfer radical polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA). Elemental analysis, FTIR, HRTEM, TGA and zeta potential analysis were used to confirm the successful synthesis of ND-polymer brushes. It was shown that the ND-brushes were capable of condensing plasmid DNA into stable nanoparticles, protecting DNA from enzyme degradation. Transfection studies demonstrated that the ND-brushes could not only efficiently deliver plasmids into COS-7 cells, but also mediate higher expression than PEI25k with lower cytotoxicity. The green fluorescence of ND-brushes could also be detected by laser scanning confocal microscopy, making the nanodiamond-polymer brushes an excellent multifunctional gene vector with not only high transfection efficiency but allowing for bioimaging.
Co-reporter:Tao Bai, Peng Zhang, Yanjiao Han, Yuan Liu, Wenguang Liu, Xiaoli Zhao and William Lu
Soft Matter 2011 vol. 7(Issue 6) pp:2825-2831
Publication Date(Web):01 Feb 2011
DOI:10.1039/C0SM01108H
A high strength hydrogel was fabricated by one-step copolymerization of dipole–dipole interaction-containing monomer, acrylonitrile, super-hydrophilic comonomer, 2-methacryloyloxyethyl phosphorylcholine and crosslinker, polyethylene glycol diacrylate (Mn = 575, PEGDA575). This dipole–dipole reinforced (DDR) hydrogel demonstrated intriguing combinations of properties such as withstanding several MPa tensile stress, tens of MPa compressive strength, excellent fatigue resistance and no yielding during tensile tests. The equilibrium water content and transparency of DDR hydrogels could be tuned by varying monomer concentration and monomer ratio. The gels exhibited low cytotoxicity and antifouling characteristic. Biodegradable high strength hydrogel could also be constructed by merely replacing PEGDA575 with bioreducible crosslinker. The method reported here offers a general strategy to design biocompatible high-strength hydrogels for tissue engineering scaffolds by copolymerizing monomer containing dipole–dipole pairing with other hydrophilic monomer.
Co-reporter:Peng Sun;Xinyun Zhai;Yongfeng Luo;Chaonan Ma;Jun Xu
Journal of Applied Polymer Science 2011 Volume 121( Issue 2) pp:874-882
Publication Date(Web):
DOI:10.1002/app.33584
Abstract
PEI-grafted chitosan (PEI-CMCS) copolymer was synthesized through EDC-mediated amidation reaction between carboxymethyl chitosan and low-molecular-weight polyethyleneimine (LMW PEI). PEI-CMCS and CS/DNA complexes were characterized. Compared with pristine chitosan, the PEI-CMCS exhibited an enhanced ability to condense DNA. Incorporation of LMW PEI to chitosan was found to achieve higher transfection efficiency and much lower cytotoxicity than PEI25K at an optimum weight ratio of 15 in COS-7 cells. However, PEI-CMCS was incompetent to transfer refractory pulmonary epithelial cells. It was demonstrated that doping complex medium or treating cells with a steroid hormone—β-estradiol significantly improved the transfection efficiency of 16HBE and A549 cells. This study suggests that steroid hormone may become an additive for other cationic polymers to facilitate gene transfection in pulmonary cells. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Co-reporter:Xinyun Zhai;Peng Sun;Yongfeng Luo;Chaonan Ma;Jun Xu
Journal of Applied Polymer Science 2011 Volume 121( Issue 6) pp:3569-3578
Publication Date(Web):
DOI:10.1002/app.34156
Abstract
In view of the analogous transmembrane function to cell penetrating peptides, guanidine group was incorporated into chitosan by chemical modification to enhance the transfection performance of chitosan vectors. Guanidinylated chitosan (GCS) was shown to be well soluble in neutral aqueous solution. The interaction between GCS with plasmid DNA was characterized by agarose retardation experiment and ethidium bromide displacement assay. GCS formed more stable complexes with DNA under physiological pH than chitosan. The transfection efficiency of GCS was evaluated employing COS-7 cell line—GCS polyplexes demonstrated higher transfection efficiency and lower cytotoxicity relative to chitosan. The optimum efficiency of GCS was achieved in the vicinity of the critical complexing ratio. The results of flow cytometry indicated that guanidinylation promoted an eightfold increase in the cell uptake. The study revealed that guanidinylated chitosan is a promising candidate as an effective nonviral vector for in vivo gene delivery. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Co-reporter:Lei Tang, Yang Yang, Tao Bai, Wenguang Liu
Biomaterials 2011 32(7) pp: 1943-1949
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.11.019
Co-reporter:Fengying Dai, Wenguang Liu
Biomaterials 2011 32(2) pp: 628-638
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.09.021
Co-reporter:Lei Tang;Guipei Liu
Advanced Materials 2010 Volume 22( Issue 24) pp:2652-2656
Publication Date(Web):
DOI:10.1002/adma.200904016
Co-reporter:Peng Zhang, Wenguang Liu
Biomaterials 2010 31(11) pp: 3087-3094
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.01.007
Co-reporter:Jianhai Yang, Peng Zhang, Lei Tang, Peng Sun, Wenguang Liu, Pei Sun, Aijun Zuo, Dongchun Liang
Biomaterials 2010 Volume 31(Issue 1) pp:144-155
Publication Date(Web):January 2010
DOI:10.1016/j.biomaterials.2009.09.027
In this work, thermoresponsive diblock copolymers, poly[2-(2-methoxyethoxy) ethyl methacrylate]-b-poly(2-hydroxyethyl methacrylate) (PMEO2MA-b-PHEMA) with low polydispersity were synthesized by atomic transfer radical polymerization(ATRP). Low molecular weight (LWM) polyethylenimine (PEI, 1200Da) was then grafted to 1,1′-carbonyldiimidazole (CDI)-activated PMEO2MA-b-PHEMA to fabricate PEI-g-(PMEO2MA-b-PHEMA) (PEIMH) copolymer vectors. The LCSTs of PEIMHs with 3 and 8 grafted PEI side chains, separately termed as PEIMH-1 and PEIMH-2, were 32.5 and 38.7 °C in PBS solution. Variable temperature agarose retardation, Zeta potential and time-resolved fluorescence assays were performed to elucidate the temperature sensitive DNA condensation. It showed that DNA was condensed more efficiently by PEIMH, and the collapse of PMEO2MA chains led to more exposure of surface positive charges of PEIMH-1/pDNA complexes while temperature was above LCST. Variable temperature time-resolved fluorescence measurement of lifetimes of bound and free ethidium bromide (EB) unveiled that the population of EB at different states was dependent on temperature. At a temperature above LCST, the collapsed PMEO2MA polymer chains squeezed the loosely bound EB out of complex to become free species; thereby DNA was more tightly packaged by PEIMH-1. Temporary cooling was shown to improve the transfection efficiency of PEIMH-1 in COS-7 and HEK293 cell lines. The variable temperature protocol is more efficient in improving gene expression level in HEK293 cells. The transfection efficiency was equivalent or superior to that of PEI25K at an optimal weight ratio of vector/DNA. Furthermore, the cytotoxicity of PEIMH-1 was considerably lower than that of control PEI25K.
Co-reporter:Fengying Dai, Peng Sun, Yongjie Liu, Wenguang Liu
Biomaterials 2010 31(3) pp: 559-569
Publication Date(Web):
DOI:10.1016/j.biomaterials.2009.09.055
Co-reporter:Fengying Dai;Lei Tang;Jianhai Yang
Journal of Materials Science: Materials in Medicine 2009 Volume 20( Issue 4) pp:967-974
Publication Date(Web):2009 April
DOI:10.1007/s10856-008-3632-x
Thermoresponsive BAB-type HEMA/NIPAAm triblock copolymers (A = NIPAAm, B = HEMA) were prepared by atomic transfer radical polymerization (ATRP). BAB1-6 with shorter PNIPAAm blocks failed to form stable gel; while a relatively stable gel could be achieved by BAB1-8 with longer PNIPAAm blocks when copolymer aqueous solution was heated up. Introducing radiopaque agent (RA) was shown to slightly increase the transition temperature and gelation time, but the gelling ability was strengthened due to slightly weakening dehydration of copolymer in the mixture of water and RA. BAB1-8 aqueous solution about 5 wt% in the presence of RA was demonstrated to successfully occlude the cerebral rete mirabiles (RMs) and renal arteries of pigs. Within 3-month surgery, no recanalization was observed and the embolized kidney shrank considerably. Histological assay of embolized kidney demonstrated interstitial fibrosis and calcification as well as the thickening of renal small artery. This temperature sensitive copolymer with well-defined architecture holds a great potential as an embolic agent for treating arteriovenous malformations (AVMs) and renal disease due to the design flexibility of ATRP.
Co-reporter:GuiXiang Ye;ZhiQiang Cao;Lin Lin;DaYong Chen
Science Bulletin 2008 Volume 53( Issue 15) pp:
Publication Date(Web):2008 August
DOI:10.1007/s11434-008-0291-8
Previously we successfully prepared poly(vinyldiaminotriazine)(PVDT)-based non-viral vectors which complexed plasmid DNA via hydrogen bonding with adenine-thymine base pairs. In this report, surface charges and complex sizes of this system were further examined. The results showed that PVDT-based polymer could cover surface charges of DNA resulting in slightly negative or neutral complexes. It was also found that the complex sizes were governed by two events: the aggregation induced by the instability of neutral particles, and more compact complexes produced by PVDT-based polymers. In the study of cellular uptake, chlorpromazine and filipin III were used to inhibit clathrin-and caveolae-mediated endocytosis, respectively. We found that PVDT-based systems were transported into cells via a non-clathrin, non-caveolae mediated endocytosis. This special process was studied by temperature inhibition and kinetics assays. It was revealed that such a pathway was characterized by (i) a more energy dependent process and (ii) a much slow transfection-effective internalization.
Co-reporter:Z. Q. Cao;W. G. Liu;D. C. Liang;G. Guo;J. Y. Zhang
Advanced Functional Materials 2007 Volume 17(Issue 2) pp:
Publication Date(Web):19 DEC 2006
DOI:10.1002/adfm.200600271
A novel gene transfer system that complexes plasmid DNA (pDNA) through complementary hydrogen bonding of guests with base pairs is reported. Poly(vinyldiaminotriazine) (PVDT) homopolymer and its copolymers with poly(1-vinyl-2-pyrrolidone) are synthesized via conventional radical random polymerization, and water-soluble fractions are collected. These PVDT-based polymers efficiently complex pDNA and displace ethidium bromide (EB) in EB-intercalated pDNA solutions because of the hydrogen-bonding-induced constrained state of pDNA. It is also found that upon complexation, pDNA seems to undergo B–C conformation change and circular dichroism spectra assumed a polymer-and-salt-induced (psi)-type pattern that is rationally ascribed to a certain change in the high-order structure of DNA condensates. Transmission electron microscopy presented several morphologies of spheres and toroids within aggregates ≥ 100 nm, resembling DNA condensation induced by cationics. In transfection studies using pDNA-encoding luciferase or enhanced green fluorescent protein, this system could efficiently transfect COS-1 cells. Compared to the commercial polycation system, ExGen 500, these H-bonding vectors display several merits such as higher transfection efficiency, lower cytotoxicity, better serum compatibility, and stability in the presence of bovine serum albumin (BSA). The results suggest that PVDT-based polymers are superior to polycation counterparts with regard to their potential in vivo applications.
Co-reporter:Zhiqiang Cao;Guixiang Ye;Xiaoli Zhao;Xiaoze Lin;Kangde Yao;Peng Gao
Macromolecular Chemistry and Physics 2006 Volume 207(Issue 24) pp:2329-2335
Publication Date(Web):5 DEC 2006
DOI:10.1002/macp.200600365
Summary: Tri-arm star diblock copolymers, poly(2-hydroxyethyl methacrylate)-block-poly(N-isopropylacrylamide) [P(HEMA-b-NIPAAm)] with PHEMA and PNIPAAm as separate inner and outer blocks were synthesized via a two-step ATRP at room temperature. The formation, molecular weight and distribution of polymers were examined, and the kinetics of the reaction was monitored. The PDI of PHEMA was shown to be lower, indicating well-controlled polymerization of trifunctional macro-initiator and resultant star copolymers. The thermoresponsive behavior of diblock copolymer aqueous solution were studied by DSC, phase diagrams, temperature-variable 1H NMR, TEM and DLS. The results revealed that introducing a higher ratio of HEMA into copolymers could facilitate the formation of micelles and the occurrence of phase transition at lower temperatures. TEM images showed that I-(HEMA40-NIPAAm320)3 solutions developed into core-shell micelles with diameters of approximately 100 nm. I-(HEMA40-NIPAAm320)3 was used as a representative example to elucidate the mechanism underlying temperature-induced phase transition of copolymer solution. In this study we proposed a three-stage transition process: (1) separately dispersed micelles state at ≈17–22 °C; (2) aggregation and fusion of micelles at ≈22–29 °C; (3) sol-gel transition of PNIPAAm segments at ≈29–35 °C, and serious syneresis of shell layers.
Co-reporter:Nan Cheng, Wenguang Liu, Zhiqiang Cao, Weihang Ji, Dongchun Liang, Gang Guo, Jingyu Zhang
Biomaterials 2006 Volume 27(Issue 28) pp:4984-4992
Publication Date(Web):October 2006
DOI:10.1016/j.biomaterials.2006.05.017
A thermoresponsive poly(N-isopropylacrylamide)/poly(l-arginine)bioconjugate (PNIPArg) was prepared by radical polymerization and EDC-activated coupling. The lower critical solution temperature (LCST) of PNIPArg aqueous solution determined by turbidimetry was around 35.2 °C. The transmission electron microscope (TEM) showed that the PNIPArg/DNA complexes appeared uniform nanospheres with size about 50–120 nm. Variable temperature circular dichroism (CD) and gel electrophoresis results revealed that the association and dissociation of PNIPArg/DNA complexes could be tuned by varying temperature; polyarginine (PArg) showed no temperature-controllable change of DNA condensate. Incorporation of PNIPAAm considerably decreased the cytotoxicity of PArg. The transfection level of PNIPArg and PArg was evaluated with COS-1 cells using two different reporter genes, pGL3-Control encoding luciferase and pEGP-C1 encoding green fluorescent protein (GFP). The transfection efficiency of PNIPArg incubated at 37 °C for 22 h, 20 °C for 2 h and 37 °C for 24 h was enhanced to a different extent depending on PNIPArg/DNA ratios compared to that incubated at 37 °C for 48 h. Encouragingly, at PNIPArg/DNA mass ratio of 3/1, the transfection efficiency of PNIPArg obtained with variable temperature route was equivalent to that of LipofectamineTM 2000.
Co-reporter:Xiaowei Li, Wenguang Liu, Guixiang Ye, Bingqi Zhang, Dunwan Zhu, Kangde Yao, Zuoqin Liu, Xizhong Sheng
Biomaterials 2005 Volume 26(Issue 34) pp:7002-7011
Publication Date(Web):December 2005
DOI:10.1016/j.biomaterials.2005.05.094
In this article, thermosensitive N-isopropylacrylamide (NIPAAm)–N-propylacrylamide (NPAAm)–vinyl pyrrolidone (VP) terpolymers (PNINAVP) were prepared by varying feed ratios with free radical copolymerization method. The composition ratios and molecular weights of PNINAVP were examined by NMR and GPC. The thermo-responsive behaviors of copolymer solutions in the absence and with addition of Iohexol, a radiopaque agent, were investigated by differential scanning calorimetry (DSC) and rheometer. The sol–gel transition of the copolymer solutions occurred reversibly within 1 min in response to temperature. Incorporation of Iohexol increased the transition time and transition temperature of PNINAVP solutions; the rheological properties were also influenced. It was observed that at body temperature, PNINAVP and Iohexol could form an integrated bulky hydrogel presumably due to the hydrogen bonding between them, which was favorable for the clinical follow-up and reducing toxic side effects. In vitro embolic model experiment indicated that 5 wt% 16:16:1H PNINAVP solution containing Iohexol displayed a satisfactory embolization effect. This solution was injected into the rete mirabiles (RM) of six swines through a microcatheter. The angiographical results obtained immediately after the operation showed a complete occlusion of the RM, and no recanalization was observed at postoperative month 1. The histological examination demonstrated no acute inflammatory reaction inside the RM and surrounding tissue. This work could provide a beneficial guidance for designing a new temperature-sensitive polymer-based embolic agent.
Co-reporter:Wenguang Liu, Shujun Sun, Zhiqiang Cao, Xin Zhang, Kangde Yao, William W. Lu, K.D.K. Luk
Biomaterials 2005 Volume 26(Issue 15) pp:2705-2711
Publication Date(Web):May 2005
DOI:10.1016/j.biomaterials.2004.07.038
In this work, to eliminate the effect of the hydrophobicity of N-acetyl groups in chitosan on the interaction between chitosan and DNA, a water soluble chitosan with molecular weight of 5000 and deacetylated degree of 99% was selected to complex with DNA at varied charged ratios. The physicochemical properties of chitoplexes were investigated by means of FTIR, circular dichroism (CD), static fluorescence spectroscopy, and atomic force microscopy (AFM). The results indicated that upon interacting with chitosan, the DNA molecules saved a B conformation, and the binding affinity of chitosan to DNA was dependent on pH of media. At pH 5.5, highly charged chitosan had a strong binding affinity with DNA; whereas in pH 12.0 medium, only weak interactions existed. The CD spectra of Hoechst 33258 competitive displacement revealed that chitosan was partially bound to the minor groove of DNA. The morphology of chitosan/DNA complexes was strongly dependent upon the charge ratios. At charge ratio (+/−) of 1:4, not all DNA could be entrapped in the complex; at ratio of 8:1, the spherical complexes with mean size of nanoscale were formed without free DNA, but no typical toroid patterns were observed, which might stem from the strong compact of DNA caused by highly charged chitosan. It was supposed that the strong interaction of chitosan with DNA possibly prevented gene unpacking from chitosan vector, consequently restraining gene expression in nucleus.
Co-reporter:Wenguang Liu;Jianrong Zhang;Nan Cheng;Zhiqiang Cao;Kangde Yao
Journal of Applied Polymer Science 2004 Volume 94(Issue 1) pp:
Publication Date(Web):27 JUL 2004
DOI:10.1002/app.20711
N-Sulfofurfuryl chitosan (SuCS) was prepared through the coupling of 5-formyl-2-furansulfonic acid (FFSA) with chitosan via Schiff's base reaction in an aqueous solution of acetic acid. Fourier transform infrared spectra confirmed the formation of SuCS, and elemental analysis indicated that the concentration of the sulfonic acid groups in modified chitosan increased as the feeding ratio of FFSA increased. A protein adsorption experiment revealed that at higher concentrations of the sulfonic acid groups, glucose aldehyde crosslinked SuCS membranes were inclined to adsorb bovine serum albumin, but the adsorption of fibrinogen was hindered to some extent. Circular dichroism demonstrated that SuCS significantly altered the conformation of thrombin, whereas no obvious variation in the conformation of thrombin was observed with the addition of chitosan. The anticoagulation activity of glucose aldehyde crosslinked SuCS and chitosan membranes was evaluated through assays of the prothrombin time (PT), thrombin time (TT), and activated partial thromboplastin time (APTT). APTT of an SuCS membrane was prolonged in comparison with that of its chitosan counterpart and showed a rising trend with an increasing concentration of the sulfonic acid moieties. However, PT and TT were not markedly affected. The anticoagulant mechanism of the SuCS membranes supposedly originated from an intrinsic pathway to the inhibition of coagulation enzymes. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 53–56, 2004
Co-reporter:Wen Guang Liu;Xiao Wei Li;Gui Xiang Ye;Shu Jun Sun;Dunwan Zhu;Kang De Yao
Polymer International 2004 Volume 53(Issue 6) pp:
Publication Date(Web):5 APR 2004
DOI:10.1002/pi.1358
Gelatin and DNA were mixed together in various ratios followed by the addition of glutaraldehyde as a cross-linker. FT-IR spectroscopy confirmed the formation of a semi-interpenetrating polymer network (semi-IPN) between the gelatin and DNA. The gelatin–DNA semi-IPN hydrogel underwent, reversibly, remarkable changes in swelling degree in response to the variation of pH. In the low-pH range, the hydrogel showed a lower swelling degree; with an increment in pH, the hydrogel was highly swollen, which is considered to originate from the complexation and de-complexation between gelatin and DNA, as was verified by turbidity measurements. Higher contents of DNA result in an increase in the swelling degree, which is presumably due to the easy outward expansion of free DNA moieties. The permeability coefficient, P, for a model molecule, cimetidine, through the semi-IPN hydrogel membranes was determined in pH 1.0 and pH 12.0 buffer solutions. The results show that the permeation of cimetidine is responsive to pH change, and an evident variation in the P values occurs in response to the pH of the media. Copyright © 2004 Society of Chemical Industry
Co-reporter:Bing Xu, Tao Bai, Andrew Sinclair, Wei Wang, Qian Wu, Fei Gao, Huizhen Jia, Shaoyi Jiang, Wenguang Liu
Materials Today Chemistry (October–December 2016) Volumes 1–2() pp:15-22
Publication Date(Web):1 October 2016
DOI:10.1016/j.mtchem.2016.10.002
•A diaminotriazine hydrogen bonding-reinforced conductive hydrogel can be simply prepared by post-coating with polyaniline.•A conductive high-strength hydrogel supports the attachment and proliferation of NSCs.•This conductive hydrogel can modulate the specific differentiation of NSCs under electrical stimulation.Stem-cell-based neural regeneration has received significant attention, as it has potential to restore functionality to diseased or damaged neural tissues that have a limited ability to self-repair or regenerate. Culturing neural stem cells (NSCs) on hydrogel substrates has been shown to facilitate differentiation to neural progenitors, but this has only been achieved on very soft hydrogels, greatly increasing the difficulty of manufacture and limiting their wide applications. Here, we realized the differentiation of NSCs to neural and glial progenitors on high-strength hydrogels. Hydrogen-bonding-strengthened conductive hydrogels (PVV-PANI) were synthesized through one-pot copolymerization of 2-vinyl-4,6-diamino-1,3,5-triazine, 1-vinylimidazole and polyethylene glycol diacrylate, followed by post-coating with polyaniline (PANI). Diaminotriazine-diaminotriazine hydrogen bonding dramatically increases their mechanical strength, while copolymerization with VI pronouncedly promotes the adsorption of PANI particles, endowing the hydrogels with electrical conductivity. These hydrogels exhibit tensile strengths up to 1.16 MPa, a 559% breaking strain, a 9.9 MPa compressive strength and up to 16.7 mS/cm conductivity. Importantly, PVV-PANI hydrogels support the attachment, proliferation, and differentiation of NSCs, and allow the efficient induction of neural and glial differentiation via electrical stimulation. This work demonstrates high-strength conductive hydrogels can serve as an electroactive soft-wet platform for modulating the specific differentiation of NSCs, a significant step towards cell-based therapies for neurological diseases.A conductive high-strength hydrogel supports the attachment and proliferation of NSCs and efficiently induces neuronal differentiation by weak electrical stimulation. This work demonstrates PANI-coated high-strength conductive hydrogels can serve as an electroactive soft-wet platform for modulating the specific differentiation of NSCs to improve therapeutic efficacy of neurological muscular diseases.Download high-res image (265KB)Download full-size image
Co-reporter:Ning Wang, Lei Tang, Wenguang Liu
Nanomedicine: Nanotechnology, Biology and Medicine (February 2016) Volume 12(Issue 2) pp:462
Publication Date(Web):February 2016
DOI:10.1016/j.nano.2015.12.044
Co-reporter:Ning Wang, Lei Tang, Wenguang Liu
Nanomedicine: Nanotechnology, Biology and Medicine (February 2016) Volume 12(Issue 2) pp:462
Publication Date(Web):February 2016
DOI:10.1016/j.nano.2015.12.044
Co-reporter:Rui Bao, Baoyu Tan, Shuang Liang, Ning Zhang, Wei Wang, Wenguang Liu
Biomaterials (April 2017) Volume 122() pp:
Publication Date(Web):April 2017
DOI:10.1016/j.biomaterials.2017.01.012
Previous studies suggested that a stiffer hydrogel system exhibited a better performance to promote heart function after myocardial infarction (MI). However, the nature of myocardium, a tissue that alternately contracts and relaxes with electrical impulses, leads us to hypothesize that a soft and conductive hydrogel may be in favor of mechanical and electrical signals transmission to enhance heart function after MI. In this work, π-π conjugation interaction was first employed to produce a soft injectable hydrogel with conductive property. Melamine with π-π conjugation ring was used as a core to synthesize a multi-armed crosslinker PEGDA700-Melamine (PEG-MEL), which could crosslink with thiol-modified hyaluronic acid (HA-SH) to form an injectable hydrogel rapidly. By incorporating graphene oxide (GO), the injectable PEG-MEL/HA-SH/GO hydrogel exhibited a soft (G’ = 25 Pa) and anti-fatigue mechanical property and conductive property (G = 2.84 × 10−4 S/cm). The hydrogel encapsulating adipose tissue-derived stromal cells (ADSCs) was injected into MI area of rats. The significant increase in α-Smooth Muscle Actin (α-SMA) and Connexin 43 (Cx43) expression confirmed that the gel efficiently promoted the transmission of mechanical and electrical signals. Meanwhile, a significant improvement of heart functions, such as distinct increase of ejection fraction (EF), smaller infarction size, less fibrosis area, and higher vessel density, was achieved.
Co-reporter:Xuran Zhang, Bing Xu, Fei Gao, Pengbin Zheng and Wenguang Liu
Journal of Materials Chemistry A 2017 - vol. 5(Issue 28) pp:NaN5596-5596
Publication Date(Web):2017/06/19
DOI:10.1039/C7TB01279A
Efficient repair of critical-size volumetric bone defects remains a challenge due to the additional complicated surgery required for fixation. In this work, we first synthesized hydrogen bonding crosslinked supramolecular polymer (SP) hydrogels termed as P(NAGA-VPA) by copolymerizing two carefully selected monomers, N-acryloyl glycinamide (hydrogen bonding monomer) and vinylphosphonic acid (mineralization active monomer) directly in a concentrated aqueous solution. The P(NAGA-VPA) hydrogels were then subjected to in situ precipitation mineralization to generate novel high strength mineralized SP hydrogels. The concerted dual physical crosslinkages of NAGA H-bonds and nanocrystal–polymer interaction led to the best comprehensive mechanical performances with a tensile strength of over 1 MPa and a compressive strength of 5 MPa in an equilibrium swelling state. The mineralized SP hydrogel tubular scaffold was fabricated and encapsulated with bone morphogenetic protein-2 (BMP-2). The BMP-2-loaded mineralized SP hydrogel tube was finely sleeved over the murine radial defect without resorting to any additional surgical fixation. The outcome of 8-weeks implantation demonstrated that this hybrid tubular scaffold contributed to an efficient repair of volumetric bone defect by accelerating new bone formation and seamlessly bonding to the bone surface.
Co-reporter:Peng Zhang, Jianhai Yang, Wenchen Li, Wei Wang, Changjun Liu, May Griffith and Wenguang Liu
Journal of Materials Chemistry A 2011 - vol. 21(Issue 21) pp:NaN7764-7764
Publication Date(Web):2011/04/20
DOI:10.1039/C1JM10813A
A novel cationic nanodiamond-polymer brush was synthesized by 2-bromoisobutyrate-modified nanodiamond (ND) surface-initiated atomic transfer radical polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA). Elemental analysis, FTIR, HRTEM, TGA and zeta potential analysis were used to confirm the successful synthesis of ND-polymer brushes. It was shown that the ND-brushes were capable of condensing plasmid DNA into stable nanoparticles, protecting DNA from enzyme degradation. Transfection studies demonstrated that the ND-brushes could not only efficiently deliver plasmids into COS-7 cells, but also mediate higher expression than PEI25k with lower cytotoxicity. The green fluorescence of ND-brushes could also be detected by laser scanning confocal microscopy, making the nanodiamond-polymer brushes an excellent multifunctional gene vector with not only high transfection efficiency but allowing for bioimaging.
Co-reporter:Xinyun Zhai, Wei Wang, Chuandong Wang, Qin Wang and Wenguang Liu
Journal of Materials Chemistry A 2012 - vol. 22(Issue 44) pp:NaN23586-23586
Publication Date(Web):2012/09/27
DOI:10.1039/C2JM35502G
Serum stability is one of the key factors influencing the transfection efficiency of cationic vector-mediated gene delivery in vivo. In this work, we used an atomic transfer radical polymerization (ATRP) method to construct p(2-(dimethylamino) ethyl methacrylate)-b-p(N-(3-(methacryloylamino) propyl)-N,N-dimethyl-N-(3-sulfopropyl) ammonium hydroxide) (PDMAEMA-b-PMPDSAH) diblock copolymer brushes-modified ε-polylysine (ε-Ply-DMA-MPD) non-viral vectors. The agarose gel electrophoresis assay indicated that conjugation of sulfobetaine only slightly decreased the DNA condensation ability of PDMAEMA homopolymer brushes-modified ε-polylysine (ε-Ply-DMA70), but increased the stability of complexes in heparin sodium due to the anti-polyelectrolyte effect of polysulfobetaine. The transfection efficiencies of PEI25K and ε-Ply-DMA70 vectors under the serum conditions from 0% to 50% were shown to decrease dramatically; while ε-Ply-DMA70-MPDp vectors remained more stable for gene transfection in concentrated serum, and the efficiency of ε-Ply-DMA70-MPD20 is more than 10-fold higher than that of PEI25K. PDMAEMA-r-PMPDSAH random copolymer brushes-modified ε-polylysine (ε-Ply-DMA70-r-MPD20) showed no improved serum tolerant gene transfection. The MTT assays revealed that the cytotoxicity of ε-Ply-DMA70-MPDp vectors was much lower than that of ε-Ply-DMA70 due to the shielding of positive charges by polysulfobetaine. The expression of red fluorescence protein (RFP) was evaluated by a small animal in vivo fluorescence imaging system and the results showed that the expression of RFP was much higher in the mice injected with ε-Ply-DMA70-MPD20/pDNA-RFP than with ε-Ply-DMA70/pDNA-RFP.
Co-reporter:Liang Sun, Sijie Zhang, Jinlong Zhang, Ning Wang, Wenguang Liu and Wei Wang
Journal of Materials Chemistry A 2013 - vol. 1(Issue 32) pp:NaN3939-3939
Publication Date(Web):2013/06/04
DOI:10.1039/C3TB20553C
A chemical-crosslinked, biocompatible and injectable hydrogel was formed by Fenton reaction initiated polymerization. The gelation time of N-(2-hydroxyethyl)acrylamide and PEG-diacrylate, which are two representative monomers, was shown to be tunable from instant to 15 min at an H2O2 concentration below several mmol L−1 in neutral medium. The strength of the hydrogel could be regulated by the concentration of the monomer and the Fenton's reagent. The hydrogels prepared by H2O2/Fe2+ initiation showed low cytotoxicity. The bone marrow mesenchymal stem cells and L929 cells encapsulated in the gels exhibited high viability even after 7 days of co-culture. Both the L929 cells encapsulated in situ into the hydrogels and those co-cultured with the hydrogel showed negligible cell death and apoptosis. It is anticipated that the familiar Fenton reaction may act as a new initiator system to fabricate biocompatible injectable hydrogels.
Co-reporter:Yongmao Li, Jianhai Yang, Liang Sun, Wei Wang and Wenguang Liu
Journal of Materials Chemistry A 2014 - vol. 2(Issue 24) pp:NaN3878-3878
Publication Date(Web):2014/04/15
DOI:10.1039/C4TB00294F
This study demonstrates a strategy to enhance gene delivery via photoregulated gene unpacking from its vector. Photoresponsive polycationic vectors composed of a middle azobenzene moiety and two terminal blocks of poly[2-(dimethylamino)ethyl methacrylate], termed as Azo-PDMAEMA, are synthesized using a difunctional azobenzene-based initiator via atomic transfer radiator polymerization (ATRP). The Azo-PDMAEMA exhibits trans to cis isomerization under alternate Vis-UV irradiation, and is capable of condensing plasmid DNA into nanocomplexes. Hydrophobic azobenzene groups in the cationic polymers are shown to enhance the interaction of complexes with the cell membrane, thus improving cell uptake and transfection efficiency. Increased gene expression in COS-7 cells, HepG-2 cells and CHO-K1 cells is achieved after UV irradiation due to UV-triggered intracellular gene unpacking. Time-resolved fluorescence assays further indicate that the trans to cis photoisomerization of Azo-PDMAEMA induces less compacted complexes, contributing to more exposure of genes for transcription.
Co-reporter:Wei Wang, Yongmao Li, Lu Cheng, Zhiqiang Cao and Wenguang Liu
Journal of Materials Chemistry A 2014 - vol. 2(Issue 1) pp:NaN48-48
Publication Date(Web):2013/10/30
DOI:10.1039/C3TB21370F
Water-soluble phosphorus-containing carbon dots (PCDs) with strong green fluorescence were synthesized through a facile one-step microwave assisted approach using phosphorus-rich phytic acid as a carbon source. Owing to their strong green fluorescence and low cytotoxicity, the PCDs are promising as bio-imaging agents.
Co-reporter:Junfei Song, Pengfei Zhang, Lu Cheng, Yue Liao, Bing Xu, Rui Bao, Wei Wang and Wenguang Liu
Journal of Materials Chemistry A 2015 - vol. 3(Issue 20) pp:NaN4241-4241
Publication Date(Web):2015/04/20
DOI:10.1039/C5TB00205B
Nano hybrid materials have attracted extensive attention in the biomedical field. However, it is still a challenge to make biofunctional nanoparticles homogenously distributed in 3D scaffolds. In this research, histidine (His) was covalently cross-linked into collagen (Coll) scaffolds and the imidazole derived from His was employed as a template to chelate silver ions which were then reduced in situ to form silver nanoparticle (Ag NP)–hybridized Coll scaffolds. The resultant nanocomposite demonstrated an increased mechanical strength and the Ag NPs showed a narrow size distribution and were dispersed homogeneously in the 3D Coll/His scaffolds. Moreover, these hybrid scaffolds exhibited better biocompatibility and antibacterial properties against both Gram positive and Gram negative bacteria than Coll scaffolds. The Coll/His/Ag NPs scaffolds were transplanted to the infected full-thickness burn skin of the SD rat model; the results revealed excellent regeneration effects after three weeks compared with the groups not treated with Ag NPs. This study has offered a facile method to construct functional nanoparticle hybridized scaffolds for efficiently healing infected wounds.
Co-reporter:Peng Zhang, Wenchen Li, Xinyun Zhai, Changjun Liu, Liming Dai and Wenguang Liu
Chemical Communications 2012 - vol. 48(Issue 84) pp:NaN10433-10433
Publication Date(Web):2012/09/04
DOI:10.1039/C2CC35966A
Highly fluorescent polymerizable carbon nanodots (PCNDs), synthesized by microwave assisted pyrolysis and subsequent surface vinylation, were copolymerized with several model monomers to form different functional fluorescent polymeric materials in solution or the solid-state, indicating a simple and versatile approach to novel fluorescent polymer materials.
Co-reporter:Xinyun Zhai, Peng Zhang, Changjun Liu, Tao Bai, Wenchen Li, Liming Dai and Wenguang Liu
Chemical Communications 2012 - vol. 48(Issue 64) pp:NaN7957-7957
Publication Date(Web):2012/06/21
DOI:10.1039/C2CC33869F
Carbon nanodots (CDs) with a low cytotoxicity have been synthesized by one-step microwave-assisted pyrolysis of citric acid in the presence of various amine molecules. The primary amine molecules have been confirmed to serve dual roles as N-doping precursors and surface passivation agents, both of which considerably enhanced the fluorescence of the CDs.
Co-reporter:Xiaohuan Shi, Haijun Gao, Fengying Dai, Xuequan Feng and Wenguang Liu
Biomaterials Science (2013-Present) 2016 - vol. 4(Issue 11) pp:NaN1681-1681
Publication Date(Web):2016/09/29
DOI:10.1039/C6BM00597G
Our team has previously reported a high strength thermoplastic supramolecular polymer hydrogel. However, the hydrogel required injection temperatures outside the physiological range therefore preventing its use in a living environment. In this article, we reported a thermoresponsive supramolecular copolymer hydrogel p(N-acryloyl glycinamide-co-acrylamide) (PNAGA-PAAm), which can be injected at temperatures within the physiological range. We used rheological measurements to demonstrate that the transition temperature (upper critical solution temperature) of both the moduli and gel–sol could be finely adjusted by controlling both the ratio and concentration of the monomer. Adding iohexol (contrast agent) in PNAGA-PAAm hydrogels contributed to the decreased moduli and gel–sol transition temperature due to weakening of the hydrogen bonding interactions. The cytocompatible and hemocompatible PNAGA-PAAm sol mixed with iohexol was injected into the renal arteries of rabbits through a microcatheter at a temperature within the high biological range. The transition from the injection temperature (high biological range) to body temperature (basal for the animals) quickly solidified the embolic agent without the occurrence of dehydration, therefore overcoming the main limitation of LCST-typed poly(N-isopropylacrylamide) previously reported. Angiography and histological examination demonstrated the successful embolization of both renal arteries and no recanalization was observed after 8 weeks. The PNAGA-based supramolecular copolymer hydrogel is a novel embolic agent that allows for the occlusion of larger sized arteries in a biocompatible environment.
Co-reporter:Wei Wang, Yongmao Li, Lu Cheng, Zhiqiang Cao and Wenguang Liu
Journal of Materials Chemistry A 2015 - vol. 3(Issue 16) pp:NaN3392-3392
Publication Date(Web):2015/03/23
DOI:10.1039/C5TB90055G
Correction for ‘Water-soluble and phosphorus-containing carbon dots with strong green fluorescence for cell labeling' by Wei Wang et al., J. Mater. Chem. B, 2014, 2, 46–48.
Co-reporter:Zongqing Ren, Yinyu Zhang, Yongmao Li, Bing Xu and Wenguang Liu
Journal of Materials Chemistry A 2015 - vol. 3(Issue 30) pp:NaN6354-6354
Publication Date(Web):2015/07/02
DOI:10.1039/C5TB00781J
A hydrogen bonded and calcium ion crosslinked hydrogel, termed PVDT-PAA, was synthesized by one-step photo-polymerization of 2-vinyl-4,6-diamino-1,3,5-triazine (VDT), acrylic acid (AA), and polyethylene glycol diacrylate (PEGDA, Mn = 4000). Combined physical crosslinking from inter-diaminotriazine and coordination of Ca2+ with carboxyls contributed to a significant enhancement in the mechanical properties of the PVDT-PAA hydrogels. Furthermore, reversible Ca2+ crosslinking imparted shape memory properties to the hydrogel allowing it to firmly memorize multiform shapes and return to its initial state in response to Ca2+. Interestingly, PVDT-PAA hydrogels with weaker H-bonding interactions demonstrated a sharp volume change phenomenon induced by Ca2+. This volume change could be utilized to trigger unharmful cell detachment from the hydrogel surface, which was thought to be due to Ca2+-induced marked variation in mechanotransduction between the cells and the substrate interface. This H-bonding and ionic crosslinking strategy opens up a new opportunity for designing and constructing multifunctional high strength hydrogels for biomedical applications.
Co-reporter:Hongbo Wang, Jianhai Yang, Yongmao Li, Liang Sun and Wenguang Liu
Journal of Materials Chemistry A 2013 - vol. 1(Issue 1) pp:NaN51-51
Publication Date(Web):2012/10/24
DOI:10.1039/C2TB00203E
Monodisperse magnetic nanoparticles (MNPs) were prepared through an organic phase process, and the obtained MNPs were capped with poly[2-(2-methoxyethoxy)ethyl methacrylate]-b-poly[2-(dimethylamino)ethyl methacrylate] synthesized by surface-initiated atom transfer radical polymerization (ATRP). The MNPs-polymer brushes exhibited both superparamagnetic and thermoresponsive behaviors, and could condense plasmid DNA into nanocomplexes with a size of 100–120 nm at appropriate complexing ratios. Enhanced gene expression in COS-7 cells and HepG-2 cells was achieved under a magnetic field and variable temperature conditions due to magnetic force-facilitated internalization of nanocomplexes, and temporary cooling-triggered intracellular gene unpacking. Amazingly, combining magnetic field and temperature dual stimuli contributed to a 50–100- and 25–45-fold increase of the transfection efficiency in HepG-2 cells compared to conventional protocol and PEI25k, respectively.
Co-reporter:Yuan Liu, Jianhai Yang, Peng Zhang, Changjun Liu, Wei Wang and Wenguang Liu
Journal of Materials Chemistry A 2012 - vol. 22(Issue 2) pp:NaN519-519
Publication Date(Web):2011/10/31
DOI:10.1039/C1JM13063C
A collagen/poly(2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt) (collagen/PNaAMPS) interpenetrating polymer network (IPN) hydrogel was prepared by simultaneous reaction of EDC/NHS-mediated crosslinking of concentrated collagen solution and poly(ethylene glycol) diacrylate crosslinking NaAMPS in a sealed syringe. The collagen/PNaAMPS hydrogels were freeze-dried and immersed in an aqueous solution of PDMAEMA-capped ZnO quantum dots (QDs) to construct a ZnO QDs-laden collagen/PNaAMPS IPN hydrogel. The composite hydrogel containing nearly 90% water exhibited light transmission from 85% to 96%. Introducing the PNaAMPS network considerably improved the mechanical strength of the pristine collagen gel, whereas loading ZnO QDs only slightly affected the optical properties, mechanical properties and water absorption. Strikingly, the loaded ZnO QDs were found to serve dual roles – tracking the degradation of collagen by observing directly the reduction of fluorescence intensity in hydrogels; and as a collagenase inhibitor by the proposed interaction with metalloenzyme, an important characteristic which could be used to prolong the degradation time of pure collagen without physical screening of the IPN network. We also demonstrated that anionic PNaAMPS was able to dampen the cytotoxicity of composite hydrogels by neutralizing positive charges of ZnO QDs. The composite hydrogels carrying rabbit corneal anterior stromal fibroblasts and PolyJet™/DNA complexes could achieve the efficient expression of luciferase and EGFP genes. The model composite hydrogels offer an approach to design a novel corneal substitute with integrated functions of real-time degradation tracking, degradation inhibition and gene delivery for the specific treatment of ophthalmic diseases.
Co-reporter:Changjun Liu, Peng Zhang, Feng Tian, Wenchen Li, Fan Li and Wenguang Liu
Journal of Materials Chemistry A 2011 - vol. 21(Issue 35) pp:NaN13167-13167
Publication Date(Web):2011/08/08
DOI:10.1039/C1JM12744F
Strong photoluminescent carbon nanodots (C-dots) were synthesized by one-step microwave assisted pyrolysis of glycerol in the presence of 4,7,10-trioxa-1,13-tridecanediamine (TTDDA). The formation and surface passivation of C-dots were accomplished simultaneously. The obtained C-dots exhibited excellent biocompatibility and preeminent multicolor photoluminescent properties for bioimaging.
![Pentacyclo[9.5.1.13,9.15,15.17,13]octasiloxane, 1,3,5,7,9,11,13,15-octakis(3-chloropropyl)-](/data/chemimg/130100/161678-38-2.png)
![Pentacyclo[9.5.1.13,9.15,15.17,13]octasiloxane, 1,3,5,7,9,11,13,15-octakis(3-chloropropyl)-](/data/chemimg/130100/161678-38-2_b.png)
