Co-reporter:Ershuai Zhang, Junjie Li, Yuhang Zhou, Pengcheng Che, ... Fanglian Yao
Acta Biomaterialia 2017 Volume 55(Volume 55) pp:
Publication Date(Web):1 June 2017
DOI:10.1016/j.actbio.2017.04.003
Peritoneal adhesion is very common after abdominal and pelvic surgery, which leads to a variety of severe complications. Although numerous pharmacological treatments and barrier-based devices have been investigated to minimize or prevent postoperative adhesion, the clinical efficacy is not very encouraging. In this work, a biodegradable and thermoreversible galactose modified xyloglucan (mXG) hydrogel was developed and the efficacy of mXG hydrogel in preventing postoperative peritoneal adhesion was investigated. The 4% (w/v) mXG solution was a free flowing sol at low temperature, but could rapidly convert into a physical hydrogel at body temperature without any extra additives or chemical reactions. In vitro cell tests showed that mXG hydrogel was non-toxic and could effectively resist the adhesion of fibroblasts. Moreover, in vitro and in vivo degradation experiments exhibited that mXG hydrogel was degradable and biocompatible. Finally, the rat model of sidewall defect-cecum abrasion was employed to evaluate the anti-adhesion efficacy of the mXG hydrogel. The results demonstrated that mXG hydrogel could effectively prevent postoperative peritoneal adhesion without side effects. The combination of suitable gel temperature, appropriate biodegradation period, and excellent postoperative anti-adhesion efficacy make mXG hydrogel a promising candidate for the prevention of postsurgical peritoneal adhesion.Statement of significanceDespite numerous drugs or barrier-based devices have been developed to prevent postoperative adhesion, few solutions have proven to be uniformly effective in subsequent clinical trials. In the present study, we developed a biodegradable and thermoreversible galactose modified xyloglucan (mXG) hydrogel by green enzymatic reaction without using any organic reagents. The developed physical mXG hydrogel not only showed excellent injectability, appropriate gelation time and temperature, but also exhibited excellent biocompatibility and biodegradability both in vitro and in vivo. In addition, mXG hydrogel was easy to handle and could effectively prevent postoperative adhesion without side effects in a rat model of sidewall defect-bowel abrasion. Our study provide a safe and effective postoperative anti-adhesion material which may have potential applications in clinical practice.Download high-res image (133KB)Download full-size image
Co-reporter:Yuhang Zhou, Junjie Li, Ying Zhang, Dianyu Dong, Ershuai Zhang, Feng Ji, Zhihui Qin, Jun Yang, and Fanglian Yao
The Journal of Physical Chemistry B 2017 Volume 121(Issue 4) pp:
Publication Date(Web):January 6, 2017
DOI:10.1021/acs.jpcb.6b10355
Prediction of the diffusion coefficient of solute, especially bioactive molecules, in hydrogel is significant in the biomedical field. Considering the randomness of solute movement in a hydrogel network, a physical diffusion RMP-1 model based on obstruction theory was established in this study. The physical properties of the solute and the polymer chain and their interactions were introduced into this model. Furthermore, models RMP-2 and RMP-3 were established to understand and predict the diffusion behaviors of proteins in hydrogel. In addition, zwitterionic poly(sulfobetaine methacrylate) (PSBMA) hydrogels with wide range and fine adjustable mesh sizes were prepared and used as efficient experimental platforms for model validation. The Flory characteristic ratios, Flory–Huggins parameter, mesh size, and polymer chain radii of PSBMA hydrogels were determined. The diffusion coefficients of the proteins (bovine serum albumin, immunoglobulin G, and lysozyme) in PSBMA hydrogels were studied by the fluorescence recovery after photobleaching technique. The measured diffusion coefficients were compared with the predictions of obstruction models, and it was found that our model presented an excellent predictive ability. Furthermore, the assessment of our model revealed that protein diffusion in PSBMA hydrogel would be affected by the physical properties of the protein and the PSBMA network. It was also confirmed that the diffusion behaviors of protein in zwitterionic hydrogels can be adjusted by changing the cross-linking density of the hydrogel and the ionic strength of the swelling medium. Our model is expected to possess accurate predictive ability for the diffusion coefficient of solute in hydrogel, which will be widely used in the biomedical field.
Co-reporter:Rui Niu;Zhihui Qin;Feng Ji;Meng Xu;Xinlu Tian;Junjie Li
Soft Matter (2005-Present) 2017 vol. 13(Issue 48) pp:9237-9245
Publication Date(Web):2017/12/13
DOI:10.1039/C7SM02005H
The lack of sufficient mechanical properties restricts the application of polysaccharide-based hydrogels in the field of biomedicine, especially load-bearing tissue repair. Nowadays, double network (DN) hydrogels have aroused great interest through special cooperation between two contrasting networks. Inspired by this idea, here, we devised a new strategy to prepare a pectin–Fe3+/polyacrylamide hybrid DN hydrogel using a simple two-step method. The introduction of Fe3+ ions into a pectin network to produce strong reversible ionic complexation, results in excellent toughness. Under optimal conditions, our hybrid DN hydrogels possessed tensile strength as high as 0.9 MPa, corresponding to a high strain of 1300%. Besides, our hybrid DN hydrogels also exhibited superb stiffness (elastic modulus ∼ 1.46 MPa), toughness (fracture energy ∼ 3785 J m−2), and water absorption capacity (85%). Loading–unloading tests showed that the internal fracture process of the hydrogels was continuous. Owing to the reversible structure of Fe3+–pectin complexation, the hybrid DN hydrogels also showed good fatigue resistance, notch-insensitivity and recoverability. This type of polysaccharide-based hydrogel has potential to broaden the application in the load-bearing tissue repair field.
Co-reporter:Lei Ye, Yabin Zhang, Qiangsong Wang, Xin Zhou, Boguang Yang, Feng Ji, Dianyu Dong, Lina Gao, Yuanlu Cui, and Fanglian Yao
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 24) pp:15710-15723
Publication Date(Web):June 1, 2016
DOI:10.1021/acsami.6b03098
In this work, a novel starch-based zwitterionic copolymer, starch-graft-poly(sulfobetaine methacrylate) (ST-g-PSBMA), was synthesized via Atom Transfer Radical Polymerization. Starch, which formed the main chain, can be degraded completely in vivo, and the pendent segments of PSBMA endowed the copolymer with excellent protein resistance properties. This ST-g-PSBMA copolymer could self-assemble into a physical hydrogel in normal saline, and studies of the formation mechanism indicated that the generation of the physical hydrogel was driven by electrostatic interactions between PSBMA segments. The obtained hydrogels were subjected to detailed analysis by scanning electron microscopy, swelling ratio, protein resistance, and rheology tests. Toxicity and hemolysis analysis demonstrated that the ST-g-PSBMA hydrogels possess excellent biocompatibility and hemocompatibility. Moreover, the cytokine secretion assays (IL-6, TNF-α, and NO) confirmed that ST-g-PSBMA hydrogels had low potential to trigger the activation of macrophages and were suitable for in vivo biomedical applications. On the basis of these in vitro results, the ST-g-PSBMA hydrogels were implanted in SD rats. The tissue responses to hydrogel implantation and the hydrogel degradation in vivo were determined by histological analysis (Hematoxylin and eosin, Van Gieson, and Masson’s Trichrome stains). The results presented in this study demonstrate that the physical cross-linking, starch-based zwitterionic hydrogels possess excellent protein resistance, low macrophage-activation properties, and good biocompatibility, and they are a promising candidate for an in vivo biomedical application platform.
Co-reporter:Dianyu Dong, Junjie Li, Man Cui, Jinmei Wang, Yuhang Zhou, Liu Luo, Yufei Wei, Lei Ye, Hong Sun, and Fanglian Yao
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 7) pp:4442
Publication Date(Web):January 28, 2016
DOI:10.1021/acsami.5b12141
Three-dimensional (3D) cell encapsulation in hydrogel provides superb methods to investigate the biochemical cues in directing cellular fate and behaviors outside the organism, the primary step of which is to establish suitable “blank platform” to mimic and simplify native ECM microenvironment. In this study, zwitterionic starch-based “clickable” hydrogels were fabricated via a “copper- and light- free” Michael-type “thiol–ene” addition reaction between acylated-modified sulfobetaine-derived starch (SB-ST-A) and dithiol-functionalized poly(ethylene glycol) (PEG-SH). By incorporating antifouling SB-ST and PEG, the hydrogel system would be excellently protected from nontarget protein adsorption to act as a “blank platform”. The hydrogels could rapidly gel under physiological conditions in less than 7 min. Dynamic rheology experiments suggested the stiffness of the hydrogel was close to the native tissues, and the mechanical properties as well as the gelation times and swelling behaviors could be easily tuned by varying the precursor proportions. The protein and cell adhesion assays demonstrated that the hydrogel surface could effectively resist nonspecific protein and cell adhesion. The degradation study in vitro confirmed that the hydrogel was biodegradable. A549 cells encapsulated in the hydrogel maintained high viability (up to 93%) and started to proliferate in number and extend in morphology after 2 days’ culture. These results indicated the hydrogel presented here could be a potential candidate as “blank platform” for 3D cell encapsulation and biochemical cues induced cellular behavior investigation in vitro.Keywords: 3D cell encapsulation; blank platform; ECM; hydrogel; “thiol−ene” click chemistry
Co-reporter:Lei Ye, Yabin Zhang, Boguang Yang, Xin Zhou, Junjie Li, Zhihui Qin, Dianyu Dong, Yuanlu Cui, and Fanglian Yao
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 7) pp:4385
Publication Date(Web):February 2, 2016
DOI:10.1021/acsami.5b10811
Over the last few decades, nanoparticles have been emerging as useful means to improve the therapeutic efficacy of drug delivery and medical diagnoses. However, the heterogeneity and complexity of blood as a medium is a fundamental problem; large amounts of protein can be adsorbed onto the surface of nanoparticles and cause their rapid clearance before reaching their target sites, resulting in the failure of drug delivery. To overcome this challenge, we present a rationally designed starch derivative (SB-ST-OC) with both a superhydrophilic moiety of zwitterionic sulfobetaine (SB) and a hydrophobic segment of octane (OC) as functional groups, which can self-assemble into “stealth” micelles (SSO micelles). The superhydrophilic SB kept the micelles stable against aggregation in complex media and imbued them with “stealth” properties, eventually extending their circulation time in blood. In stability and hemolysis tests the SSO micelles showed excellent protein resistance properties and hemocompatibility. Moreover, a phagocytosis test and cytokine secretion assay confirmed that the SSO micelles had less potential to trigger the activation of macrophages and were more suitable as a drug delivery candidate in vivo. On the basis of these results, doxorubicin (DOX), a hydrophobic drug, was used to investigate the potential application of this novel starch derivative in vivo. The results of the pharmacokinetic study showed that the values of the plasma area under the concentration curve (AUC) and elimination half-life (T1/2) of the SSO micelles were higher than those of micelles without SB modifications. In conclusion, the combination of excellent protein resistance, lower macrophage activation, and longer circulation time in vivo makes this synthesized novel starch derivative a promising candidate as a hydrophobic drug carrier for long-term circulation in vivo.Keywords: drug release; long-term circulation; micelle; starch; zwitterionic
Co-reporter:Wancai Fang, Hong Zhang, Jianwei Yin, Boguang Yang, Yabin Zhang, Junjie Li, and Fanglian Yao
Crystal Growth & Design 2016 Volume 16(Issue 3) pp:1247
Publication Date(Web):January 31, 2016
DOI:10.1021/acs.cgd.5b01235
Natural polysaccharides play an important role in the formation of nanohydroxyapatite (nHA) crystals in biological systems. In this study, we synthesized nHA crystals in the presence of four polysaccharides, i.e., pectin, carrageenan, chitosan, and amylose, referred as PeHA, CaHA, CsHA, and AmHA, respectively. X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, scanning electron microscope, and thermogravimetric analysis were used to investigate the formation of nHA crystals. The shape of prepared nHA crystals is needle/rod-like in all cases, whereas the size increases in the order of PeHA, CaHA, CsHA, and AmHA. The presence of polysaccharides induces the heterogeneous nucleation of nHA and further modulates the crystal growth. Our data suggest that the interaction intensity between nHA and polysaccharides is in the decreasing order of PeHA, CaHA, CsHA, and AmHA, resulting in the smallest nHA crystals with pectin. It is also demonstrated that a high polysaccharide concentration and short reaction time are adverse to nHA crystals, especially for the polysaccharides with carboxyl groups. This study can provide insight into the effects of polysaccharides with different chemical functional groups (−COOH, −OSO3H, −NH2, −OH) on the formation of nHA crystals.
Co-reporter:Yan Wang, Lina Li, Junjie Li, Boguang Yang, Changyong Wang, Wancai Fang, Feng Ji, Yan Wen and Fanglian Yao
RSC Advances 2016 vol. 6(Issue 21) pp:17728-17739
Publication Date(Web):28 Jan 2016
DOI:10.1039/C5RA25505H
To improve the circulation stability of polyamidoamine (PAMAM) based drug delivery systems in complex biological microenvironments, a series of generation-3.0 PAMAM-graft-poly[3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate] (PAMAM3.0-g-PDMAPS) copolymers are synthesized via atom transfer radical polymerization. The zwitterionic PDMAPS segments serve as a shell to stabilize the unimolecular micelles, whereas the PAMAM3.0 dendrimers constitute a hydrophobic core. The sizes of the PAMAM3.0-g-PDMAPS unimolecular micelles range from 6.5 to 8.5 nm. Furthermore, PAMAM3.0-g-PDMAPS can keep the micelle-like structure when it is diluted by large volumes of fluids. More importantly, the PDMAPS shell layer can suppress non-specific protein adsorption on the surface of the micelles. The excellent stability to dilution and anti-biofouling are beneficial for prolonged circulation time in a complex biological microenvironment. In addition, anticancer doxorubicin (DOX) can be encapsulated both in the PAMAM3.0 core via hydrophobic interactions and the PDMAPS shell layer via hydrogen bonds. Drug release studies confirm the pH-responsive nature of PMAMA3.0-g-PDMAPS micelles by achieving 65.23% DOX release at pH 5.1 as compared to 16.38% at pH 7.4. Based on these results, the cytotoxicity and anticancer effects against human hepatocellular carcinoma cells (HepG2) of the PAMAM3.0-g-PDMAPS system loaded with DOX are investigated. The results suggest that the PDMAPS shell layer can significantly decrease the cytotoxicity via decreasing/shielding of the positive charges on the PAMAM dendrimers. After internalization by HepG2 cells, DOX is released from the micelles to the nucleus and further inhibits the proliferation of HepG2. Therefore, these PAMAM3.0-g-PDMAPS unimolecular micelles are a potential platform for anticancer drug delivery.
Co-reporter:Ershuai Zhang, Chuanshun Zhu, Jun Yang, Hong Sun, Xiaomin Zhang, Suhua Li, Yonglan Wang, Lu Sun, Fanglian Yao
Materials Science and Engineering: C 2016 Volume 58() pp:278-285
Publication Date(Web):1 January 2016
DOI:10.1016/j.msec.2015.08.032
•PDLLA/PLGA composite membranes were obtained by electrospinning at high flow rates.•The degradation rate of composite membranes increased with increasing PLGA content.•The composite membranes showed excellent cell-occlusiveness in vitro.•PDLLA/PLGA (50/50) composite membranes could prevent cellular infiltration in vivo.With the aim to explore a membrane system with appropriate degradation rate and excellent cell-occlusiveness for guided tissue regeneration (GTR), a series of poly(d, l-lactic acid) (PDLLA)/poly(d, l-lactic-co-glycolic acid) (PLGA) (100/0, 70/30, 50/50, 30/70, 0/100, w/w) composite membranes were fabricated via electrospinning. The fabricated membranes were evaluated by morphological characterization, water contact angle measurement and tensile test. In vitro degradation was characterized in terms of the weight loss and the morphological change. Moreover, in vitro cytologic research revealed that PDLLA/PLGA composite membranes could efficiently inhibit the infiltration of 293T cells. Finally, subcutaneous implant test on SD rat in vivo showed that PDLLA/PLGA (70/30, 50/50) composite membranes could function well as a physical barrier to prevent cellular infiltration within 13 weeks. These results suggested that electrospun PDLLA/PLGA (50/50) composite membranes could serve as a promising barrier membrane for guided tissue regeneration due to suitable biodegradability, preferable mechanical properties and excellent cellular shielding effects.
Co-reporter:Yabin Zhang, Lei Ye, Jing Cui, Boguang Yang, Hong Sun, Junjie Li, and Fanglian Yao
ACS Biomaterials Science & Engineering 2016 Volume 2(Issue 4) pp:544
Publication Date(Web):March 22, 2016
DOI:10.1021/acsbiomaterials.5b00535
In general, the design of a scaffold should imitate certain advantageous properties of native extracellular matrix (ECM) to operate as a temporary ECM for cells. From this perspective, a biomimetic scaffold was prepared using poly(vinyl alcohol) and carrageenan in which axially oriented pore structure can be formed through a facile unidirectional freeze–thaw method. We examined the feasibility of this oriented scaffold, which has better physicochemical properties than a non-oriented scaffold fabricated by the conventional method. The microenvironment of this oriented scaffold could imitate biochemical and physical cues of natural cartilage ECM for guiding spatial organization and proliferation of cells in vitro, indicating its potential in cartilage repair strategy. Furthermore, the biocompatibility of the scaffold in vivo was demonstrated in a subcutaneous rat model, which revealed uniform infiltration and survival of newly formed tissue into the oriented scaffold after 4 weeks with only a minimal inflammatory response being observed over the course of the experiments. These results together indicated that the present biomimetic scaffold with oriented microarchitecture could be a promising candidate for cartilage tissue engineering.Keywords: carrageenan; oriented scaffold; poly(vinyl alcohol); tissue engineering
Co-reporter:Boguang Yang, Changyong Wang, Yabin Zhang, Lei Ye, Yufeng Qian, Yao Shu, Jinmei Wang, Junjie Li and Fanglian Yao
Polymer Chemistry 2015 vol. 6(Issue 18) pp:3431-3442
Publication Date(Web):17 Mar 2015
DOI:10.1039/C5PY00123D
Non-specific protein adsorption adversely affects the application of thermoresponsive polymers in the biomedical field. To overcome this disadvantage, thermoresponsive N-vinylcaprolactam (VCL) and anti-biofouling zwitterionic sulfobetaine methacrylate (SBMA) monomers with various VCL/SBMA ratios were used for the synthesis of poly(VCL-co-SBMA) (P(VCL-co-SBMA)) copolymers via free radical solution polymerization. The P(VCL-co-SBMA) copolymers exhibited both a lower critical solution temperature (LCST) and an upper critical solution temperature (UCST) in aqueous solutions. Furthermore, both the UCST and LCST of the copolymer shift to higher temperatures with the increase of PSBMA segments, and they shift to lower temperatures with the increase of salt concentrations in the solution. Based on these results, P(VCL-co-SBMA) hydrogels were prepared using N,N′-methylenebisacrylamide (MBAA) as the crosslinker. Compared with the PVCL hydrogel, the P(VCL-co-SBMA) hydrogels exhibit better mechanical properties. Notably, the P(VCL-co-SBMA) hydrogel retained the temperature sensitivity of PVCL, and it could be modulated by varying the PVCL/PSBMA segment ratios. In addition, all the hydrogels exhibit good cytocompatibility. More importantly, the protein adsorption and cell adhesion of the hydrogel can be controlled by temperature. The non-specific protein adsorption was effectively suppressed at physiological temperatures. The switchable anti-biofouling nature of P(VCL-co-SBMA) hydrogel together with their temperature sensitivity can be potentially used in drug, cell or enzyme delivery.
Co-reporter:Jinmei Wang, Hong Sun, Junjie Li, Dianyu Dong, Yabin Zhang, Fanglian Yao
Carbohydrate Polymers 2015 Volume 117() pp:384-391
Publication Date(Web):6 March 2015
DOI:10.1016/j.carbpol.2014.09.077
•Three ionic starch-based hydrogels were synthesized.•The C-Starch hydrogel had low protein resistance at all ionic strengths.•The A-Starch hydrogel resisted protein adsorption at certain ionic strengths.•The Z-Starch hydrogel resisted protein adsorption at all ionic strengths.•The A- and Z-Starch hydrogels both resisted cell adhesion.Non-fouling materials bind water molecules via either hydrogen bonding or ionic solvation to form a hydration layer which is responsible for their resistance to protein adsorption. Three ionic starch-based polymers, namely a cationic starch (C-Starch), an anionic starch (A-Starch) and a zwitterionic starch (Z-Starch), were synthesized via etherification reactions to incorporate both hydrogen bonding and ionic solvation hydration groups into one molecule. Further, C-, A- and Z-Starch hydrogels were prepared via chemical crosslinking. The non-fouling properties of these hydrogels were tested with different proteins in solutions with different ionic strengths. The C-Starch hydrogel had low protein resistance at all ionic strengths; the A-Starch hydrogel resisted protein adsorption at ionic strengths of more than 10 mM; and the Z-Starch hydrogel resisted protein adsorption at all ionic strengths. In addition, the A- and Z-Starch hydrogels both resisted cell adhesion. This work provides a new path for developing non-fouling materials using the integration of polysaccharides with anionic or zwitterionic moieties to regulate the protein resistance of materials.
Co-reporter:Yabin Zhang, Lei Ye, Man Cui, Boguang Yang, Junjie Li, Hong Sun and Fanglian Yao
RSC Advances 2015 vol. 5(Issue 95) pp:78180-78191
Publication Date(Web):09 Sep 2015
DOI:10.1039/C5RA11331H
Poly(vinyl alcohol) (PVA) hydrogels have gained comprehensive attention in the biomedical area. However, their resistance to cell adhesion is a drawback for applications such as tissue engineering. Besides, the controllability of the porous structure of PVA-based hydrogels during lyophilization needs to be further improved. Herein, we prepared PVA–carrageenan (CAR) composite hydrogels as tissue engineering scaffolds using the freeze–thaw technique. The hydrogels were found to possess deformation resistance, preserving their shape during the lyophilization process without shrinkage. Besides, ATDC5 cells showed good adherence and proliferation activity on the composite hydrogels. In addition, the PVA–CAR composite hydrogels possess good hemocompatibility and did not cause any adverse effects in the inflammatory response from RAW 264.7 macrophage cells. Overall, the results obtained indicate that the PVA–CAR composite hydrogels show potential applications in the field of tissue engineering based on their good structural stability, excellent biocompatibility and mild fabrication process.
Co-reporter:Junjie Li, Shuangzhuang Guo, Min Wang, Lei Ye and Fanglian Yao
RSC Advances 2015 vol. 5(Issue 25) pp:19484-19492
Publication Date(Web):11 Feb 2015
DOI:10.1039/C4RA14376K
To improve the stability of micelles and decrease the burst release behaviours of hydrophobic drugs, poly(lactic acid)/poly(ethylene glycol) (PLA/PEG) block copolymer based shell or core cross-linked micelles are successfully fabricated. First, PLA–PEG diblock and PLA–PEG–PLA triblock copolymers terminated with acryloyl end groups are synthesized and characterized by 1H NMR and Fourier Transform Infrared (FTIR). These PLA/PEG block copolymers can spontaneously form micelles, exposing hydrophilic PEG segments outside while hiding hydrophobic PLA segments inside the micelles. The methacryloyl groups, exposed on the outer of shell in the PLA–PEG methacrylate copolymer micelles, are copolymerized with N-vinylpyrrolidone and lead to the formation of shell cross-linked (SCL) micelles. On the contrary, the core cross-linked (CCL) micelles are fabricated through the photo-crosslinking reaction of acryloyl end groups inside the core of PLA–PEG–PLA diacrylate copolymer micelles using poly(ethylene glycol) diacrylate as cross-linker. TEM and DLS are used to investigate the morphology and size of SCL and CCL micelles. Results suggest that the size of these micelles depends on the length of PLA segments in the PLA/PEG diblock micelles and the cross-linking degree. Besides, the shell cross-linking increases the size of the micelles, while the core cross-linking decreases the size of the micelles. Notably, both SCL and CCL micelles retain higher stability than that of uncross-linked micelles. Based on these results, hydrophobic tetrandrine (TED), as the model drug, is used to evaluate the controlled release behaviours of SCL or CCL micelles. Results show that both SCL and CCL micelles can decrease the burst release phenomenon in the initial period. The release performance can be controlled via changing the length of PLA segments in the copolymers. It is indicated that these SCL or CCL micelles are useful for a hydrophobic drug-carrier system.
Co-reporter:Yan Wen, Fanglian Yao, Fang Sun, Zhilei Tan, Liang Tian, Lei Xie, Qingchao Song
Materials Science and Engineering: C 2015 Volume 48() pp:220-227
Publication Date(Web):1 March 2015
DOI:10.1016/j.msec.2014.11.066
•The nanoparticles exerted antibacterial activity in a sequent event-driven manner.•Electrostatic interaction and surface adsorption shared roles in antibacterial mode.•The two factors were controlled by the compacted conformation of nanoparticles.The action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles (CM-HTCC/PAMAM) against Escherichia coli (E. coli) was investigated via a combination of approaches including measurements of cell membrane integrity, outer membrane (OM) and inner membrane (IM) permeability, and scanning electron microscopy (SEM). CM-HTCC/PAMAM dendrimer nanoparticles likely acted in a sequent event-driven mechanism, beginning with the binding of positively charged groups from nanoparticle surface with negative cell surface, thereby causing the disorganization of cell membrane, and subsequent leakage of intracellular components which might ultimately lead to cell death. Moreover, the chain conformation of polymers was taken into account for a better understanding of the antibacterial action mode by means of viscosity and GPC measurements. High utilization ratio of positive charge and large specific surface area generated from a compacted conformation of CM-HTCC/PAMAM, significantly different from the extended conformation of HTCC, were proposed to be involved in the antibacterial action.
Co-reporter:Junjie Li;Boguang Yang;Yufeng Qian;Qiyu Wang;Ruijin Han;Tong Hao;Yao Shu;Yabin Zhang;Changyong Wang
Journal of Biomedical Materials Research Part B: Applied Biomaterials 2015 Volume 103( Issue 7) pp:1498-1510
Publication Date(Web):
DOI:10.1002/jbm.b.33339
Abstract
In this study, we have developed ι-carrageenan/chitosan/gelatin (CCG) scaffold containing multiple functional groups (-NH2, -OH, -COOH, and –SO3H) to resemble the native extracellular matrix (ECM), using the ion-shielding technology and ultrasonic dispersion method. Fourier transform infrared spectroscopy (FTIR) of the CCG scaffolds suggests that the formation of CCG network involves electrostatic interactions between ι-carrageenan (ι-CA) and chitosan/gelatin, and the covalent cross-linking among amino groups of chitosan and/or gelatin. Scanning electron microscopic (SEM) observation reveals that the porous structure of scaffolds can be modulated by the ratio of ι-CA to chitosan/gelatin. The swelling ratio of the hydrogels increases as the ι-CA contents increase. Using differential scanning calorimetry, we found that the double helix structure of ι-CA is only stabilized at low contents of ι-CA in the CCG scaffolds (e.g., 5 wt %). The scaffolds containing 5% ι-CA showed the best protein adsorption capacity (4.46 ± 0.63 μg protein/mg scaffold) and elastic modulus (5.37 ± 1.03 MPa). In addition, the CCG scaffolds exhibit excellent support for adipose-derived mesenchymal stem cells (ADMSCs) attachment and proliferation, and they can improve the osteogenic differentiation and neovascularization capacities of ADMSCs. Overall, we conclude that the CCG may represent an ideal scaffold material for bone tissue engineering. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1498–1510, 2015.
Co-reporter:Xiaoyang Zhang, Jun Zhao, Yan Wen, Chuanshun Zhu, Jun Yang, Fanglian Yao
Carbohydrate Polymers 2013 Volume 98(Issue 2) pp:1326-1334
Publication Date(Web):6 November 2013
DOI:10.1016/j.carbpol.2013.08.005
•Carboxymethyl chitosan-grafted-poly(amidoamine) dendrimers were synthesized.•The dendrimers self-assemble into core–shell nanoparticles.•Structure and size of the core–shell nanoparticles are pH-responsive.•The core–shell nanoparticles release their cargo's enzymatic activity selectively.Intracellular delivery of native, active proteins is challenging due to the fragility of most proteins. Herein, a novel polymer/protein polyion complex (PIC) nanoparticle with core–shell structure was prepared. Carboxymethyl chitosan-grafted-terminal carboxyl group-poly(amidoamine) (CM-chitosan-PAMAM) dendrimers were synthesized by amidation and saponification reactions. 1H NMR was used to characterize CM-chitosan-PAMAM dendrimers. The TEM images and results of lysozyme loading efficiency indicated that CM-chitosan-PAMAM dendrimers could self-assemble into core–shell nanoparticles, and lysozyme was efficiently encapsulated inside the core of CM-chitosan-PAMAM dendrimer nanoparticles. Activity of lysozyme was completely inhibited by CM-chitosan-PAMAM Dendrimers at physiological pH, whereas it was released into the medium and exhibited a significant enzymatic activity in an acidic intracellular environment. Moreover, the CM-chitosan-PAMAM dendrimer nanoparticles did not exhibit significant cytotoxicity in the range of concentrations below 3.16 mg/ml. The results indicated that these CM-chitosan-PAMAM dendrimers have excellent properties as highly potent and non-toxic intracellular protein carriers, which would create opportunities for novel applications in protein delivery.
Co-reporter:Yang Yu;Hong Zhang;Hong Sun;Dandan Xing
Frontiers of Chemical Science and Engineering 2013 Volume 7( Issue 4) pp:388-400
Publication Date(Web):2013 December
DOI:10.1007/s11705-013-1355-0
With the excellent biocompatibility and osteoconductivity, nano-hydroxyapatite (nHA) has shown significant prospect in the biomedical applications. Controlling the size, crystallinity and surface properties of nHA crystals is a critical challenge in the design of HA based biomaterials. With the graft copolymer of chitosan and poly(N-isopropylacrylamide) in coil and globule states as a template respectively, a novel composite from chitosan-g-poly(N-isopropylacrylamide) and nano-hydroxyapatite (CS-g-PNIPAM/nHA) was prepared via coprecipitation. Zeta potential analysis, thermogravimetric analysis and X-ray diffraction were used to identify the formation mechanism of the CS-g-PNIPAM/nHA composite and its morphology was observed by transmission electron microscopy. The results suggested that the physical aggregation states of the template polymer could induce or control the size, crystallinity and morphology of HA crystals in the CS-g-PNIPAM/nHA composite. The CS-g-PNIPAM/nHA composite was then introduced to chitosan-gelatin (CS-Gel) polyelectronic complex and the cytocompatibility of the resulting CSGel/composite hybrid film was evaluated. This hybrid film was proved to be favorable for the proliferation of MC 3T3-E1 cells. Therefore, the CS-g-PNIPAM/nHA composite is a potential biomaterial in bone tissue engineering.
Co-reporter:Miao Tian, Jinmei Wang, Ershuai Zhang, Junjie Li, Cuimi Duan, and Fanglian Yao
Langmuir 2013 Volume 29(Issue 25) pp:8076-8085
Publication Date(Web):May 28, 2013
DOI:10.1021/la4007668
A novel polysaccharide-based zwitterionic copolymer, agarose-graft-poly[3-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate] (agarose-g-PDMAPS) with UCST, depending both on hydrogen bonding and electrostatic interaction, was synthesized by ATRP, and its aggregation behavior in aqueous media was investigated in detail. Proton nuclear magnetic resonance spectroscopy, Fourier transform-infrared spectroscopy, and gel-permeation chromatography were performed to characterize the copolymer. Thermosensitive behaviors of the copolymers in water, NaCl, and urea solution were tracked by ultraviolet, dynamic light scattering, and transmission electron microscopy analysis. It was found that the copolymers existed as “core–shell” spheres at an elevated temperature, as a result of the self-assembly of the agarose backbones located in the “core” driven by hydrogen-bonding interactions. When the copolymer solution was cooled below UCST, the core–shell spheres began to aggregate because of the electrostatic interactions and collapse of PDMAPS side chains in the “shell” layer. UCST of the copolymer could be tuned in a wide range, depending on the chain lengths of PDMAPS. This is the first example to investigate the thermosensitivity, combining ionic interactions of the zwitterionic side chains with hydrogen bondings from the biocompatible agarose backbones. The synthetic strategy presented here can be employed in the preparation of other novel biomaterials from a variety of polysaccharides.
Co-reporter:Yuxi Liu, Jing Yang, Ziqi Zhao, Junjie Li, Rui Zhang, Fanglian Yao
Journal of Colloid and Interface Science 2012 Volume 379(Issue 1) pp:130-140
Publication Date(Web):1 August 2012
DOI:10.1016/j.jcis.2012.04.058
With natural polysaccharides carrageenan (Car) and chitosan (Cs) as the polyanion and polycation, respectively, multilayer hollow nanocapsules have been fabricated via sequential layer-by-layer (LbL) electrostatic self-assembly from the sacrificed templates nanospheres (SiO2–NH2). The LbL assembly process with the polysaccharides on SiO2–NH2 core was followed by ζ-potential and size analysis. The fabrication of (Car/Cs)x nanocapsules and the removing of the SiO2–NH2 core templates were confirmed by TGA and EDS analysis. The morphology of SiO2(Car/Cs)x nanospheres and (Car/Cs)x nanocapsules were observed by TEM analysis. The size analysis of (Car/Cs)x nanocapsules indicated that the cyst wall thickness and cavity volume of the nanocapsules are pH and ionic strength dual responsive. Due to the biocompatibility of the natural polysaccharides carrageenan and chitosan and the responsiveness of nanocapsules to pH and ionic strength, the (Car/Cs)x multilayer nanocapsules are expected to be used as nanoreactors or nanocontainers to control the synthesis, encapsulation, and releasing behaviors of bioactive molecules.Graphical abstractHighlights► Amino-modified SiO2 nanospheres were used as sacrificial templates. ► The cavity volume of the nanocapsule was controlled by the core templates. ► Natural polysaccharides were selected to build the LbL assembly cyst wall. ► The cyst wall of the nanocapsule was pH and ionic strength dual responsive.
Co-reporter:Yan Wen, Zhilei Tan, Fang Sun, Li Sheng, Xiaoyang Zhang, Fanglian Yao
Materials Science and Engineering: C 2012 Volume 32(Issue 7) pp:2026-2036
Publication Date(Web):1 October 2012
DOI:10.1016/j.msec.2012.05.019
With the aim to develop a novel water-soluble modified chitosan nanoparticle with tuned size and improved antibacterial activity, quaternized carboxymethyl chitosan/poly(amidoamine) dendrimers (CM-HTCC/PAMAM) were synthesized. Firstly low-generation amino-terminated poly(amidoamine) (PAMAM) dendrimers were prepared via repetitive reactions between Michael addition and amidation, which were then employed for modifying quaternized carboxymethyl chitosan (CM-HTCC). Prior to the reaction of CM-HTCC with PAMAM, carboxylic groups in CM-HTCC were activated with EDC/NHS in order to enhance the reaction efficiency. FT-IR, 1H NMR, elemental analysis and XRD were performed to characterize CM-HTCC/PAMAM dendrimers. Turbidity measurements showed that CM-HTCC/PAMAM dendrimers had good water-solubility. TEM images indicated that CM-HTCC/PAMAM dendrimers existed as smooth and spherical nanoparticles in aqueous solution. The results of antibacterial activity explored that CM-HTCC/PAMAM dendrimer nanoparticles displayed higher antibacterial activity against Gram-negative bacteria Escherichia coli (E. coli), whereas they showed much less efficiency against Gram-positive bacteria Staphylococcus aureus (S. aureus) compared to quaternized chitosan (HTCC).Highlights► Novel CM-HTCC/PAMAM dendrimers were successful1y synthesized. ► They self-aggregated as core–shell nanoparticles in water with good dispersivity. ► The nanoparticles showed better antibacterial activity against E. coli than HTCC.
Co-reporter:Junjie Li, Hong Sun, Da Sun, Yuli Yao, Fanglian Yao, Kangde Yao
Carbohydrate Polymers 2011 Volume 85(Issue 4) pp:885-894
Publication Date(Web):1 July 2011
DOI:10.1016/j.carbpol.2011.04.015
Nano-hydroxyapatite/chitosan–pectin (nHCP) composite was prepared via mineralization of a chitosan–pectin network. Then nHCP/chitosan–gelatin (nHCP/CG) scaffolds were prepared via the blending of nHCP and chitosan–gelatin solution. Results suggested that nHCP/CG scaffolds have appropriate porosity, water absorption ability and degradation behaviors. nHCP can be fused into the pore wall of nHCP/CG scaffold via chemical crosslinking interactions, which avoids the agglomeration and migration of nHA particles. Moreover, the compressive strength of nHCP/CG scaffold ranges from 10.4 ± 1.64 to 13.5 ± 3.85 MPa. nHCP/CG scaffolds have stable physical and chemical structures, which can provide appropriate microenvironments for cells to attach and proliferate for MC 3T3-E1 cells. Therefore, nHCG/CG is a potential biomaterial in bone tissue engineering.
Co-reporter:Junjie Li, Dunwan Zhu, Jianwei Yin, Yuxi Liu, Fanglian Yao, Kangde Yao
Materials Science and Engineering: C 2010 30(6) pp: 795-803
Publication Date(Web):
DOI:10.1016/j.msec.2010.03.011
Co-reporter:Junjie Li;Hong Sun;Rui Zhang;Ruyue Li;Yuji Yin;Hui Wang;Yuxi Liu;Kangde Yao
Journal of Biomedical Materials Research Part B: Applied Biomaterials 2010 Volume 95B( Issue 2) pp:308-319
Publication Date(Web):
DOI:10.1002/jbm.b.31715
Abstract
In this article, the chitosan/gelatin/pectin (CGP) network films were prepared to build appropriate physicochemical and mechanical microenvironment for attachment, proliferation, and differentiation of mesenchymal stem cells (MSCs). Results suggested that the hydrophilicity and mechanical character of CGP composites films could be modulated via adjusting the pectin content in the composites. The investigations of attachment and proliferation behaviors of mesenchymal stem cells (MSCs) on the CGP films were carried out. The morphology of cells was observed with hematoxylin/eosin staining (HE) and scanning electron microscope (SEM). The osteogenic differentiation of MSCs was investigated via ALP and polymerase chain reaction (PCR). Results suggested that the CGP films have excellent biocompatibility. MSCs seeded on CGP (0.1) film show higher proliferation capacity compared with other samples. Moreover, osteogenic differentiation of MSCs also depends on the properties of the substrate. The MSCs seeded on CGP (0.5) expressed the highest ALP activity, osteogenic gene expression and mineral formation capacity. These results suggest that the composition of the CGP network films could effectively modulate their physicochemical and mechanical properties and further regulate the cell behaviors of MSCs. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.
Co-reporter:Min Wang, Wei Chen, Hong Zhang, Xiulan Li, Yang Zhang, Kangde Yao, Fanglian Yao
European Polymer Journal 2007 Volume 43(Issue 11) pp:4683-4694
Publication Date(Web):November 2007
DOI:10.1016/j.eurpolymj.2007.08.012
Poly(l-lactic acid)–poly(l-lactic acid-co-citric acid)–poly(ethylene glycol) multiblock copolymers (PLLA–PLCA–PEG) were synthesized through polycondensation reaction and characterized by 1H NMR and DSC. The three-dimensional ultrafine fibre microporous PLLA/PLLA–PLCA–PEG scaffolds were then fabricated by modifying PLLA with PLLA–PLCA–PEG through blending and characterized as well. Properties of scaffolds such as swelling and degradation behaviors, morphology and mechanical moduli were fully investigated. Tetrandrine-loaded PLLA/PLLA–PLCA–PEG scaffolds were also fabricated and their drug releasing behaviors were taken into consideration. Compressive testing research shows that the mechanical flexibility improves as the content of PLLA–PLCA–PEG copolymers in the scaffolds increases. The TED encapsulation efficiency of the scaffold is enhanced when the amount of PLLA–PLCA–PEG increases because of the acid–base interaction between carboxylic acid groups of the copolymer with TED. The releasing velocity of TED speeds up while the PLLA–PLCA–PEG blocks ratios in scaffolds increase. So modification of PLLA scaffold with PLLA–PLCA–PEG shall broaden its applications in tissue engineering.
Co-reporter:Fanglian Yao, Yun Bai, Wei Chen, Xiaoyan An, Kangde Yao, Pingchuan Sun, Hai Lin
European Polymer Journal 2004 Volume 40(Issue 8) pp:1895-1901
Publication Date(Web):August 2004
DOI:10.1016/j.eurpolymj.2004.04.017
Oligomers of l-lactic acid and citric acid (PLCA) were synthesized by reacting lactic acid with citric acid in the presence of stannous chloride. The chemical compositions of these multicarboxylated oligomers were verified by FT-IR and 1H-NMR spectroscopy. The thermal characteristics of the oligomers, such as glass transition temperature Tg, melting temperature Tm and melting enthalpy, were confirmed by DSC. The crystallinity of the oligomers were determined by DSC and WXRD. Meanwhile, the acid–base surface characteristics of PLCA have been determined by contact angle. The results implicated that these oligomers may be used to entrap the cospecies on PLLA surface in tissue engineering.
Co-reporter:Fanglian Yao;Chang Liu;Wei Chen;Yun Bai;Zhiyuan Tang;Kangde Yao
Macromolecular Bioscience 2003 Volume 3(Issue 11) pp:653-656
Publication Date(Web):6 NOV 2003
DOI:10.1002/mabi.200350035
Chitosan grafted oligo(L-lactic acid) copolymers with different length of side chain were prepared through the reaction of terminal aldehyde group of oligo(L-lactic acid) (OLLA) and amino groups of chitosan. The mean molecular mass of the grafting OLLA chain was ca. 600 ∼ 5 000. The graft copolymers are soluble in DMSO, DMF and acetic acid. The synthesis method and structure described here provide chitosan-g-OLLA copolymers with broad applicability.
