Xylan hemicellulose improves chitosan hydrogel for bone tissue regeneration

The hemicellulose xylan, which has immunomodulatory effects, has been combined with chitosan to form a composite hydrogel to improve the healing of bone fractures. This thermally responsive and injectable hydrogel, which is liquid at room temperature and gels at physiological temperature, improves the response of animal host tissue compared with similar pure chitosan hydrogels in tissue engineering models. The composite hydrogel was placed in a subcutaneous model where the composite hydrogel is replaced by host tissue within 1 week, much earlier than chitosan hydrogels. A tibia fracture model in mice showed that the composite encourages major remodeling of the fracture callus in less than 4 weeks. A non‐union fracture model in rat femurs was used to demonstrate that the composite hydrogel allows bone regeneration and healing of defects that with no treatment are unhealed after 6 weeks. These results suggest that the xylan/chitosan composite hydrogel is a suitable bone graft substitute able to aid in the repair of large bone defects. Copyright © 2016 John Wiley & Sons, Ltd.     

温敏性半乳糖基化壳聚糖水凝胶的制备及其对HL-7702细胞增殖行为影响的研究

以壳聚糖(CS)为原料,在1-乙基-3-(3-二甲胺丙基)碳-二亚胺盐酸盐(EDC.HCL)和N-羟基琥珀酰亚胺(NHS)的活化作用下,合成了半乳糖基化壳聚糖(GC)单体,并与N-异丙基丙烯酰胺(NIPAAm)反应,制备了温敏性半乳糖基化壳聚糖N-异丙基丙烯酰胺共聚水凝胶(Gal-CS-g-PNIPAAm).通过红外光谱(FTIR)、光电子能谱(XPS)和扫描电子显微镜(SEM)等测试方法对其成分和结构进行了表征,并对其溶胀率和表面亲疏水性进行了研究.在Gal-CS-g-PNIPAAm凝胶表面培养人正常肝细胞系(HL-7702),研究其生长、脱附及转载(再增殖)行为.结果表明Gal-CS-g-PNIPAAm水凝胶具有良好的温度响应性和生物相容性,与PNIPAAm水凝胶相比,Gal-CS-g-PNIPAAm凝胶表面更有利于HL-7702细胞增殖.将温度降低至临界温度(LCST,32.5℃)以下,细胞可以从凝胶表面自发脱附,与酶消化脱附相比,细胞损伤更少.Gal-CS-g-PNIPAAm凝胶表面脱附的细胞比PNIPAAm凝胶表面脱附的细胞活性更高,表明PNIPAAm水凝胶引入GC单体后,凝胶的生物相容性得到改善,且脱附后细胞的增殖活力明显增加.     

Gelation time and degradation rate of chitosan-based injectable hydrogel

Gelation time and degradation rate of thermally-sensitive aqueous solutions of chitosan/Gp (glycerophosphate disodium salt) have been studied. The effects of different parameters such as Gp salt concentration, solution temperature, degree of deacetylation of chitosan (DDA) and drug loading on the gelation time have been investigated. Gravimetric analysis, gel permeation chromatography and FTIR spectrophotometry were used to investigate the influence of the DDA and concentration of chitosan solution on hydrogel degradation. The presented results indicated that gelation time decreases by increasing Gp salt concentration, temperature, concentration and DDA of chitosan solutions, while drug loading has no significant effect on gelation time. Slower degradation profile was recorded for hydrogel with the higher DDA and concentration of chitosan in the primary solution. FTIR studies indicated that the chemical structure of chitosan macromolecules does not change significantly during the degradation. It could be concluded that biodegradation of chitosan hydrogel occurred via its surfaces.     

Biocompatible hydrogel for cartilage repair with adjustable properties

Synthesis of hydrogel at mild conditions is considered one most important challenge, especially if the hydrogel will be used for hosting bioactive materials or drugs. The procedure of hydrogel preparation should have no effect on the properties of the hosted materials. Hyaluronic acid (HA) was modified by adding dialdehyde groups to its structure to facilitate formation of hydrogel at very mild conditions. Dialdehyde HA (DHA) was prepared through oxidation of HA using sodium metaperiodate as oxidizing agent. The prepared DHA was characterized by Fourier‐transform infrared (FTIR) spectroscopy and X‐ray diffraction (XRD) and aldehyde content. A hydrogel was prepared using different chitosan/DHA molar ratio and fixed amount of glutaraldehyde at 25°C. The prepared hydrogel has tunable properties and pores size depending on the chitosan/DHA molar ratio. Sodium diclofenac was loaded on the hydrogel as a model drug. The hydrogel was characterized by FTIR spectroscopy, swelling rate, gel fraction, drug release profile, and cytotoxicity. The results obtained indicated that the properties of the prepared hydrogel, including gelling time, gel fraction, swelling, pores size, and drug release profile are highly tuned depending on the chitosan/DHA molar ratio. The drug loading efficiency was in the range of 70% to 85%. The cytotoxicity results reveal that the prepared hydrogel has a very low toxicity in presence and absence of sodium diclofenac.     

Baked hydrogel from corn starch and chitosan blends cross‐linked by citric acid: Preparation and properties

Citric acid (CA)–modified hydrogels from corn starch and chitosan were synthesized using a semidry condition. This strategy has great benefits of friendly environment because of the absence of organic solvents and compatible with the industrial process. The hydrogel blends were prepared with starch/chitosan ratios of 75/25, 50/50, and 25/75. The thermal stability, morphology, water absorption, weight loss in water, and methylene blue absorption were determined. Multi‐carboxyl structure of CA could result in a chemical cross‐linking reaction between starch, chitosan, and CA. The cross‐linking reaction between free hydroxyl groups of starch, amino groups of chitosan, and carboxyl groups of CA has been confirmed by attenuated total reflectance infrared (ATR‐IR) spectroscopy, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) analysis. The water absorption properties of CA‐modified hydrogel blends were increased significantly compared with the native starch and chitosan. Moreover, the hydrogel blends modified with CA showed good water resistance and gel content. The morphology study confirmed the complete chemical cross‐linking and porous structure of hydrogel blends. The hydrogel blend with the starch/chitosan ratio of 50/50 presented powerful absorption of methylene blue as well as chemical cross‐linking reaction and dense structure. In sum, the hydrogel blend comprising 50% starch and 50% chitosan has the potential to be applied for water maintaining at large areas, for example, in agriculture.     

Modified chitosan III,superabsorbency, salt‐ and pH‐sensitivity of smart ampholytic hydrogels from chitosan‐g‐PAN

Polyacrylonitrile (PAN) grafted chitosan was prepared by ceric‐initiated graft polymerization of acrylonitrile onto chitosan in a homogenous medium. The copolymer chitosan‐g‐PAN product was then hydrolyzed to yield a novel smart hydrogel (H‐chitoPAN) with superabsorbing properties. The influence of add‐on values as well as temperature and time of hydrolysis of the initial chitosan‐g‐PAN on swelling behavior of the hydrogel was evaluated in water and various salt solutions. The swelling kinetics of the superabsorbing hydrogel was studied as well. The hydrogels exhibited ampholytic and pH‐sensitivity characteristics. Several sharp swelling changes were observed in lieu of pH variations in a wide range (pH 2–13). The swelling variations were explained according to swelling theory based on the hydrogel chemical structure. Superabsorbency, pH‐ and salt‐sensitivity of the chitosan‐based hydrogel was briefly compared with the classical starch‐based superabsorbent, H‐SPAN. The pH‐reversibility and on–off switching behavior of the intelligent H‐chitoPAN hydrogels makes them good candidates for considering as potential drug carries. Copyright © 2004 John Wiley & Sons, Ltd.     

Preparation and release profiles of pH/temperature-responsive carboxymethyl chitosan/P(2-(dimethylamino) ethyl methacrylate) semi-IPN amphoteric hydrogel

Thermo- and pH-responsive semi-IPN polyampholyte hydrogels were prepared by using carboxymethyl chitosan and P(2-(dimethylamino) ethyl methacrylate) with N N'-Methylenebisacrylamide (BIS) as crosslinking agent. It was found that the semi-IPN hydrogel shrunk most at the isoelectric point (IEP) and swelled when pH deviated from the IEP. Its swelling ratio dramatically decreased between 30 and 50 °C at pH 6.8 buffer solution. It also showed good reversibility. The UV results showed that when the pH values of drug release medium were 3.7, 6.8, and 9 at 25 °C, the cumulative release rates reached 83.1, 51.5, and 72.2%, respectively. The release rate of coenzyme A (CoA) was higher at 50 °C than 37 and 25 °C at pH 6.8 solution. The release rate decreased with increasing the content of carboxymethyl chitosan at 25 °C in pH 6.8 solution. The results showed that semi-IPN hydrogel seems to be of great promise in pH/temperature drug delivery systems.     

Thermosensitive Chitosans as Novel Injectable Biomaterials

Two kinds of water soluble thermosensitive chitosan copolymers were prepared by graft polymerization of N-isopropylacrylamide (NIPAAm) onto chitosan using cerium ammonium nitrate (CAN) as an initiator (chitosan-g-NIPAAm) and by coupling monocarboxy Pluronic^® with chitosan using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxysuccin-imide (NHS) as coupling agents (chitosan-Pluronic^®). The physicochemical properties of the resulting copolymers were characterized and they formed thermally reversible hydrogel, which exhibits a lower critical solution temperature (LCST) at 34°C in aqueous solutions. The human mesenchymal stem cells (hMSCs) were cultured in the chiotsan-g-NIPAAm in vitro. Chondrogenic differentiation was induced in the chitosan-g-NIPAAm gel. Therefore, chondrogenic differentiated cells from MSCs with a thermo-sensitive chitosan-g-NIPAAm could be used as an injectable cell-polymer complex. In summary, chitosan-g-NIPAAm and chitosan-Pluronic^® attest to their usefulness as injectable materials because of their thermally reversible property and relatively good biocompatibility.     

Surface modification by deposition of IPA plasma and gellan gum/chitosan hybrid hydrogel onto thermoplastic polyurethane for controlled release of N‐acetylcysteine

A thin film system composed of gellan gum and chitosan was fabricated through a combination of polyelectrolyte blend and hybrid hydrogel gelation for controlled release of drug. In this study, precursor isopropyl alcohol (IPA) was used to plasma deposit on the surface of thermoplastic polyurethane (TPU) to form a hydrophilic film. The features of the thin film were evaluated using water contact angle (WCA) measurement, scanning electron microscopy (SEM), Fourier transform infra‐red (FTIR), UV/Vis spectroscopy, and studies of controlled release of drugs. The hybrid hydrogel, pH‐sensitive, was tested at pH values of 1.2 and 7.4 of buffer solution and at a temperature of 37°C to observe its swelling ratio and drug delivery properties with N‐acetylcysteine as a drug material for controlled release. Furthermore, at pH 7.4, the hybrid hydrogel has an outstanding release ratio of up to about 90% absorption amounts of N‐acetylcysteine after 8 hr. The mechanism of drug release from thin film devices (n = 0.684) is anomalous (non‐Fickian) transport, the value of n lies between 0.43 and 0.85.     

温敏性乙二醇壳聚糖水凝胶的制备及药物缓释性能

以乙二醇壳聚糖为原料, 乙酸酐为酰化剂, 通过N-乙酰化反应, 制得了新型温敏性高分子乙酰化乙二醇壳聚糖. 通过核磁共振氢谱(¹H NMR)、 傅里叶变换红外光谱(FTIR)及试管倒置法对乙酰化乙二醇壳聚糖的结构及温敏性进行了表征, 通过扫描电子显微镜(SEM)和紫外-可见分光光度计(UV-Vis)对水凝胶的微观形貌和体外药物释放性能进行了研究. 结果表明, 随着反应时间和乙酸酐与乙二醇壳聚糖氨基摩尔比的增加, 产物的乙酰度逐渐增加; 乙酰化乙二醇壳聚糖溶液具有热可逆温敏性溶胶-凝胶转变行为, 可以通过控制乙酰化乙二醇壳聚糖的乙酰度和溶液浓度, 使溶胶-凝胶转变温度处于室温至体温(25~37 ℃)之间; 乙酰化乙二醇壳聚糖水凝胶具有“高度孔隙化且孔隙之间相互连通”的结构特点, 通过控制乙酰度和溶液浓度, 可使其孔径大小处于1~40 μm范围内; 乙酰化乙二醇壳聚糖水凝胶的乙酰度为89.90%时, 质量分数为5%~7%的水凝胶对抗癌药物吉西他滨具有缓释作用, 载药凝胶的释药时间可达3~5 d. 乙酰化乙二醇壳聚糖有望在药物释放及组织工程等领域得到广泛应用.     

糖化温敏凝胶的制备及其与HepG2细胞相互作用研究

利用自由基聚合法合成了半乳糖糖化温敏凝胶(P(NIPAAm-co-GAC))和壳聚糖糖化温敏凝胶(P(NIPAAm-co-CSA)),对其温度响应性和溶胀性能进行了研究,结果表明,两种糖化温敏凝胶在水中和细胞培养基中均显示较好的温度响应性,以及比聚(N-异丙基丙烯酰胺)温敏凝胶(PNIPAAm)更好的溶胀性能.进一步研究人肝肿瘤细胞(HepG2)在凝胶表面的细胞行为发现,HepG2在P(NIPAAm-co-GAC)、PNIPAAm凝胶表面吸附量及活性较高,表现出良好的生长趋势,而在P(NIPAAm-co-CSA)凝胶表面吸附量和活性很低,其增殖受到抑制;通过降低环境温度,能使培养在P(NIPAAm-co-GAC)和PNIPAAm凝胶表面的HepG2细胞发生自动脱附,避免了酶解法对细胞功能造成的损伤,并且细胞片层比单个细胞表现出更快的脱附速率;研究细胞转载行为表明,通过温度诱导得到的细胞片层,其生物活性远远大于通过酶解法得到的细胞的生物活性.     

Oxidized Xanthan Gum Crosslinked NOCC: Hydrogel System and Their Biological Stability from Oxidation Levels of the Polymer

Dynamic hydrogel systems from N,O-carboxymethyl chitosan (NOCC) are investigated in the past years, which has facilitated their widespread use in many biomedical engineering applications. However, the influence of the polymer's oxidation levels on the hydrogel biological properties is not fully investigated. In this study, chitosan is converted into NOCC and introduced to react spontaneously with oxidized xanthan gum (OXG) to form several injectable hydrogels with controlled degradability. Different oxidation levels of xanthan gum, as well as NOCC/OXG volume ratios, are trialed. The infrared spectroscopy spectra verify chemical modification on OXG and successful crosslinking. With increasing oxidation levels, more dialdehyde groups are introduced into the OXG, resulting in changes in physical properties including gelation, swelling, and self-healing efficiency. Under different volume ratios, the hydrogel shows a stable structure and rigidity with higher mechanical properties, and a slower degradation rate. The shear-thinning and self-healing properties of the hydrogels are confirmed. In vitro assays with L929 cells show the biocompatibility of all formulations although the use of a high amount of OXG15 and OXG25 limited the cell proliferation capacity. Findings in this study suggested a suitable amount of OXG at different oxidation levels in NOCC hydrogel systems for tissue engineering applications.     

PEG-grafted chitosan as an injectable thermoreversible hydrogel

PEG-grafted chitosan was formulated such that its solution undergoes a thermally reversed phase transition from an injectable free-flowing solution at low temperature to a gel at body temperature. Aqueous solutions of PEG-grafted chitosan can be prepared at physiological pH values, thereby allowing safe incorporation of bioactive molecules. This injectable thermoreversible hydrogel is potentially suitable for a wide range of biomedical applications, particularly in sustained in vivo drug release and tissue engineering. An aqueous solution of PEG-grafted chitosan polymer is injectable at low temperatures but forms a gel at body temperature.     

Synthesis and characterization of chitosan–poly(acrylamide–co-acrylic acid) magnetic nanocomposite hydrogels for use in catalysis

A novel hydrogel based on chitosan–poly(acrylamide-co-acrylic acid) (CAA) with different formulations were synthesized by the effect of gamma radiation. The magnetic CAA hydrogels were also synthesized and characterized by using different techniques, e.g., TEM and XRD. The prepared hydrogels and magnetic hydrogel nanocomposite were utilized for in situ cobalt nanoparticle preparation and employed as a reaction media in catalytic reduction of 2-nitrophenol (2-NP), to 2-aminophenol (2-AP). The experimental parameters that affect the reduction rates such as temperature and amount of catalyst were also, investigated.     

聚乙烯醇/羧甲基壳聚糖共混水凝胶的辐射合成及性能

采用电子加速器辐照法制备了聚乙烯醇(PVA)/羧甲基壳聚糖(CMCH)共混水凝胶;研究了PVA与CMCH的配比、辐照剂量、温度以及pH值对PVA/CMCH共混水凝胶性能的影响.实验发现,PVA与CMCH在辐照剂量为40 kGy、配比为w(PVA)/w(CMCH)=5/1的条件下可得到强度较好的PVA/CMCH共混水凝胶,该水凝胶具有一定的温度和pH敏感性:在5~20℃时具有较高的溶胀率,温度在20℃以上溶胀率较低;水凝胶在pH<4.0和pH>6.0时溶胀率均较大,而当pH为4.0~6.0时溶胀率较小.     

Preparation and characterization of poly(2-acrylamido-2-methylpropane-sulfonic acid)/Chitosan hydrogel using gamma irradiation and its application in wastewater treatment

Radiation grafting of chitosan with 2-acrylamido-2-methyl propane sulfonic acid (AMPS) has been successfully performed. The effect of absorbed dose (kGy) and the chitosan:AMPS ratio on graft hydrogelization was studied. The structure of the prepared hydrogel was confirmed using infrared spectroscopy (IR). Thermal properties were simultaneously studied by thermogravimetric analysis (TGA). The effect of the polymerization variables on the swelling % of the prepared hydrogel was investigated. The highest equilibrium degree of swelling (38.6 g/g) and gel % (94.7%) of the prepared chitosan–AMPS hydrogel was at 40% AMPS and absorbed dose of 10 kGy. The removal of methylene blue, acid red dye, Cd (II) and Cr (III) from composed wastewater was also investigated. The effect of pH, the chitosan:AMPS ratio and the concentration of the pollutant on the adsorption process were studied.     

Spectral–luminescent study of a hydrogel based on hyaluronic acid dialdehyde and chitosan succinate containing the Lucentis drug

A spectral-luminescent study of the hydrogel formed by the crosslinking of chitosan succinate and hyaluronic acid dialdehyde (HAD) macromolecules, which is a dosage form of the Lucentis drug (active ingredient, ranibizumab), has been conducted. The individual fluorescence (FL) spectra of Lucentis (λ_max = 336 nm), HAD (λ_max = 328 and 438 nm), and the hydrogel (λ_max = 396 nm) have been obtained. An analysis of these spectra suggests the participation of carbonyl groups and proteins contained in HAD in its gelation with chitosan succinate. The diffusion of Lucentis from the hydrogel into a physiological solution was studied by a FL method to demonstrate the high prolonged-release properties of the new dosage form.     

Evaluation of the potential of chitosan hydrogels to extract polar organic species from nonpolar organic solvents: application to the extraction of aminopyridines from hexane

The extraction of a series of aminopyridines (APs) utilizing chitosan hydrogels in hexane was investigated. The chitosan hydrogel was prepared using glutaraldehyde as a cross-linking agent. Experiments were carried out to determine the maximum extraction efficiency, distribution coefficient, sorption capacity, and adsorption and desorption mechanisms. The efficiency of extraction of aminopyridines attained a maximum value of ca. 100% with the distribution coefficients for the transfer of the aminopyridines from hexane to chitosan hydrogel increasing in the order of ortho-相似文献   

Effect of organic and inorganic acids on chitosan/glycerophosphate thermosensitive hydrogel

The influence of organic and inorganic acids on chitosan/glycerophosphate (CS/GP) hydrogel has been investigated by dissolving chitosan in different acids. The results of gelation showed that all of the chitosan dissolved in monovalent acid solutions (i.e., formic, acetic, propionic, butyric, isobutyric, lactic, nitric, hydrochloric, and chloroacetic acid), when neutralized by GP solution, could transform into hydrogel after 2–5 min at 37 °C, while those dissolved in multivalent acids failed in gel formation. The inner structures of CS/GP hydrogels prepared with monovalent acids depended on the ionic strength and chain length of acids. Morphological examination by scanning electron microphotography demonstrated that large pores occurred during the gel-forming process, and the aperture size was also related to different acids. The cytotoxicity studies indicated that CS/GP systems prepared by dissolving chitosan in tested acids except chloroacetic acid were nontoxic to mouse embryonic fibroblasts and Hela cells.     

Horseradish peroxidase immobilized in macroporous hydrogel for acrylamide polymerization

Thermosensitive hydrogel made up of poly(N‐isopropylacrylamide) (PNIPA)‐chitosan semi‐interpenetrating network (semi‐IPN) with ultrarapid responding rate was synthesized. Horseradish peroxidase (HRP) was then immobilized on this hydrogel that acted as an enzyme‐carrier by glutaraldehyde bridge. Polymerization of acrylamide was initiated by a redox system (hydrogen peroxide/acetylacetone (Acac)) and was catalyzed by the immobilized enzyme at room temperature. The attention was focused on the properties of the carrier‐enzyme systems. The hydrogel was proofed to be macroporous by environmental scanning electron microscope images. Swelling properties of the hydrogel such as swelling ratio and deswelling–reswelling kinetics were measured. The properties of the immobilized enzyme such as enzyme activity, storage stability, and thermostability were also studied. The immobilized enzyme could be used repeatedly. Gel permeation chromatography measurement of the resulted polyacrylamide (PAAm) showed that the molecular weight reduced as the repeated times of the immobilized enzyme catalysis increased. In conclusion, the macroporous hydrogel would be a suitable enzyme carrier for practical applications in future. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2222–2232, 2008