壳聚糖智能水凝胶研究进展

概述了壳聚糖智能水凝胶的优点和发展,主要介绍了温度敏感型、pH敏感型、温度/pH双重敏感型壳聚糖水凝胶的研究进展及应用,详细介绍了壳聚糖水凝胶在医学领域如药物释放、组织工程方面的应用。指出了目前壳聚糖水凝胶存在的问题以及未来发展趋势。     

温度/pH敏感型壳聚糖水凝胶的制备及其性能

以天然可降解高分子壳聚糖为载体,选择温度敏感单体N-异丙基丙烯酰胺以及pH敏感单体2-丙烯酰胺基-2-甲基丙磺酸,以偶氮二异丁腈为引发剂,N,N-亚甲基双丙烯酰胺为交联剂,通过自由基接枝共聚反应制备壳聚糖水凝胶。通过红外(IR)、扫描电镜(SEM)对其结构及形貌进行了表征,并探讨了影响水凝胶溶胀率的因素。结果表明,当单体配比NIPAM∶AMPS为6∶4、引发剂用量为单体总质量4%、交联剂用量为单体总质量的4%、反应温度为45℃形成的水凝胶在水中溶胀率可达95%左右。该水凝胶具有一定的温度和pH敏感性,预计在药物控释、组织工程、抗凝血材料等领域拥有广阔的应用前景。     

电场敏感智能水凝胶的研究进展

水凝胶对于环境微小的物理化学刺激,如温度、pH值,离子强度、电场、磁场,光、压力等能够通过感知和自身作功来响应外界环境变化,因此水凝胶具有"智能凝胶"、"软性机械"之称.在众多外界响应条件中,电场由于易操作易调控等优点使得电场响应水凝胶具有更广阔的应用前景.本文对近年来已见报道的几类典型的电场敏感水凝胶进行了较为详细的综述.同时介绍了静电场、渗透压等电场敏感水凝胶的响应机理及其在人工爬虫、化学阀和仿生驱动器等方面的应用.     

丙烯酸接枝壳聚糖水凝胶的制备及其pH敏感性

利用迈克尔加成反应制备了两性聚电解质物质-丙烯酸接枝壳聚糖(ACS),利用FTIR和1HNMR对ACS进行结构表征,制备了丙烯酸接枝壳聚糖水凝胶(ACSG),并研究其pH敏感性和溶胀行为.结果如下:通过迈克尔加成反应,在壳聚糖分子链上引入了羧乙基基团;ACSG在pH值1.2～9.0溶液中均有较强的pH敏感性,酸敏,性优于碱敏性;ACSG在不同pH值溶液中的溶胀行为各不相同,在偏酸和偏碱性时溶胀度较大,pH值5.0时溶胀度最小;随着交联荆用量的增加,ACSG的溶胀度逐渐降低;随着取代度的增大,ACSG的溶胀度则先增大后减小.     

混合酸制备壳聚糖温敏水凝胶的研究

提出了以醋酸-盐酸混合液为溶剂,制备壳聚糖-αβ甘油磷酸钠水凝胶。探讨了它们对壳聚糖水凝胶性能的影响,并从分子间相互作用力的角度对各种现象进行了理论解释。实验结果表明:采用混合酸为溶剂,能够简单地对凝胶的粘度和凝胶化时间进行控制,并且pH对这种体系影响较小。     

磁性壳聚糖水凝胶的制备及表征

采用戊二醛作为交联剂,将磁性Fe3O4纳米粒子引入壳聚糖水凝胶中,制得磁性壳聚糖水凝胶。并采用傅里叶变换红外光谱仪、X射线衍射仪和同步差热-热重分析仪对制得的磁性壳聚糖水凝胶进行表征,结果表明,成功制备出了磁性壳聚糖水凝胶。     

壳聚糖-β-环糊精杂化水凝胶的制备

以壳聚糖为原料,合成壳聚糖-β-环糊精杂化水凝胶。结果表明,当壳聚糖量为0.2 g时,苯甲醛用量为0.05 mL,凝胶化温度为55℃时,制备的水凝胶溶胀度最大,而且品质优良。     

壳聚糖水凝胶溶胀性能的研究

壳聚糖水凝胶在pH7.0,0.2%甘氨酸缓冲溶液中的最高溶胀比R为637.5,溶胀体积比Rv为12.75;当pH≤7.0时,表现强的吸水性;pH>8.5时脱水收缩;在<1%NaCl溶液中,表现出不同程度的吸胀性;在≥1%NaCl溶液中,无吸胀性,随着环境温度的升高,吸胀性下降;甲醇作为成胶介质,凝胶的吸胀性最强;交链度与壳聚糖水凝胶的Rv成反比。因此认为,壳聚糖水凝胶在农业、医药、化工和生物学的应用及研究中将表现重要作用。     

敏感性水凝胶制备研究

本文研究了用溶液聚合及辐照聚合两种方法制备敏感性水凝胶,发现聚合温度、赶氧充分性、引发剂浓度是聚合成功的关键因素。并对两种方法对其凝胶敏感性的影响进行了比较。     

壳聚糖接枝聚丙烯酰胺水凝胶的制备及性质研究

通过接枝共聚反应制备了几种壳聚糖接枝聚丙烯酰胺水凝胶，其中过硫酸钾为自由基引发剂，亚甲基双丙烯酰胺或甲醛为交联剂，并研究了实验因素，如交联剂浓度和单体比率对水凝胶溶胀能力的影响。实验表明水凝胶具有离子强度、pH值和温度敏感性。这种可随外界因素响应及“开关”的性质，使此类智能水凝胶有望成为生物制品载体，例如药物载体。     

Studies on preparation and swelling properties of the N-isopropylacrylamide/chitosan semi-IPN and IPN hydrogels

Semi-interpenetrating network (semi-IPN) polymer gels and interpenetrating network (IPN) polymer gels with thermosensitivity were prepared by introducing a biodegradable polymer, chitosan, into the N-isopropyacrylamide (PNIPAAm) gel system. The swelling behavior, temperature sensitivity, pH sensitivity, gel strength, and drug-release behavior of PNIPAAm/chitosan semi-IPN and IPN hydrogels were investigated. The results indicated that the NIPAAm/chitosan semi-IPN and IPN hydrogels exhibited pH and temperature-sensitivity behavior and could slow drug release and diffusion from the gels. From the stress–strain curves of the hydrogels, the compression moduli of IPN gels containing crosslinked chitosan were higher than those of semi-IPN gels. This is because IPN gels have a more compact structure. The morphology of PNIPAAm/chitosan hydrogels was also investigated. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 2487–2496, 2001     

Synthesis,properties, and permeation of solutes through hydrogels based on poly(ethylene glycol)-co-poly(lactones) diacrylate macromers and chitosan

Triblock copolymers from poly(ethylene glycol) (PEG) and D,L -lactide or ε-caprolactone were synthesized to prepare semi-interpenetrating polymer networks (semi-IPNs) with chitosan by ultraviolet (UV) irradiation method. Then, the solute permeation through these semi-IPNs hydrogels were investigated. The structures of semi-IPNs were confirmed by Fourier transform infrared (FTIR) spectroscopy and wide-angle X-ray diffractometer (WAXD). The equilibrium water content (EWC) of these hydrogels was in the range of 67–75%. The crystallinity, thermal properties, and mechanical properties of semi-IPNs hydrogels were studied. All the hydrogels revealed a remarkable decrease in crystallinity as compared with the PEG macromer itself. The tensile strengths of semi-IPNs hydrogels in a dry state were rather high, but those of hydrogels in a wet state decreased drastically. The permeabilities of solutes of hydrogels followed the swelling behaviors and were regulated by solute size. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 2151–2158, 1999     

Structural change and swelling mechanism of pH‐sensitive hydrogels based on chitosan and D,L‐lactic acid

Graft copolymerization of D,L ‐lactic acid (LA) onto chitosan (CS) was attempted without using a catalyst. pH‐sensitive hydrogels were obtained which are based on two different components: a natural polymer and a synthetic polymer. These polyester substituents provide the basis for hydrophobic interactions that contribute to the formation of hydrogels. The swelling mechanisms in enzyme‐free simulated gastric fluid (SGF, pH 2.2) or simulated intestinal fluid (SIF, pH 7.4) at 37°C were investigated. Meanwhile, structural changes of the graft copolymers in the different pH buffers were studied by FTIR, and these are discussed together with the swelling mechanisms. The effect of pH on the water uptake of hydrogel was investigated by using McIlvaine buffer with the same ionic strength. The morphological change of hydrogels in different aqueous solutions is investigated by scanning electron microscopy (SEM). © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 3186–3192, 1999     

Preparation and properties of hydrogels based on hemicellulose

Xylan with glucuronic acid functionalities, separated from birchwood, was converted into hydrogels by dissolving it together with chitosan in acidic conditions. The hydrogels were formed at certain xylan/chitosan compositions. The mechanism of the gel formation was investigated with FTIR. Complexation between glucuronic acid functionalities of xylan and amino groups of chitosan is suggested to be responsible for network formation. The swelling behavior of these hydrogels was studied at various pH levels and salt concentrations, and the hydrogels responded in a reversible manner to various stimuli. DMA of the films showed separated transitions that may correspond to different phases. Imaging with AFM in TappingMode™ of the surfaces indicated discrete xylan and chitosan phases. A sponge-like microporous structure, as shown with SEM, was formed when a hydrogel was freeze dried. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 69: 1661–1667, 1998     

Semi‐interpenetrating polymer network hydrogels based on aspen hemicellulose and chitosan: Effect of crosslinking sequence on hydrogel properties

Semi‐interpenetrating network hydrogel films were prepared using hemicellulose and chemically crosslinked chitosan. Hemicellulose was extracted from aspen by using a novel alkaline treatment and characterized by HPSEC, and consisted of a mixture of high and low molecular weight polymeric fractions. HPLC analysis of the acid hydrolysate of the hemicellulose showed that its major constituent sugar was xylose. X‐ray analysis showed that the relative crystallinity of hydrogels increased with increasing hemicellulose content up to 31.3%. Strong intermolecular interactions between chitosan and hemicellulose were evidenced by FT‐IR analysis. Quantitative analysis of free amino groups showed that hemicellulose could interrupt the chemical crosslinking of chitosan macromolecules. Mechanical testing and swelling experiments were used to define the effective network crosslink density and average molecular weight between crosslinks. Swelling ratios increased with increasing hemicellulose content and mainly consisted of H‐bonded bound water. Results revealed that by altering the hydrogel preparation steps and hemicellulose content, crosslink density and swelling behavior of semi‐IPN hydrogels could be controlled without deteriorating their mechanical properties. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Star‐shaped polycaprolactone/chitosan composite hydrogels: fabrication and characterization

Star‐shaped polycaprolactone (stPCL)/chitosan composite hydrogel was fabricated by simply melt/solution blending between chitosan/dicarboxylic acid solution and melted stPCL, using 1‐(3‐dimethylaminopropyl)‐3‐ethylcarbodiimide hydrochloride and N‐hydroxysuccinimide as conjugating agents to obtain a composite hydrogel. Here, stPCL and modified stPCL were investigated. The stPCL was modified to have a carboxyl‐terminated chain (stPCL‐COOH). The composite hydrogels were transparent. The network structure of the composite hydrogels was investigated. stPCL‐OH had no chemical bond to the chitosan network but stPCL‐COOH could co‐crosslink with the chitosan network. The porous structure and porosity of the composite hydrogels were similar to those of chitosan hydrogel. However, the hydrophobicity of stPCL resulted in a lower swelling ratio compared to chitosan hydrogel. The rheological analysis of the composite hydrogel exhibited a stable crosslinked network. Compression testing of the composite hydrogel obtained from stPCL‐COOH at a mole ratio of stPCL‐COOH and chitosan of 1:1 had optimum compressive mechanical properties comparable to chitosan hydrogel due to a synergistic effect of the flexibility in stPCL and the co‐crosslinking of stPCL‐COOH with the chitosan network. © 2020 Society of Chemical Industry     

Swelling behavior of polyelectrolyte complex hydrogels composed of chitosan and hyaluronic acid

Polyelectrolyte complex (PEC) hydrogels composed of various weight ratios of chitosan and hyaluronic acid were prepared. The PEC hydrogels were formed by the reaction of the oppositely charged chitosan polymers. The PEC films swelled in water rapidly, reaching equilibrium within 30 min, and exhibited relatively high swelling ratios, 243–322%, at 25°C. The swelling ratio increased with increasing temperature. The transport phenomena of all PEC samples were non‐Fickian and diffusion and relaxation controlled. The diffusion coefficients of the PEC films ranged from 2.22 × 10^?6 to 10.05 × 10^?6 cm²/s. The activation energy of the polyelectrolyte complexes ranged from 37.14 to 54.58 kJ/mol and proved to be hydrophilic. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1097–1101, 2004     

Production of chitosan PVA PCL hydrogels to bind heparin and induce angiogenesis

New blood vessel formation is an essential part of wound healing to provide cells with the nutrients and oxygen for their survival. Many nonhealing ulcers fail to heal because of poor blood supply and skin grafts will also fail to take on poorly vascularized wound beds. There is a real need for proangiogenic biomaterials to assist wound healing. In vivo heparin binds proangiogenic growth factors and helps regulate new blood vessel formation, hence heparin containing biomaterials are attractive. To achieve a hydrogel with high heparin binding capacity a composite of chitosan, poly(vinyl alcohol) (PVA) and polycaprolactone (PCL) was produced. Chitosan is a biodegradable natural polymer with great potential for biomedical applications due to its biocompatibility, high charge density and nontoxicity. PVA is biocompatible and nontoxic with good chemical stability, film-forming ability, and high hydrophilicity. PCL has physicochemical and mechanical properties comparable to those of the biological tissues and due its hydrophilic nature helps in the sustained release of drugs. Accordingly in this study we explored a range of PCL concentrations from 4% to 16% added to hydrogels composed of chitosan and PVA. Heparin was blended into the polymer mixture and the nanoporous structure was created by freeze-drying the PCL hydrogel. The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR) and XPS confirmed the presence of sulfur on the surface of the hydrogels. Their porous morphology was investigated by scanning electron microscope (SEM). The Chick Chorionic Allantoic Membrane (CAM) assay was used to study the angiogenic potential of these materials and histology (H&E and Goldner trochome) was used to confirm the presence of new blood vessels inside the hydrogels. We report that the addition of 8% PCL to the hydrogels gave porous structures containing heparin, which significantly increased new blood vessel formation into the hydrogels. These hydrogels offer a new approach to biomaterials, which could be added to wounds to improve vascularization.     

Preparation and characterization of eugenol‐grafted chitosan hydrogels and their antioxidant activities

The hydrogels composed of chitosan and eugenol were prepared to enhance and sustain antioxidant activities. The vinyl groups of eugenol monomer were directly grafted on the amino groups of chitosan, using ceric ammonium nitrate. The graft of eugenol onto chitosan was confirmed by using Fourier‐transform infrared and proton nuclear magnetic resonance spectroscopies. Results from the swelling behavior, thermal stability, and wide‐angle X‐ray diffraction revealed that the equilibrium water content decreased with increase of graft yields, because of the hydrophobicity of eugenol, although the introduction of eugenol as a side chain disturbed the ordered arrangement of chitosan's crystalline structure. The eugenol‐grafted chitosan hydrogels showed lower pH sensitivity in comparison with chitosan alone, because the amino groups, which were pH sensitive, of chitosan were grafted with eugenol. The scavenging activity of the tested hydrogels increased with graft yield of eugenol, because phenolic groups in the eugenol could play a major role as potent free‐radical terminators, in the results of improved antioxidant activity in eugenol‐grafted chitosan hydrogel in comparison with chitosan alone. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 99:3500–3506, 2006     

利用二醛木聚糖一锅法制备纳米银抗菌水凝胶

利用二醛木聚糖(DAX)可与羧甲基壳聚糖(CMCS)以及银氨溶液同时反应的特性,即DAX的醛基与CMCS的氨基发生席夫碱反应形成亚胺键,同时,DAX含有的大量醛基与银氨溶液发生银镜反应,在室温条件下很快地还原出银纳米粒子(SNPs),一锅法制备出了具有优异抗菌性能的羧甲基壳聚糖-纳米银抗菌水凝胶。加入生物相容性良好的聚乙烯醇(PVA)并通过冻融法形成了与CMCS互穿的双网络结构,进一步提高了水凝胶的结构稳定性。采用FTIR、热重、TEM、XRD和SEM对DAX,SNPs和水凝胶的形貌、结构进行了表征。结果表明DAX在整个反应中起到了十分有效的双功能作用,成功的与CMCS和PVA发生反应,共同构成了双网络结构的水凝胶,从而提高了水凝胶的力学性能。同时,DAX将银氨溶液中的SNPs还原出来,且粒径在20-80 nm之间,具有较好的分散性,从而显著提高了水凝胶的抗菌性。本文中所制备的水凝胶具有伤口敷料方面的应用潜力。