响应性水凝胶及其在生物医药领域应用研究进展

响应性水凝胶又称"智能水凝胶",是以水凝胶为基础,经修饰响应多种理化性质及微小环境变化,从而改变自身性质的一类水凝胶。响应性水凝胶目前广泛应用于生物医药领域、材料领域等,如:制备pH响应性水凝胶负载阿霉素(DOX)治疗癌症,温度响应性水凝胶制作3D生物打印材料用于创伤修复,葡萄糖响应性水凝胶治疗糖尿病足等。本文介绍了响应性水凝胶研究的国内外发展动态,包括响应性水凝胶的制备、修饰方法及其在生物医药领域的应用,并对未来的发展方向进行了讨论与展望。     

智能纳米水凝胶的刺激响应性研究进展

智能纳米水凝胶在药物输送与可控释放、医学诊断、生物传感器、微反应器、催化剂载体等方面有良好的应用前景。结合本课题组近年来的研究成果,分别介绍了具有温度刺激响应性、pH刺激响应性、光刺激响应性、磁场刺激响应性、分子识别刺激响应性和多重刺激响应性智能纳米水凝胶的研究进展。另外,对这几种智能纳米水凝胶目前存在的问题和今后的发展方向提出了一些粗浅的看法。     

基于胆固醇的有机超分子智能凝胶

胆固醇分子具有特色的多环、多手性碳结构,因此可用于构筑有机超分子凝胶智能材料。该凝胶体系除了对温度有良好的感知响应性外,对其他的外界刺激,如光、pH、超声等也能够感知并响应。由于胆固醇分子是生命体中普遍存在的生物分子,基于胆固醇的有机超分子智能凝胶在生命现象模拟、药物输运等方面具有天然的优势。本文先根据胆固醇凝胶体系的不同种类,包括光响应型、氧化还原响应型、酸碱响应型、超声响应型,金属离子响应型以及触变响应型等,对该体系的结构与性能进行了介绍,然后介绍了对凝胶因子的修饰方法,最后结合目前的研究现状,探讨了胆固醇有机超分子凝胶的应用方向及前景。     

电场敏感的智能性水凝胶*

电场敏感水凝胶是一类在电刺激下可以溶胀、收缩或弯曲的智能性水凝胶,其主要特点是可以将电能转化为机械能。本文对近年来已见报道的电场敏感水凝胶的研究进行了较为详细的综述。同时,对电场敏感水凝胶的响应机理、影响水凝胶响应性的因素以及其在能量转换装置、人工肌肉等方面的应用也作了相应的介绍。     

智能型水凝胶结构及响应机理的研究进展

综述了智能型水凝胶研究的新进展,简要介绍了几类新型的刺激响应性水凝胶,分析了影响水凝胶敏感性的结构因素,介绍了水凝胶的有关理论,动力学研究和敏感性机理。     

智能性水凝胶

“智能”材料具有传感、处理和执行功能，水凝胶作为智能材料其应用前景良好。本文综述了智能水凝胶的近期研究发展，以Ｆｌｏｒｙ的溶胀理论着重探讨了刺激响应性，并介绍了化学机械现象及凝胶相转变。     

具有环境响应性的纤维素基水凝胶

随着对可再生资源开发利用的逐渐重视,基于纤维素环境响应型水凝胶结构设计及其响应性能的研究备受关注.环境响应纤维素基水凝胶不仅具有良好的生物相容性和生物可降解性,还表现出对环境因素特定的检出识别能力及明显响应性,拓展了水凝胶材料在生物医用、仿生智能材料等领域的应用.本综述首先从环境响应型纤维素水凝胶材料的结构设计出发,以交联方式分类简要介绍了纤维素基水凝胶的合成方法,具体包括物理交联、化学交联和其他交联方式等.接着,从水凝胶功能性入手,重点介绍了以一种或多种化学信号、物理信号为刺激源响应的纤维素基水凝胶材料;并以药物载体、形状记忆材料和伤口敷料等方面研究成果为例,阐述了环境响应型纤维素基水凝胶的相关应用,以及其在智能软体机器人和环保生物传感器等领域的巨大应用潜力.     

响应性支化聚合物的合成、组装及其生物医药应用

环境响应性超支化聚合物作为超支化聚合物中一类智能聚合物,备受研究者关注,已被广泛用于生物医药领域.本文主要介绍了本课题组在响应性支化聚合物的合成、组装及其生物医药应用方面的部分研究工作.主要包括以下三方面的内容:第一部分介绍了酸响应性支化聚合物、温敏性支化聚合物、还原响应性支化聚合物和光响应性支化聚合物的合成;第二部分介绍了含有二硫键的温敏性超支化聚合物在温度诱导下的自组装及自交联反应制备纳米凝胶、纳米胶囊和交联复合囊泡;第三部分介绍了响应性支化聚合物在药物传递和基因传递方面的应用.     

智能响应型水凝胶药物控释体系及其应用

药物控释体系可改善药物分子在机体内的释放、吸收、代谢和排泄过程,显著提高药物利用率并减弱药物的毒副作用。智能响应型水凝胶凭借其刺激响应性、亲水性和无毒性在药物控释方面得到了广泛的关注。本文介绍了智能响应型水凝胶药物控释体系的概念、机理和应用,详细归纳了智能响应型水凝胶药物控释体系的研究进展。按照刺激源不同将智能响应型水凝胶药物控释体系分为pH响应型、温度响应型、光响应型、生物分子(如葡萄糖、酶)响应型、外场(如电场、磁场)响应型、压力响应型、氧化还原响应型及多重响应型水凝胶药物控释体系。进一步介绍了智能响应型水凝胶药物控释体系在治疗癌症、急性肾损伤、眼病、糖尿病等疾病及抗菌、防止伤口感染等方面的应用。最后,基于目前智能响应型水凝胶药物控释体系存在的一些问题(如生物相容性差、存在突释或滞释现象、不可降解等)对其发展做出了展望。     

光响应性微凝胶的分子设计和智能材料构筑

微凝胶能够在外界刺激下改变自身尺寸,是一类重要的智能材料构筑基元。光刺激具有可远程控制、能快速切换等特点,在刺激响应性材料的设计中受到了广泛关注。将光刺激响应性基元引入到微凝胶体系,可以得到一系列具有重要应用前景的智能材料。本文综述了近年来光响应微凝胶的研究进展,总结了赋予微凝胶光响应性的四种分子设计,包括光致异构化型、光致生热型、光致(解)交联型、光致生酸型;介绍了光响应微凝胶在调光材料、药物控释、信息显示和自修复凝胶等领域的应用;展望了该领域的研究方向、发展和应用前景。     

Synthesis,swelling properties,and network structure of new stimuli‐responsive poly(N‐acryloyl‐N′‐ethyl piperazine‐co‐N‐isopropylacrylamide) hydrogels

Poly(N‐acryloyl‐N′‐ethyl piperazine‐co‐N‐isopropylacrylamide) hydrogels were prepared by thermal free‐radical copolymerization of N‐acryloyl‐N′‐ethyl piperazine (AcrNEP) and N‐isopropylacrylamide (NIPAM) in solution using N, N′‐methylene bisacrylamide as the crosslinking agent. The gels were responsive to changes in external stimuli such as pH and temperature. The pH and temperature responsive character of the gels was greatly dependent on the monomer content, namely AcrNEP and NIPAM, respectively. The gels swelled in acidic (pH 2) and de‐swelled in basic (pH 10) solutions with a response time of 60 min. With increase in temperature from 23 to 80 °C the swelling of the gels decreased continuously and this effect was different in acidic and basic solutions. The temperature dependence of equilibrium water content of the gels was evaluated by the Gibbs–Helmholtz equation. Detailed analysis of the swelling properties of these new gels in relation to molecular heterogeneity in acidic (pH 2) and basic (pH 10) solutions were performed. Water transport property of the gels was studied gravimetrically. In acidic solution, the diffusion process was non‐Fickian (anomalous) while in basic solution, the diffusion was quasi‐Fickian. The effect was more evident in solution of pH 2 than in pH 10. Various structural parameters of the gels such as number‐average molar mass between crosslink (M_c), the crosslink density (ρ_c), and the mesh size (ξ) were evaluated. The mesh sizes of the hydrogels were between 64 and 783 Å in the swollen state in acidic solution and 20 and 195 Å in the collapsed state in basic solution. The mesh size increased between three to four times during the pH‐dependent swelling process. The amount of unbound water (free water) and bound water of the gels was also evaluated using differential scanning calorimetry. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Multi‐Stimuli‐Responsive Polymer Materials: Particles,Films, and Bulk Gels

Stimuli‐responsive polymers have received tremendous attention from scientists and engineers for several decades due to the wide applications of these smart materials in biotechnology and nanotechnology. Driven by the complex functions of living systems, multi‐stimuli‐responsive polymer materials have been designed and developed in recent years. Compared with conventional single‐ or dual‐stimuli‐based polymer materials, multi‐stimuli‐responsive polymer materials would be more intriguing since more functions and finer modulations can be achieved through more parameters. This critical review highlights the recent advances in this area and focuses on three types of multi‐stimuli‐responsive polymer materials, namely, multi‐stimuli‐responsive particles (micelles, micro/nanogels, vesicles, and hybrid particles), multi‐stimuli‐responsive films (polymer brushes, layer‐by‐layer polymer films, and porous membranes), and multi‐stimuli‐responsive bulk gels (hydrogels, organogels, and metallogels) from recent publications. Various stimuli, such as light, temperature, pH, reduction/oxidation, enzymes, ions, glucose, ultrasound, magnetic fields, mechanical stress, solvent, voltage, and electrochemistry, have been combined to switch the functions of polymers. The polymer design, preparation, and function of multi‐stimuli‐responsive particles, films, and bulk gels are comprehensively discussed here.     

Sodium and pH responsive hydrogel formation by the supramolecular system calix[4]pyrrole derivative/tetramethylammonium cation

We report and rationalize the formation of gels, responsive to sodium cations or pH changes, in aqueous media by a supramolecular system constituted of an aryl extended calix[4]pyrrole receptor and the tetramethylammonium guest.     

Synthesis and characterization of polyhedral oligomeric silsesquioxane hybrid co‐crosslinked poly(N‐isopropylacrylamide‐co‐dimethylaminoethyl methacrylate) hydrogels

Polyhedral oligomeric silsesquioxane hybrid temperature and pH double‐responsive hydrogels with organic–inorganic co‐crosslinked networks are synthesized by in situ, free‐radical polymerization of N‐isopropylacrylamide and dimethylaminoethyl methacrylate in the presence of both organic crosslinker N,N′‐methylenebis(acrylamide) (BIS) and inorganic crosslinker octavinyl polyhedral oligomeric silsesquioxane (OvPOSS) in tetrahydrofuran media. The resulting hydrogels (OR‐OvP gels) display obvious temperature and pH double responsiveness, OvPOSS particles dispersed in polymer make a dominant effect on the properties of gels. With the increase of OvPOSS, the aggregation of particles on nano‐ or microscale happens and causes a considerable change on the properties of gels, such as the lower critical solution temperature and better compression strength. Specially, the interconnected microporous structure of gels ascribed to the microphase separation results in faster deswelling rate, which makes the gel become attractive. Besides, the crosslink by BIS intensifies the heterogeneity of gels significantly, which could also be used to adjust the properties of gels. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013 , 51, 1494–1504     

A new pH and thermo-responsive chiral hydrogel for stimulated release

Chirality of the amphiphile to promote gelation in the given solvent medium is narrated in a new catanionic surfactant mixture from a twin-chiral, twin-tailed surfactant derived from tartaric acid and cetyltrimethylammonium bromide (CTAB). The surfactant bis(decyloxy) succinic acid (BDSA), a chiral Gemini-type surfactant with a rigid spacer, in association with CTAB formed pH and temperature responsive vesicles and hydrogels. Molecular chirality gave rise to supertwisted fibrillar hydrogels at a BDSA:CTAB molar ratio of 1:2 and in 31% water content. The hydrogels from enantiomeric BDSA were reversibly pH and irreversibly temperature responsive at pH<6.2 and at 55 degrees C, respectively, whereas the corresponding sodium succinates formed transparent clear gels reversible to both pH and temperature. The hydrogels were able to entrap and release model dye molecules, Rhodamine B, and Congo red, responding to thermal and pH stimuli. Circular dichroism unraveled the chiro-optical behavior of the assembled fibers, allowing monitoring of aggregation and packing. The presence and the relative configuration of the stereogenic centers in the structure of this low molecular weight gelator have been observed to be critical to form gels. The high curvature Gaussian gel network was modeled based on the chiral elastic membrane approach and the pitch angle of the Gaussian twist was estimated to be 45 degrees.     

Inducing pH responsiveness via ultralow thiol content in polyacrylamide (micro)gels with labile crosslinks

Here we present the synthesis and characterization of pH responsive polyacrylamide microgels, synthesized via free radical polymerization of acrylamide and bis (acryloylcystamine) (BAC). The gels were made with ultralow amounts of thiol functional groups incorporated into the polymer. The resulting gel monoliths were mechanically chopped into microgel particles with size distributions ranging from 80 to 200 mum. The gels exhibit an interesting reversible pH-dependent rheological behavior which led to gelling of the colloidal suspension when the pH was increased, and a low-viscosity suspension was obtained when the pH was taken back to the original value. The viscosity of the colloidal system containing MBA crosslinked microgels remained insensitive to pH. This observation motivated further analysis; viscosity measurements of the highly viscous (gel-like) state of the BAC crosslinked microgel colloidal suspension were carried out to further understand the rheological behavior of the colloidal system. Electrophoretic mobility measurements as function of pH of the BAC and MBA crosslinked colloidal polyacrylamide microgel suspensions were performed. The swelling behavior of the microgels for both colloidal systems was also determined as function of pH using static light scattering. This swelling behavior was used to rationalize the observed rheological behavior. The work presented here demonstrates that free thiol groups present within a polymer gel matrix confer pH responsive behavior to the gel in solution. The viscosity of a BAC crosslinked microgel suspension was also measured under reducing conditions. The viscosity of the microgel suspension reduced with time, due to the breakage of the disulfide bonds in the crosslinkers.     

Multi‐Stimuli‐Responsive Polymeric Materials

Stimuli‐responsive materials are of immense importance because of their ability to undergo alteration of their properties in response to their environment. The properties of such materials can be tuned by subtle adjustments in temperature, pH, light, and so forth. Among such smart materials, multi‐stimuli‐responsive polymeric materials are of pronounced significance as they offer a wide range of applications and their properties can be tuned through several mechanisms. Here, we aim to highlight some recent studies showcasing the multi‐stimuli‐responsive character of these polymers, which are still relatively little known compared to their single‐stimuli‐responsive counterpart.     

壳聚糖基智能凝胶材料及其应用

壳聚糖是一种通过超分子作用形成凝胶的氨基多糖,可形成配合物,如聚电解质配合物,共价配合物和自组装配合物等。壳聚糖基智能凝胶在控制释放载体、分离膜、固定化基质、人工细胞外基质和场响应材料等方面应用前景广阔。     

Self‐Assembling Peptide Gels for 3D Prostate Cancer Spheroid Culture

Progress in prostate cancer research is presently limited by a shortage of reliable in vitro model systems. The authors describe a novel self‐assembling peptide, bQ13, which forms nanofibers and gels useful for the 3D culture of prostate cancer spheroids, with improved cytocompatibility compared to related fibrillizing peptides. The mechanical properties of bQ13 gels can be controlled by adjusting peptide concentration, with storage moduli ranging between 1 and 10 kPa. bQ13's ability to remain soluble at mildly basic pH considerably improved the viability of encapsulated cells compared to other self‐assembling nanofiber‐forming peptides. LNCaP cells formed spheroids in bQ13 gels with similar morphologies and sizes to those formed in Matrigel or RADA16‐I. Moreover, prostate‐specific antigen (PSA) is produced by LNCaP cells in all matrices, and PSA production is more responsive to enzalutamide treatment in bQ13 gels than in other fibrillized peptide gels. bQ13 represents an attractive platform for further tailoring within 3D cell culture systems.