微尺度水凝胶与组织工程

水凝胶已被广泛应用于组织工程、药物控释、生物传感器等生物医学领域。随着微制造技术的发展,在纳微米尺度范围内制备形状和尺寸与自然组织相匹配的工程化水凝胶为解决血管化困难、复杂组织结构模拟、多细胞接种等组织工程难题带来了曙光。本文将主要讨论微尺度水凝胶在组织工程领域的研究现状,重点介绍微尺度水凝胶的合成方法及其在血管化和复杂组织结构模拟方面的应用。     

海藻酸钠水凝胶的制备及其在药物释放中的应用

近年来,由于智能水凝胶在药物的控制释放、基因传送、组织工程等领域的应用前景诱人,研究者对智能水凝胶的研究十分活跃。合成类水凝胶常用的单体有丙烯酸及其衍生物、丙烯酰胺及其衍生物等,合成水凝胶具有较好的稳定性,但其生物降解性和生物相容性较差。天然类水凝胶的原料主要有壳聚糖、海藻酸钠、纤维素、淀粉等。由于这些天然多糖具有较好的生物相容性和生物降解性,同时价廉易得,因此,天然类水凝胶在药物控制释放领域更具有优势。海藻酸钠是β-D-甘露糖醛酸(β-D-mannuronic,M)和α-L-古洛糖醛酸(α-L-guluronic,G)按照(1→4)糖苷键连接而成的线型聚合物,每个糖醛酸单元上含有一个羧基,因此,海藻酸钠在中性或碱性条件下呈现聚阴离子电解质的性质。本文综述了海藻酸钠水凝胶的制备方法,包括物理交联法、化学交联法、酶交联法、互穿聚合物网络等;概述了海藻酸钠水凝胶在药物释放中的应用,包括口服给药、皮下给药、黏膜给药、肺部给药、经皮给药等;最后讨论了海藻酸钠水凝胶在研究与应用中存在的问题。     

酶促水凝胶的合成及生物传感应用研究进展

近年来,聚合物基水凝胶材料已经成为一种独特的修饰材料,为新型生物传感器的设计提供了新思路.酶具有特异性高、毒性低、催化效率高等良好特性,已被用于催化聚合各种新型水凝胶.本文综述了几种酶促水凝胶的合成方法及其在细胞代谢物、组织工程、伤口愈合和癌症监测等方面的潜在应用,并对基于酶促水凝胶反应的生物传感器的制备与应用进行了总...     

可拉伸超韧水凝胶的制备和应用

综述了可拉伸超韧水凝胶的设计原理及其在组织工程和柔性电子器件领域的应用. 通过将网络结构层次、 化学结构、 增韧机制与宏观力学性能相结合, 重点讨论了单网络水凝胶、 双网络水凝胶、 纳米复合水凝胶及其它水凝胶等可拉伸超韧水凝胶的研究进展, 并总结和展望了新思路和新方向.     

含儿茶酚基团的湿态组织粘附水凝胶

湿态粘附作用对于生命的孕育和发展具有重要意义。水凝胶是一类兼具固液特性的智能材料，组织粘附水凝胶因多功能性和生物相容性而被广泛应用于伤口闭合和修复、细胞工程、组织工程等领域。然而，湿态组织表面的水合层阻碍了组织粘附水凝胶与组织表面形成界面粘附键。面对这一挑战，受海洋贻贝足丝蛋白中DOPA的儿茶酚基团是水下粘附的关键结构的启发，含儿茶酚基团的湿态组织粘附水凝胶的研究引起了广泛关注。本综述介绍了贻贝足丝蛋白(Mfps)的结构及湿态粘附机理，并将儿茶酚衍生物分为天然Mfps或利用基因工程合成的Mfps、含儿茶酚基团的小分子化合物、儿茶酚基团改性的天然高分子以及含儿茶酚基团的合成功能高分子；随后，概述近十年含儿茶酚基团的湿态组织粘附水凝胶在组织创口修复材料、生物涂层材料、靶向型药物输送材料、生物电子设备材料的研究进展；文末，展望了此类水凝胶材料未来发展面临的机遇和挑战。     

用于基因传递系统控制释放的可生物降解高分子材料

综述了用于基因传递系统控制释放的各类高分子材料包括天然高分子及其衍生物、合成高分子,并介绍了它们在基因治疗和组织工程领域中的应用.     

自愈合水凝胶的合成及在药物制剂中的应用进展

自愈水凝胶通过重新连接水凝胶基质内断裂的链路,实现裂纹闭合。自愈合水凝胶在物理损伤后恢复原来结构和功能,并且具有多重特性,如可注射性、导电性、粘合性,近年来越来越受到重视,并且广泛应用于制药工程、生物医学等领域。但是其韧性与快速愈合的相容性仍有待解决,在人体环境中的应用仍有待进一步研究。介绍了近年来具有快速自愈合能力和机械韧性水凝胶的创新型合成方法。以及其在医药学中的广泛应用。相信自愈合水凝胶在未来具有长远的发展前景及巨大的可能性。     

可注射水凝胶及其在再生医学领域的应用

近年来,由工程生物材料制成的可注射治疗剂正变得越来越流行,并推动传统的临床实践走向微创化.可注射水凝胶由于其可调控的物理及化学特性、可控的降解性能、高含水量以及在微创方式下实现递送的能力,在组织工程和药物递送领域中变得越来越重要.研究者们已开发出例如原位交联水凝胶、大孔水凝胶、水凝胶微粒、动态交联水凝胶等一系列性能独特的可注射水凝胶.通过调控水凝胶的固含量和交联密度,并引入适当的共价或非共价相互作用,例如静电相互作用、疏水相互作用等,这些水凝胶可在注射过程中实现生物活性分子的递送.同时,可注射水凝胶亦可用于细胞的递送,提供细胞培养所需的三维环境,并通过调控力学性能、化学修饰、生物功能化修饰等手段调控细胞黏附、增殖、分化等行为.本文旨在回顾近年来可注射水凝胶的设计和制备的相关进展,以及其在再生医学中的应用,并对该领域存在的挑战和潜力进行了展望.     

甲基丙烯酰胺基明胶水凝胶研究进展

甲基丙烯酰胺基明胶(GelMA)水凝胶的制备及其在生物医学领域的应用是最近十几年的研究热点。GelMA水凝胶因其独特的光致交联特性,可以加工成不同形貌的水凝胶支架材料,同时,因其具有可控的力学性能、降解性能,以及优秀的生物相容性,已成为具有广泛应用前景的生物高分子聚合物材料。本文主要介绍了GelMA水凝胶在止血材料、创伤敷料、组织工程支架、药物控释、骨缺损修复等领域的研究进展。     

光聚合水凝胶及其在组织工程中的应用

水凝胶是一种亲水性聚合物网络,可以溶胀大量水,其物理性质接近软组织.光聚合与传统的聚合方法相比,具有反应速率快、反应条件缓和、反应放热低等特点.因此,光聚合水凝胶广泛应用于生物医学领域.本文介绍了光聚合水凝胶材料,并详细论述了光聚合水凝胶在药物释放体系、组织工程支架材料、细胞受控生长、细胞微囊化和可注射水凝胶等方面的应用.可以预见光聚合水凝胶作为生物材料在组织工程及再生医学领域中具有良好的应用前景.     

Hydrogels based on polycarboxylic acid-agar-agar complexes

IR spectroscopy and viscometry data have shown that poly(acrylic acid) and poly(methacrylic acid) form complexes with agar-agar in aqueous solutions as they do with other polysaccharides. The polyacid-agar-agar complexes are typical hydrogels. The swelling index of hydrogels based on the poly(methacrylic acid)-agar-agar complex has been found to be markedly lower than that of poly(acrylic acid)-agaragar complex. The hydrogels based on the complex of cross-linked poly(acrylic acid) with agar-agar can be of practical interest as polymeric carriers for drugs.     

“Smart” carboxymethylchitosan hydrogels crosslinked with poly(N-isopropylacrylamide) and poly(acrylic acid) for controlled drug release

Carboxymethylchitosan (CMC) hydrogels containing thermo-responsive poly(N-isopropylacrylamide) (poly(NIPAAm)) and pH-responsive poly(acrylic acid) (poly(AA)) were prepared via a free radical polymerization in the presence of hexamethylene-1,6-di-(aminocarboxysulfonate) crosslinking agents. A proper ratio of CMC to NIPAAm and AA used in the reaction was investigated such that the thermo- and pH-responsive properties of the hydrogels were obtained. Water swelling of the hydrogels was improved when the solution pH was in basic conditions (pH 10) or the temperature was below its lower critical solution temperature (LCST). Effects of the change in solution temperature and pH on water swelling properties of the hydrogel as well as the releasing rate of an entrapped drug were also investigated. The hydrogels were not toxic and showed antibacterial activity against Straphylococcus aureus (S. aureus). The pH- and thermo-responsive properties of this novel “smart” hydrogel might be efficiently used as dual triggering mechanisms in controlled drug release applications.     

Sucrose diacrylate: A unique chemically and biologically degradable crosslinker for polymeric hydrogels

A series of degradable hydrogels based on different vinyl monomers such as acrylamide, sucrose-1′-acrylate, and acrylic acid were synthesized using sucrose-6,1′-diacrylate (SDA) as a crosslinking agent. SDA was prepared by enzymatic transesterification of vinyl acrylate with sucrose in pyridine. Base catalyzed hydrolysis of SDA in aqueous solution was studied as a function of pH. As expected, hydrolysis of SDA was faster at higher pHs such that poly(acrylamide), poly(sucrose 1′-acrylate), and poly(acrylic acid) hydrogels underwent substantial degradation at and above pH 7, 9, and 13, respectively. The degradation was characterized by changes in the swelling ratios of the hydrogels indicating breakage of the crosslinking agent. Degradation of the hydrogels at their chemically stable pHs was studied in presence of enzymes. Enzymes, including pepsin and a fungal Lipase, were able to degrade the poly(acrylamide) hydrogel at pH 4 and 5, respectively. Poly(acrylic acid) hydrogel was degraded in presence of a fungal protease at pH 7.8. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 2221–2229, 1997     

Synthesis and Properties of Poly(AAm‐KMA‐MA) Hydrogels

In this investigation, poly(acrylamide‐co‐potassium methacrylate‐co‐maleic acid) hydrogels, poly(AAm‐KMA‐MA) were synthesized by redox copolymerization in aqueous solution. The effect of reaction parameters, such as concentration of maleic acid, crosslinking agent, initiator and activator, on the swelling behavior was investigated in detail. The swelling/diffusion characteristics were also evaluated for 1,4‐butanediol diacrylate (BDDA) and 1,2‐ethyleneglycol dimethacrylate (EGDMA) crosslinked hydrogels having different amounts of maleic acid. The results indicate that the water diffusion of hydrogels was of a non‐Fickian type. The hydrogels were characterized by IR spectroscopy and thermogravimetric analysis (TGA). Their surface characteristics were observed by using scanning electron microscopy (SEM). Furthermore, their swelling phenomena in different pH and salt solutions and simulated biological fluids was also studied.     

自由基引发的可注射PLA-b-PEG-b-PLA大分子单体和α-CD超分子结构水凝胶的合成与表征

以数均分子量为6000的聚乙二醇为引发剂,以辛酸亚锡为催化剂引发丙交酯开环,再用甲基丙烯酸酐进行封端生成大分子单体.然后将大分子单体和α-环糊精混合,分别用维生素C和硫酸亚铁与过硫酸铵组成的氧化还原引发剂引发聚合,得到了两种不同结构的超分子结构水凝胶.用1HNMR,FTIR,TGA和XRD等分析测试手段对大分子单体及形成的水凝胶进行了表征.流变仪测试结果表明,该水凝胶固化时间合适,并具有可注射性.     

咪唑盐类聚离子液体抗菌剂的制备及其在水凝胶敷料中的应用

皮肤伤口的感染严重威胁患者的生命安全,虽然传统的含有银离子或小分子抗生素的抗菌水凝胶伤口敷料具有广谱的杀菌功效,但这些抗菌水凝胶敷料中的抗菌剂存在一定的生物毒性和耐药性风险,无法满足临床长期使用的要求.咪唑盐类聚离子液体由于其含有较强的正电荷效应以及疏水链段,因此其作为新型的聚合物抗菌剂具有较强的抗菌效果.本研究首先通...     

How much weighs the swelling pressure

We are presenting a new method to study the swelling of gels by following the apparent weight increase during confined swelling. This method, compared to other procedures, is characterized by its simplicity and versatility to study the influence of the experimental conditions such as composition of the swelling agent and temperature. Examples are given for poly(acrylic acid) and poly(N-isopropyl acrylamide) hydrogels and the influence of ethanol content, pH, and temperature in the water pool.     

Unusual salt stability in highly charged diblock co-polypeptide hydrogels

The stability and properties of dilute solution hydrogels, synthesized by transition metal mediated polymerization of amino acid N-carboxyanhydrides (NCAs), have been studied in deionized (DI) water as well as various ionic media. These hydrogels are diblock amphiphilic copolymers of hydrophilic, charged segments of poly(l-lysine HBr) or poly(l-glutamic acid sodium salt), and helical, hydrophobic segments of poly(l-leucine). While many of these samples are able to form strong gels in deionized water at polymer concentrations as low as 0.25 wt %, stability in salt or buffer solutions was found to be only achieved at moderately higher polymer concentrations ( approximately 3.0 wt %). We have adjusted relative copolymer compositions and molecular weights to optimize hydrogel strength and polymer solubility in salt concentrations up to 0.5 M NaCl, as well as in cell growth media and aqueous buffers of varying pH. These materials are unique since they do not collapse in high ionic strength media, even though gel formation is contingent upon the presence of highly charged polyelectrolyte segments. The remarkable properties of these hydrogels make them excellent candidates for use as scaffolds in biomedical applications, such as tissue regeneration.     

Photo cross-linked biodegradable hydrogels for enhanced vancomycin loading and sustained release

A series of biodegradable hydrogels based on dextran and poly（L-glutamic acid） were fabricated for effective vancomycin loading and release. The preparation of hydrogels was simply achieved by photo cross-linking of methacrylated dextran and poly（L-glutamic acid）-g-hydroxyethyl methacrylate （PGH） in the presence of photoinitiator 12959. The structures of hydrogels were characterized by FTIR and SEM. The swelling and enzymatic degradation behaviors of hydrogels were examined to be dependent on the poly（L-glutamic acid） content in the hydrogels. The higher content of poly（L-glutamic acid） in the gel, the higher swelling ratio and quicker degradation were observed. More interestingly, the hydrogel with higher PGH ratio showed higher vancomycin （VCM） loading content, which might be due to the electrostatic interaction between carboxylate groups in hydrogel and ammonium group of VCM. In vitro drug release from the VCM-loaded hydrogels in aqueous solution exhibited sustained release of VCM up to 72 h, while the in vitro antibacterial test based on the VCM-loaded hydrogel showed an efficient Methicillin-Resistant S. aureus （MRSA） inhibition extending out to 7 days. These results demonstrated that the biodegradable hydrogels which formed by in situ photo-cross linking would be promising as scaffolds or coatings for local antibacterial drug release in tissue engineering.     

Removal of cationic dyes by poly(acrylamide-co-acrylic acid) hydrogels in aqueous solutions

Poly(acrylamide-co-acrylic acid (poly(AAm-co-AAc)) hydrogels prepared by irradiating with γ-radiation were used in experiments on swelling, diffusion, and uptake of some cationic dyes such as Safranine-O (SO) and Magenta (M). Poly(AAm-co-AAc) hydrogels irradiated at 8.0 kGy have been used for swelling and diffusion studies in water and cationic dye solutions. The maximum swellings in water, and SO, and M solutions observed are 2700%, 3500%, and 4000%, respectively. Diffusions of water and cationic dyes within hydrogels have been found to be non-Fickian in character. Adsorption of the cationic dyes onto poly(AAm-co-AAc) hydrogels is studied by the batch adsorption technique. The adsorption type was found Langmuir type in the Giles classification system. The moles of adsorbed dye for SO and M per repeating unit in hydrogel (binding ratio, r) have been calculated as 3834×10⁻⁶ and 1323×10⁻⁶, respectively. These results show that poly(AAm-co-AAc) hydrogels can be used as adsorbent for water pollutants such as cationic dyes.