【作者】 贺盟；

【导师】 张俐娜；

【作者基本信息】 武汉大学 ， 材料物理与化学， 2014， 博士

【摘要】 仿生和生物医用材料已成为国际前沿领域之一。仿荷叶和蝉翅微结构制备的自清洁材料、仿洋葱结构多层凝胶以及仿高硬度骨骼的组织工程支架已日益引人注目。这些性能卓越的材料往往与它们表界面独特微观结构以及表、界面相互作用有关。纤维素和甲壳素是地球上最丰富的生物质资源,属于碳水聚合物,统称为天然聚多糖。它们具有安全、无毒、生物相容和生物降解等特点,是构筑仿生及生物医用功能材料理想的原料。本工作利用纤维素和甲壳素为原料,分别经碱/尿素水溶液低温溶解后通过非共价键力并基于表、界面相互作用创建出新型功能材料。同时,通过固体核磁共振碳谱(13CNMR)、红外光谱(FT-IR)、X射线衍射(XRD)、扫描电子显微镜(SEM)、透射电子显微镜(TEM)、热重分析(TCA)、示差扫描量热(DSC)、水接触角测试仪、流变仪、紫外-可见光谱仪(uv)、荧光光谱仪(FL)和力学性能测试等表征材料的结构和性能,并研究了它们结构与功能之间构效关系以及表面界面相互作用。同时,通过生物试验评价它们在生物医用领域的应用前景。由此,为利用聚多糖构建一系列生物质大分子功能性材料开辟新途径。本工作的主要创新点包括：(1)基于羟基磷灰石与纤维素界面间氢键相互作用,构建出生物相容纤维素/羟基磷灰石纳米复合膜,并使纳米粒子均匀分散;(2)通过两相间界面相互作用构建出纤维素/Si02纳米复合膜,并揭示其湿气响应性机理；(3)基于亲水-疏水界面相互作用,首次利用纤维素凝胶膜微米及亚微米级孔洞作为基底,实现硬脂酸、羟基硬脂酸(HOA)等疏水性晶体有序可控的生长,创建出高疏水性纤维素膜以及仿毛发生长“自清洁”荧光膜；(4)利用固液界面快速接触,成功制备出高强度和生物相容多层纤维素水凝胶；(5)基于甲壳素与聚乙烯醇(PVA)及羟基磷灰石的界面相互作用构建出高强度甲壳素/PVA复合凝胶以及甲壳素/HAP复合塑料,并证明它们具有优良生物相容性。本论文的主要研究内容和结论包括以下七部分。通过一种简便、价廉的方法在NaOH[/尿素水溶剂体系中将羟基磷灰石纳米粒成功引入纤维素基体。TEM和FTIR结果证明纤维素和羟基磷灰石间存在强氢键力,导致羟基磷灰石纳米粒(20-40nnm)牢固地固定和均匀分散在纤维素膜中,并保持纳米尺寸,形成有机/无机纳米复合膜。复合膜中羟基磷灰石粒子呈现很好的结晶性。这种杂化膜的力学强度和热稳定性随羟基磷灰石的加入而提高。尤其,293T细胞培养实验证明这种无机/有机杂化膜具有无毒和良好的生物相容性。因此,它们在生物医学领域具有作为骨骼修复材料的应用前景。基于SiO2与水和纤维素间的氢键相互作用,在预冷的LiOH/汞素水溶剂体系中成功地引入SiO2纳米粒子到纤维素基体,经凝固、再生后形成无机/有机纳米复合膜。实验结果证明纤维素和Si02纳米粒子间强氢键相互作用导致Si02纳米粒子均匀分散在纤维素基底,使复合膜显示良好的相容性。透光率和力学性能证明Si02纳米粒子明显提高了纤维素凝胶的力学性能和透光性以及纤维素膜的力学性能。尤其,纤维素/Si0：纳米复合膜在干态时为乳白色,然而浸入水中则变为透明膜。结构分析证明：在大量水分存在下,SiO2与水和纤维素之间形成氢键并产生均匀的网络结构,致使相容性和透光率明显提高。这种纤维素/Si02智能复合膜显示对湿气的响应性,它在湿度和溶剂检测方面具有应用前景。硬脂酸是一种天然产物,具有生物可降解性。利用再生纤维素凝胶的孔洞结构,通过溶剂挥发诱导结晶,实现硬脂酸晶体在纤维素膜表面可控生长。这些硬脂酸微晶体能够牢固嵌入纤维素孔洞,同时纤维素孔壁诱导硬脂酸形成具有微纳二级结构片状微晶体,导致表面高粗糙度。XRD、SEM和水接触角测试结果证明硬脂酸以竖立微晶片均匀分布在纤维素膜表面,微晶片间大量空隙可捕获大量空气导致纤维素膜高疏水性。实验证明,复合膜具有高疏水性、生物降解性、安全和价廉,可望用于环境友好的防水包装材料。基于亲水-疏水界面相互作用,羟基硬脂酸晶体能够在纤维素亚微米孔洞中实现可控的有序及竖立生长,模仿“毛发生长”。多孔纤维素基体不仅为羟基硬脂酸晶体固定提供了孔洞基底,而且其亲水性外壳与疏水羟基硬脂酸间不相容性诱导羟基硬脂酸晶体纵向独立地生长,形成有序的类似“短毛”晶体。羟基硬脂酸尾端的羟基与纤维素形成氢键从而固定在纤维素基底,同时亲水-疏水界面相互作用导致羟基硬脂酸晶体沿亲水性纤维素孔壁上向上生长,并形成光滑表面。通过改变溶剂挥发温度和羟基硬脂酸浓度可以调控晶体形貌和尺寸,而且在适宜实验条件可制备出完美的蠕虫状羟基硬脂酸晶体。纤维素/羟基硬脂酸亚微米复合膜具有高疏水性和自清洁性。尤其,4-(1,2,2-三苯乙烯)苯甲酸(TPE-COOH)可以和羟基硬脂酸一起通过疏水作用结合并迁移到纤维表面而产生聚集激发荧光,进而得到纤维素/HOA/TPE-COOH荧光、疏水双功能复合膜。由此,开辟了利用天然产物和一步法在纤维素多孔基底上设计仿生材料的新途径,并可模拟自然界动物毛发生长。基于附着醋酸琼脂球或棒与纤维素溶液间快速固／液界面接触,成功制备出洋葱状和多层管状纤维素凝胶。通过琼脂芯表面醋酸与纤维素溶液快速接触导致纤维素包合物迅速破坏而引起纤维素链快速自聚集,形成凝胶层。同时,调节纤维素溶液浓度、凝胶芯直径和固／液界面接触时间可以控制多层纤维素凝胶层厚和层间空隙。由于凝胶中纤维素链束紧密堆积,致使多层纤维素凝胶具有较高压缩强度。此外,多层纤维素凝胶具有良好的结构稳定性,它对乙醇、丙酮、N,N-二甲基乙酰胺(DMAc)和NaOH水溶液等具有优异抗性。生物实验证明小鼠成纤维细胞(L929)在纤维素凝胶层上以及层间黏附和增殖,表现出无毒性和良好的生物相容性。这种具有可控结构和尺寸的多层纤维素凝胶在生物医用领域具有应用前景。基于部分化学交联以及冷冻-解冻过程诱导聚乙烯醇(PVA)结晶以及分子间氢键连接,构建出高强度甲壳素/PVA复合凝胶。当PVA含量为25%时(RCP75凝胶),通过甲壳素和PVA链密集堆积以及分子取向和连接形成有序排列而具有类似海蜇凝胶状结构。固体13CNMR、XRD、SEM结果说明反复冷冻-解冻过程可诱导甲壳素和PVA链紧密堆积及分子间氢键键接增强,同时由冰晶和PVA晶体产生微相分离导致复合凝胶层状多孔结构形成。这种双交联层状网络多孔结构能在屈服点附近很好地分散应力,因而RCP75凝胶的压缩强度迅速增加,远高于其它RCP凝胶。此外,甲壳素/PVA复合凝胶具有优异的生物相容性和安全无毒性,可以满足组织工程材料的要求。因而这种复合凝胶在生物医用领域具有应用前景。基于甲壳素水凝胶在真空干燥过程中甲壳素链上羟基裸露导致其分子间氢键键合引起凝聚,于是分子重新排列,并沿平面各个方向取向和紧密堆积形成新的聚集态结构,从而改变材料材料形状和尺寸,构建出新一类甲壳素塑料。同时,基于甲壳素水凝胶具有多孔结构和对金属离子强吸附作用,在甲壳素孔洞中原位合成羟基磷灰石粒子。羟基磷灰石和甲壳素间存在着强相互作用,从而明显提高甲壳素复合塑料力学性能。尤其,小鼠胚胎成骨细胞(MC3T3-E1)培养实验证明羟基磷灰石的引入显著增强甲壳素塑料对成骨细胞的粘附能力。因此,该复合塑料作为骨骼修复材料具有应用前景。本学位论文利用碱／尿素水溶液作为溶剂低温溶解难溶性的纤维素和甲壳素,并且成功创建出一系列纤维素和甲壳素功能材料。同时阐明了表、界面相互作用以及材料结构与性能之间的关系。由此,为设计高疏水纤维素膜、“自清洁”纤维素荧光膜、高强度生物相容多层纤维素凝胶、高强度甲壳素／无机物复合凝胶以及甲壳素复合塑料等功能材料提供了新思路和新方法。这些基础研究结果具有明显创新性和学术价值,同时符合可持续发展战略。因此本论文具有重要的科学意义和应用前景。更多还原

【Abstract】 Biomimetic and biomedical materials have become one of the international frontiers. Lotus leaf and cicada wing inspired self-cleaning materials, onion inspired multi-layered hydrogels and tough bone inspired tissue engineering scaffolds have attracted more and more attentions. Such extraordinary biomimetic and biomedical materials are associated with their unique micro structures on the surface and interface as well as the interaction. Cellulose and chitin are the most abundant bio mass resources on earth, and they belong to carbohydrate polymers, generally known as the natural polysaccharides. They exhibit characteristics of safe, nontoxic, biocompatible and biodegradable, so they are ideal raw materials for the construction of biomimetic and biomedical functional materials.Utilizing cellulose and chitin as raw materials, novel functional materials were fabricated directly from solutions through non covalent bond interaction as well as surface and interface interaction in this work, which were dissolved in alkli/urea aqueous solutions at low temperature, respectively. Meanwhile, the structure and properties of materials were characterized by solid state13C NMR, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), water contact angle measurement, rheological measurements, thermogravimetric analysis (TGA), UV-vis spectroscopy(UV), photoluminescence spectra (PL) and mechanical testing. The correlation between structure and properties as well as surface and interface interaction was also studied. Meanwhile, the potential application in biomedical fields was also evaluated by biological experiments. Thus, it could develop novel pathways by using polysaccrides for the construction of a series of biopolymer-based functional materials.The innovation of this work was listed as follows:(1) Biocompatible cellulose/hydroxyapatite nanocomposite films were constructed and nano hydroxyapatite particles (nHAP) were dispersed evenly as a result of the interfacial hydrogen bonding interaction between hydroxyapatite and cellulose;(2) Cellulose/SiO2nanocomposite films were constructed through two-phase interfacial interaction, and the corresponding moisture responsive mechanism was clarified;(3) Based on the hydrophilic-hydrophobic interfacial interaction, the micro and submicron pores of cellulose gel sheets were used for the first time to control the stearic acid and12-Hydroxyoctadecanoic acid (HOA) crystals grow orderly for the fabrication of high hydrophobic cellulose films and hair growth inspired "self-cleaning" fluorescent cellulose films;(4) High strength and biocompatible multi-layered cellulose hydrogels were successfully constructed by the fast contact of solid-liquid interface;(5) Based on the interfacial interaction between chitin and poly(vinyl alcohol)(PVA) as well as hydroxyapatite, high strength chitin/PVA composite hydrogels and chitin/HAP plastics with excellent biocompatibility were constructed.The primary contents and conclusions of this work can be divided into seven parts.The nHAP were successfully incorporated into the cellulose matrix in NaOH/urea aqueous solvent through a simple and low cost method. The TEM and FTIR results demonstrated that the strong hydrogen bonding force induced the tight fixation and homogenous dispersion of nHAP (20-40nm) in the cellulose film, forming organic/inorganic hybrid films with primary hydroxyapatite size. The nHAP exhibited good crystallinity in the cellulose film. The mechanical strength and thermal stability increased with the incorporation of nHAP. Especially, the293T cell culture experiment demonstrated that the hybrid films exhibited nontoxicity and good biocompatibility. Therefore, they would have potential application as bone repairing materials in the biomedical field.Based on the hydrogen bonding interaction among SiO2, water and cellulose, SiO2nanoparticles were introduced into the cellulose matrix, forming organic/inorganic hybrid films through coagulation and regeneration. The strong hydrogen bonding interaction induced the homogenous dispersion of SiO2in the cellulose matrix, displaying good compatibility. The results of transmittance and mechanical property revealed that the SiO2nanoparticles increased the mechanical property and transparency of cellulose hydrogels as well as the mechanical property of cellulose film. Especially, the cellulose/SiO2nanocomposite film displayed milky color at dry state and changed to transparent film when it was soaked into water. The structure analysis demonstrated that the SiO2, water and cellulose could form hydrogen bonding with the existence of abundant water to create uniform network structure, resulting in the increase of compatibility and transmittance. This kind of cellulose/SiO2smart composite film exhibited moisture responsive property, showing potential application in moisture and solvent detection.Stearic acid is a natural product, and it is biodegradable. Stearic acid crystals could grow controllably on the cellulose film by using the porous structure of regenerated cellulose gels through the solvent-vaporized induced crystallization method. The stearic acid crystals were fixed in the pores of the cellulose matrix tightly, and the controllable stearic acid crystallization was induced by the pore wall to form plate-like micro crystals with a micronano binary structure, resulting in high surface roughness. The results of XRD、SEM and water contact angle measurements demonstrated that vertical microplate-like stearic acid crystals could distribute evenly on cellulose film surface, the interspaces among the crystals could trap abundant air for the improvement of hydrophobicity. Therefore, the cellulose/stearic acid films were highly hydrophobic, biodegradable, safe, and inexpensive, showing potential applications in biodegradable waterproof packaging.Based on hydrophilic-hydrophobic interfacial interaction, HOA crystals could grow orderly and vertically in the submicron cavities of cellulose, resembling "hair growth" The porous cellulose matrix supplied not only cavities for the HOA crystals fixation, but the incompatibility between hydrophilic shells and hydrophobic HOA also favored the longitudinal and isolated growth of the HOA crystals, forming orderly "short hair" like crystals. The HOA with a few hydroxyls on the tail end could form hydrogen bonds with cellulose to be fixed in the cellulose matrix. The hydrophobic-hydrophilic interfacial interaction could induce the growth of the relatively hydrophobic HOA crystals along the pore wall of the hydrophilic cellulose separately, which exhibited a smooth surface. The HOA crystal morphologies can be controlled by changing the temperature and HOA concentration, and the perfect wormlike crystals could be fabricated at the suitable experimental conditions. The cellulose/HOA submicron composite films exhibited high hydrophobicity with self-clean ability. Especially,4-(1,2,2-triphenylethenyl) benzoic acid,(TPE-COOH) could interact with HOA through hydrophobic interaction to migrate onto the cellulose film surface and aggregate to emit, so the bifunctional photoluminescent and hydrophobic cellulose/HOA/TPE-COOH films were constructed. Thus, it would open up a novel one-step pathway to facilely design bio-inspired materials in the porous cellulose matrix by utilizing natural products, to resemble "hair growth" on the animal skin in the nature.Onion-like and multi-layered tubular cellulose hydrogels were constructed successfully through a fast contact of the solid-liquid interface between the gel spheres and rods loaded with acid and the cellulose solution. Due to the instant destruction of the cellulose inclusion complex (IC) by contact with acid on the surface of the gel core, the cellulose hydrogel layer could be constructed rapidly along the gel surface through the quick self-aggregation between cellulose chains. The layer thickness and inter-layer space could be controlled by adjusting the cellulose concentrations, the gel core diameter and the contacting time of the solid-liquid interface. Meanwhile, the multi-layered cellulose hydrogels exhibited relative high compressive strength, as a result of the relatively close packing of the cellulose chain bundles. The hydrogels had good architectural stability and solvent resistance against ethanol, acetone, Dimethylacetamide (DMAc) and NaOH aqueous solution. The biological experiment demonstrated that the L929cells could adhere and proliferate on the surface of the layers and in the inter-layer space, showing non-cytotoxicity and good biocompatibility. The controllable architecture and layer size of the multi-layered cellulose hydrogels are important in the application as biomedical materials.Novel chitin/PVA gels with high strength and excellent biocompatibility were fabricated by partially chemical crosslinking and treating with freezing-thawing process to induce the formation of PVA crystals and the intermolecular hydrogen bonds. When PVA content was25wt%for RCP75hydrogel, a regular jellyfish gel-like structure occurred, as a result of the formation of a dense packing pore wall consisted of chitin and PVA chains as well as the intermolecular hydrogen bonds to form oriented arrangement. The results of solid13C NMR、XRD and SEM revealed that the repeated freezing/thawing cycles induced a dense packing of physically and chemically crosslinked chains between chitin and PVA, enhanced intermolecular hydrogen bonding as well as a phase separation caused by the crystalline ice and the PVA crystals of the composite gels, leading to the layered porous structure. The mechanical properties of RCP75were improved rapidly and much higher than the other RCP gels and pure chitin gels, as a result of the broadly dispersed stress near a crack tip caused by the layered porous structure with bi-crosslinked networks. Furthermore, the chitin/PVA hydrogel had excellent biocompatibility and safety. The chitin/PVA hydrogels will be of considerable interest for utilizations in the biomedical field, because its biocompatibility and biodegradability could appropriately meet the requirement of tissue engineering.Based on hydrogen bonding interaction among chitin chains with exposed hydroxyl groups during the vacuum drying process, condensation occured and chitin molecules rearranged along the plane in all directions and packed tightly to create new aggragation states, so a new class of chitin plastic was constructed successfully by changing the shape and size. Meanwhile, hydroxyapatite particles were in situ synthesized in chitin matrix on the basis of its porous structure and good metal ions adsorption ability. There was strong interaction between chitin and hydroxyapatite, thus the mechanical property of chitin composite plastic was improved by the introduction of hydroxyapatite. Especially, MC3T3-E1cell culture experiments proved that the introduction of hydroxyapatite significantly improved the cell adhesion ability and promoted the proliferation ability. Therefore, the composite plastic had application prospect as bone repairing material in biomedical field.This thesis developed a series of cellulose and chitin functional materials by using alkali/urea aqueous solvents at low temperature, and the relationships between the structure and properties of materials as well as the surface and interface interaction were clarified. Thus, it could provide novel ideas and methods for the construction of high hydrophobic cellulose film,"self-cleaning" fluorescent cellulose film, high strength and biocompatible multi-layered cellulose hydrogels, high strength chitin composite hydrogels as well as chitin/inorganic composite plastic. These basic researches exhibit obvious creativity and academic value, and are in accordance with national sustainable strategy. Therefore, this thesis exhibits scientific significance and application prospect.更多还原