| Hydrogel consisting of three-dimensional polymer chains network and large amount of water is similar with human soft tissues, and considerd to be the best candidate of biomaterials. Chitosan, the unique alkaline polysaccharide in nature, not only possesses the common properties of biopolymer including biocompatibility, biodegradability and bio-safety, but also exhibits some special properties, such as bioactivity, antibacterial activity, anti-oxygenation, pH-sensitivity, strong affinity and tissue adhesion. Hence, chitosan based hydrogels have attracted widespread attention, and show promising application potential in the fields of tissue engineering, drug release, DNA/RNA carrying and transcription, wastewater treatment, food and agriculture industry. However, the poor mechanical properties just as the "Achilles’heel" of chitosan hydrogels are serious impediments for their practical applications. To date, several methods such as chemical cross-linking, nanofillers reinforcement and blending with other polymers have been used to enhance their mechanical strength, but these techniques result in only a moderate enhancement and sometimes even partly sacrifice the intrinsic properties of chitosan. Moreover, the pH-sensitivity of chitosan hydrogels is beneficial for construction of smart hydrogels. Unfortunately, its excellent pH-sensitivity has not got enough attention, and there are few reports and literatures about chitosan smart hydrogels. Therefore, the main aim of the thesis is to find and seek a new strategy to construct robust chitosan hydrogels, and re-evaluate their biocompatibility and pH-sensitivity. Furthermore, based on its excellent mechanical properties and pH-sensitivity, some worthy endeavor should be carry out to fabricating chitosan-based smart hydrogels, and evaluate their potential applications in biomedicine. This work involves interdisciplinary fields of polymer physics, polymer chemistry and biomedical application, and also one of the international research frontiers of polymer science.The innovative points of this work are as follows:(1) a novel alkali/urea aqueous solvent was used to successfully dissolve chitosan via the freezing-thawing process, for the first time. Subsequently, high strength hydrogels with unique nanofibrous architecture, remarkable pH-sensitivity and biocompatibility were constructed from the chitosan alkaline solution; (2) Based on the alkali/urea solvent system, a series of self-shaping bilayer hydrogels and soft actuators based on chitosan were fabricated, for the first time; (3) Based on the alkali/urea solvent system, surface self-wrinkling chitosan microspheres were constructed by electrostatic assistanted layer-by-layer coating Au nanoparticles on swollen chitosan microspheres, for the first time. Meanwhile, the formation and regulatory mechanism of wrinkling structure was studies; (4) Based on the alkali/urea solvent system, a robust and conductive hydrogel with high strength, ultra-stretchability and force-sensitivity was fabricated by in-suit synthesis polyacrylamide and polyaniline in closely packed swollen chitosan colloids, for the first time, which could be an ideal candidate for electronic skin devices; (5) Novel magnetic cellulose/TiO2 nanocomposite microspheres were fabricated by in-suit synthesis of TiO2 nanoparticles in the pores of magnetic cellulose microspheres, for the first time, which exhibited remarkably selective enrichment of trace phosphopeptides from peptide mixtures; (6) Based on the special sol-gel transformation properties of agarose, a robust and thermoplastic hydrogel was fabricated, for the first time. Meanwhile, a theory model was built for predicting and evaluating thermoplasticity of different hydrogel samples.The main contents and conclusions in this project are divided into the following parts. A new solvent system composed of 4.5 wt% LiOH/7 wt% KOH/8 wt% urea aqueous solution with cooling was developed successfully to dissolve chitosan. Furthermore, high strength chitosan hydrogels with unique structure were constructed from the chitosan alkaline solution, for the first time. The chitosan in the alkaline solution easily self-assembled to form compact regenerated nanofibers induced by heating, which then facilely entangled and cross-linked with each other through hydrogen bonds to form the hydrogels at elevated temperature and concentration. The novel chitosan hydrogels had homogeneous architecture and excellent mechanical properties, and their compression fracture stress was nearly 100 times that of the chitosan hydrogels prepared by traditional acid dissolving method. This was as a result of the strong networks woven with the perfect chitosan nanofibers, which greatly contributed to the reinforcement of the hydrogels. Moreover, the novel chitosan hydrogels exhibited excellent biocompatibility, pH sensitivity, and smart controlled drug release behavior. Therefore, this work would be very important to construct smart chitosan hydrogels with high strength and biocompatibilities for the potential applications in the fields of tissue engineering and drug controlled release.By mimicking the bilayer structures of plant organs, smart bi-directionally self-rolling bilayer hydrogels composed of chitosan (CS) layer and cellulose/ carboxymethylcellulose (C/CMC) layer were constructed successfully from their hydrogels fabricated in alkali/urea aqueous system, for the first time. The chemical crosslinked networks occurred in the CS and C/CMC hydrogels, and the strong electrostatic attraction induced by the positively charged CS and negatively charged C/CMC layers existed in the bilayer hydrogels, leading to the tight interface adhesion. The bilayer hydrogels exhibited rapid, reversible and bidirectional deformation actuated by pH-triggered swelling/de-swelling process, and could be programmatically transformed into various 3D structures including rings, tubules, flower, helix, bamboo and wave-like shapes. The significant difference in the swelling behavior between the chitosan and C/CMC layers generated enough forces for the performing as soft grippers to lift up objects and smart encapsulators to capture targets. Therefore, the self-rolling hydrogels based on environmentally friendly natural polymers would be important in the biomaterial fields, because of their safety, biocompatibility, soft, transparence and biodegradability.Based on the remarkably acid-triggered swelling behavior of chitosan microspheres, a novel surface self-wrinkling microspheres were fabricated by electrostatic assistanted layer-by-layer coating Au nanoparticles on swollen chitosan microspheres, for the first time. The Au nanoparticles were strongly anchored on the surface of microspheres by the electrostatic, hydrogen bonds and coordination interaction with chitosan and alginate. Meanwhile, the wrinkling structure could be controlled by changing the layers of Au coating. In addition, the swelling behavior and surface coating were essential for formation of wrinkling structures. The surface self-wrinkling chitosan microspheres would be applied in the fields of enzyme immobilization, catalysis, oil/water separation, cell identification and screening.Robust and force-sensitive hydrogels (MC-Gel) were constructed, for the first time, by in-situ synthesizing polyacrylamide and PANI in the closely packed swollen chitosan microspheres containing nanofibers. The hydrogels had a novel two-phase composite structure composed of tough chitosan microspheres as the disperse phase and the multi-network PAAm and PANI loose architecture as continuous phase to form multi-interpenetrating polymers networks. The unique chitosan microspheres as microscale joint regions dramatically reinforcing the strength and enhancing of the energy dissipation, leading to the high strength, ultra-stretchability (strain exceeding 600%) and good mechanical stability of MC-Gel. Furthermore, the mismatch of swelling and mechanical properties between compact chitosan microspheres and their matrix caused surface self-wrinkling of hydrogels, resulting in the excellent force- sensitivity of MC-Gel. Moreover, the conductive hydrogels exhibited high sensitivity for subtle pressures and enabled detection over a broad range of compression or tensile force from 100 Pa to several MPa, as well as excellent electrical stability and rapid response speed. The hydrogels as electronic skin devices could precisely monitor grasping motions of human hands and the vertical motion of a jumping toy frog, showing potential applications in soft biomimetic machines.A new facile synthetic route to fabricate magnetic cellulose/TiO2 nanocomposite microspheres by using cellulose microspheres as matrix was successfully realized. The micro-nano porous structures of the microspheres played an important role to in-situ synthesize TiO2 nanoparticles, and to protect the native structure and character of TiO2, leading to the process of enrichment at a harsh environment. The MCTiMs exhibited high efficiency for selective enrichment trace phosphopeptides from tryptic digest of β-casein and human serum samples, as a result of the strong capturing capability. It is worth noting that the selective enrichment of phosphopeptides from mixtures of β-casein and BSA with a molar ratio of 1:1000 by using MCTiMs was available, which was much better than commercial TiO2 nanoparticles. In our finding, the TiO2 nanoparticles embedded in the magnetic cellulose microspheres had high contents and specific surface areas, as well as good adsorbing nature, leading to a strong Lewis acid-base interaction. Therefore, MCTiMs will be an excellent candidate for enrichment of phosphopeptides in the complex systems with MS analysis.Based on the special sol-gel transformation behavior of agarose, a robust and thermoplastic hydrogel (TPG) with double network structures was fabricated by photo-Initiation polymerization of acrylamide in agarose hydrogel matrix, for the first time. Agarose rigid network woven by nanofibers acted as backbone endowed the high strength of TPG. Polyacrylamide flexible network with low crosslinking density interpenetrating with agarose network resulted in the high toughness of TPG. During large deformation process, agarose network as sacrificed bonds could dissipated large amount of rupture energy, and prevent stress concentration and formation of destructive cracks, resulting in the robust mechanical properties of TPG. Moreover, agarose network could reversibly disrupt and reform by heating and cooling treatment, resulting in the mechanical recoverability and thermoplasticity of TPG. Similar to common plastics, TPG could reversibly soften by heating and harden by cooling, which exhibited excellent thermoplasticity, could carry out macroscale and microscale deformation through hot working treatment to transform into various 3D-shaped and micro- patterning hydrogels. Furthermore, a theory mold was built for predict and evaluate the thermoplasticity of different hydrogels. Therefore, the robust and thermoplastic hydrogels have potential applications for tissue engineering, microfluidics, biochips and smart sensor devices.In summary, the original work mentioned above successfully solve the bottlenecks of poor mechanical properties of chitosan and other polysaccharides, and constructed a series of robust and smart hydrogels materials, which dramatically extended their application range. It is not hard to imagine that these excellent hydrogels based on polysaccharides will have a bright application prospect in biomedicine. |
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