Synthesis And Biomedical Applications Of Blood Responsive Hydrogels

Hydrogels have been defined as two-or multi-component systems consisting of a three-dimensional network of polymer chains and water that fills the space between macromolecules.There are many criteria for classifying hydrogels,including classification by origin,cross-linking method,degradation properties,response to external stimuli,size structure and functional applications.According to the response to the external environment,hydrogels can be classified into conventional hydrogels and intelligent hydrogels.Among them,intelligent hydrogels are sensitive to small changes or stimuli in the external environment.In the face of different changes and stimuli,the hydrogel will quickly respond to volume expansion or contraction.The emergence of intelligent hydrogels provides new material options for the biomedical field with very broad prospects and application potential.Chitosan is a natural material with good biocompatibility obtained from the deacetylation of natural chitin in shrimp and crab shells.The abundant amino（-NH₂）and hydroxyl（-OH）groups enable the material to exhibit broad-spectrum antibacterial/antiviral properties and water solubility.In recent years,chitosan derivatives modified with mussel-inspired compounds have drawn extensive attention in the research of various functional materials.Mussel-inspired compounds such as dopamine,caffeic acid,gallic acid,tannic acid,etc.can impart chitosan with a variety of properties such as excellent wet adhesion,antioxidant,antibacterial,coating ability,high reactivity,chelating and coordinating ability,bioactivity and biocompatibility,and can make chitosan itself more water soluble to realize its potential,which largely expands the biomedical applications of chitosan materials.applications in biomedicine.Oxidized cellulose can promote blood clotting through contact with the wound and are one of the most commonly used cellulose derivatives for wound dressings.Oxide microcrystalline cellulose is a novel hemostatic material.Compared with other oxidized cellulose that has been used in a large number of clinical applications,oxide microcrystalline cellulose has the advantages of larger specific surface area,low polymerization,low crystallinity,high biosafety and low cost,which is a promising new cost-effective biological material for hemostasis.In this thesis,we synthesized the caffeic acid grafted chitosan/gallic acid grafted chitosan/oxidized microcrystalline cellulose（CHI-C/CSG/OMCC）ternary compos ites which could be used as blood responsive hydrogel.We used hemoglobin to cataly ze the cross-linking of CHI-C and CSG to form the hydrogel;the blood responsivenes s of this hydrogel material was induced by using the strategy of in situ release of hemo globin from red blood cells broken by OMCC.In addition,the introduction of OMCC can also exhibit its good antibacterial and hemostatic abilities.Subsequently,we conducted biomedical application experiments of CHI-C/CSG/OMCC blood-responsive hydrogels.CHI-C/CSG/OMCC can perform rapid and effective hemostasis in mouse liver injury model and mouse tail amputation model.The hydrogel also exhibited excellent wound healing promotion in a mouse cutaneous defect model.In antimicrobial testing,CHI-C/CSG/OMCC hydrogel combined the antimicrobial properties of each component and showed good inhibition for both Gram-positive and Gram-negative bacteria.Then,we applied CHI-C/CSG/OMCC hydrogels to a porcine model of acute gastrointestinal bleeding.The experimental results showed that the hydrogel was able to perform effective hemostasis for the esophagus,stomach and intestine in about 2 minutes,and no rebleeding occurred.In the postoperative period,the recovery effect of the hydrogel group was also better than that of the control group.These results indicate that CHI-C/CSG/OMCC ternary composite blood-responsive hydrogel is a promising new multifunctional biomedical material.