Preparation Of Multifunctional Biomedical Hydrogel Based On Dynamic Acyl Hydrazone Bond

As a new kind of biomedical material,hydrogel has been widely concerned and applied in many fields.Benefiting from the three-dimensional hydrophilic network,the hydrogels as wound dressings can supply a moist and airtight microenvironment for oxygen exchange and nutrients penetration.At the same time,the network structure of the hydrogel allows for efficient loading and controlled release of various functional drugs.Polyphosphate(Poly P)is present in human platelets,and platelet-derived polyphosphate secretion is associated with increased thrombus and activation of coagulation factor XII,which can enhance multiple interactions in the coagulation system to promote coagulation.In this thesis,polyphosphate was introduced into the polymer to prepare a multifunctional hydrogel containing polyphosphate that can quickly stop bleeding and promote wound healing.On the other hand,the hydrogel can also be used as an antitumor drug carrier,and the acute toxicity of the drug can be reduced through the slow-release process.The DOX was coupled to pec-Ald to prepare pec-AD with aldehyde groups and covalently coupled DOX.Moreover,the limonin as a lung cancer targeted traditional herbal medicine was loaded into the injectable hydrogel to enhance the therapy efficacy of lung cancer combined the advantages of the two drugs.This thesis mainly includes following three parts:1.Hydrogels containing Poly P were designed and investigated for their effective hemostatic characteristics.Polyphosphate groups were introduced into P(NIPAM-co-AH)to produce functional polymers with acyl hydrazide to provide a hemostatic moiety.Then,the selfhealing hydrogel with hemostatic properties,good elasticity and sealing effect was constructed by dynamic hydrazone bond with PEO dialdehyde(PEO DA)cross-linking.The hydrogel showed good biocompatibility through cytotoxicity and hemolysis assay,and showed controlled drug release behavior.More importantly,the hemostatic effect was investigated in vitro and in vivo through a bleeding model.The results showed that polyphosphate-containing hydrogels showed good tissue adhesion,reduced coagulation time and blood loss,as well as the effect of surgical sealants.This polyphosphate hemostatic hydrogel has great potential for application in open wound control and related biological applications.2.The degradability of biomedical materials has been concerned by researchers.The undegradable materials used in the living body may cause secondary damage to the living body in long time scale.Poly P was introduced into a modified biocompatible Pectin(Pec-H),and a multifunctional hydrogel with biodegradability was prepared through dynamic hydrazone bonds to stop bleeding and promote wound healing.Cytotoxicity test and hemolysis test showed that the hydrogel had good biocompatibility and the in vivo hemostasis experiment showed excellent hemostasis performance.The pectin based hemostatic hydrogel could degrade effectively in vitro by pectinase and in vivo.In mouse wound repair experiments,vancomycinloaded hydrogels reduced the risk of wound infection and accelerated wound healing in mice.3.Malignant tumor is one of the most threatening diseases that cause abnormal human death.Chemotherapy is one of the most popular treatments for tumors,but most of these chemotherapy drugs are also toxic to the living body.The acute toxicity of the drug can be reduced by the sustained-release properties of the hydrogel.In this part,the DOX was coupled onto aldehyde group bearing pec-Ald,and self-healing hydrogel containing covalent coupled DOX was prepared to enhance the sustained release effect.At the same time,the herbal medicine drug of limonin was loaded to combine to the advantages of the two drugs.The in vitro cell experiments and animal tumor models experiment showed the enhanced therapeutic effect and the self-healing hydrogel could degrade in the mice body,which can improve the therapeutic effect of lung cancer and has broad application prospects.