A Study Of Preparation And Mechanism Of Bio-Based Stimuli-Responsive Materials For Biomedical Applications

Due to the safety,biocompatibility and versatility,bio-based stimuli-responsive materials have been widely used in many fields.However,only a handful of natural bio-based materials show responsiveness to external stimuli.The bio-based stimuli-responsive materials are relatively limited.It is difficult to meet the diverse needs of the medical field.Therefore,in this thesis,by doping,modifying and replacing,the selected bio-based materials with responsiveness could be obtained.The mechanism of the prepared bio-based stimuli-responsive materials were analyzed.This could explore and broaden the application of bio-based stimuli-responsive materials in medical fields.The main contents and results are as follows:(1)Here we introduced a concept of long-term time responsiveness.Due to the stable structure of polylactic acid(PLA)and compact molecular chain structure of polyglycerol,long-term time indicators were obtained and in-tablet anti-counterfeiting could be achieved.The functional relationship between the diffusion coefficient and the size of the probe molecule or the molecular structure of the material was clarified.Compared with the current time indicator which are mainly limited to short-term timing(about one week),the prepared bio-based response materials could achieve long-term timing(several months to years).In addition,the fitting model shows that fluorescence recovery curve of the material is unique,indicating that the prepared time-responsive material also has the function of anti-counterfeiting while timing.(2)We applied coaxial electrospinning technology to prepare coaxial microfibers with polyurethane(PU)core and cellulose acetate phthalate(CAP)shell.The mechanical strength of the coaxial fiber is 13.27±2.32 MPa.Comparing with CAP fiber(0.2±0.03 MPa)the tensile strength of coxical fiber significant increased.The relationship between the mechanical strength of the fiber and the structure of the fiber molecular chain is clarified.The ratio of the flexible segment and the rigid segment in the polymer molecular could affect tensile strength of the fiber as well.In addition,CAP gives the coaxial fiber the pH responsiveness.The model drug was applied to verified the relationship between the deprotonation of CAP polymer and its pH responsive drug release.(3)The metal oxide and bio-based polycaprolactone(PCL)were doped and electrospun to obtain PCL fiber mats loaded with iron oxide nanoparticles.The composite fiber mats could achieve intracellular drug delivery under laser irradiation.By changing the parameter of electrospinning,the distribution of metal nanoparticles in polymer fibers could be controllable.The mechanism of the response of metal nanoparticles to laser was studied.Due to the release of model drug from polyvinylpyrrolidone(PVP)film,the relationship between the concentration of polymer and the rate of drug release is revealed.Small fluorescent molecule probe was applied to prove the prepared material could absorb and convert laser energy,thereby achieving intracellular drug delivery.(4)The polylactic acid(PLA)film loaded with Fe₃O₄nanoparticles was prepared by doping and spinning coating.It is revealed that metal nanoparticles could form clusters spontaneously in polymer solution with high viscosity coefficient.The effect of the viscosity coefficient of polymer solution and the cluster aggregation was studied.By changing the concentration of polymer solution,the size and spatial distribution of the metal nanoparticle clusters could be controlled.The mechanism of laser responsiveness of metal nanoparticle clusters was explored.The absorption and transformation of laser energy by Fe₃O₄ clusters could achieve spatially selective killing of tumor cells,and its killing accuracy could reach single-cell level.The fluorescent macromolecules proved that the prepared material could also achieve intracellular delivery under laser irradiation.