Construction Of(Hierarchical)micro-nanostructure Of Polycaprolactone With Electrospinning And Its Blood Compatibility

Foreign body reaction,hemolysis and immune response are obstacles for the development of blood-contact biological materials.In this study,polycaprolactone(PCL)is used as a skeleton with the surface being modified.Micro-nano fibers are produced based on the electrospinning method to improve blood compatibility.We obtained a three-dimension micro-nano fiber with a stable structure,which not only owns good biocompatibility,no foreign body reaction,but also maintains cell with normal morphology and activity by the drug releasing in response to changes of the microenvironment of cell.The specific plan is presented as follows:Hemolysis of stored erythrocytes is a big difficulty for the development of new plasticizer-free polymer.Hemolysis is mainly caused by cation leaks from the intracellular fluid in the early stage.In order to construct an anti-hemolytic surface with a plasticizer-free,the micro-nanofiber was composed of acylated poly(caprolactone)(PCL-A),4-acrylamide-benzo-18-crown-6 ether(BCAm),anti-oxidation drug L-ascorbic acid-2-glucoside(AA-2G)through reactive electrospinning with poly(ethylene glycol)diacrylate(PEGDA-575)as a crosslinking agent.During the process,PCL-A was cross-linked with BCAm and the AA-2G was wrapped.Experiments show that PCL-A/BCAm/AA-2G micro/nanofibers have hydrophilic and antioxidant properties,low cytotoxicity,and can release drugs in response to high K~+ concentrations,reduce cell hemolysis rate,maintain cell positive morphology,and maintain Na/K-ATPase enzyme activity.Considering that the cell microenvironment is affected by many factors,we prepared a biomimetic extracellular matrix(ECM)-K~+/oxidation dual-response micro-nano fiber material inspired by the native extracellular matrix(ECM).The strategy can mainly coordinate the concentration of K~+ and ROS to a state of balance after pathological changes of the cell microenvironment,which effectively improves the sensitivity of regulatory response.We introduced ROS response into the material based on the first system.We synthesized dual-responsive tripolymer(PEGDA-EDT-BCAm),which has thioether segments that respond to ROS and a crown ether segments that respond to high concentration of K~+.The fiber composed of PEGDA-EDT-BCAm and PCL-A that encapsulate ascorbic acid-2-glucoside(AA-2G)is fabricated on an elastomer substrate with electrospinning to mimic ECM.During that process,the micro-nano fibers formed a core-shell structure with PETMP as a crosslinking agent to initiate crosslinking by UV radiation.The biomimetic ECM was characterized in terms of morphometry,cytotoxicity,oxidation response,K~+ response,blood compatibility and blood transfusion model in vivo.Experiments have shown that biomimetic ECM has good blood compatibility and can respond sensitively to small changes in the extracellular environment.When the cell microenvironment in unbalanced,the Na/K-ATPase is sensitive to ROS,resulting in activity decreases,then the external K~+ concentration is increased,and the fiber can response the excess K~+ to release AA-2G.This mechanism can reduce ROS in the environment and simultaneously activates Na/K-ATPase to promote the recovery of cation homeostasis;another pathway will be activated to lead quickly AA-2G release when the ROS concentration is overload,accelerating the recovery of the extracellular environment.In vivo blood transfusion experiments,by testing the K~+ concentration and inflammatory factors in the blood,they indicate that the biomimetic ECM can effectively reduce the fluctuation of the microenvironment and maintain a stable state.