Development Of Sulfobetaine Polymer Coating For Continuous Glucose Monitoring Sensor

Continuous Glucose Monitoring sensor(CGMs)provides an effective way to control blood glucose to near normal level,which can effectively delay or prevent the occurrence and development of diabetic complications.However,as an implantable medical device,its biocompatibility problems and foreign body reaction in vivo seriously affect the accuracy and long-term stability of the sensor.In this paper,a biocompatible zwitterionic polymer was grafted onto the surface of the existing sensor by"graft to"method,and the biocompatibility of the glucose sensor in vivo was solved by using the anti-adsorption property of the coating,so as to ensure the stable transmission of the current signal of the sensor and prolong the effective monitoring time of the probe.In this paper,the synthesis of epoxidized sulfonated betaine copolymer,the determination of surface modification conditions of polyurethane materials,the biocompatibility and stability of the coating were discussed.(1)Synthesis of polymer:firstly,the polymerization solvent of glycidyl methacrylate(GMA)and Sulfobetaine Methacrylate(SBMA)was optimized.Finally,the epoxidized betaine sulfonate polymer was obtained by using AIBN as initiator and reacting in methanol/acetonitrile mixed solvent at 70?for 6 h.The molecular weight and distribution of the epoxidized betaine sulfonate polymer were moderate and narrow,and the epoxy functional groups were well retained.(2)Optimization of coating modification conditions:firstly,aminosiloxane was modified on the surface of polyurethane mass transfer resistance regulating layer,and then the epoxy functional group contained in zwitterionic copolymer was grafted with silane anchored amino group catalyzed by organic tertiary amine.Enzyme linked immunosorbent assay(ELISA)was used to evaluate the conditions of amphoteric copolymer modified medical polyurethane materials,including aminosiloxane concentration,polymer concentration,concentration and type of organic amine catalyst,monomer ratio and catalytic time.Finally,when the concentration of isopropanol of aminosiloxane was 100 ppm,the molar dosage of GMA was 20%,the concentration of polymer was 7 mg/m L,the DABCO of organic amine was 0.01 mg/m L,and the catalytic time was 1 h,the relative protein adsorption of PU membrane was reduced to about 5%,and the relative protein adsorption of PU membrane was reduced by 99%at 6 h.Under this condition,the electrochemical signal of the original probe was not changed.(3)Characterization of the coating performance:the biocompatibility and stability of the coating were tested by cytotoxicity,blood compatibility and long-term stability of the coating in vitro.The results showed that the surface of PU modified by zwitterionic polymer was relatively flat,PU,PU-NH₂ and PU polymer did not show cytotoxicity,hemolysis and promoting coagulation,and both PU and PU-NH₂ surfaces adhered There are platelets and platelets have been activated,but platelets rarely adhere to the surface of PU polymer.After soaking for 1,14,30,60 and 90 days,the relative protein adsorption capacity of PU-polymer surface is still less than 5%,and the cells do not adhere to the surface of the membrane.The anti-protein adsorption effect can last for 90 days or more.In addition,when zwitterionic polymer coating was applied to insulin injection tube(TPU)and stainless steel,the relative protein adsorption capacity could be reduced by 85%and 95%respectively,and TPU,TPU-NH₂ and TPU-polymer also showed good cell compatibility.The epoxidized sulfonated betaine zwitterionic polymer coating improves the blood compatibility and histocompatibility of the materials,and provides a new idea for the development of anti-adsorption materials and blood compatibility materials.The epoxidized zwitterionic polymer has high application value in the field of CGM,and provides a good help for solving the biocompatibility and foreign body reaction of CGM implantable medical devices.It has great social benefits to relieve the pain of patients with diabetes and reduce the complications of patients.In addition,the coating acts on the insulin delivery pipeline,which provides a good help for the realization of the concept of artificial pancreas.