Construction Of Iridium Nanoenzymes Integrated Conductive Microneedle Patches And Their Application In Myocardial Infarction Repair

BackgroundIn recent years,the impact of cardiovascular diseases on human health has become increasingly significant,among which myocardial infarction(MI)has become one of the major diseases threatening human health due to its high incidence and mortality rate.By engineering biomaterials,myocardial patches have demonstrated good repair potential in promoting cardiac function.However,the tendency of myocardial patches to detach and the failure of the material to electrically couple with normal tissues have limited the performance of MI repair.Considering the electrophysiological properties of the normal myocardial tissue and the series of inflammatory reactions triggered by the ischemia of the infarct,this project constructs an iridium nanoenzyme-integrated conductive hydrogel microneedle patch and makes some preliminary studies for its application in the treatment of heart infarcts.ObjectiveBased on the electrical conductivity of polypyrrole and acrylic acid,an iridium nanopatch with integrated conductive hydrogel was constructed by combining the ROS scavenging effect of caffeic acid and iridium nanopatch.In vitro and in vivo experiments were carried out to investigate its repairing effect.Methods1.After preparing iridium nanoenzyme,synthesizing pyrrole-grafted chitosan and caffeic acid-grafted chitosan,acrylic acid was introduced to construct iridium nanoenzyme-integrated conductive hydrogel scaffolds with good electrical conductivity.Then microneedle perfusion was performed with the pre-gel solution.Material science characterization of iridium nanoenzyme,iridium nanoenzymeintegrated conductive hydrogel and microneedles was performed.2.Evaluation of biocompatibility of the prepared iridium nanozymes and iridium nanozymes-integrated conductive hydrogels using primary cardiomyocytes.To detect the effect of iridium nanase integrated conductive hydrogel on the stretching and functionalization of primary cardiomyocytes.To test the ability of iridium nanozymes and iridium nanozymes integrated conductive hydrogels to scavenge ROS to protect primary cardiomyocytes.3.A rat infarction model was constructed by ligating the left anterior descending branch of the coronary artery.Then different groups of conductive hydrogel microneedle patches were transplanted,and echocardiography and immunofluorescence staining were performed on the rats after four weeks to investigate the effects of different groups of materials on the function,vascularization and inflammatory response of the damaged hearts.Results1.UV spectra illustrate the successful synthesis of polyvinylpyrrolidone(PVP)coated iridium nanoenzymes.transmission electron microscopy and particle size analysis illustrate the good dispersion and homogeneous particle size of the prepared iridium nanoenzymes in aqueous solution.Infrared and UV spectra show that the successfully synthesized CS-Py and CS-CA.the constructed iridium nanoenzyme integrated conductive hydrogel has good electrical conductivity.The micro-needle patches of iridium nanase integrated conductive hydrogel possess good mechanical strength sufficient to puncture the heart.In addition,the iridium nanoenzyme possesses ROS scavenging activity.2.Iridium nanoenzymes and iridium nanoenzymes integrated conductive hydrogels possess good biocompatibility and ROS scavenging activity.The iridium nanase integrated conductive hydrogel promotes primary cardiomyocyte stretch and expression of related characteristic proteins,Promotes the maturation of primary cardiomyocytes and protects cardiomyocytes from oxidative stress damage induced by ROS.3.The rat infarction model was further constructed by ligating the left anterior descending branch of the coronary artery,and different groups of conductive hydrogel microneedle patches were transplanted in the rat heart.Four weeks later,echocardiography was performed on the rats,and immunofluorescence staining was performed after sectioning the hearts to investigate the effects of different groups of materials on the function,vascularization and inflammatory responses of the damaged hearts.ConclusionWe have developed an iridium nanoparticle-enzyme integrated conductive hydrogel microneedle patch with good electrical conductivity and ROS scavenging activity.In vitro experiments have demonstrated its biocompatibility and ability to protect myocardial cells from oxidative stress damage.In vivo experiments have shown that the patch has a good repair effect on damaged hearts.This provides a new idea for the treatment of myocardial infarction.