Study On The Effect Of Microenvironment Of Engineered Nanocomposite Hydrogel On Cardiac Repair Of MSC

Background:As a symbol of life and vitality,the heart is the dynamic organ of the pulmonary circulation and systemic circulation of a wide range of mammals.The maintenance of the physiological function of the heart mainly depends on the myocardial tissue formed by the interweaving of key functional units such as cardiomyocytes,fibroblasts and vascular smooth muscle cells,which are regularly arranged and step-coupling,and particularly important for ensuring the energy metabolism of various organs and the normal activities of the body.However,ischemic heart disease and heart failure continue to be major causes of disability and death worldwide.Even saving a surviving patient may expose you to the risk of secondary myocardial damage and failure following ischemia-reperfusion and scar repair.Even survivors who are rescued and effective in ischemic heart disease or heart failure may be at risk of secondary myocardial injury and failure following ischemia-reperfusion and scar repair.Therefore,for bottlenecks in cardiac repair and regeneration difficulties,we need to mine more effective therapies than the current routine clinical treatment.In recent years,as the field of tissue engineering and regenerative medicine marching forward,innovative strategies based on biocompatible and biodegradable hydrogel encapsulated stem cells for target organ delivery to enhance stem cell function in tissue repair and regeneration,in vitro and in vivo,have been showing specific safety and effectiveness and harbor great potential for clinical applications.However,its therapeutic effect is not good in terms of stability and persistence in the heart system.This is largely due to the fact that traditional hydrogel materials cannot effectively solve the key scientific and technical problems that stem cells cannot be long-term resident and stably integrated in myocardial tissue that continuously undergoes torsional motion.The use of advanced,suitable,non-toxic nanoparticulate materials to profoundly improve the specific properties of hydrogels to promote long-term colonization of encapsulated stem cells is an innovative strategy to address this challenge.Objective:This study will be the first exploration to investigate the use of injectable hydrogels functionalized with titanium dioxide nanoparticles(Ti02 NP)and loaded with mesenchymal stem cells(MSCs)with high dispersion and spherical morphology to carry out tissue repair and regeneration in the myocardium undergoing ischemia-reperfusion injury(IRI).This study will clarify the physicochemical properties of the novel nanocomposite hydrogels and clarify the mechanisms by which they exert therapeutic effects,and hopefully will provide a scientific basis for the in-depth innovative research and application of ideal nano-modified hydrogels for stem cell therapy to improve cardiac repair and regeneration.Method:Select gelatin/alginate nanocomposite hydrogels(GE/ALG)and polyethylene glycol/chitosan composite hydrogels(PG/CTS),which are emerging and potentially suitable for topical application of the heart,as two starting biomaterials.MSC was used as the "seed" cell of the study.A rigorous mainline program for "screening→synthesis→application" in rodent cardiomyocytes and biology testing methods,we will conduct empirical studies both in vivo and in vitro.Results:The biological characteristics of PG/CTS compared with GE/ALG-loaded MSC are better in this study,and its myocardial affinity is higher.The mass percentage of 10%-15%spherical TiO2 NP functionalization significantly improved the mechanical stability.Compared with the control group,the TiO2 NP-PG/CTS-MSC treatment group improved the cardiac function and pathological manifestations of the IRI heart,and the therapeutic function of MSC was improved with persistence.Conclusion:The PG/CTS composite hydrogel prepared by the spherical TiO2 NP functionalization is an advanced polymer biomaterial.It enhances the long-term residence of MSCs in the IRI myocardium,thereby amplifying the biological effects of its own tissue repair and regeneration.This study provides theoretical support for its suitable bioavailable materials for heart repair and regeneration research and application.