Application Of Carbon-based Conductive Cryogel In Myocardial Tissue Engineering

BackgroundCardiovascular disease is still the leading cause of death worldwide.Since cardiomyocytes are not renewable,necrotic cardiomyocytes is replaced by fibers tissue after myocardial infarction.These will seriously affect cardiac function and then lead to irreparable situations such as ventricular remodeling and heart failure.As donors for heart transplantation are limited,the current treatment methods are mainly antithrombotics,thrombolysis,and endovascular therapy,which are supporting the retained cardiomyocytes.With the development of various new biomaterials,engineering cardiac patches are regarded as a new method to repair myocardial infarction with high hope.Due to the unique electrophysiological characteristics of cardiomyocytes,providing electrical conductivity is an important part of the construction of engineered cardiac patches.Carbon-based conductive materials have excellent electrical conductivity and stable chemical properties.They can endow the cardiac patch with a good electrical integration function,then establish electrical activity and improve electrical conduction between myocardial tissue and myocardial infarction tissue.Cryogel is a type of scaffold that gels at low temperatures.In a low-temperature environment,the ice crystals form in the scaffold during the cross-linking process and cross-linked and interconnected network structures are fabricated after thawing.The hydrogel formed by collagen-derived gelatin via cryogelation can facilitate the stretching and adhesion of cells and the delivery of nutrients in the scaffold is a good scaffold for fabricating engineering cardiac patches.Combining carbon-based conductive materials to construct conductive cryogels can be a new choice for myocardial tissue engineering.ObjectiveTo use carbon-based conductive materials to design engineered cardiac patches with appropriate mechanical properties and electrophysiological characteristics,and to conduct preclinical research on carbon-based conductive cryogels in the treatment of myocardial infarction.Method1.Synthesize methacrylated gelatin,dopamine MBA crosslinker,Poly(ethylene glycol)diacrylate,and conductive MXene-titanium carbide.Prepare carbon-based conductive hydrogel by cryogelation.The physical property and biocompatibility of the as-prepared cryogels were further evaluated.2.Engineering cardiac patches were fabricated with carbon-based conductive cryogel and cardiomyocytes.The in vitro cell function of cardiomyocytes in the engineering cardiac patch was evaluated.The cardiac patches were transplanted on the hearts of the rats with myocardial infarction,and the repair effect is evaluated3.To further improve the carbon-based conductive cryogel,elastin,F127,and carbon nanotubes were used to synthesize an injectable pre-shaped shape memory carbon-based conductive cryogel.Also,we constructed an injectable functional cardiac patch and validated its application for myocardial repair in minipigs with myocardial infarctionResult1.The titanium carbide cryogel exhibited mechanical properties and electrical conductivity closed to natural myocardial tissue and exhibited good biocompatibility.2.After compounding cardiomyocytes,the Ti2C cryogel engineered patch exhibited a good effect in promoting the maturation of cardiomyocytes,and showed the overall beating of the patch under the naked eye.After compounding with vascular endothelial cells,the engineered Ti2C-cryogel showed a three-dimensional shape of blood vessels.When the cardiac patches were implanted into the rats with myocardial infarction,they built a good microenvironment for infarction repair.The heart function of rats is improved,and the area of myocardial infarction is greatly reduced.3.The improved carbon-based conductive hydrogel exhibits superior electrical conductivity and elasticity.The engineered cardiac patch can be delivered to the heart of minipigs under thoracoscopy.When injected onto the heart surface of the MI minipigs,the engineered patches reduced myocardial infarction scars in minipigs with myocardial infarction and promoted revascularization in the area of myocardial infarction.This research provides a preliminary experimental basis for clinical application.ConclusionThe in vitro and in vivo studies indicated that carbon-based conductive cryogels had good biocompatibility,promoted cardiomyocyte maturation,reduced fibrosis,and improved cardiac function of the myocardial infarcted rats and minipigs.The carbon-based conductive cryogels have good prospects in myocardial repair.