Bioactive Magnesium Silicate Activating Myocardial Energy Metabolism For Infarcted Myocardium Repair

The heart is a highly energy-dependent organ, developing bioenergy-activating biomaterials to activate myocardial adenosine triphosphate (ATP) production and restore dysregulated energy homeostasis is a promising solution for its functional recovery. Inorganic biomaterials with tunable properties may deliver multiple physicochemical cues for bioenergy-activation. However, there is currently a lack of systematic design and study on inorganic biomaterials-derived physicochemical cues for myocardial bioenergy-activation. This study proposes a bioenergy-activating bioink based on inorganic biomaterials. Through the dual design of the chemical composition and physical morphology cues, the bioinks containing magnesium silicate (MS) nanoparticles with different morphologies were developed, and the corresponding 3D bioprinted cardiac patches were prepared. It was found that the magnesium and silicon components of MS are well beneficial to ATP production and myocardial maturation. More importantly, the morphology of MS nanoparticles could regulate the mitochondria-targeted effects after endocytosis and the dynamic stiffness of the hydrogel matrix, thus systematically modulating ATP production and myocardial function. Furthermore, the patches with MS nanotubes significantly promoted heart repair and functional recovery in both rat and minipig animal models. This study proposes a new bioink design strategy based on biocompatible inorganic biomaterials for bioenergy-activation to promote heart repair, offering more potential avenues for the clinical treatment of damaged, complex tissue.