3D bioprinted epicardial patch of GelMA containing VEGF-loaded chitosan nanoparticles and human bone marrow mesenchymal stem cells for the treatment of myocardial infarction

Abstract The transplantation of human bone marrow mesenchymal stem cells (hMSCs) exhibits promising therapeutic effects in the treatment of myocardial infarction (MI), however, its clinical application is limited due to the low survival rate of the transplanted cells. 3D bioprinted tissue engineering patches have demonstrated efficacy as a delivery approach to enhance the viability and engraftment of stem cells. In this study, we have developed a novel hMSCs tissue-engineered patch equipped with a nano-slow-release system using 3D bioprinting technology. The patch is based on a matrix material consisting of methacrylated gelatin (GelMA) and chitosan nanoparticles loaded with vascular endothelial growth factor (VEGF), which possesses pro-angiogenic effects. The resulting patch demonstrated excellent compatibility with hMSCs and enabled stable, sustained VEGF release. In vivo results showed that the patch significantly reduced cardiomyocyte apoptosis three days after myocardial infarction, and improved cardiac function and myocardial fibrosis at 28 days post-surgery. These effects were closely associated with the patch's potent angiogenic properties and favorable stem cell survival. In conclusion, this study successfully developed a 3D-printed tissue engineering patch with strong potential for clinical application, offering a promising new approach for the treatment of myocardial infarction.