Advanced Scaffold-Guided Stem Cell Therapies for Myocardial Regeneration: Integrating Biomaterials, Cell Engineering,...

Myocardial infarction remains a leading cause of mortality worldwide, primarily due to the limited regenerative capacity of adult cardiac tissue. Recent advances in regenerative medicine aim to address this limitation through stem cell therapies supported by bioengineered scaffolds and targeted delivery systems. This review highlights current progress in scaffold-guided cardiac regeneration, focusing on the therapeutic potential of embryonic, mesenchymal, induced pluripotent, and cardiac-resident stem cells. The integration of natural and synthetic biomaterials, including hydrogels, decellularized extracellular matrices, and smart polymers, is discussed in relation to cell survival, engraftment, and paracrine signaling. Moreover, we examine innovative delivery strategies, such as temperature-responsive cell sheets, injectable hydrogel systems, and 3D-printed constructs. Key challenges, including poor cell retention, immune rejection, and variability in scaffold performance, are addressed along with emerging solutions like bioresponsive materials and multimodal imaging for in vivo cell tracking. Finally, we propose translational perspectives to accelerate the clinical application of scaffold-assisted stem cell therapies for heart repair. Overall, this review synthesizes current advances and emerging technologies to provide a comprehensive roadmap for optimizing scaffold-based stem cell strategies in cardiac regeneration.