Micro and Nanoengineered Cardiac Spheroids and Organoids: Toward Translational Applications

ABSTRACT Micro‐ and nanoengineering have significantly advanced cardiac tissue engineering by overcoming the structural and functional limitations of conventional systems and enabling precise recreation of the native cardiac microenvironment. These technologies support the development of 3D cardiac spheroids and organoids that bridge the gap between traditional 2D cultures and the complex myocardium. Cardiac spheroids, typically composed of induced‐pluripotent‐stem‐cell‐derived cardiomyocytes and supporting cells, provide rapid, reproducible, and scalable platforms for high‐throughput drug screening, disease modeling, and regenerative studies. In contrast, cardiac organoids capture greater structural and functional complexity, including multicellular diversity, chamber‐like morphology, and electromechanical coupling, making them highly relevant for translational research, though challenges in standardization and production remain. Both platforms still face limitations in maturation, functional integration, and physiological performance. Micro‐ and nanoengineering strategies such as microwell fabrication, microfluidics, conductive nanomaterials, and integrated biosensors enhance these systems by promoting tissue alignment, vascularization, electrophysiological development, and real‐time functional assessment. This review discusses recent engineering innovations that improve 3D cardiac models, evaluates their roles in regeneration, biosensing, drug screening, and toxicology, and compares the scalability of spheroids with the physiological fidelity of organoids. It also outlines remaining challenges and future directions toward clinically translatable cardiac constructs.