Ultra-Tiny Scale Technology for iPSC-Based Cardiac Tissue Engineering.

Abstract

Integration of nanoscale technologies into cardiac tissue engineering significantly advances strategies for enhancing the maturation and functional performance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). However, despite their significant potential, hiPSC-CMs exhibit structural and functional immaturity that limits their therapeutic application. Nanoscale engineered scaffolds offer precise control over the cellular microenvironment, providing biophysical cues through topographical features that significantly influence cell alignment, differentiation, and maturation. Among these, ultra-tiny nanoscale engineering approaches have emerged as a transformative strategy to more accurately replicate the microenvironmental cues essential for hiPSC-CMs maturation. Therefore, this review aims to examine recent advancements in nanoscale technologies, focusing on promoting the structural and functional maturation of hiPSC-CMs to mimic native myocardial microenvironment. It explores the role of various nanostructures and nanobridge scaffolds in enhancing microenvironmental mimicry and delivering biophysical stimulation including mechanical and electrical cues to address persistent challenges associated with hiPSC-CMs immaturity. Additionally, this review emphasizes the application of nanotechnology assisted hiPSC-CMs models in advancing cardiac tissue regeneration, drug screening and toxicity assessment, and disease modeling. Finally, it evaluates the commercialization potential and current limitations of nanoengineered cardiac regeneration platforms, focusing on scalability, integration, and physiological relevance to assess their transformative effect for cardiac regenerative medicine.