Engineering Smart Biomaterial Interfaces for iPSC-CM Maturation: A Biophysical and Metabolic Reprogramming Approach...

Area of Science:

• Biomaterial Engineering
• Stem Cell Biology
• Cardiovascular Research

Background:

• Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) show immature phenotypes, hindering cardiac regenerative medicine.
• Current differentiation platforms fail to achieve the electrophysiological and metabolic maturity needed for clinical applications.

Purpose of the Study:

• To review strategies for engineering "smart" biomaterial interfaces to promote iPSC-CM maturation.
• To explore synergistic biophysical and metabolic reprogramming for enhanced iPSC-CM development.

Main Methods:

• Integrating nanotopographical patterning, mechanoelectric coupling, and tunable substrate stiffness.
• Implementing metabolic interventions like mitochondrial substrate optimization and fatty acid oxidation induction.
• Utilizing bioactive scaffolds and extracellular vesicle (EV)-functionalized hydrogels in 2D and 3D cultures.

Main Results:

• Cell-matrix crosstalk, sarcomeric organization, calcium handling, and oxidative metabolism are consistently linked to maturation.
• Bioactive scaffolds and EV-hydrogels can mimic the native myocardial environment.
• Recurring maturation patterns observed, but gaps in standardization and stability persist.

Conclusions:

• Convergence of biomaterial engineering and metabolic programming is crucial for iPSC-CM maturation.
• This integrated approach improves iPSC-CM fidelity for disease modeling, drug screening, and regenerative therapies.
• Scalability and translational implementation remain challenges for clinical success.