Scalable technologies in the manufacture and deployment of cell-free cardiac therapies.

Despite demonstrated therapeutic potential, cell-based cardiac therapies face substantial manufacturing, practical, and biological limitations which constrain their clinical translation. We examine selected emerging acellular approaches that could overcome these limitations while maintaining therapeutic efficacy. Biomaterial engineering has enabled the creation of acellular scaffolds from natural and synthetic sources that provide mechanical support and deliver bioactive signals to the injured heart. As an alternative, platelet-derived extracellular vesicles (EVs) can carry complex bioactive cargoes which can act on multiple therapeutic pathways while leveraging existing blood-banking infrastructure. Lastly, synthetic fabricated nanocarriers can form controlled release systems for therapeutic factor delivery. We describe how these three simplified therapeutic approaches can address key requirements including achieving commercial scale manufacturability and biological efficacy to enable broader therapeutic deployment.