Harnessing biomaterial-based immunomodulation for cardiac repair and regeneration

Ischemic heart disease is the leading cause of global morbidity and mortality. The immune system plays a pivotal role in the physiological and pathological processes within the cardiovascular system. The dysregulated inflammatory microenvironment in the heart can severely prevent infarcted cardiac repair by matrix degradation, cardiomyocyte death, and fibrosis—ultimately facilitating heart failure. Recent advances have highlighted the potential of leveraging immunomodulation to enhance cardiac tissue repair and regeneration. This review first provides an overview of the immune cells involved in infarcted heart injury and repair. We then highlight three major categories of biomaterial-mediated immunomodulation strategies, including nanoparticle-based delivery systems, injectable hydrogels, and implantable cardiac patches, to deliver immunotherapeutic reagents for facilitating cardiac repair and regeneration. Finally, we discuss emerging trends and translational challenges in the development of biomaterial-mediated immunomodulation for myocardial infarction treatment, and offer insights to guide future research and revolutionize cardiovascular regenerative medicine.