Micronized Acellular Matrix Biomaterial Leverages Eosinophils for Postinfarct Cardiac Repair

Visual Abstract

Highlights

• •

  A micronized acellular matrix biomaterial redirects pericardial and myocardial inflammation to stimulate adaptive postinfarct cardiac repair mechanisms.

• •

  Pericardial delivery of the micronized biomaterial increases pericardial and myocardial eosinophil counts in a small animal experimental MI model.

• •

  The matrix biomaterial increases myocardial concentrations of pro-reparative IL-4 and VEGF proteins.

• •

  The acellular matrix biomaterial increases neovascularization in the myocardial border zone and preserves postinfarct cardiac function.

• •

  Genetic depletion of eosinophils using a knockout mouse model negates biomaterial-mediated benefits to neovascularization and cardiac function, demonstrating that eosinophils may play a critical role in biomaterial-mediated cardiac repair.

Summary

After ischemic injury, immune cells mediate maladaptive cardiac remodeling. Extracellular matrix biomaterials may redirect inflammation toward repair. Pericardial fluid contains pro-reparative immune cells, potentially leverageable by biomaterials. Herein, we explore how pericardial delivery of a micronized extracellular matrix biomaterial affects cardiac healing. In noninfarcted mice, pericardial delivery increases pericardial and myocardial eosinophil counts. This response is sustained after myocardial infarction, stimulating an interleukin 4 rich milieu. Ultimately, the biomaterial improves postinfarct vascularization and cardiac function; and eosinophil-knockout negates these benefits. For the first time, to our knowledge, we demonstrate the therapeutic potential of pericardial biomaterial delivery and the eosinophil’s critical role in biomaterial-mediated postinfarct repair.