Rapid manufacturing of angiogenic cellular collagen patches for ischemic cardiomyopathy

Stem Cells Transl Med. 2025 Sep 11;14(9):szaf035. doi: 10.1093/stcltm/szaf035.

Abstract

Background: One in ten Americans carry a lifetime risk of ischemic heart failure, the most severe form of ischemic heart disease. Carrying a nearly 50% five‑year mortality rate, no interventional therapy exists to treat the underlying cause, microvascular malperfusion. In efforts to combat microvascular malperfusion, our group has utilized synergistic application of endothelial progenitor cells (EPCs) and smooth muscle cells (SMCs) to induce angiogenesis in ischemic myocardium.

Methods: Cells are then embedded into a rapidly manufacturable compressed collagen (CC) patch to provide a biosimilar scaffold ready for transplantation. The performance of the cellular compressed collagen patch was then tested on a rodent acute myocardial infarction model of ischemic heart failure.

Results: By post‑transplantation Day 28, the cellular CC patch improved left ventricular ejection fraction when compared to an acellular CC patch and control (cellular: 49.1 ± 1.8%; acellular: 38.0 ± 2.6%; control: 39.2 ± 2.1%; ANOVA P = .0006). Cellular CC patch transplantation also induced mature angiogenesis as shown by arteriolar density (cellular: 1084 ± 98 αSMA+vWF+/mm2; acellular: 338 ± 57 αSMA+vWF+/mm2; control: 449 ± 39 αSMA+vWF+/mm2; ANOVA P = .0003) and vascular maturation index (cellular: 0.67 ± 0.04; acellular: 0.48 ± 0.02; and control: 0.46 ± 0.04, P = .001).

Conclusions: In conclusion, transplantation of a rapidly manufacturable EPC‑SMC‑based compressed collagen patch effectively rescues myocardial function by enhancing neovascularization and attenuating post‑infarction myocardial injury.

Keywords: angiogenesis; biomaterials; collagen patch; endothelial progenitor cells; ischemic cardiomyopathy; myocardial infarction; tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cardiomyopathies* / therapy
  • Collagen*
  • Disease Models, Animal
  • Endothelial Progenitor Cells* / cytology
  • Endothelial Progenitor Cells* / metabolism
  • Endothelial Progenitor Cells* / transplantation
  • Humans
  • Male
  • Myocardial Infarction / therapy
  • Myocardial Ischemia* / therapy
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / transplantation
  • Neovascularization, Physiologic*
  • Rats
  • Tissue Scaffolds / chemistry

Substances

  • Collagen