Injectable hyaluronic acid based microrods provide local micromechanical and biochemical cues to attenuate cardiac fibrosis after myocardial infarction

Biomaterials. 2018 Jul;169:11-21. doi: 10.1016/j.biomaterials.2018.03.042. Epub 2018 Mar 24.

Abstract

Repairing cardiac tissue after myocardial infarction (MI) is one of the most challenging goals in tissue engineering. Following ischemic injury, significant matrix remodeling and the formation of avascular scar tissue significantly impairs cell engraftment and survival in the damaged myocardium. This limits the efficacy of cell replacement therapies, demanding strategies that reduce pathological scarring to create a suitable microenvironment for healthy tissue regeneration. Here, we demonstrate the successful fabrication of discrete hyaluronic acid (HA)-based microrods to provide local biochemical and biomechanical signals to reprogram cells and attenuate cardiac fibrosis. HA microrods were produced in a range of physiological stiffness and shown to degrade in the presence of hyaluronidase. Additionally, we show that fibroblasts interact with these microrods in vitro, leading to significant changes in proliferation, collagen expression and other markers of a myofibroblast phenotype. When injected into the myocardium of an adult rat MI model, HA microrods prevented left ventricular wall thinning and improved cardiac function at 6 weeks post infarct.

Keywords: Biomaterials; Cardiovascular disease; Mechanotransduction; Photolithography; Tissue engineering.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • Cellular Reprogramming Techniques*
  • Fibrosis / therapy
  • Humans
  • Hyaluronic Acid*
  • Mice
  • Microspheres*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • Myocardium / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Engineering*

Substances

  • Hyaluronic Acid