Differential regeneration of myocardial infarction depending on the progression of disease and the composition of biomimetic hydrogel

J Biosci Bioeng. 2014 Oct;118(4):461-8. doi: 10.1016/j.jbiosc.2014.04.001. Epub 2014 May 23.

Abstract

Hydrogel has been used for regenerating myocardial infraction (MI) as a delivery vehicle for cells and growth factors. This study showed that injectable hyaluronic acid (HA)-based hydrogels alone would effectively regenerate the damaged infarcted heart tissue. We found that there are two major factors of regeneration in MI. One is molecular weight of HA and another is the progression of MI; sub-acute and chronic. Rat MI model was prepared by ligating the left anterior descending coronary artery (LAD). Four weeks after injection of hydrogel, functional analysis of the heart and histological analysis was assessed. When different molecular weight HA-based hydrogels with 50 kDa, 130 kDa, and 170 kDa were applied to the infarcted area in the sub-acute model, 50 kDa HA-based hydrogel showed the most significant regeneration of myocardium as well as functional recovery among samples. For the disease progression, 50 kDa HA-based hydrogels were injected to sub-acute and chronic MI models. The regeneration activity was significantly decreased in the chronic models reflecting that injection timing of the therapeutic agents is also major determinants in the regeneration process. These results suggest that injection time and composition of hydrogel are two major points treating MI.

Keywords: Chronic myocardial infarction; Heart function; Hyaluronic acid; Injectable hydrogel; Molecular weight; Tissue regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacology*
  • Cardiotonic Agents / chemistry
  • Cardiotonic Agents / pharmacology*
  • Chronic Disease
  • Disease Models, Animal
  • Heart / drug effects*
  • Heart / physiopathology
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology*
  • Hydrogels
  • Male
  • Molecular Weight
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Regeneration / drug effects*
  • Time Factors

Substances

  • Cardiotonic Agents
  • Hydrogels
  • Hyaluronic Acid