Infarct stabilization and cardiac repair with a VEGF-conjugated, injectable hydrogel

Biomaterials. 2011 Jan;32(2):579-86. doi: 10.1016/j.biomaterials.2010.08.098. Epub 2010 Oct 6.

Abstract

Injectable scaffolds made of biodegradable biomaterials can stabilize a myocardial infarct and promote cardiac repair. Here, we describe the synthesis of a new, temperature-sensitive, aliphatic polyester hydrogel (HG) conjugated with vascular endothelial growth factor (VEGF) and evaluate its effects on cardiac recovery after a myocardial infarction (MI). Seven days after coronary ligation in rats, PBS, HG, or HG mixed or conjugated with VEGF (HG + VEGF or HG-VEGF, respectively) was injected around the infarct (n = 8-11/group). Function was evaluated by echocardiography at multiple time points. Pressure-volume measurements were taken and infarct morphometry and blood vessel density were assessed at 35 days after injection. HG-VEGF provided localized, sustained VEGF function. Compared with outcomes in the PBS group, fractional shortening, ventricular volumes, preload recruitable stroke work, and end-systolic elastance were all preserved (p < 0.05) in the HG and HG + VEGF groups, and further preserved in the HG-VEGF group. Conjugated VEGF also produced the highest blood vessel density (p < 0.05). The infarct thinned and dilated after PBS injection, but was smaller and thicker in hearts treated with HG (p < 0.05). Our temperature-sensitive HG attenuated adverse cardiac remodeling and improved ventricular function when injected after an MI. VEGF delivery enhanced these effects when the VEGF was conjugated to the HG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry*
  • Injections
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / therapy*
  • Neovascularization, Physiologic
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Engineering / methods
  • Tissue Scaffolds / chemistry
  • Vascular Endothelial Growth Factor A / chemistry*
  • Vascular Endothelial Growth Factor A / therapeutic use*

Substances

  • Vascular Endothelial Growth Factor A
  • Hydrogel, Polyethylene Glycol Dimethacrylate