Enzyme-responsive progelator cyclic peptides for minimally invasive delivery to the heart post-myocardial infarction

Nat Commun. 2019 Apr 15;10(1):1735. doi: 10.1038/s41467-019-09587-y.

Abstract

Injectable biopolymer hydrogels have gained attention for use as scaffolds to promote cardiac function and prevent negative left ventricular (LV) remodeling post-myocardial infarction (MI). However, most hydrogels tested in preclinical studies are not candidates for minimally invasive catheter delivery due to excess material viscosity, rapid gelation times, and/or concerns regarding hemocompatibility and potential for embolism. We describe a platform technology for progelator materials formulated as sterically constrained cyclic peptides which flow freely for low resistance injection, and rapidly assemble into hydrogels when linearized by disease-associated enzymes. Their utility in vivo is demonstrated by their ability to flow through a syringe and gel at the site of MI in rat models. Additionally, synthetic functionalization enables these materials to flow through a cardiac injection catheter without clogging, without compromising hemocompatibility or cytotoxicity. These studies set the stage for the development of structurally dynamic biomaterials for therapeutic hydrogel delivery to the MI.

Publication types

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

MeSH terms

  • Animals
  • Cardiac Catheters
  • Hydrogels / administration & dosage
  • Hydrogels / chemistry*
  • Hydrogels / therapeutic use
  • Myocardial Infarction / therapy*
  • Myocardium / pathology
  • Peptides, Cyclic / administration & dosage
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / therapeutic use
  • Rats

Substances

  • Hydrogels
  • Peptides, Cyclic