An injectable alginate/extra cellular matrix (ECM) hydrogel towards acellular treatment of heart failure

Drug Deliv Transl Res. 2019 Feb;9(1):1-13. doi: 10.1007/s13346-018-00601-2.

Abstract

As treatments for myocardial infarction (MI) continue to improve, the population of people suffering from heart failure (HF) is rising significantly. Novel treatment strategies aimed at achieving long-term functional stabilisation and improvement in heart function post MI include the delivery of biomaterial hydrogels and myocardial matrix-based therapies to the left ventricle wall. Individually alginate hydrogels and myocardial matrix-based therapies are at the most advanced stages of commercial/clinical development for this potential treatment option. However, despite these individual successes, the potential synergistic effect gained by combining the two therapies remains unexplored. This study serves as a translational step in evaluating the minimally invasive delivery of dual acting alginate-based hydrogels to the heart. We have successfully developed new production methods for hybrid alginate/extracellular matrix (ECM) hydrogels. We have identified that the high G block alginate/ECM hybrid hydrogel has appropriate rheological and mechanical properties (1.6 KPa storage modulus, 29 KPa compressive modulus and 14 KPa dynamic modulus at day 1) and can be delivered using a minimally invasive delivery device. Furthermore, we have determined that these novel hydrogels are not cytotoxic and are capable of enhancing the metabolic activity of dermal fibroblasts in vitro (p < 0.01). Overall these results suggest that an effective minimally invasive HF treatment option could be achieved by combining alginate and ECM particles.

Keywords: Acellular hydrogel; Alginate; Decellularized ECM; Heart failure; Minimally invasive delivery catheter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / administration & dosage*
  • Alginates / chemistry
  • Alginates / therapeutic use
  • Animals
  • Biocompatible Materials / administration & dosage*
  • Biocompatible Materials / chemistry
  • Drug Delivery Systems
  • Extracellular Matrix / chemistry*
  • Heart / diagnostic imaging
  • Heart / drug effects
  • Heart Failure / therapy*
  • Humans
  • Hydrogels / administration & dosage
  • Hydrogels / chemistry
  • Injections
  • Mechanical Phenomena
  • Microscopy, Electron, Scanning
  • Rheology
  • Swine

Substances

  • Alginates
  • Biocompatible Materials
  • Hydrogels