Development and characterization of a naturally derived lung extracellular matrix hydrogel

J Biomed Mater Res A. 2016 Aug;104(8):1922-35. doi: 10.1002/jbm.a.35726. Epub 2016 Apr 6.

Abstract

The complexity and rapid clearance mechanisms of lung tissue make it difficult to develop effective treatments for many chronic pathologies. We are investigating lung derived extracellular matrix (ECM) hydrogels as a novel approach for delivery of cellular therapies to the pulmonary system. The main objectives of this study include effective decellularization of porcine lung tissue, development of a hydrogel from the porcine ECM, and characterization of the material's composition, mechanical properties, and ability to support cellular growth. Our evaluation of the decellularized tissue indicated successful removal of cellular material and immunogenic remnants in the ECM. The self-assembly of the lung ECM hydrogel was rapid, reaching maximum modulus values within 3 min at 37°C. Rheological characterization showed the lung ECM hydrogel to have a concentration dependent storage modulus between 15 and 60 Pa. The purpose of this study was to evaluate our novel ECM derived hydrogel and measure its ability to support 3D culture of MSCs in vitro and in vivo delivery of MSCs. Our in vitro experiments using human mesenchymal stem cells demonstrated our novel ECM hydrogel's ability to enhance cellular attachment and viability. Our in vivo experiments demonstrated that rat MSC delivery in pre-gel solution significantly increased cell retention in the lung over 24 h in an emphysema rat model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1922-1935, 2016.

Keywords: decellularized lung; extracellular matrix; hydrogel; mesenchymal stem cells; rheometry.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Electrophoresis, Polyacrylamide Gel
  • Extracellular Matrix / metabolism*
  • Gene Expression Regulation / drug effects
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology*
  • Inflammation / pathology
  • Kinetics
  • Lung / metabolism*
  • Male
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Pancreatic Elastase
  • Rats, Sprague-Dawley
  • Rheology
  • Sus scrofa

Substances

  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Pancreatic Elastase