title: Development and characterization of a naturally derived lung extracellular matrix hydrogel.
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.
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Pouliot
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Link
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Nabil S
authors.initials: NS
authors.lastname: Mikhaiel
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Schneck
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Valentine
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Franck J
authors.initials: FJ
authors.lastname: Kamga Gninzeko
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Herbert
authors.affiliation: Department of Pharmaceutics, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakagami
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia.|Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Heise
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D007249:Inflammation / Q000473:pathology; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism; D010196:Pancreatic Elastase; D017207:Rats, Sprague-Dawley; D012212:Rheology; D034421:Sus scrofa
chemical_list: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D010196:Pancreatic Elastase
keywords: decellularized lung; extracellular matrix; hydrogel; mesenchymal stem cells; rheometry