title: Degradable hydrogels derived from PEG-diacrylamide for hepatic tissue engineering.
abstract: Engineered tissue constructs have the potential to augment or replace whole organ transplantation for the treatment of liver failure. Poly(ethylene glycol) (PEG)-based systems are particularly promising for the construction of engineered liver tissue due to their biocompatibility and amenability to modular addition of bioactive factors. To date, primary hepatocytes have been successfully encapsulated in non-degradable hydrogels based on PEG-diacrylate (PEGDA). In this study, we describe a hydrogel system based on PEG-diacrylamide (PEGDAAm) containing matrix-metalloproteinase sensitive (MMP-sensitive) peptide in the hydrogel backbone that is suitable for hepatocyte culture both in vitro and after implantation. By replacing hydrolytically unstable esters in PEGDA with amides in PEGDAAm, resultant hydrogels resisted non-specific hydrolysis, while still allowing for MMP-mediated hydrogel degradation. Optimization of polymerization conditions, hepatocellular density, and multicellular tissue composition modulated both the magnitude and longevity of hepatic function in vitro. Importantly, hepatic PEGDAAm-based tissues survived and functioned for over 3 weeks after implantation ectopically in the intraperitoneal (IP) space of nude mice. Together, these studies suggest that MMP-sensitive PEGDAAm-based hydrogels may be a useful material system for applications in tissue engineering and regenerative medicine. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3331-3338, 2015.
authors: Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139.
authors: Kelly R
authors: KR
authors: Stevens
authors: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, 19104.
authors: Jordan S
authors: JS
authors: Miller
authors: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, 19104.
authors: Brandon L
authors: BL
authors: Blakely
authors: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, 19104.
authors: Christopher S
authors: CS
authors: Chen
authors: Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139.|Howard Hughes Medical Institute, Cambridge, Massachusetts, 02139.|Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139.
authors: Sangeeta N
authors: SN
authors: Bhatia
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D022781:Hepatocytes / Q000378:metabolism*; D020100:Hydrogels / Q000737:chemistry*; D008099:Liver; D019164:Liver, Artificial; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D011917:Rats, Inbred Lew; D023822:Tissue Engineering
chemical_list: D020100:Hydrogels; D011092:Polyethylene Glycols; C000595209:polyethylene glycol 1000
keywords: PEGDAAm; liver; matrix metalloproteinase; polyethylene glycol diacrylamide; tissue engineering