Degradable hydrogels derived from PEG-diacrylamide for hepatic tissue engineering
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...
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2017
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| Online Access: | http://hdl.handle.net/1721.1/110772 https://orcid.org/0000-0002-1293-2097 |
| _version_ | 1826196386681454592 |
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| author | Miller, Jordan S. Blakely, Brandon L. Chen, Christopher S. Stevens, Kelly R. Bhatia, Sangeeta N |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Miller, Jordan S. Blakely, Brandon L. Chen, Christopher S. Stevens, Kelly R. Bhatia, Sangeeta N |
| author_sort | Miller, Jordan S. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:26:03Z |
| format | Article |
| id | mit-1721.1/110772 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:26:03Z |
| publishDate | 2017 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/1107722022-09-30T21:06:31Z Degradable hydrogels derived from PEG-diacrylamide for hepatic tissue engineering Miller, Jordan S. Blakely, Brandon L. Chen, Christopher S. Stevens, Kelly R. Bhatia, Sangeeta N Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Stevens, Kelly R. Bhatia, Sangeeta N 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. National Institutes of Health (U.S.) (R01EB008396) National Institutes of Health (U.S.) (R01DK85713) National Institutes of Health (U.S.) (EB00262) 2017-07-19T13:57:56Z 2017-07-19T13:57:56Z 2015-04 2015-04 Article http://purl.org/eprint/type/JournalArticle 1549-3296 1552-4965 http://hdl.handle.net/1721.1/110772 Stevens, Kelly R.; Miller, Jordan S. and Blakely, Brandon L. “Degradable Hydrogels Derived from PEG-Diacrylamide for Hepatic Tissue Engineering.” Journal of Biomedical Materials Research Part A 103, 10 (April 2015): 3331–3338. © 2015 The Authors https://orcid.org/0000-0002-1293-2097 en_US http://dx.doi.org/10.1002/jbm.a.35478 Journal of Biomedical Materials Research Part A Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Wiley Blackwell Wiley |
| spellingShingle | Miller, Jordan S. Blakely, Brandon L. Chen, Christopher S. Stevens, Kelly R. Bhatia, Sangeeta N Degradable hydrogels derived from PEG-diacrylamide for hepatic tissue engineering |
| title | Degradable hydrogels derived from PEG-diacrylamide for hepatic tissue engineering |
| title_full | Degradable hydrogels derived from PEG-diacrylamide for hepatic tissue engineering |
| title_fullStr | Degradable hydrogels derived from PEG-diacrylamide for hepatic tissue engineering |
| title_full_unstemmed | Degradable hydrogels derived from PEG-diacrylamide for hepatic tissue engineering |
| title_short | Degradable hydrogels derived from PEG-diacrylamide for hepatic tissue engineering |
| title_sort | degradable hydrogels derived from peg diacrylamide for hepatic tissue engineering |
| url | http://hdl.handle.net/1721.1/110772 https://orcid.org/0000-0002-1293-2097 |
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