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dc.contributor.authorCeliz, Adam D.
dc.contributor.authorRajamohan, Divya
dc.contributor.authorDavies, Martyn C.
dc.contributor.authorAlexander, Morgan R.
dc.contributor.authorDenning, Chris
dc.contributor.authorPatel, Asha
dc.contributor.authorAnderson, Daniel Griffith
dc.contributor.authorLanger, Robert S
dc.date.accessioned2016-02-09T19:49:11Z
dc.date.available2016-02-09T19:49:11Z
dc.date.issued2015-05
dc.date.submitted2015-05
dc.identifier.issn01429612
dc.identifier.issn1878-5905
dc.identifier.urihttp://hdl.handle.net/1721.1/101143
dc.description.abstractCardiomyocytes from human stem cells have applications in regenerative medicine and can provide models for heart disease and toxicity screening. Soluble components of the culture system such as growth factors within serum and insoluble components such as the substrate on which cells adhere to are important variables controlling the biological activity of cells. Using a combinatorial materials approach we develop a synthetic, chemically defined cellular niche for the support of functional cardiomyocytes derived from human embryonic stem cells (hESC-CMs) in a serum-free fully defined culture system. Almost 700 polymers were synthesized and evaluated for their utility as growth substrates. From this group, 20 polymers were identified that supported cardiomyocyte adhesion and spreading. The most promising 3 polymers were scaled up for extended culture of hESC-CMs for 15 days and were characterized using patch clamp electrophysiology and myofibril analysis to find that functional and structural phenotype was maintained on these synthetic substrates without the need for coating with extracellular matrix protein. In addition, we found that hESC-CMs cultured on a co-polymer of isobornyl methacrylate and tert-butylamino-ethyl methacrylate exhibited significantly longer sarcomeres relative to gelatin control. The potential utility of increased structural integrity was demonstrated in an in vitro toxicity assay that found an increase in detection sensitivity of myofibril disruption by the anti-cancer drug doxorubicin at a concentration of 0.05 μM in cardiomyocytes cultured on the co-polymer compared to 0.5 μM on gelatin. The chemical moieties identified in this large-scale screen provide chemically defined conditions for the culture and manipulation of hESC-CMs, as well as a framework for the rational design of superior biomaterials.en_US
dc.description.sponsorshipEngineering and Physical Sciences Research Council (Engineering, Tissue Engineering and Regenerative Medicine Fellowship Award EP/1017801/1)en_US
dc.description.sponsorshipBritish Heart Foundation (Grant P437352)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant R01 DE016516)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.biomaterials.2015.05.019en_US
dc.rightsCreative Commons Attribution 4.0 International Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceElsevieren_US
dc.titleA defined synthetic substrate for serum-free culture of human stem cell derived cardiomyocytes with improved functional maturity identified using combinatorial materials microarraysen_US
dc.typeArticleen_US
dc.identifier.citationPatel, Asha K., Adam D. Celiz, Divya Rajamohan, Daniel G. Anderson, Robert Langer, Martyn C. Davies, Morgan R. Alexander, and Chris Denning. “A Defined Synthetic Substrate for Serum-Free Culture of Human Stem Cell Derived Cardiomyocytes with Improved Functional Maturity Identified Using Combinatorial Materials Microarrays.” Biomaterials 61 (August 2015): 257–65.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Institute for Medical Engineering & Scienceen_US
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorPatel, Ashaen_US
dc.contributor.mitauthorAnderson, Daniel Griffithen_US
dc.contributor.mitauthorLanger, Roberten_US
dc.relation.journalBiomaterialsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsPatel, Asha K.; Celiz, Adam D.; Rajamohan, Divya; Anderson, Daniel G.; Langer, Robert; Davies, Martyn C.; Alexander, Morgan R.; Denning, Chrisen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-5629-4798
dc.identifier.orcidhttps://orcid.org/0000-0002-7266-9251
dc.identifier.orcidhttps://orcid.org/0000-0003-4255-0492
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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