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    Research Article

    Tunable Hydrogels Derived from Genetically Engineered Extracellular Matrix Accelerate Diabetic Wound Healing
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    • Aaron H. Morris
      Aaron H. Morris
      Department of Biomedical Engineering  and  Vascular Biology and Therapeutics Program, Yale University, New Haven, Connecticut 06511, United States
      More by Aaron H. Morris
    • Hudson Lee
      Hudson Lee
      Vascular Biology and Therapeutics Program, Yale University, New Haven, Connecticut 06511, United States
      More by Hudson Lee
    • Hao Xing
      Hao Xing
      Department of Biomedical Engineering  and  Vascular Biology and Therapeutics Program, Yale University, New Haven, Connecticut 06511, United States
      More by Hao Xing
    • Danielle K. Stamer
      Danielle K. Stamer
      Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06511, United States
      More by Danielle K. Stamer
    • Marina Tan
      Marina Tan
      Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06511, United States
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    • Themis R. Kyriakides*
      Themis R. Kyriakides
      Department of Biomedical Engineering,  Department of Pathology  and  Vascular Biology and Therapeutics Program, Yale University, New Haven, Connecticut 06511, United States
      *E-mail: [email protected]. 10 Amistad St. Room 301C, New Haven, CT 06519, United States.
      More by Themis R. Kyriakides
      Orcidhttp://orcid.org/0000-0002-1937-5764
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    ACS Applied Materials & Interfaces

    Cite this: ACS Appl. Mater. Interfaces 2018, 10, 49, 41892–41901
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    https://doi.org/10.1021/acsami.8b08920
    Published November 14, 2018
    Copyright © 2018 American Chemical Society
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    Abstract

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    Hydrogels composed of solubilized decellularized extracellular matrix (ECM) are attractive materials because they combine the complexity of native ECM with injectability and ease of use. Nevertheless, these materials are typically only tunable by altering the concentration, which alters the ligand landscape, or by incorporating synthetic components, which can result in an unfavorable host response. Herein, we demonstrate the fabrication of genetically tunable ECM-derived materials, by utilizing wild type (WT) and (thrombospondin-2 knockout) TSP-2 KO decellularized skins to prepare hydrogels. The resulting materials exhibited distinct mechanical properties characterized by rheology and different concentrations of collagens when characterized by quantitative proteomics. Mixtures of the gels achieved intermediate effects between the WT and the KO, permitting tunability of the gel properties. In vivo, the hydrogels exhibited tunable cell invasion with a correlation between the content of TSP-2 KO hydrogel and the extent of cell invasion. Additionally, TSP-2 KO hydrogels significantly improved diabetic wound healing at 10 and 21 days. Furthermore, hydrogels derived from genetically engineered in vitro cell-derived matrix mimicked the trends observed for tissue-derived matrix, providing a platform for faster screening of novel manipulations and easier clinical translation. Overall, we demonstrate that genetic engineering approaches impart tunability to ECM-based hydrogels and can result in materials capable of enhanced regeneration.

    Copyright © 2018 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.8b08920.

    • Rheology of tissue-derived hydrogels at 4 and 6 mg/mL, diffusion through hydrogels, in vitro fibroblast migration into hydrogels, and SDS–PAGE of pre-gel solutions (PDF)

    • Proteomics data for all unique proteins detected (Table S1) (XLSX)

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    This article is cited by 34 publications.

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    ACS Applied Materials & Interfaces

    Cite this: ACS Appl. Mater. Interfaces 2018, 10, 49, 41892–41901
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsami.8b08920
    Published November 14, 2018
    Copyright © 2018 American Chemical Society
    Request reuse permissions

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