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Engineered vascularized tissues in vitro exhibit the potential for transplantation therapy and disease odeling. Despite efforts to design hydrogels as cell culture platforms for in vitro vascularization, development of vascularized tissues recapitulating the natural structures and functions remains difficult due to a poor understanding of the relationships between the matrix microstructures and tube formation of endothelial cells. Herein, we developed microfiber network hydrogels with microporous structures by controlling the liquid−liquid phase separation (LLPS) of proteins and matrix structures in hydrogels. Extracellular matrix protein gelatin was modified with hydrogen-bonding moieties and mixed with hyaluronic acid sodium salt to form microfiber network structures. Gelatin gelation and hyaluronic acid sodium salt dissolution led to the formation of a microporous microfiber network hydrogel formation. Matrix structures of hydrogels were modified by controlling LLPS that affects endothelial cell tube formation. Vascularization was improved using laminin peptides and coculturing with mesenchymal stem cells. Overall, our approach exhibits the potential to induce in vitro vascularization for regenerative medicine and disease modeling applications.

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  This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in American Chemical Society, copyright © 2024 American Chemical Society after peer review. To access the final edited and published work see https://doi.org/10.1021/acs.biomac.4c00836

Keyword: Regenerative medicine, Hydrogel, Liquid-liquid phase separation, Porous material

Date published: 2024-09-09

Publisher: American Chemical Society (ACS)

Journal:

• Biomacromolecules (ISSN: 15257797) vol. 25 issue. 9 p. 6146-6154

Funding:

• Inamori Foundation
• Japan Society for the Promotion of Science 22H03962
• Japan Society for the Promotion of Science 23H01718
• Uehara Memorial Foundation

Manuscript type: Author's version (Submitted manuscript)

MDR DOI: https://doi.org/10.48505/nims.4789

First published URL: https://doi.org/10.1021/acs.biomac.4c00836

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Updated at: 2024-10-02 12:30:25 +0900

Published on MDR: 2024-10-02 12:30:25 +0900