Article Injectable microcapillary network hydrogels engineered by liquid-liquid phase separation for stem cell transplantation

Akihiro Nishiguchi SAMURAI ORCID (National Institute for Materials ScienceROR) ; Shima Ito SAMURAI ORCID (National Institute for Materials ScienceROR) ; Kazuhiro Nagasaka ; Hiyori Komatsu SAMURAI ORCID (National Institute for Materials ScienceROR) ; Koichiro Uto SAMURAI ORCID (National Institute for Materials ScienceROR) ; Tetsushi Taguchi SAMURAI ORCID (National Institute for Materials ScienceROR)

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Akihiro Nishiguchi, Shima Ito, Kazuhiro Nagasaka, Hiyori Komatsu, Koichiro Uto, Tetsushi Taguchi. Injectable microcapillary network hydrogels engineered by liquid-liquid phase separation for stem cell transplantation. Biomaterials. 2023, 305 (), 122451. https://doi.org/10.1016/j.biomaterials.2023.122451
SAMURAI

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(abstract)

Injectable hydrogels are promising carriers for cell delivery in regenerative medicine. However, injectable hydrogels composed of crosslinked polymer networks are often non-porous and prevent biological communication with host tissues through signals, nutrients, oxygen, and cells, thereby limiting graft survival and tissue integration. Here we report injectable hydrogels with liquid-liquid phase separation-induced microcapillary networks (µCN) as stem cell-delivering scaffolds. The molecular modification of gelatin with hydrogen bonding moieties induced liquid-liquid phase separation when mixed with unmodified gelatin to form µCN structures in the hydrogels. Through spatiotemporally controlled covalent crosslinking and dissolution processes, porous µCN structures were formed in the hydrogels, which can enhance mass transport and cellular activity. The encapsulation of cells with injectable µCN hydrogels improved cellular adhesion, spreading, migration, and proliferation. Transplantation of mesenchymal stem cells with injectable µCN hydrogels enhanced graft survival and recovered hindlimb ischemia by enhancing material-tissue communication with biological signals and cells through µCN. This facile approach may serve as an advanced scaffold for improving stem cell transplantation therapies in regenerative medicine.

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

Date published: 2023-12-28

Publisher: Elsevier BV

Journal:

  • Biomaterials (ISSN: 01429612) vol. 305 122451

Funding:

  • Japan Society for the Promotion of Science 20K20207
  • Japan Society for the Promotion of Science 22H03962
  • Japan Society for the Promotion of Science 23H01718
  • Uehara Memorial Foundation

Manuscript type: Author's version (Accepted manuscript)

MDR DOI: https://doi.org/10.48505/nims.4692

First published URL: https://doi.org/10.1016/j.biomaterials.2023.122451

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Updated at: 2025-12-28 08:30:10 +0900

Published on MDR: 2025-12-28 08:16:37 +0900

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