4.8 Article

Capturing dynamic biological signals via bio-mimicking hydrogel for precise remodeling of soft tissue

Journal

BIOACTIVE MATERIALS
Volume 6, Issue 12, Pages 4506-4516

Publisher

KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.04.039

Keywords

Biological signals; Physiological phase; Hydrogel; Chemotactic; Soft tissue remodeling

Funding

  1. National Key Research and Development Program of China [2020YFA0908200]
  2. National Natural Science Foundation of China General Program [81930051]
  3. Postdoctoral Research Foundation of China [2020M681319]
  4. Interdisciplinary Program of Shanghai Jiao Tong University [YG2019ZDA05, ZH2018ZDA04]
  5. Foundation of National Facility for Translational Medicine (Shanghai) [TMSK-2020-117]
  6. Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20171906]

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The bio-mimicking hydrogel designed through thiol-ene click reaction captures early physical and chemical signals to facilitate cell anchoring, migration, and invasion in a 3D matrix, and promotes endothelial cell functional differentiation through HIF-1α dependent signaling pathway.
Soft tissue remodeling is a sophisticated process that sequentially provides dynamic biological signals to guide cell behavior. However, capturing these signals within hydrogel and directing over time has still been unrealized owing to the poor comprehension of physiological processes. Here, a bio-mimicking hydrogel is designed via thiol-ene click reaction to capture the early physical signal triggered by inflammation, and the chemical signals provided with chemokine and natural adhesion sites, which guaranteed the precise soft tissue remodeling. This bio-mimicking hydrogel efficiently facilitated cell anchoring, migration, and invasion in the 3D matrix due to the permissive space and the interaction with integrin receptors. Besides, the covalently grafted chemokine-like peptide is optimal for colonization and functional differentiation of endothelial cells through a HIF-1 alpha dependent signal pathway. Furthermore, the early polarization of macrophages, collagen deposition and angiogenesis in rat acute wound model, and the increased blood perfusion in mouse skin flap model have confirmed that the bio-mimicking hydrogel realized precise soft tissue remodeling and opens new avenues for the phased repair of different tissues such as nerve, myocardium, and even bone.

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