Efficient protein incorporation and release by a jigsaw-shaped self-assembling peptide hydrogel for injured brain regeneration

Atsuya Yaguchi, Mio Oshikawa, Go Watanabe, Hirotsugu Hiramatsu, Noriyuki Uchida, Chikako Hara, Naoko Kaneko, Kazunobu Sawamoto, Takahiro Muraoka () and Itsuki Ajioka ()
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Atsuya Yaguchi: Tokyo University of Agriculture and Technology
Mio Oshikawa: Center for Brain Integration Research (CBIR), Tokyo Medical and Dental University (TMDU)
Go Watanabe: Kanagawa Institute of Industrial Science and Technology (KISTEC)
Hirotsugu Hiramatsu: National Yang Ming Chiao Tung University
Noriyuki Uchida: Tokyo University of Agriculture and Technology
Chikako Hara: Center for Brain Integration Research (CBIR), Tokyo Medical and Dental University (TMDU)
Naoko Kaneko: Nagoya City University Graduate School of Medical Sciences
Kazunobu Sawamoto: Nagoya City University Graduate School of Medical Sciences
Takahiro Muraoka: Tokyo University of Agriculture and Technology
Itsuki Ajioka: Center for Brain Integration Research (CBIR), Tokyo Medical and Dental University (TMDU)

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract During injured tissue regeneration, the extracellular matrix plays a key role in controlling and coordinating various cellular events by binding and releasing secreted proteins in addition to promoting cell adhesion. Herein, we develop a cell-adhesive fiber-forming peptide that mimics the jigsaw-shaped hydrophobic surface in the dovetail-packing motif of glycophorin A as an artificial extracellular matrix for regenerative therapy. We show that the jigsaw-shaped self-assembling peptide forms several-micrometer-long supramolecular nanofibers through a helix-to-strand transition to afford a hydrogel under physiological conditions and disperses homogeneously in the hydrogel. The molecular- and macro-scale supramolecular properties of the jigsaw-shaped self-assembling peptide hydrogel allow efficient incorporation and sustained release of vascular endothelial growth factor, and demonstrate cell transplantation-free regenerative therapeutic effects in a subacute-chronic phase mouse stroke model. This research highlights a therapeutic strategy for injured tissue regeneration using the jigsaw-shaped self-assembling peptide supramolecular hydrogel.

Date: 2021
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DOI: 10.1038/s41467-021-26896-3

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