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

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.

Peptide-Based Hydrogels: New Materials for Biosensing and Biomedical Applications

“…The hydrogels were used to support in the vitro chondrogenesis of human chondrocytes, and the authors reported the improved cell growth and cartilage-specific ECM production useful for cartilage tissue engineering. Yaguchi et al employed a cell-adhesive, fiber-forming peptide hydrogel to imitate the jigsaw-shaped hydrophobic surface in the dovetail-packing motif of glycophorin A as an artificial extracellular matrix for regenerative therapy [ 146 ]. This hydrogel provided controlled release of vascular endothelial growth factor, and their results on a subacute-chronic phase mouse stroke model revealed the cell transplantation-free regenerative therapeutic effects, highlighting a great potential of this hydrogel for using in injured tissue regeneration.…”

Self-assembling Molecular Medicine for the Subacute Phase of Ischemic Stroke

“…In 2021, Muraoka, Ajioka, and coworkers developed a jigsaw-shaped self-assembling peptide (JigSAP, Fig. 4 a) [ 48 ]. This cell-adhesive fiber-forming self-assembling peptide can efficiently incorporate and release VEGF and demonstrate cell transplantation-free regenerative therapeutic effects at the subacute phase of ischemic stroke in mice.…”

Leading‐Edge Pulmonary Gene Therapy Approached by Barrier‐Permeable Delivery System: A Concise Review on Peptide System

“…[90,91] In addition, we have sighted these peptide hydrogels that provided regenerative recovery in other mucus-harbored tissues, including brain and ocular tissue. [92][93][94] In the pulmonary area, a unique pulmonary surface-anchorable peptide hydrogel system was introduced to the ex vivo study on porcine lung by Hoang and Schneider last year. [95] This surface-filled hydrogel (SFH) has drawn special attention due to its special surface-fill property to fit the pleural cavity, caused by surgical debulking of mesothelioma, and then released miRNA 215 or 206 Figure 6.…”