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   Among cerebrovascular disorders, the third leading cause of death in Japan, ischemic stroke accounts for more than 75% of all cases. Neurons, which play a central role in brain function, have poor regenerative ability and often suffer from residual effects such as paralysis of limbs and speech impairment. Even if the patient survives, residual effects often remain, accounting for 25% of Japan's causes of "bedridden" patients. It is a social problem that significantly reduces the quality of life of patients and their families.

   A medical doctor also concerns about it. The current treatment methods, thrombolytic therapy, and thrombectomy therapy, are only available for patients immediately after the onset of the ischemic stroke. The cure rate is only about 5% for patients achieving a therapeutic effect. Medical doctors are also looking for innovative therapies effective for patients with severe stroke.

   Kanagawa Institute of Industrial Science and Technology (KISTEC) supported our Strategic Research Seeds Development Project "Scaffold Materials for Ischemic Stroke Therapy" in 2019-2020. Our team has developed a jigsaw-shaped peptide that performs the basic functions of the extracellular matrix (ECM), serving as an artificial ECM for injured tissue regeneration. We designed a jigsaw-shaped self-assembling peptide (JigSAP) that mimics the hydrophobic surface of the dovetail-packing motif of the intracellular protein glycophorin A. JigSAP formed a hydrogel with evenly distributed nanofibers under physiological conditions. The arrangement of these fibers enabled the incorporation and release of vascular endothelial growth factor (VEGF), facilitating regenerative therapeutic effects in the sub-acute phase of mouse stroke model (Nature Commun 2021). In this Promising Seeds Development Project (2021-2024), we aim to develop this supramolecular peptide hydrogel into an innovative drug.

   Three researchers conduct this project as a cross-disciplinary research project: Itsuki Ajioka (TMDU), who specializes in developmental neurobiology; Takahiro Muraoka (TUAT), who specializes in organic chemistry; and Go Watanabe (Kitasato U), who specializes in computational physics.