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Self-Assembled Hydrogel from Pyrene-Modified Peptide as 3D Matrices for Neuronal Cell

Devi Wahyuningtyas, Ya-Ting Yu, Chin-Yun Hsieh, Yung-An Huang, Ruei‐Yu He, Tzu-Hung Teng, Bryan Po-Wen Chen, Jung-Ren Huang, David T. Wu, Joseph Jen‐Tse Huang

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Abstract

High Resolution Image Download MS PowerPoint Slide Self-assembled hydrogels offer biomimetic platforms for three-dimensional (3D) cell culture; yet, achieving stability and functionality under physiological conditions remains a challenge. Here, we report a series of pyrene (Py)-modified peptides designed to form hydrogels with tunable physical and biological properties. Among them, Py-L 3 K 3 uniquely formed stable, fluorescent hydrogels at both neutral and basic pH, in contrast to Py-K 6 and Py-A 3 K 3, which gelled only at basic pH. Molecular dynamics simulations revealed pH-dependent clustering as a key mechanism driving hydrogel formation. Structural analysis showed that Py-L 3 K 3 forms nanofibrillar networks with granular surface morphologies and β-sheet-rich conformations. Rheological studies demonstrated its solid-like viscoelastic behavior and self-healing capability, as determined by oscillatory shear measurements. Importantly, Py-L 3 K 3 supported neuronal cell viability, attachment, and growth under physiological conditions, highlighting its potential as a 3D culture scaffold. These findings present Py-L 3 K 3 as a promising candidate for applications in neuronal engineering and injectable regenerative biomaterials.

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