Ultrasoft alginate aldehyde-collagen hydrogels promote hESC-derived neural stem cell survival and neuronal differentiation in 3D culture

Zhu H, Huang X, Hui X, Xie H, Peng J, Shang G, Xu Z, Liao Y, Jiang Y, Li D, Boccaccini AR (2025)


Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 399

Article Number: 139040

DOI: 10.1016/j.matlet.2025.139040

Abstract

Three-dimensional (3D) hydrogels mimicking the neural extracellular matrix (ECM) are critical for enhancing human embryonic stem cell (hESC)-derived NSC viability and differentiation in neural disease modeling and regenerative therapies. Conventional hydrogels often inadequately replicate the soft stiffness and bioactivity of native neural tissues, leading to mechanotransduction disruption and poor cell outcomes. To address this, we engineered an ultrasoft hydrogel via Schiff base chemistry, combining alginate aldehyde (ADA) and collagen (COL) to synergize neural-tissue-like mechanics with sustained bioactivity. Hydrogels with varying ADA:COL ratios were synthesized, characterized rheologically, and tested for 3D hESC-NSC culture. Over 14 days, hESC-NSCs in ADA1-COL4 showed superior viability (>95 %), enhanced cell spreading with neurite extensions, and elevated neuronal differentiation markers (MAP2, βIII-tubulin) compared to pure COL, where cells remained rounded with weak differentiation. This study reports ADA-COL hydrogel as a potential cost-effective and biomimetic platform that offers significant potential for advancing neural tissue engineering and regenerative applications.

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APA:

Zhu, H., Huang, X., Hui, X., Xie, H., Peng, J., Shang, G.,... Boccaccini, A.R. (2025). Ultrasoft alginate aldehyde-collagen hydrogels promote hESC-derived neural stem cell survival and neuronal differentiation in 3D culture. Materials Letters, 399. https://doi.org/10.1016/j.matlet.2025.139040

MLA:

Zhu, Hui, et al. "Ultrasoft alginate aldehyde-collagen hydrogels promote hESC-derived neural stem cell survival and neuronal differentiation in 3D culture." Materials Letters 399 (2025).

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