Mechanically robust hybrid hydrogels of photo-crosslinkable gelatin and laminin-mimetic peptide amphiphiles for neural induction.

Autor:	Isik M; Department of Chemistry, Faculty of Science, Ankara University, 06560 Ankara, Turkey. bderkus@ankara.edu.tr., Eylem CC; Analytical Chemistry Division, Faculty of Pharmacy, Hacettepe University, 06230 Ankara, Turkey., Haciefendioglu T; Chemistry Department, Middle East Technical University, 06800 Ankara, Turkey., Yildirim E; Chemistry Department, Middle East Technical University, 06800 Ankara, Turkey.; Department of Polymer Science and Technology, Middle East Technical University, 06800 Ankara, Turkey.; Department of Micro and Nanotechnology, Middle East Technical University, 06800 Ankara, Turkey., Sari B; Department of Chemistry, Faculty of Science, Ankara University, 06560 Ankara, Turkey. bderkus@ankara.edu.tr.; Stem Cell Research Lab, Department of Chemistry, Faculty of Science, Ankara University, 06560 Ankara, Turkey., Nemutlu E; Analytical Chemistry Division, Faculty of Pharmacy, Hacettepe University, 06230 Ankara, Turkey.; Bioanalytic and Omics Laboratory, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey., Emregul E; Department of Chemistry, Faculty of Science, Ankara University, 06560 Ankara, Turkey. bderkus@ankara.edu.tr., Okesola BO; Institute of Bioengineering, Queen Mary University of London, London, E1 4NS, UK. b.okesola@qmul.ac.uk.; School of Engineering and Materials Science, Queen Mary University of London, London, E1 4NS, UK., Derkus B; Department of Chemistry, Faculty of Science, Ankara University, 06560 Ankara, Turkey. bderkus@ankara.edu.tr.; Stem Cell Research Lab, Department of Chemistry, Faculty of Science, Ankara University, 06560 Ankara, Turkey.
Jazyk:	angličtina
Zdroj:	Biomaterials science [Biomater Sci] 2021 Dec 07; Vol. 9 (24), pp. 8270-8284. Date of Electronic Publication: 2021 Dec 07.
DOI:	10.1039/d1bm01350e
Abstrakt:	Self-assembling bio-instructive materials that can provide a biomimetic tissue microenvironment with the capability to regulate cellular behaviors represent an attractive platform in regenerative medicine. Herein, we develop a hybrid neuro-instructive hydrogel that combines the properties of a photo-crosslinkable gelatin methacrylate (GelMA) and self-assembling peptide amphiphiles (PAs) bearing a laminin-derived neuro-inductive epitope (PA-GSR). Electrostatic interaction and ultraviolet light crosslinking mechanisms were combined to create dual-crosslinked hybrid hydrogels with tunable stiffness. Spectroscopic, microscopic and theoretical techniques show that the cationic PA-GSR(+) electrostatically co-assembles with the negatively charged GelMA to create weak hydrogels with hierarchically ordered microstructures, which were further photo-crosslinked to create mechanically robust hydrogels. Dynamic oscillatory rheology and micromechanical testing show that photo-crosslinking of the co-assembled GelMA and PA-GSR(+) hydrogel results in robust hydrogels displaying improved stiffness. Gene expression analysis was used to show that GelMA/PA-GSR(+) hydrogels can induce human mesenchymal stem cells (hMSCs) into neural-lineage cells and supports neural-lineage specification of neuroblast-like cells (SH-SY5Y) in a growth-factor-free manner. Also, metabolomics analysis suggests that the hydrogel alters the metabolite profiles in the cells by affecting multiple molecular pathways. This work highlights a new approach for the design of PA-based hybrid hydrogels with robust mechanical properties and biological functionalities for nerve tissue regeneration.
Databáze:	MEDLINE
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