Mechanically robust hybrid hydrogels of photo-crosslinkable gelatin and laminin-mimetic peptide amphiphiles for neural induction. (12th November 2021)

• Record Type: Journal Article
• Authors: Isik, Melis; Eylem, Cemil Can; Haciefendioglu, Tugba; Yildirim, Erol; Sari, Buse; Nemutlu, Emirhan; Emregul, Emel; Okesola, Babatunde O.; Derkus, Burak
• Is Part Of: Biomaterials science. Volume 9:Number 24(2021)
• Page Start: 8270
• Page End: 8284
• Publication Date: 2021-11-12
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d1bm01350e
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : A supramolecular hydrogel providing a biomimetic neural microenvironment with improved mechanical properties presents a laminin-derived neuro-inductive peptide epitope that induces multipotent stem cells into neural-lineage cells. Abstract : 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.