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    3D-Printable, Self-Stiffening (4D) and Shape Morphing Hydrogel through Single-Step Orthogonal Crosslinking of Phenolic Biopolymers for Dynamic Tissue Engineering
    (Wiley, 2025) Gungor, Nuriye Nazet; Kurt, Tugce; Sari, Buse; Isik, Melis; Okesola, Babatunde O.; Arslan, Yavuz Emre; Derkus, Burak
    Particularly for dynamic, shape-changing, or fibrillar tissues such as muscles and blood vessels, the development of innovative biomaterials is crucial for advancing tissue engineering and regenerative medicine. This study introduces a novel multicomponent hydrogel created from silk fibroin (SF), tyramine-modified hyaluronic acid (HA_Tyr), and tyramine-modified gelatin (G_Tyr). Using an enzymatic orthogonal covalent bonding between phenolic groups, i.e., tyrosine and tyramine moieties of SF, HA_Tyr, and G_Tyr, a dynamically stiffening SF/HA_Tyr/G_Tyr (SHG) multicomponent hydrogel is achieved with enhanced mechanical properties. Utilizing an extrusion-based 3D printing approach, the precise fabrication of constructs with tailored geometries and functionalities is demonstrated. The emerging 3D-printed hydrogels undergo morphologic changes (4D) under 37 degrees C/phosphate buffer saline (PBS) conditions. The observed morphological change results from the conformational change and folding of SF leading to fibrillation. These multicomponent hydrogels also show significant promise in creating bio-instructive materials that meet the mechanical and functional requirements necessary for in situ tissue engineering. The study highlights the potential of these self-stiffening biomaterials to recover dynamic and fibrillar tissues, supported by both in vitro and pre-clinical chorioallantoic membrane (CAM) model evaluations that underscore their biocompatibility and pro-angiogenic properties.
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    Öğe
    Xenogenic Neural Stem Cell-Derived Extracellular Nanovesicles Modulate Human Mesenchymal Stem Cell Fate and Reconstruct Metabolomic Structure
    (Wiley-V C H Verlag Gmbh, 2022) Derkus, Burak; Isik, Melis; Eylem, Cemil Can; Ergin, Irem; Camci, Can Berk; Bilgin, Sila; Elbuken, Caglar
    Extracellular nanovesicles, particularly exosomes, can deliver their diverse bioactive biomolecular content, including miRNAs, proteins, and lipids, thus providing a context for investigating the capability of exosomes to induce stem cells toward lineage-specific cells and tissue regeneration. In this study, it is demonstrated that rat subventricular zone neural stem cell-derived exosomes (rSVZ-NSCExo) can control neural-lineage specification of human mesenchymal stem cells (hMSCs). Microarray analysis shows that the miRNA content of rSVZ-NSCExo is a faithful representation of rSVZ tissue. Through immunocytochemistry, gene expression, and multi-omics analyses, the capability to use rSVZ-NSCExo to induce hMSCs into a neuroglial or neural stem cell phenotype and genotype in a temporal and dose-dependent manner via multiple signaling pathways is demonstrated. The current study presents a new and innovative strategy to modulate hMSCs fate by harnessing the molecular content of exosomes, thus suggesting future opportunities for rSVZ-NSCExo in nerve tissue regeneration.