Research progress on stiffness controllable scaffolds based on gelatin methacryloyl hydrogels for tissue repair and...

The extracellular matrix (ECM) maintains tissue morphology and regulates cellular behavior through its network of biochemical components and biophysical signals. Matrix stiffness, as a key physical parameter in cell-matrix interactions, has attracted widespread attention and has been recognized as a crucial regulator of cellular behavior. Tissue engineering mimics the biomechanical environment of the ECM to promote the repair of damaged tissues. In this context, gelatin methacryloyl (GelMA), a photocrosslinkable hydrogel, has emerged as a pivotal platform in tissue engineering due to its excellent biocompatibility, biodegradability, and tunable mechanical properties. This review systematically summarizes various strategies for modulating GelMA stiffness, including adjusting the crosslinking density, incorporating nanomaterials, optimizing photopolymerization parameters, and integrating bioactive components. Furthermore, the mechanisms by which GelMA stiffness influences cellular behavior through mechanotransduction are discussed, with a focus on integrin signaling pathways, cytoskeletal remodeling, and transcription factors such as YAP/TAZ. The review also highlights applications of tuned-stiffness GelMA scaffolds in bone, skin, cardiac, and neural tissue engineering, underscoring their potential for functional repair via biomimetic mechanics. Finally, the review emphasizes the need for future research to further explore synergistic interactions between stiffness, dynamic degradation, and biological signaling mechanisms, to advance the clinical translation of GelMA in regenerative medicine.