Liu Siyuan, Chen Guobao, Chen Zhongmin, Wang Fuping, Lv Yonggang
School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, PR China.
School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, PR China.
Int J Biol Macromol. 2025 Sep;321(Pt 3):146485. doi: 10.1016/j.ijbiomac.2025.146485. Epub 2025 Jul 31.
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.
细胞外基质（ECM）通过其生化成分和生物物理信号网络维持组织形态并调节细胞行为。基质刚度作为细胞-基质相互作用中的关键物理参数，已引起广泛关注，并被认为是细胞行为的关键调节因子。组织工程模仿ECM的生物力学环境以促进受损组织的修复。在此背景下，甲基丙烯酰化明胶（GelMA）作为一种可光交联水凝胶，因其优异的生物相容性、可生物降解性和可调机械性能，已成为组织工程中的关键平台。本综述系统总结了调节GelMA刚度的各种策略，包括调整交联密度、掺入纳米材料、优化光聚合参数以及整合生物活性成分。此外，还讨论了GelMA刚度通过机械转导影响细胞行为的机制，重点关注整合素信号通路、细胞骨架重塑以及YAP/TAZ等转录因子。该综述还强调了刚度可调的GelMA支架在骨、皮肤、心脏和神经组织工程中的应用，突出了它们通过仿生力学实现功能修复的潜力。最后，该综述强调未来研究需要进一步探索刚度、动态降解和生物信号机制之间的协同相互作用，以推动GelMA在再生医学中的临床转化。
