Guo Xuran, Gao Ying, Yu Jiajia, Qiu Sha, Wang Xiaoli, Wang Shasha, Zhang Chunling, Yi Bingcheng, Gao Yinghua
Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, China.
Adv Healthc Mater. 2025 May 13:e2500277. doi: 10.1002/adhm.202500277.
Substrate stiffness regulates fibroblast phenotype through focal adhesion-mediated mechanotransduction pathways to facilitate tissue repair and regeneration. To analyze the effects of dynamic mechanical stimulation of substrates on cell behavior and skin wound healing, collagen-like hydrogel nanofibers are fabricated using coaxial electrospinning of gelatin methacryloyl (GelMA) and poly-L-lactic acid (PLLA). These nanofibers are then grafted with thermoresponsive poly(N-vinylcaprolactam) (PNVCL) via dehydration condensation reaction, providing temperature-dependent mechanical signals. The incorporation of PLLA significantly enhanced the mechanical properties of the GelMA hydrogel nanofibers, while the subsequent grafting of PNVCL effectively reduced the swelling ratio and porosity. Upon exposure to temperatures above the lowest critical solution temperature (LCST), PNVCL molecules underwent a phase transition and self-contraction, improving mechanical properties by forming robust hydrogen bonds with GelMA and expelling water molecules from the polymer matrix. This dynamic mechanical stimulation further promoted cytoskeletal remodeling of mouse skin fibroblasts (MSFs) without significantly affecting cell proliferation and migration. Additionally, it stimulated the differentiation of fibroblasts into myofibroblasts, thereby enhancing extracellular matrix secretion and skin regeneration in vivo. Overall, the engineering of thermoresponsive hydrogel nanofibers with dynamic mechanical stimulation introduces a novel design paradigm in functional tissue engineering, enabling precise regulation of cellular behaviors for effective skin wound healing.
底物刚度通过粘着斑介导的机械转导途径调节成纤维细胞表型，以促进组织修复和再生。为了分析底物的动态机械刺激对细胞行为和皮肤伤口愈合的影响，使用甲基丙烯酰化明胶（GelMA）和聚-L-乳酸（PLLA）的同轴静电纺丝制备了胶原样水凝胶纳米纤维。然后通过脱水缩合反应将热响应性聚（N-乙烯基己内酰胺）（PNVCL）接枝到这些纳米纤维上，提供温度依赖性机械信号。PLLA的加入显著增强了GelMA水凝胶纳米纤维的机械性能，而随后PNVCL的接枝有效地降低了溶胀率和孔隙率。当暴露于高于最低临界溶液温度（LCST）的温度时，PNVCL分子发生相变并自我收缩，通过与GelMA形成强大的氢键并从聚合物基质中排出水分子来改善机械性能。这种动态机械刺激进一步促进了小鼠皮肤成纤维细胞（MSF）的细胞骨架重塑，而不会显著影响细胞增殖和迁移。此外，它刺激成纤维细胞分化为肌成纤维细胞，从而增强体内细胞外基质分泌和皮肤再生。总体而言，具有动态机械刺激的热响应性水凝胶纳米纤维工程在功能组织工程中引入了一种新的设计范式，能够精确调节细胞行为以实现有效的皮肤伤口愈合。
