Cartilage cannot self-repair and thus regeneration is a promising approach to its repair. Here we developed new electrospun nanofibers, made of poly (ε-caprolactone)/polytetrahydrofuran (PCL-PTHF urethane) and collagen I from calf skin (termed PC), to trigger the chondrogenic differentiation of mesenchymal stem cells (MSCs) and the cartilage regeneration in vivo. We found that the PC nanofibers had a modulus (4.3 Mpa) lower than the PCL-PTHF urethane nanofibers without collagen I from calf skin (termed P) (6.8 Mpa) although both values are within the range of the modulus of natural cartilage (1–10 MPa). Both P and PC nanofibers did not show obvious difference in the morphology and size. Surprisingly, in the absence of the additional chondrogenesis inducers, the softer PC nanofibers could induce the chondrogenic differentiation in vitro and cartilage regeneration in vivo more efficiently than the stiffer P nanofibers. Using mRNA-sequence analysis, we found that the PC nanofibers outperformed P nanofibers in inducing chondrogenesis by specifically blocking the NF–kappa B signaling pathway to suppress inflammation. Our work shows that the PC nanofibers can serve as building blocks of new scaffolds for cartilage regeneration and provides new insights on the effect of the mechanical properties of the nanofibers on the cartilage regeneration.

软骨不能自我修复，因此再生是一种有前途的修复方法。在这里，我们开发了新的电纺纳米纤维，由聚（ε-己内酯）/聚四氢呋喃（PCL-PTHF聚氨酯）和来自小牛皮肤的I型胶原蛋白（称为PC）制成，可触发间充质干细胞（MSC）的软骨分化和软骨再生体内。我们发现，PC 纳米纤维的模量 (4.3 Mpa) 低于小牛皮中不含胶原蛋白 I（称为 P）的 PCL-PTHF 聚氨酯纳米纤维 (6.8 Mpa)，尽管这两个值都在天然软骨的模量范围内 (1 –10 兆帕）。P和PC纳米纤维在形态和尺寸上没有表现出明显的差异。令人惊讶的是，在没有额外的软骨形成诱导剂的情况下，较软的PC纳米纤维可以比较硬的P纳米纤维更有效地诱导体外软骨分化和体内软骨再生。通过 mRNA 序列分析，我们发现 PC 纳米纤维通过特异性阻断 NF-kappa B 信号通路来抑制炎症，在诱导软骨形成方面优于 P 纳米纤维。我们的工作表明，PC 纳米纤维可以作为软骨再生新支架的构建块，并为纳米纤维的机械性能对软骨再生的影响提供了新的见解。