Abstract

Fibrosis is a common problem in soft tissue regeneration, often caused by the differentiation of fibroblasts into myofibroblasts. Because of the nanoscale topology that regulates the mechanical transduction of cells, nanofibers or nanoparticles are commonly used to modulate fibroblast differentiation. However, the strength of nanofibers is insufficient, and the physiological toxicity of nanoparticles still remains to be verified. In this study, self-induced crystallization was used to construct nano-protrusions on the random and aligned polycaprolactone microfibers to regulate the behavior of fibroblasts. The results revealed that the mechanical properties of microfibers with a nanoscale topology were improved. Immunofluorescence staining manifested that nano-protrusions impeded the activation of integrins and vinculins, thereby inhibiting the nuclear transfer of Yes-associated protein, resulting in a decrease in the expression of α- smooth muscle actin. Nanoscale topology of microfibers hampered the activation of the Rho/ROCK signalling pathway. In general, we used a simple process to construct a fibrous scaffold with a micro-nano multilevel structure. This structure can hinder the transformation of fibroblasts into myofibroblasts on both random and aligned fibers, which is expected to prevent fibrosis. Graphical abstract