Influence of micro- and nanoscale cues on immune factors secretion: implications for immunomodulation

Immune factors secreted by immune cells play a pivotal role in orchestrating inflammatory responses and facilitating tissue regeneration. Fiber dressings, owing to their extracellular matrix-like architecture and tunable physical properties, have emerged as promising candidates in regenerative medicine. Beyond serving as passive structural supports, fibers are increasingly recognized as active modulators of cell behavior through their inherent physical characteristics. However, how fiber diameter at the micro- and nanoscale influences the immune factor secretion profile of immune cells remains poorly defined. In this study, three types of fibers with distinct diameter scales were fabricated to systematically assess their immunomodulatory effects. In vitro analyses revealed that microscale fibers markedly enhanced the secretion of pro-regenerative and anti-inflammatory factors, such as VEGF, EGF, IL-10 and TGF-β1, while suppressing pro-inflammatory factors including TNF-α and IL-6. Mechanistic investigations indicated that this size-dependent immunomodulation may be driven by activation of the FAK-Wnt signaling pathway triggered by topographical cues. In vivo, microscale fibers significantly promoted neovascularization, attenuated inflammatory responses and accelerated tissue repair, further corroborating their immunoregulatory potential in a physiological setting. These findings establish fiber diameter as a critical physical cue for shaping the immune microenvironment and present a new strategy for immunoregulation through structural design. This work provides a conceptual framework for the development of biomaterials with intrinsic immunomodulatory properties and offers new therapeutic insights for the treatment of chronic inflammation-associated disorders.