Regulation of immune factor secretion by nanofiber microstructures.

Abstract

The imbalance of immune factor secretion plays a critical role in the dysregulation of immune homeostasis, contributing to chronic inflammation and impaired tissue regeneration. Nanofiber microstructures have emerged as promising biomaterials in tissue regeneration due to their ability to modulate immune cell behavior. However, the mechanisms by which nanofiber microstructures regulate immune factor secretion remain poorly understood. In this study, we fabricated three types of nanofibers with varying degrees of alignment microstructures and investigated their effects on immune factor secretion of immune cells. In vitro analyses revealed that highly aligned nanofibers significantly enhanced the secretion of anti-inflammatory factors such as TGF-β1 and IL-10, while suppressing pro-inflammatory factors including TNF-α and IL-6. These effects were mediated through the modulation of immune cell adhesion receptors and mechanotransduction pathways. Furthermore, in vivo experiments demonstrated that highly aligned nanofibers optimized the immune microenvironment at wound sites, promoting angiogenesis and accelerating tissue regeneration. This study introduces an alternative perspective on biomaterial-based immune regulation, highlighting the critical role of nanofiber microstructures in directing immune cell functions. These findings provide a foundation for the rational design of biomaterials with tailored microstructures to achieve precise immune modulation, offering strategies for enhancing wound healing and advancing regenerative medicine. STATEMENT OF SIGNIFICANCE: Dysregulated immune factor secretion is a major contributor to chronic inflammation and impaired tissue regeneration. Current strategies that rely on exogenous cytokines are constrained by short half-lives and uncontrollable release kinetics. Given that immune cells are the primary source of these factors, direct modulation of their local secretory profiles offers a more stable and sustained alternative. Here, we introduce a nanofiber microstructure-based approach to program immune cell secretory behavior. We demonstrate, for the first time, that highly aligned nanofibers remodel the immune secretome via the integrin α10β1/PI3K/AKT signaling pathway, thereby reestablishing a pro-regenerative immune microenvironment and enhancing tissue repair. This study establishes a new paradigm in which biomaterials precisely reprogram immune secretory function, laying the foundation for programmable immunoregulatory materials with strong translational potential.