Nanofiber-Based Mechanochemical and Immunological Regulation of Bone–Tendon Interface Regeneration

Abstract

The bone–tendon interface (BTI), a heterogeneous composite structure connecting bone and tendon, poses significant challenges for regeneration due to its graded mechanical properties, complex biochemical signaling, and dynamic immune microenvironment. Conventional repair strategies often fail to achieve functional reconstruction owing to mechanical mismatch and insufficient bioactivity. Recently, nanofiber-based materials, featuring biomimetic architecture, multi-signal integration, and dynamic responsiveness, have emerged as promising candidates for BTI regeneration. This review provides a systematic analysis of the key regulatory mechanisms of nanofibers in BTI regeneration. From the mechanical perspective, gradient stiffness design, biomimetic topology, and dynamic mechanical responsiveness enable smooth stress transfer and direct cell differentiation via YAP/TAZ and FAK/ERK mechanotransduction pathways, thereby alleviating interfacial stress concentration. At the biochemical level, core–shell architectures and stimulus-responsive release systems achieve spatiotemporally controlled delivery of growth factors, while ionic modulation regulates redox balance and enzymatic activity to reconstruct the regenerative microenvironment. In terms of immune regulation, spatiotemporal programming strategies orchestrate the sequential “anti-inflammation–repair–remodeling” process, preventing chronic inflammation and fibrotic scarring. Finally, we propose a “mechanical–biochemical–immunological” multidimensional paradigm for spatiotemporal regeneration, offering a replicable prescription for challenging BTI injuries such as rotator cuff tears, and discuss future prospects involving multi-responsive hybrid systems, immune–metabolic crosstalk, and integrated 3D printing–electrospinning technologies.