UTX Responds to Nanotopography to Suppress Macrophage Inflammatory Response by Remodeling H3K27me3 Modification

Abstract Peri‐implantitis is the leading cause of implant failure, primarily due to weak defense at the implant–soft tissue interface, which disrupts the local immune microenvironment. As an integral part of this microenvironment, the implant–tissue interface plays a critical role in shaping immune cell function. Thus, engineering the surface topography of implants has emerged as a novel strategy for sustained immunomodulation following implantation. This study investigated the mechanical regulation of macrophage function by nanopatterned topographies. Titanium nanotubes (TNTs) surfaces reduce the expression of phosphorylated myosin light chain (pMLC) and promote the retention of the UTX histone methyltransferase in the nucleus. This process attenuates the enrichment of the repressive H3K27me3 histone marker at the Abca1 gene locus, increasing Abca1 expression and suppressing inflammation. This study reveals the mechanosensitivity of UTX and provides a new target for the development of therapeutic strategies that integrate mechanical signaling and immune modulation.