Scalable and Tunable 1D/2D Wrinkled MXene Topographies Regulate Osteoimmune Cell Interactions

Successful integration of biomedical implants depends on coordinated regulation of bone regeneration and immune responses at the tissue-biomaterial interface. While biochemical features of biomaterials, such as drug release systems, have been widely explored, the role of surface topography, particularly the combined effects of feature size and shape, in osteoimmune modulation remains underexplored. Here, we developed MXene multilayer coatings with precisely engineered 1D and 2D wrinkled nano- and microtopographies using bottom-up layer-by-layer (LbL) assembly followed by thermal shrinkage. These tunable surface topographies were evaluated for their ability to modulate macrophage polarization and preosteoblast behavior. Notably, 1D microtopographies significantly promoted macrophage elongation and polarization toward the anti-inflammatory M2 phenotype, marked by elevated expression of CD206, IL-4, IL-10, and BMP-2. Simultaneously, these surfaces enhanced preosteoblast adhesion, spreading, and osteogenic differentiation, as evidenced by increased ALP activity, calcium deposition, and expression of Runx2 and osteocalcin (OCN). Indirect coculture studies further revealed that macrophage-derived cytokines enhanced osteogenesis, confirming synergistic immune-osteogenic crosstalk. This work presents the first demonstration of MXene coatings with shape- and size-tuned wrinkled topographies that direct both immunomodulation and osteogenesis. This scalable strategy offers a promising platform for engineering next-generation implant surfaces that coordinate tissue regeneration with immune modulation.