Designer Micro-/Nanocrumpled MXene Multilayer Coatings Accelerate Osteogenesis and Regulate Macrophage Polarization.

Effective tissue regeneration and immune responses are essential for the success of biomaterial implantation. Although the interaction between synthetic materials and biological systems is well-recognized, the role of surface topographical cues in regulating the local osteoimmune microenvironment─specifically, their impact on host tissue and immune cells, and their dynamic interactions─remains underexplored. This study addresses this gap by investigating the impact of surface topography on osteogenesis and immunomodulation. We fabricated MXene/hydroxyapatite (HAP)-coated surfaces with controlled 2.5D nano-, submicro-, and microscale topographical patterns using our custom bottom-up patterning method. These engineered surfaces were employed to assess the behavior of osteoblast precursor cells and macrophage polarization. Our results demonstrate that MXene/HAP-coated surfaces with microscale crumpled topography significantly influence osteogenic activity and macrophage polarization: these surfaces notably enhanced osteoblast precursor cell spreading, proliferation, and differentiation and facilitated a shift in macrophages toward an anti-inflammatory, prohealing M2 phenotype. The observed cell responses indicate that the physical cues from the crumpled topographies, combined with the chemical cues from the MXene/HAP coatings, synergistically create a favorable osteoimmune microenvironment. This study presents the first evidence of employing MXene/HAP-multilayer coated surfaces with finely crumpled topography to concurrently facilitate osteogenesis and immunomodulation for improved implant-to-tissue integration. The tunable topographic patterns of these coatings coupled with a facile and scalable fabrication process make them widely applicable for various biomedical purposes. Our results highlight the potential of these multilayer coatings with controlled topography to improve the in vivo performance and fate of implants by modulating the host response at the material interface.