Multiscale Hybrid Surface Topographies Orchestrate Immune Regulation, Antibacterial Defense, and Tissue Regeneration.

Implant-associated complications-including infection, adverse immune responses, and poor tissue integration-pose significant risks to patients, often leading to implant failure, revision surgeries, or chronic disease. Current chemical-based strategies, such as antibiotic or drug-releasing systems, are limited by short-term efficacy, narrow therapeutic windows, and potential toxicity. Surface topography offers a promising alternative, but most designs target single cell types and overlook the complex, multicellular dynamics at the implant-host interface. Here, a new multifunctional platform is introduced based on nano-micro hybrid wrinkled topographies fabricated via a custom nanofabrication method that combines layer-by-layer (LbL) self-assembly with mechanical nanomanufacturing. This system simultaneously modulates bacteria, immune cells, and tissue progenitors to enable antibacterial activity, immune regulation, and tissue regeneration. On hybrid surfaces, nanoscale features disrupt bacterial adhesion (>50% biofilm reduction vs. flat controls), while microscale features enhance macrophage polarization (≈3-fold increase in M2 markers) and osteogenic differentiation (>8-fold increase in ALP activity), indicating strong pro-healing responses. Notably, macrophages exhibit context-dependent behavior-driving inflammation during bacterial infection and repair in its absence-creating an immune-balanced microenvironment for implant integration. The modular nature of this platform allows expansion to other cell types and disease contexts, offering a broadly applicable strategy for next-generation biomaterials.