Tunable wrinkled topographies direct dendritic cell maturation and immune phenotypes

Dendritic cells (DCs) are potent regulators of immunity with therapeutic potential in cancer, autoimmune disorders, and implant tolerance. However, clinical translation is limited by poor scalability, limited survival/retention after delivery, and difficulty controlling DC immune responses. Biomaterials have been explored to address these challenges, but the role of surface topography in DC regulation remains poorly understood. Here, we used a custom bottom-up nanofabrication method to create wrinkled multilayer coatings with precisely tunable nano-, submicro-, and microscale topographies. Using this platform, we systematically investigated the impact of topographical cues on DC behavior, using the DC2.4 cell line and primary bone marrow-derived DCs (BMDCs) as biological models. We found that distinct topographies drive DCs toward divergent phenotypes. Microscale wrinkles promoted an immunogenic mature state, with elevated pro-inflammatory cytokines (IL-6, IL-12, and TNF-α), high co-stimulation and NF-κB activation, and strong T-cell activation potential. Submicro-scale patterns induced an intermediate mature state with homeostatic and tolerogenic potential. Submicro exhibited increased TGF-β and IL-10, reduced cross-presentation, and weak T-cell activation in the DC2.4 cell line. However, BMDCs expressed intermediate maturation marker levels and NF-κB activation without increased cytokine secretion. In contrast, nanoscale wrinkles and planar controls preserved DC immaturity with high antigen uptake and low maturation, though planar surfaces showed poor adhesion, limiting their utility for delivery or ex vivo culture. These findings identify surface topography as a key regulator of DC immune programming. Our versatile, scalable fabrication strategy provides a broadly applicable platform for probing immune cell-material interactions and advancing biomaterials for DC-based immunotherapies and related applications. STATEMENT OF SIGNIFICANCE: Immune therapies increasingly rely on dendritic cells (DCs), yet current biomaterials mainly use biochemical signals to guide their behavior. This study introduces a new approach using precisely engineered surface topographies to influence DC function through physical cues alone. By creating tunable wrinkled MXene coatings, we show for the first time that different topographical scales can maintain DC immaturity or induce maturation with either homeostatic or immunogenic polarization potential. Unlike prior studies that focus on general surface roughness or chemistry, we demonstrate a topography-specific effect validated in both cell line and primary DCs. This work establishes surface architecture as a powerful design parameter for immune-instructive biomaterials, with potential to improve vaccine development and cell-based immunotherapies.