Temporal-spatial hierarchical immunomodulating dressing promotes high-quality wound healing through M2 macrophage...

The skin is a highly complex organ with multiple layers and diverse cell types, each residing in specific locations. Effective wound healing requires precise coordination of cellular activities both temporally and spatially. However, this synchronization is often overlooked in traditional treatments, making optimal healing difficult to achieve. In this study, we introduce Temporal-Spatial Hierarchical Immunomodulating Dressing (T-shield), a programmable wound dressing that combines 3D printing technology with controlled drug release. T-shield is designed to mimic the skin's multilayer structure and deliver cell modulators at specific times, simulating the natural stages of wound healing. By integrating these modulators within the dressing's layers and allowing for controlled degradation, T-shield ensures that the release of cell modulators aligns with healing process. Importantly, T-shield promotes the transition from the pro-healing phase to the pro-remodeling phase by modulating the shift from the M2a to the M2c macrophage sub-phenotype. Our results show that this strategy not only accelerates wound closure but also significantly improves the quality of healing. Wounds treated with T-shield displayed increased mechanical strength, more mature tissue structures, and enhanced functional properties-features often neglected by conventional therapies. Therefore, T-shield represents a promising approach to improving complex wound healing and highlights the importance of designing materials that align with physiological processes to optimize therapeutic outcomes.