Abstract
Organ functionalization is inherently complex and dynamic, involving multilayered tissue structures and continuous cellular remodeling. To address the clinical need for long-segment tracheal reconstruction, we propose a dynamic tissue engineering (DTE) strategy using a bio-adaptive physical hydrogel (BP-Gel) to emulate native tracheal development and enable dynamic regeneration of key tissue components. Here we show that chondrocytes cultured within BP-Gel form cartilage rings through an embryo-like chondrification process, during which the gel's percolation network adapts to cell migration and aggregation. The resulting cartilage exhibits a native-like multilayered morphology that enhances mechanical stability and resists degradation. Before transplantation, BP-Gel loaded with anti-inflammatory cytokines (IL-Gel) is introduced into inter-ring spaces to suppress inflammation and promote vascularization and epithelial maturation. In a rabbit tracheal defect model, this strategy reconstructs a functional trachea mimicking native structure and physiology, offering a promising, clinically relevant route to tracheal reconstruction.