A bio-adaptive physical hydrogel enables dynamic tissue engineering for tracheal reconstruction

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.