Converging Pvt1 signaling and 3D-bioprinting technology for next-generation biodegradable tracheal replacement constructs

The present study elucidates the mechanoregulatory role of long non-coding RNA Pvt1 in controlling endothelial cell proliferation and focal adhesion dynamics during tracheal regeneration. Using extrusion-based three-dimensional bioprinting, patient-specific tracheal stents were fabricated with hierarchically optimized architectures that combined polylactic acid–glycolic acid (PLGA) copolymers with endothelial progenitor cell (EPC)-recruiting motifs. Computational fluid dynamics-guided nozzle path planning and in situ piezoelectric characterization enabled sub-200 μm resolution in replicating native tracheal microtopography while maintaining 94% EPC viability after printing. Pvt1-enriched bioinks significantly enhanced vascularization, producing a 2.3-fold increase in neovascularization compared with controls in rat tracheal defect models, along with a 38% reduction in fibrotic markers. The dual-stage biodegradation profile (30% mass loss at 8 weeks) provided mechanical compatibility with tissue ingrowth patterns, confirmed through micro-CT–based strain mapping. The findings establish a convergence of lncRNA biology and precision bioprinting, offering an off-the-shelf solution for complex tracheal reconstruction that addresses current challenges in graft epithelialization and immunomodulatory response. The study advances the translational potential of bioengineered airway substitutes through molecularly informed design principles.