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

Abstract

Tracheal reconstruction remains a major clinical challenge due to persistent limitations in graft vascularization, epithelialization, and long-term mechanical compatibility. Conventional synthetic scaffolds and autologous grafts often fail to achieve durable integration, underscoring the need for innovative biofabrication strategies. In the present study, we elucidate the mechanoregulatory role of the long non-coding (lnc) RNA Pvt1 in controlling endothelial cell proliferation and focal adhesion dynamics during tracheal regeneration. Patient-specific tracheal stents were fabricated using extrusion-based three-dimensional bioprinting with hierarchically optimized architectures that combined polycaprolactone (PCL) 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, yielding a 2.3-fold increase in neovascularization compared with controls in rat tracheal defect models, alongside a 38% reduction in fibrotic markers. The constructs exhibited a dual-stage biodegradation profile (30% mass loss at eight weeks), providing mechanical compatibility with tissue ingrowth patterns as confirmed by micro-computed tomography-based strain mapping. Collectively, these findings demonstrate the convergence of lncRNA biology and precision bioprinting, delivering an off-the-shelf solution for complex tracheal reconstruction that addresses current barriers in graft epithelialization and immunomodulatory response. The study advances the translational potential of bioengineered airway substitutes through molecularly informed design principles.  

Keywords

Biodegradable materials / Endothelial cells / Personalized treatment / Pvt1 / Tracheal repair / Three-dimensional printing

Funding

This study was supported by the National Natural Science Foundation of China (82260015), Jiangxi Key Research and Development Plan (No.20243BBI91018), the Jiangxi Provincial Health Commission Science and Technology Project (No.202410200), the Jiangxi Province Traditional Chinese Medicine Science and Technology Project (No.2023A0302), the Shenzhen Baoan People’s Hospital academic leader research start-up fund (No.202400120201), and the Shenzhen Baoan District Medical Health Research Project (No.BAGZL2024036).

Conflict of Interest

The author(s) declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article.

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