3D printing as an innovative tool in personalized management of complex airway diseases: a literature review.

Abstract

<h4>Background and objective</h4>Personalized medicine tailors interventions to a patient's unique anatomy and physiology. Three-dimensional printing (3DP) enables this precision for complex airway disease, including tracheal stenosis, tracheobronchomalacia, aerodigestive fistulas, and segmental defects, where conventional silicone or metallic stents and surgical reconstruction often fail to provide durable, anatomically congruent solutions. Tissue engineering and 3DP promise patient-specific devices and regenerative scaffolds that maintain patency, resist collapse, and minimize immunogenicity. This review synthesizes clinical and preclinical progress, highlighting materials, design strategies, biologic integration, and translational barriers.<h4>Methods</h4>A comprehensive literature search was conducted in PubMed (January 1, 2015-June 1, 2025). Inclusion criteria encompassed studies utilizing 3DP to fabricate implantable devices for tracheobronchial reconstruction, with <i>in vivo</i> implantation. Pediatric (<18 years), egg/mouse/rat preclinical studies, review articles, and abstracts were excluded. Data extracted included publication details, participant characteristics, device materials and printing methods, and outcomes.<h4>Key content and findings</h4>From 808 records, 16 clinical and 56 preclinical studies were analyzed. Clinically, indirect 3DP with silicone or metallic alloys predominated, creating Y-stents or straight stents for post-lung transplant (LTx) stenosis, tracheobronchomalacia, granulomatosis with polyangiitis, malignant obstruction, and aerodigestive fistulas. 3DP technologies facilitate the synthesis of customized stents that can better conform to individual airway geometries, offering more precise therapeutic options than conventional one-size-fits-all devices. In parallel, preclinical studies aim to address the limitations observed within clinical settings by focusing on long-term, regenerative solutions. Preclinical studies focused on biodegradable scaffolds, commonly polycaprolactone (PCL), enhanced through surface modification or hybridization with hydrogels such as gelatin methacryloyl (GelMA) or silk fibroin and bioactive factors like transforming growth factor-β (TGF-β) or stromal cell-derived factor-1 (SDF-1). Bilayer constructs with epithelial and chondrogenic components supported epithelialization, cartilage formation, and vascularization. Advanced strategies such as exosome use, ferroptosis inhibition, and heterotopic preconditioning improved integration.<h4>Conclusions</h4>3DP enables anatomically tailored airway implants and promising regenerative scaffolds. Translation is limited by technical variability, regulatory complexity, and sparse long-term data. Standardized protocols, rigorous trials, and multidisciplinary collaboration are essential to bring 3DP airway reconstruction into clinical practice.