The trachea is the vital passage that sustains breathing. However, when extensive tracheal reconstruction is required due to tumor invasion, trauma, or other causes, there has been a long-standing lack of stable and durable substitute materials clinically—making this one of the most formidable challenges in thoracic surgery. With long-term support from the National Science and Technology Council (NSTC), a research team led by Distinguished Professor Jin-Shing Chen and Assistant Professor Wan-Ting Hung of the Department of Surgery, College of Medicine, National Taiwan University, has provided evidence-based mechanistic insights into the cartilage-regeneration phenomenon observed when cryopreserved aortic allograft is used for tracheal reconstruction. The findings were recently published in the internationally renowned journal “Advanced Healthcare Materials”.
In the early stages, the team pursued 3D-printed artificial tracheas combined with stem cells and successfully established comprehensive small- and large-animal experimental models. However, major challenges remained in biocompatibility when translating these approaches to human implantation. Inspired by a clinical research from France, the team subsequently pivoted to using cryopreserved aorta for tracheal reconstruction. In 2021, they completed Asia’s first human clinical trial of tracheal reconstruction using a cryopreserved aortic allograft, successfully treating a patient with severe tracheal stenosis. To date, the team has accumulated six clinical surgical cases.
Although clinical observations show that a cryopreserved aortic graft implanted into a tracheal defect can transform into trachea-like tissue and even generate cartilage, the regenerative mechanism underlying how vascular tissue can trigger cartilage formation has remained an unresolved scientific mystery. In addition, during the “transition period” before cartilage regeneration is complete, patients still require temporary tracheal stents for structural support. Such stents may lead to complications such as granulation tissue formation, posing substantial challenges to broader clinical adoption.
To address these barriers, the team brought the clinical question back to the laboratory. Through animal studies, they demonstrated that the aortic graft functions not merely as a passive “patch” to fill a tracheal defect, but also acts as an active in vivo regenerative scaffold, guiding the recipient’s own tissues to regenerate new tracheal cartilage. The newly formed cartilage originated from the recipient’s migrating chondroprogenitor cells that entered the graft and differentiated into chondrocytes, rather than from residual donor cells within the cryopreserved aorta—supporting the concept that the aorta can induce host-driven regeneration. The study further identified three core elements that enable this regenerative process: (1) good biocompatibility and early angiogenesis, which help provide the environment and nutrients required for regeneration; (2) key signaling proteins retained within the cryopreserved aortic allograft, including fibroblast growth factor 2 (FGF-2), which can attract chondroprogenitor cells and promote their migration and differentiation; and (3) the extracellular matrix (ECM) structure of the aortic tissue itself, which provides a microenvironment favorable for cell adhesion and migration.
This work not only fills a critical knowledge gap in clinical application, but also demonstrates substantial translational medical value. Looking ahead, these insights may be further developed into operative guidelines and material-development directions—optimizing the surgical technique for interfacing the aortic graft with the recipient’s tracheal perichondrium, and helping establish quality assessment indicators for donated aortic materials to improve consistency and overall quality of tracheal reconstruction outcomes. The team is integrating clinical application with foundational biological research to develop a regenerative medicine strategy that makes tracheal reconstruction safer and more widely available.
Media Contact：
Yih-Ru Chen
Program Manager
Department of Life Sciences
National Science and Technology Council
Phone: +886-02-2737-7461
E-mail: cyr202407@nstc.gov.tw
