Chondrogenic Potential of Cryopreserved Aortic Allografts: Guiding Perichondrial Regeneration in Tracheal Repair

Native tracheal cartilage exhibits limited regenerative capacity, making the search for suitable biomaterials for tracheal repair a persistent challenge. In this study, a non-decellularized cryopreserved aortic allograft (CAo) is investigated as a scaffold for tracheal cartilage regeneration. Originally used to reconstruct infected aortas, CAo retains key features of a large artery-abundant elastic fibers and smooth muscle cells-and demonstrates favorable in vitro biocompatibility with chondrocytes. A trachea-CAo patch construct maintains tensile properties comparable to native trachea and tolerates normal expiratory forces. In a rabbit patch-defect model, CAo elicits only a mild-to-moderate immune response that gradually subsides. Within one month of implantation, robust neocartilage formation is observed, along with angiogenesis and epithelial regeneration. Over the next 12 months, the original aortic scaffold progressively degrades, while newly formed cartilage-originating from recipient perichondrial chondroprogenitor cells-replaces it. Proteomic analyses show that CAo is enriched in cytoskeletal, adhesion, cell migration, and extracellular matrix (ECM)-related proteins, with fibroblast growth factor 2 emerging as a critical mediator of chemotaxis and chondrogenic differentiation. These findings indicate that CAo serves as both a structural and biological scaffold, activating tracheal cartilage regeneration through synergistic biocompatibility, growth factor signaling, and ECM support.