冷凍保存主動脈同種移植物的生物特性及其在氣管軟骨再生中的作用

Abstract

氣管原生軟骨具有有限的再生能力，使得尋找適合的氣管修補生物材料成為持續的挑戰。本研究探討未經去細胞化之冷凍保存主動脈同種異體移植物作為氣管軟骨再生支架的角色。原本應用於感染性主動脈重建的冷凍保存異體主動脈，具有作為大型動脈的特徵，包括豐富的彈性纖維與平滑肌細胞，並在體外展現出良好的軟骨細胞生物相容性。氣管-冷凍保存異體主動脈修補構造展現出與原生氣管相近的抗拉性能，且能耐受正常呼氣壓力。在兔子的氣管缺損修補模型中，冷凍保存異體主動脈僅引發輕至中度的免疫反應，且反應隨時間逐漸消退。植入一個月內，即可觀察到新生軟骨、血管新生及上皮再生。於後續十二個月中，原有的主動脈支架逐步降解，並由新生的軟骨組織——來源於受贈者的軟骨前驅細胞——取代。蛋白質體分析顯示，冷凍保存異體主動脈富含細胞骨架、細胞黏附、遷移及細胞外基質相關蛋白質。在富含的生長因子中，成纖維細胞生長因子2被確認為促進細胞趨化與軟骨分化的關鍵因子之一；此外，來自冷凍保存異體主動脈的細胞外基質亦展現對軟骨前驅細胞與軟骨細胞的趨觸效應。綜合本研究結果，冷凍保存異體主動脈不僅作為結構支架，同時也作為生物活性平台，透過協同的生物相容性、生長因子訊號傳導及細胞外基質支持，促進氣管軟骨再生。

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 adhesion, migration, and extracellular matrix (ECM)–related proteins. Among the enriched growth factors, fibroblast growth factor 2 (FGF-2) was identified as a key mediator that promotes both chemotaxis and chondrogenic differentiation. In addition, the ECM derived from CAo supports haptotactic migration of chondroprogenitor cells and chondrocytes. 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.