Gadalla Dina, Kennedy Maeve M, Lott David G
Head and Neck Regenerative Medicine Laboratory, Mayo Clinic Arizona, Phoenix, Arizona, USA,
Head and Neck Regenerative Medicine Laboratory, Mayo Clinic Arizona, Phoenix, Arizona, USA.
Cells Tissues Organs. 2025 Mar 11:1-25. doi: 10.1159/000545132.
The trachea, a vital conduit in the lower airway system, can be affected by various disorders, such as tracheal neoplasms and tracheoesophageal fistulas, that often necessitate reconstruction. While short-segment defects can sometimes be addressed with end-to-end anastomosis, larger defects require tracheal reconstruction, a complex procedure with no universally successful replacement strategy. Tissue engineering offers a promising solution for tracheal repair, particularly focusing on regenerating its epithelium, which plays a critical role in protecting the respiratory system and facilitating mucociliary clearance. However, replicating the complex structure and functionality of the tracheal epithelium remains a significant challenge, with key hurdles including proper cell differentiation, functional mucociliary clearance, and addressing the relative lack of vascular supply to the trachea.
Current tissue engineering approaches, including biomaterial scaffolds, decellularized tissues, and scaffold-free methods, have shown varying levels of success, while in vitro air-liquid interface cultures have provided valuable insights into epithelial modeling. Despite these advances, translating these findings into effective in vivo applications remains difficult due to challenges such as immune responses, inadequate integration with host tissue, and limited long-term functionality of engineered constructs. Overcoming these barriers requires further refinement of cell sources, scaffold materials, and bioactive factors that promote vascularization and sustained epithelial function.
This review evaluates the current strategies and modeling, biomaterial scaffolds, cells, and bioactive factors used in tracheal epithelium regeneration, as well as the methods employed to assess their success through histological, functional, and molecular analyses. While significant progress has been made, the development of a safe, functional, and clinically viable tracheal graft remains elusive, underscoring the need for continued innovation in airway tissue engineering. Future advancements in biomaterial design, stem cell technology, and bioreactor-based tissue maturation hold promise for addressing challenges.
气管是下呼吸道系统中的重要管道，会受到各种疾病的影响，如气管肿瘤和气管食管瘘，这些疾病往往需要进行重建。虽然短节段缺损有时可通过端端吻合术解决，但较大的缺损则需要进行气管重建，这是一个复杂的过程，目前尚无普遍成功的替代策略。组织工程为气管修复提供了一个有前景的解决方案，尤其注重气管上皮的再生，气管上皮在保护呼吸系统和促进黏液纤毛清除方面起着关键作用。然而，复制气管上皮的复杂结构和功能仍然是一项重大挑战，主要障碍包括细胞的正确分化、功能性黏液纤毛清除以及解决气管相对缺乏血管供应的问题。
目前的组织工程方法，包括生物材料支架、脱细胞组织和无支架方法，已显示出不同程度的成功，而体外气液界面培养为上皮建模提供了有价值的见解。尽管取得了这些进展，但由于免疫反应、与宿主组织整合不足以及工程构建体长期功能有限等挑战，将这些发现转化为有效的体内应用仍然困难。克服这些障碍需要进一步优化细胞来源、支架材料和促进血管化及维持上皮功能的生物活性因子。
本综述评估了用于气管上皮再生的当前策略、建模、生物材料支架、细胞和生物活性因子，以及通过组织学、功能和分子分析评估其成功与否所采用的方法。虽然已取得重大进展，但开发一种安全、功能性且临床上可行的气管移植物仍然难以实现，这突出了气道组织工程持续创新的必要性。生物材料设计、干细胞技术和基于生物反应器的组织成熟方面的未来进展有望应对挑战。
