School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
Tissue Engineering Research Group, Dept of Anatomy and Regenerative Medicine, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
Eur Respir Rev. 2021 Nov 8;30(162). doi: 10.1183/16000617.0154-2021. Print 2021 Dec 31.
Effective restoration of extensive tracheal damage arising from cancer, stenosis, infection or congenital abnormalities remains an unmet clinical need in respiratory medicine. The trachea is a 10-11 cm long fibrocartilaginous tube of the lower respiratory tract, with 16-20 tracheal cartilages anterolaterally and a dynamic trachealis muscle posteriorly. Tracheal resection is commonly offered to patients suffering from short-length tracheal defects, but replacement is required when the trauma exceeds 50% of total length of the trachea in adults and 30% in children. Recently, tissue engineering (TE) has shown promise to fabricate biocompatible tissue-engineered tracheal implants for tracheal replacement and regeneration. However, its widespread use is hampered by inadequate re-epithelialisation, poor mechanical properties, insufficient revascularisation and unsatisfactory durability, leading to little success in the clinical use of tissue-engineered tracheal implants to date. Here, we describe in detail the historical attempts and the lessons learned for tracheal TE approaches by contextualising the clinical needs and essential requirements for a functional tracheal graft. TE manufacturing approaches explored to date and the clinical translation of both TE and non-TE strategies for tracheal regeneration are summarised to fully understand the big picture of tracheal TE and its impact on clinical treatment of extensive tracheal defects.
在呼吸医学领域,如何有效修复癌症、狭窄、感染或先天畸形等导致的大范围气管损伤仍然是一个未满足的临床需求。气管是下呼吸道长约 10-11 厘米的纤维软骨管,前外侧有 16-20 个气管软骨,后有动态的气管平滑肌。当气管损伤的长度小于成人的 50%、儿童的 30%时,通常会为患有短长度气管缺陷的患者提供气管切除术,但当创伤超过气管总长度的 50%时,则需要进行替换。最近,组织工程(TE)已显示出制造生物相容性组织工程气管植入物以进行气管替换和再生的潜力。然而,由于上皮化不足、机械性能差、再血管化不足和耐久性不理想,其广泛应用受到阻碍,导致组织工程气管植入物在临床上的应用至今收效甚微。在这里,我们详细描述了历史上为满足功能性气管移植物的临床需求和基本要求而尝试的气管 TE 方法,以及从中吸取的经验教训。总结了迄今为止探索的 TE 制造方法,以及 TE 和非 TE 策略在气管再生方面的临床转化,以全面了解气管 TE 的全貌及其对广泛气管缺损的临床治疗的影响。