Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, People's Republic of China.
Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Road, Shanghai 200127, People's Republic of China; Department of Pediatric Cardiac Surgery, National Center for Cardiovascular Disease and Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, 167 Beilishi Road, Xicheng, Beijing 100037, People's Republic of China.
Acta Biomater. 2019 Oct 1;97:177-186. doi: 10.1016/j.actbio.2019.07.043. Epub 2019 Jul 26.
Long-segmental tracheal defects constitute an intractable clinical problem, due to the lack of satisfactory tracheal substitutes for surgical reconstruction. Tissue engineered artificial substitutes could represent a promising approach to tackle this challenge. In our current study, tissue-engineered trachea, based on a 3D-printed poly (l-lactic acid) (PLLA) scaffold with similar morphology to the native trachea of rabbits, was used for segmental tracheal reconstruction. The 3D-printed scaffolds were seeded with chondrocytes obtained from autologous auricula, dynamically pre-cultured in vitro for 2 weeks, and pre-vascularized in vivo for another 2 weeks to generate an integrated segmental trachea organoid unit. Then, segmental tracheal defects in rabbits were restored by transplanting the engineered tracheal substitute with pedicled muscular flaps. We found that the combination of in vitro pre-culture and in vivo pre-vascularization successfully generated a segmental tracheal substitute with bionic structure and mechanical properties similar to the native trachea of rabbits. Moreover, the stable blood supply provided by the pedicled muscular flaps facilitated the survival of chondrocytes and accelerated epithelialization, thereby improving the survival rate. The segmental trachea substitute engineered by a 3D-printed scaffold, in vitro pre-culture, and in vivo pre-vascularization enhanced survival in an early stage post-operation, presenting a promising approach for surgical reconstruction of long segmental tracheal defects. STATEMENT OF SIGNIFICANCE: We found that the combination of in vitro pre-culture and in vivo pre-vascularization successfully generated a segmental tracheal substitute with bionic structure and mechanical properties similar to the native trachea of rabbits. Moreover, the stable blood supply provided by the pedicled muscular flaps facilitated the survival of chondrocytes and accelerated epithelialization, thereby improving the survival rate of the rabbits. The segmental trachea substitute engineered by a 3D-printed scaffold, in vitro pre-culture, and in vivo pre-vascularization enhanced survival in an early stage post-operation, presenting a promising approach for surgical reconstruction of long segmental tracheal defects.
长段气管缺损是一个棘手的临床问题，因为缺乏令人满意的气管替代物用于手术重建。组织工程人工替代品可能是解决这一挑战的一种有前途的方法。在我们目前的研究中，使用基于与兔天然气管形态相似的 3D 打印聚乳酸（PLLA）支架的组织工程气管，进行节段性气管重建。3D 打印支架接种来自自体耳软骨的软骨细胞，在体外动态预培养 2 周，并在体内预血管化 2 周，以生成具有整合节段性气管器官单位的组织工程气管替代物。然后，通过移植带蒂肌瓣的工程化气管替代物来修复兔的节段性气管缺损。我们发现，体外预培养和体内预血管化的结合成功地生成了具有仿生结构和机械性能的节段性气管替代物，类似于兔的天然气管。此外，带蒂肌瓣提供的稳定血液供应有利于软骨细胞的存活并加速上皮化，从而提高了存活率。3D 打印支架、体外预培养和体内预血管化工程化的节段性气管替代物在术后早期提高了存活率，为长段气管缺损的手术重建提供了一种有前途的方法。
