Department of Orthopedic Surgery.
Matrix Biology Program, Benaroya Research Institute, Seattle, WA, USA.
J Tissue Eng Regen Med. 2018 Mar;12(3):e1383-e1391. doi: 10.1002/term.2523. Epub 2017 Nov 10.
The repair of large tracheal segmental defects remains an unsolved problem. The goal of this study is to apply tissue engineering principles for the fabrication of large segmental trachea replacements. Engineered tracheal replacements composed of autologous cells (neotracheas) were tested in a New Zealand White rabbit model. Neotracheas were formed in the rabbit neck by wrapping a silicone tube with consecutive layers of skin epithelium, platysma muscle, and an engineered cartilage sheet and allowing the construct to mature for 8-12 weeks. In total, 28 rabbits were implanted and the neotracheas assessed for tissue morphology. In 11 cases, neotracheas deemed sufficiently strong were used to repair segmental tracheal defects. Initially, the success rate of producing structurally sound neotracheas was impeded by physical disruption of the cartilage sheets during animal handling, but by the end of the study, 15 of 18 neotracheas (83.3%) were structurally sound. Of the 15 structurally sound neotracheas, 11 were used for segmental reconstruction and were left in place for up to 21 days. Histological examination showed the presence of variable amounts of viable epithelium, a vascularized platysma flap, and a layer of safranin O-positive cartilage along with evidence of endochondral ossification. Rabbits that had undergone segmental reconstruction showed good tracheal integration, had a viable epithelium with vascular support, and the cartilage was sufficiently strong to maintain a lumen when palpated. The results demonstrated that viable, trilayered, scaffold-free neotracheas could be constructed from autologous cells and could be integrated into native trachea to repair a segmental defect.
修复大段气管节段性缺损仍然是一个未解决的问题。本研究的目的是应用组织工程学原理来制造大段气管节段性替代物。在新西兰白兔模型中,测试了由自体细胞(新生气管)制成的工程化气管替代物。通过用皮肤上皮细胞、颈阔肌和工程化软骨片连续层包裹硅胶管,并允许构建体成熟 8-12 周,在兔颈部形成新生气管。总共植入了 28 只兔子,并对新生气管的组织形态进行了评估。在 11 例中,认为足够坚固的新生气管被用于修复节段性气管缺损。最初,由于动物处理过程中软骨片的物理破坏,导致产生结构坚固的新生气管的成功率受到阻碍,但在研究结束时,18 个新生气管中有 15 个(83.3%)结构坚固。在 15 个结构坚固的新生气管中,有 11 个用于节段性重建,并放置了长达 21 天。组织学检查显示存在不同数量的存活上皮、血管化颈阔肌瓣和一层番红 O 阳性软骨,以及软骨内骨化的证据。进行了节段性重建的兔子表现出良好的气管整合,有存活的上皮细胞和血管支持,软骨足够坚固,在触诊时可以维持管腔。结果表明,能够构建出具有三层结构、无支架的、源自自体细胞的新生气管,并能够整合到天然气管中以修复节段性缺损。