Byun Woo Yul, Liu Lumei, Palutsis Amanda, Tan Zheng Hong, Herster Rachel, VanKoevering Kyle, Manning Amy, Chiang Tendy
College of Medicine The Ohio State University Columbus Ohio USA.
Center for Regenerative Medicine Abigail Wexner Research Institute, Nationwide Children's Hospital Columbus Ohio USA.
Laryngoscope Investig Otolaryngol. 2024 Apr 13;9(2):e1247. doi: 10.1002/lio2.1247. eCollection 2024 Apr.
Bioengineered tracheal grafts are a potential solution for the repair of long-segment tracheal defects. A recent advancement is partially decellularized tracheal grafts (PDTGs) which enable regeneration of host epithelium and retain viable donor chondrocytes for hypothesized benefits to mechanical properties. We propose a novel and tunable 3D-printed bioreactor for creating large animal PDTG that brings this technology closer to the bedside.
Conventional agitated immersion with surfactant and enzymatic activity was used to partially decellularize New Zealand white rabbit () tracheal segments ( = 3). In parallel, tracheal segments ( = 3) were decellularized in the bioreactor with continuous extraluminal flow of medium and alternating intraluminal flow of surfactant and medium. Unprocessed tracheal segments ( = 3) were also collected as a control. The grafts were assessed using the H&E stain, tissue DNA content, live/dead assay, Masson's trichrome stain, and mechanical testing.
Conventional processing required 10 h to achieve decellularization of the epithelium and submucosa with poor chondrocyte viability and mechanical strength. Using the bioreactor reduced processing time by 6 h and resulted in chondrocyte viability and mechanical strength similar to that of native trachea.
Large animal PDTG created using our novel 3D printed bioreactor is a promising approach to efficiently produce tracheal grafts. The bioreactor offers flexibility and adjustability favorable to creating PDTG for clinical research and use. Future research includes optimizing flow conditions and transplantation to assess post-implant regeneration and mechanical properties.
NA.
生物工程气管移植物是修复长段气管缺损的一种潜在解决方案。最近的一项进展是部分脱细胞气管移植物（PDTGs），它能够使宿主上皮再生，并保留有活力的供体软骨细胞，从而对机械性能产生假定的益处。我们提出了一种新颖且可调节的3D打印生物反应器，用于制造大型动物PDTG，使这项技术更接近临床应用。
使用含有表面活性剂和酶活性的传统搅拌浸泡法对新西兰白兔（）气管段（ = 3）进行部分脱细胞处理。同时，将气管段（ = 3）置于生物反应器中进行脱细胞处理，培养基持续进行管外流动，表面活性剂和培养基交替进行管内流动。还收集了未处理的气管段（ = 3）作为对照。使用苏木精-伊红染色、组织DNA含量、活/死检测、Masson三色染色和力学测试对移植物进行评估。
传统处理方法需要10小时才能实现上皮和黏膜下层的脱细胞，软骨细胞活力和机械强度较差。使用生物反应器可将处理时间缩短6小时，并使软骨细胞活力和机械强度与天然气管相似。
使用我们新颖的3D打印生物反应器制造的大型动物PDTG是一种高效生产气管移植物的有前景的方法。该生物反应器具有灵活性和可调节性，有利于制造用于临床研究和应用的PDTG。未来的研究包括优化流动条件和移植，以评估植入后的再生和机械性能。
无。
