Bioreactor Development for Lung Tissue Engineering.
Bioreactor Development for Lung Tissue Engineering.
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DOI：
10.1007/s40472-014-0048-z
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发表时间：
2015-03
影响因子：
2.1
通讯作者：
中科院分区：
文献类型：
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近年来，肺研究者、工业界和器官移植领域对肺生物工程的兴趣越来越大，生物反应器的发展迅速，从微流体规模到人体大小的全肺系统。需要对这些模型的发现进行理解，为进一步开发生物反应器提供基础。目的是全面回顾目前肺生物反应器的发展状况。在PubMed上搜索了使用关键词“肺”和“生物反应器”或“生物工程”或“组织工程”或“体外灌注”发表的同行评议论文。从微流体规模到人体大小的全肺系统，许多新的生物反应器已经被学术界和商业机构开发出来。微流体、肺模拟和肺切片培养具有成本效益和高通量分析的优点，是药物和毒性研究的理想选择。灌注/通气啮齿类动物全肺系统可适用于肺干/祖细胞发育、细胞行为、理解和治疗肺损伤的中通量研究，以及可转化为人类肺生物工程的初步工作。人体大小的体外全肺生物反应器包括灌注和通气，可自动化，并已用于全肺脱细胞和再细胞化。临床规模的体外肺灌注系统已被开发用于肺保存和修复，目前正在临床试验中进行评估。肺工程生物反应器在微流控和宏观尺度上都取得了重大进展。最先进的是封闭系统，包括压力控制灌注和通风，并适用于自动化。体外肺灌注系统在肺保存和修复方面已进入临床试验阶段。肺生物工程面临的最大挑战只能通过解决细胞生产和组织整合问题的未来技术进步来克服。
Much recent interest in lung bioengineering by pulmonary investigators, industry and the organ transplant field has seen a rapid growth of bioreactor development ranging from the microfluidic scale to the human-sized whole lung systems. A comprehension of the findings from these models is needed to provide the basis for further bioreactor development. The goal was to comprehensively review the current state of bioreactor development for the lung. A search using PubMed was done for published, peer-reviewed papers using the keywords “lung” AND “bioreactor” or “bioengineering” or “tissue engineering” or “ex vivo perfusion”. Many new bioreactors ranging from the microfluidic scale to the human-sized whole lung systems have been developed by both academic and commercial entities. Microfluidic, lung-mimic and lung slice cultures have the advantages of cost-efficiency and high throughput analyses ideal for pharmaceutical and toxicity studies. Perfused/ventilated rodent whole lung systems can be adapted for mid-throughput studies of lung stem/progenitor cell development, cell behavior, understanding and treating lung injury and for preliminary work that can be translated to human lung bioengineering. Human-sized ex vivo whole lung bioreactors incorporating perfusion and ventilation are amenable to automation and have been used for whole lung decellularization and recellularization. Clinical scale ex vivo lung perfusion systems have been developed for lung preservation and reconditioning and are currently being evaluated in clinical trials. Significant advances in bioreactors for lung engineering have been made at both the microfluidic and the macro scale. The most advanced are closed systems that incorporate pressure-controlled perfusion and ventilation and are amenable to automation. Ex vivo lung perfusion systems have advanced to clinical trials for lung preservation and reconditioning. The biggest challenges that lie ahead for lung bioengineering can only be overcome by future advances in technology that solve the problems of cell production and tissue incorporation.