Lo Justin H, Bassett Erik K, Penson Elliot J N, Hoganson David M, Vacanti Joseph P
1 Department of Surgery, Center for Regenerative Medicine , Massachusetts General Hospital, Boston, Massachusetts.
2 Harvard Medical School , Boston, Massachusetts.
Tissue Eng Part A. 2015 Aug;21(15-16):2147-55. doi: 10.1089/ten.TEA.2014.0369. Epub 2015 Jul 16.
Chronic lower respiratory disease is highly prevalent in the United States, and there remains a need for alternatives to lung transplant for patients who progress to end-stage lung disease. Portable or implantable gas oxygenators based on microfluidic technologies can address this need, provided they operate both efficiently and biocompatibly. Incorporating biomimetic materials into such devices can help replicate native gas exchange function and additionally support cellular components. In this work, we have developed microfluidic devices that enable blood gas exchange across ultra-thin collagen membranes (as thin as 2 μm). Endothelial, stromal, and parenchymal cells readily adhere to these membranes, and long-term culture with cellular components results in remodeling, reflected by reduced membrane thickness. Functionally, acellular collagen-membrane lung devices can mediate effective gas exchange up to ∼288 mL/min/m(2) of oxygen and ∼685 mL/min/m(2) of carbon dioxide, approaching the gas exchange efficiency noted in the native lung. Testing several configurations of lung devices to explore various physical parameters of the device design, we concluded that thinner membranes and longer gas exchange distances result in improved hemoglobin saturation and increases in pO2. However, in the design space tested, these effects are relatively small compared to the improvement in overall oxygen and carbon dioxide transfer by increasing the blood flow rate. Finally, devices cultured with endothelial and parenchymal cells achieved similar gas exchange rates compared with acellular devices. Biomimetic blood oxygenator design opens the possibility of creating portable or implantable microfluidic devices that achieve efficient gas transfer while also maintaining physiologic conditions.
慢性下呼吸道疾病在美国极为普遍，对于进展至终末期肺病的患者而言，仍需要肺移植的替代方案。基于微流控技术的便携式或可植入式气体氧合器若能高效且生物相容地运行，便可满足这一需求。将仿生材料融入此类设备有助于复制天然气体交换功能，并额外支持细胞成分。在这项工作中，我们开发了微流控设备，可实现血液与超薄胶原膜（薄至2μm）之间的气体交换。内皮细胞、基质细胞和实质细胞能够轻易附着于这些膜上，与细胞成分进行长期培养会导致膜重塑，表现为膜厚度减小。在功能上，无细胞胶原膜肺设备能够介导高达约288毫升/分钟/平方米的氧气和约685毫升/分钟/平方米的二氧化碳的有效气体交换，接近天然肺中的气体交换效率。通过测试肺设备的几种配置以探索设备设计的各种物理参数，我们得出结论，更薄的膜和更长的气体交换距离会提高血红蛋白饱和度并增加pO2。然而，在所测试的设计空间中，与通过提高血流速率改善总体氧气和二氧化碳传输相比，这些影响相对较小。最后，与无细胞设备相比，用内皮细胞和实质细胞培养的设备实现了相似的气体交换速率。仿生血液氧合器设计为制造便携式或可植入式微流控设备开辟了可能性，这些设备既能实现高效的气体传输，又能维持生理条件。
