Department of Biomedical Engineering, The Charles Stark Draper Laboratory, Inc., Cambridge, MA 02139, USA.
Laboratory for Systems Biology, Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Lab Chip. 2016 Aug 16;16(17):3227-34. doi: 10.1039/c6lc00641h.
Blood oxygenators provide crucial life support for patients suffering from respiratory failure, but their use is severely limited by the complex nature of the blood circuit and by complications including bleeding and clotting. We have fabricated and tested a multilayer microfluidic blood oxygenation prototype designed to have a lower blood prime volume and improved blood circulation relative to current hollow fiber cartridge oxygenators. Here we address processes for scaling the device toward clinically relevant oxygen transfer rates while maintaining a low prime volume of blood in the device, which is required for clinical applications in cardiopulmonary support and ultimately for chronic use. Approaches for scaling the device toward clinically relevant gas transfer rates, both by expanding the active surface area of the network of blood microchannels in a planar layer and by increasing the number of microfluidic layers stacked together in a three-dimensional device are addressed. In addition to reducing prime volume and enhancing gas transfer efficiency, the geometric properties of the microchannel networks are designed to increase device safety by providing a biomimetic and physiologically realistic flow path for the blood. Safety and hemocompatibility are also influenced by blood-surface interactions within the device. In order to further enhance device safety and hemocompatibility, we have demonstrated successful coating of the blood flow pathways with human endothelial cells, in order to confer the ability of the endothelium to inhibit coagulation and thrombus formation. Blood testing results provide confirmation of fibrin clot formation in non-endothelialized devices, while negligible clot formation was documented in cell-coated devices. Gas transfer testing demonstrates that the endothelial lining does not reduce the transfer efficiency relative to acellular devices. This process of scaling the microfluidic architecture and utilizing autologous cells to line the channels and mitigate coagulation represents a promising avenue for therapy for patients suffering from a range of acute and chronic lung diseases.
血液氧合器为呼吸衰竭患者提供关键的生命支持，但由于血液回路的复杂性以及包括出血和凝血在内的并发症，其使用受到严重限制。我们已经制造并测试了一种多层微流控血液氧合原型，其设计目的是与当前的中空纤维盒式氧合器相比，具有更低的血液预充量和改善的血液循环。在这里，我们解决了在保持设备中低血液预充量的情况下，将设备向临床相关的氧气转移率扩展的问题，这是心肺支持的临床应用所必需的，最终也是慢性应用所必需的。通过扩展平面层中血液微通道网络的有效表面积以及通过增加堆叠在一起的微流层的数量来达到临床相关的气体转移率的方法，都被用来对设备进行扩展。除了降低预充量和提高气体转移效率外，微通道网络的几何特性还通过为血液提供仿生和生理现实的流动路径来提高设备的安全性。血液-表面相互作用也会影响设备的安全性和血液相容性。为了进一步提高设备的安全性和血液相容性，我们已经成功地在血液流动途径上涂覆了人内皮细胞，以赋予内皮细胞抑制凝血和血栓形成的能力。血液测试结果证实了非内皮化设备中纤维蛋白凝块的形成，而在细胞涂层设备中则记录到可忽略不计的凝块形成。气体转移测试表明，内皮衬里不会降低与无细胞设备相比的转移效率。这种扩展微流控结构并利用自体细胞来衬里通道和减轻凝血的过程，为患有一系列急性和慢性肺部疾病的患者提供了一种有前途的治疗方法。
