Micro-Channel Array in Biodegradable Tube for Interfacing with Self-Assembled Capillaries

Vascularization of 3D engineered tissue has posed a great challenge in the field of tissue engineering: without proper blood supply, cells cannot survive in the depth of an engineered tissue due to the diffusion limitation. One approach for vascularizing engineered tissue is co-cultivation with Endothelial Cells (ECs). Under pro-angiogenic conditions and the presence of supportive cells, ECs spontaneously self-assembled into a capillary network. However, the self-assembled vasculature is not organized in the right hierarchy for supporting blood supply. An attempt for designing a perfusable organized vasculature has been successfully demonstrated by integrating micro-fluidic device with self-assembled capillaries. Yet, such devices are not suitable for implantations as they are neither biodegradable nor in a tissue scale. Hence, we design a cylindrical micro-channel array that will enable physiological flow distribution from a macro vessel to capillaries. The micro-channel array was precisely fabricated in a biodegradable Polylactic acid (PLLA) tube using a unique pico-laser cylindrical drilling technique. Flow characterization was simulated by CFD model and tested by fluorescently labeled beads to confirm physiological flow distribution. In our research we show how the geometry of the engineered micro-channels exclusively guides endothelial cells to form patent micro-vessels which sprout in accordance with channel orientation. Based on this phenomenon, we demonstrate in 3 different in-vitro models how these guided engineered micro-vessels can anastomose with self-assembled vascular network. Conclusively, with our unique approach, we show for the first time that such engineered macro-vessel can be integrated with living capillaries for further maintaining a real-scale engineered tissue.