(Left) 3D reconstruction of the AngioTube using micro-CT scans showing the transparent view. (Right) Illustration of the biological process of ECs sprouting from the AngioTube with self-assembled capillaries, which spontaneously arrange after co-cultivating ECs with DPSCs in fibrin gel.The survival, function, and longevity of implanted 3D engineered tissue requires a blood supply. Now researchers at Technion-Israel Institute of Technology have designed and fabricated a biodegradable scaffold that supports the hierarchical regrowth of blood vessels, facilitates blood flow to implanted tissue, and integrates with living capillaries [Zohar et al., Acta Biomaterialia 163 (2023) 182-193, https://doi.org/10.1016/j.actbio.2022.05.026].
In living tissue, blood moves along capillaries, which possess micro-sized pores and are arranged in a dense organized network to create slow flow and large surface areas for nutrient transfer. Current microfabrication approaches have been, until now, unable to match the natural complexity of this capillary structure, lacking the architectural hierarchy to support blood supply to large-scale tissue. Moreover, attempts to create artificial vasculature have incorporated non-biodegradable materials rendering such systems unsuitable for implantation.
Instead, Shulamit Levenberg and her team fabricated biodegradable poly-L-lactic acid (PLLA) tubes into which they drilled triangular arrays of micro-channels, 50 microns in diameter, using a high-precision picosecond laser system. Termed an ‘AngioTube’, the geometrical array of micro-channels is designed to support blood flow at a similar rate and pressure as found in the body, guide the growth of implanted endothelial cells, and integrate with living capillaries. Implanted cells form a large blood vessel in the main tube from which smaller vessels can sprout through the micro-channels to create a dense array of branches.
“The fabrication of a hierarchical vessel network is essential for supporting the viability of large, engineered tissues before and after implantation,” explains PhD student Lior Debbi, who worked on the study. “The optimal design [of the] AngioTube promotes the formation of a functional multiscale blood vessel network, [which] can be used to feed large, engineered tissues [in vitro] and connect them directly to blood vessels after implantation in the body.”
The micro-vessels support the connection or anastomosis between the AngioTube and newly self-assembled capillaries to allow immediate blood flow when implanted. In a demonstration with rats, the AngioTube was able to maintain blood supply to the creatures’ hind limbs after implantation.
The researchers believe their approach not only offers a rational route to designing microfluidic devices that maintain physiological flow conditions in vivo but could also support fundamental studies.
“The accuracy of the dimensions of the main vessel and micro-channel array could be useful as a 3D in vitro model for studying the effect of channel geometry on sprouting angiogenesis in vascular biology,” points out Levenberg.