(77c) Rapid Fabrication and Sculpting of 3-D Microvascular Networks for Tissue Engineering Applications

Living systems face a fundamental challenge of orchestrating exchange of nutrients, oxygen, and waste throughout three-dimensional space in order to satisfy their metabolic needs. Vascular networks play an critical role in satisfying these needs by incorporating highly branched fractal-like architectures that are efficiently space-filling while minimizing the energy required to sustain transport. The ability to mimic the features of this vasculature in vitro would be immensely beneficial in the field of tissue engineering because the inability to construct such networks inside biomaterial scaffolds is one of the greatest obstacles to manufacturing engineered tissues at organ-level size scales. But the hierarchy of length scales that comprise vascular networks (ranging from micron to mm in diameter) and the need for these structures to be widely accessible throughout a sizeable 3-D volume present significant manufacturing challenges.

We have developed a new fabrication method that uniquely overcomes these limitations, enabling branched 3-D microvascular networks incorporating a wide range of microchannel diameters to be rapidly constructed in a variety of plastic materials. This process harnesses electron beam irradiation to implant a high level of electric charge inside a substrate so that the energy released upon discharge will be sufficiently intense to locally vaporize and fracture the surrounding material. In this way, networks of highly branched tree-like microchannels with diameters ranging from approximately 10 micron to 1 mm are produced that become permanently embedded within the substrate. Modulating the irradiation profile and discharge locations allows the networks' morphology and interconnectivity to be precisely tailored. We apply this method to construct branched microchannel networks whose underlying structural features are quantitatively similar to naturally occurring vasculature in both poly(methyl methacrylate) (PMMA) and the biodegradable polymer poly(lactic acid) (PLA). We also present new results that show how the vasculature embedded within PLA substrates can be further sculpted using a chemical etching process. This approach enables the average microchannel diameter to be fine-tuned to bring the pressure drop and shear stress into an optimal range for cell culture applications.