Rapid Fabrication of Bio‐inspired 3D Microfluidic Vascular Networks

Abstract

Adv. Mater. 2009, 21, 3567–3571 2009 WILEY-VCH Verlag G N Living systems face a fundamental challenge of orchestrating exchange of nutrients and oxygen throughout 3D space in order to satisfy their metabolic needs. In nature, vascular networks have evolved to elegantly address this problem by incorporating highly branched fractal-like architectures that are efficiently space-filling while minimizing the energy required to sustain transport. The ability to mimic these features in vitro would be immensely beneficial in the field of tissue engineering, where diffusion limitations generally restrict the maximum thickness of constructs to a few hundred microns. Here, we address this need by introducing a nearly instantaneous method to embed branched 3D microvascular networks inside plastic materials. In thismicrofabrication process, a high level of electric charge is first implanted inside a polymer dielectric using electron beam irradiation. The accumulated energy is then discharged in a controlled manner to locally vaporize and fracture the material, leaving behind a network of branched microchannels arranged in a tree-like architecture with diameters ranging from 10mm to 1mm. Modulating the irradiation profile and discharge locations allows the networks’ morphology and interconnectivity to be precisely tailored. Interconnected networks with multiple fluidic access points can be straightforwardly constructed, and quantification of their branching characteristics reveals remarkable similarity to naturally occurring vasculature. This method can be applied in a variety of polymers, and may help enable production of organ-sized tissue scaffolds containing embedded vasculature. The hierarchy of length scales that comprise vascular networks (ranging from mm–mm in diameter) and the need for these structures to be widely accessible throughout a sizeable 3D volume present significant manufacturing challenges. Photolithography-based microfabrication technology has been extensively examined as a potential avenue to address some of these issues. Here, planar micromachining is harnessed to produce 2D microchannel arrays that can be stacked in a layer-by-layer fashion to achieve a limited degree of threedimensionality. But assembly of large-scale multi-tiered structures is tedious, and the inherently planar nature of the individual layers restricts the network’s topological complexity. More recent developments have enabled fully 3D flow architectures to be produced using methods including solid freeform fabrication, stereolithography, and direct printing. But these approaches generally involve time consuming serial processes, and the optimal range of feature sizes associated with each technology is often relatively narrow. Many of these processes are also challenging to scale up toward levels feasible for mass production. We have developed a fabrication method that uniquely overcomes these limitations, enabling branched 3D microvascular networks incorporating a wide range of microchannel diameters to be rapidly constructed in a variety of plastic materials (Fig. 1). 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 are produced that become permanently embedded within the substrate. The formation and growth of these electrostatic discharge structures (i.e., Lichtenberg figures or Lichtenberg trees) are analogous to lightning phenomena that occur during thunderstorms when charge accumulation within clouds exceeds the breakdown potential of the surrounding atmosphere. We first explored applying this process to construct 3D vascular microchannel networks in acrylic plastic substrates by irradiating blocks of polished poly(methyl methacrylate) (PMMA) using a 10MeVelectron beam to implant a prescribed charge distribution (typical space charge densities are on the order of 1mC cm ), after which the energized blocks were discharged by one of two methods. In the first approach (Fig. 1a), release of the accumulated charge was achieved by striking the irradiated block with the sharp tip of a grounded electrode. The point source of electrical grounding and the mechanical stress associated with the physical impact of striking the block combine to produce an immediate and rapid energy release. Alternatively, a defect (e.g., a small hole 1mm in diameter) was intentionally introduced on the surface of the block prior to irradiation that served as a nucleation site for spontaneous discharge upon exposure to the electron beam without the need for further physical contact (Fig. 1b). In either case, the rapid and intense release of electrostatic energy instantaneously generated a hierarchically branched microchannel array penetrating throughout the entire volume of the block and originating from either the point of contact with the grounded electrode or the nucleation site created on the surface (Fig. 1c and Supporting Information Movie 1). Networks formed using the grounded contact method