(745d) Sculpting Biomaterial Scaffolds with Embedded 3D Vasculature

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. But the inability to construct these networks inside biomaterial scaffolds poses one of the greatest obstacles to manufacturing engineered tissues at organ-level size scales. We have recently developed a novel method to address this need by harnessing electrostatic discharge phenomena to embed branched 3-D microvascular networks inside plastic substrates. But although the microvascular networks we have constructed are capable of supporting flow, the pressure and corresponding internal shear stresses are higher than would be ideally desirable for cell culture applications.

Here we explore two new approaches that allow us to overcome these limitations. First, we have developed chemically-based approach whereby an enzymatic agent is injected through the microchannel network to promote etching of a biodegradable substrate (e.g., ploy (lactic acid)). Second, we describe a method whereby pressurized gas is injected into the substrate to deform the interior microchannels, yielding a global increase in channel diameter throughout the network as well as smoother sidewall profiles. We systematically investigate the parameters associated with each process to quantitatively establish their impact on pressure and shear stress within the network to produce optimal conditions for cell seeding and culture. Finally, we report new studies aimed at producing porous scaffolds with embedded vasculature using polymer/porogen composites. Here, the extent to which the vascular networks penetrate the embedded porogen is governed by the relative dielectric properties of the substrate and porogen, and can be tuned over a wide range.