Functional endothelialized microvascular networks with circular cross-sections in a tissue culture substrate

Abstract

Functional endothelialized networks constitute a critical building block for vascularized replacement tissues, organ assist devices, and laboratory tools for in vitro discovery and evaluation of new therapeutic compounds. Progress towards realization of these functional artificial vasculatures has been gated by limitations associated with the mechanical and surface chemical properties of commonly used microfluidic substrate materials and by the geometry of the microchannels produced using conventional fabrication techniques. Here we report on a method for constructing microvascular networks from polystyrene substrates commonly used for tissue culture, built with circular cross-sections and smooth transitions at bifurcations. Silicon master molds are constructed using an electroplating process that results in semi-circular channel cross-sections with smoothly varying radii. These master molds are used to emboss polystyrene sheets which are then joined to form closed bifurcated channel networks with circular cross-sections. The mechanical and surface chemical properties of these polystyrene microvascular network structures enable culture of endothelial cells along the inner lumen. Endothelial cell viability was assessed, documenting nearly confluent monolayers within 3D microfabricated channel networks with rounded cross-sections.

In vitro modeling of the microvascular occlusion and thrombosis that occur in hematologic diseases using microfluidic technology

“…For instance, our microfluidic channels are square in cross section. Although technically circular microchannels can be fabricated (15,16), we opted to use a more simplified and standard fabrication procedure to allow other researchers to readily apply this system to their own work. In addition, the presence of the cultured endothelial cells naturally "rounds out" the effective lumen, enabling the system to be more physiologic.…”

“…The ability to easily and tightly control biological conditions and the dynamic fluidic environment within the system enable microfluidics to be ideal tools for quantitatively analyzing hematologic and microvascular processes (11)(12)(13). Accordingly, researchers have recently applied microfluidic devices to study blood cell deformability, blood flow, and blood-endothelial cell interactions (14)(15)(16)(17). Some reports have described successful cross-sectional coverage of endothelial cells in microfluidic systems (18,19), but these devices were larger than the microvascular size scale relevant to the pathologic processes at that anatomic level.…”

Endothelialized Microfluidics for Studying Microvascular Interactions in Hematologic Diseases

“…For instance, our microfluidic channels are square in cross-section. Although technically circular microchannels can be fabricated 10,11 , we opted to use a more simplified and standard fabrication procedure to allow other researchers to readily apply this system to their own work. In addition, the presence of the cultured endothelial cells naturally "rounds out" the effective lumen, enabling the system to be more physiologic.…”

Fabrication of pillared PLGA microvessel scaffold using femtosecond laser ablation

“…Successful seeding of primary human umbilical vein endothelial cells was observed. 13 The nanopatterned scaffold has been demonstrated to have greater potential for bovine endothelial cell adhesion and proliferation. 14 Wang et al further utilized the anodic aluminum oxidization approach for the fabrication of PLGA microvessel scaffolds with nanostructured inner walls.…”