Fabrication of vascular tissue models by assembling multiple cell types inside hydrogel microchannels

Fabrication of vascular tissues is a promising technology in medical, biological, and tissue engineering research applications. In this paper, a new method for fabricating blood vessel-like tissues using microfluidic devices made of calcium-containing agarose hydrogel is reported. Different cell types individually dispersed in sodium alginate (NaA) solutions at high densities were introduced stepwise into the agarose hydrogel microchannel, forming Ca-alginate hydrogel layers incorporating multiple cell types on the channel surface with the help of Ca²⁺ ions diffused through the hydrogel matrix. We employed fibroblasts and myoblasts as models, and successfully obtained multilayer capillary-like tissues inside the hydrogel microchannel. The thickness and mechanical strength of the capillary-like tissues were controlled by changing the flow rate and/or the introduction periods of NaA solutions. In addition, vascular tissue models of various configurations were fabricated by employing hydrogel microchannels with desired geometries. Furthermore, the formed tissues were recovered from the hydrogel microchannel by enzymatically digesting the agarose polymer. The presented method is simple in operation and highly versatile, and would therefore pave a new way for preparing capillary-like cell constructs for various tissue engineering applications.