MICRO-AND NANOTECHNOLOGY FOR VASCULAR TISSUE ENGINEERING - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 247

FIGURE 11.2 Multilevel microchannel network (a and b). Branch dimensions range from
130 to 660 m m. Reproduced with permission from Ref. [88]. Demonstration of spatiotemporal
control of macromolecules in hydrogel networks (c). Microfluidic network formed in an
alginate hydrogel showing assisted delivery (i-iii) and assisted extraction (iv-vi) of fluorescent
conjugated dextran (70 kDa). Adapted with permission from Ref. [94].

that is not ideal for microvascular networks. Wang and coworkers were able to
engineer microfluidic systems with elastomeric poly(glycerol sebacate) (PGS) as a
more flexible alternative. 92
Three-dimensional scaffolds are necessary to recapitulate the native environment
and fully perfuse a scaffold. It still remains a challenge to develop 3D microfluidic
systems, and most success has been had in stacking 2D films to create a 3D
composite. Successful stacking was first demonstrated by King et al. in PLGA 91
and Bettinger et al. in PGS, 93 both using thermally bonding layers of 2D films. The
PGS construct was able to exhibit maximum shear stress throughout each channel,
making it attractive for microvascular systems. Unfortunately, stacking of films is not
ideal because it is difficult to scale.

11.6.3 Microfluidic Hydrogels

Microfabrication techniques were recently applied to hydrogel materials to yield
constructs amenable to cell culture and vascularization with precise control of
architecture in three dimensions. Cabodi et al. first demonstrated the creation of a
microfluidic hydrogel using soft lithographic techniques with calcium alginate, a
commonly used biomaterial whose ionic cross-links can be reversed with a calcium
chelator. 94 In this work, the group created slabs of alginate and bonded them together
by first treating the surfaces with sodium citrate, a chelator, and then adding calcium
chloride to seal the layers. This layer-by-layer approach yielded a microfluidic gel
with minimum channel dimensions of 25

m. The group also demonstrated that the
gel was permeable to both small molecule and macromolecular solutes, as needed in

m