Biomedical Engineering Reference
In-Depth Information
3 weeks, the tubes exhibited normal microvascular functions such as adhesion of leukocytes and re-
sponse to inflammatory mediators. Additionally, the authors demonstrated feasibility of incorporating
cells into the gel by mixing cells with the collagen solution before gelation. Materials such as recon-
stituted collagen gels often exhibit weak mechanical strength and may not support physiologic flow
rates through perfused vasculature. Synthetic materials provide an intriguing alternative, especially
when functionalized with photoreactive groups. Photopolymerized hydrogels allow for straightforward
tuning of mechanical properties by varying system parameters such as polymer concentration, light in-
tensity, and photoinitiator concentration. To this end, Nichol et al. utilized the needle-based approach to
demonstrate GelMA as a potential biomaterial for applications in microfluidic system and fabrication
of vascularized engineered tissues (
Nichol et al., 2010
). Cell-laden constructs with endothelial-lined
microchannels were obtained by UV radiation of a solution of GelMA within a rectangular PDMS
mold containing a needle. After the needle was withdrawn, resultant gels were perfused and evidence
of endothelial cell adhesion and aggregation within surrounding cells, in addition to elongation and
reorganization of encapsulated 3T3 cells, was evident. Detailed studies quantifying the toxicity of
photoinitiators and light sources have previously been performed (
Bryant et al., 2000
), allowing the
experimentalist to retain cell viability during cell encapsulation.
8.1.4
APPROACHES TO INTEGRATE PATTERNED VASCULATURE
IN VIVO
Although photolithographic and needle-based approaches to fabricate simple models for studying
vasculature function have been successful, more advanced constructs are desirable which closely
resemble the heterogeneity and complexity of tissues. Thus, techniques such as ink-jet printing and
stereolithography have advanced significantly, providing researchers with high-resolution printing ca-
pability and an expanded parameter space of materials from which to choose. Early efforts in ink-jet
printing involved fabricating tubular hydrogel structures with a liquid aqueous gelling medium (
Na-
kamura et al
.,
2008
). In this technique, droplets ejected from a print head containing sodium alginate
form into alginate microgel beads by contact with calcium ions and fuse to form fibers and sheets as
the ink-jet system is moved laterally and vertically (
Figure 8.2
A). Microgel beads as small as 10
m
m in
diameter were produced using this approach. To achieve 3D tubular structures on a very small scale, the
ink-jet head was moved in a circular pattern as droplets of alginate were ejected onto the substrate in a
layer-by-layer fashion to form long tubular structures. The group has also fabricated fibers, 2D sheets,
multilayered sheets, and more 3D vessels using this approach (
Nishiyama et al., 2009
). However, Cui
et al. have utilized thermal ink-jet printing technology for microvascular fabrication and have dem-
onstrated alignment and proliferation of cells inside a fibrin substrate (
Cui and Boland, 2009
). In this
study, a fibrin scaffold was printed with cells, resulting in minimal deformation of the scaffold and little,
if any, damage to cells. Fabricated microvasculature structures composed of fibrin and ECs resulted in
the cells forming contacts with each other and, ultimately, aligning themselves along the fibrin channel
to form a confluent lining. In addition, long-term scaffold integrity of the printed microvasculature was
demonstrated.
Further techniques to fabricate even more complex heterogeneous structures layer-by-layer involve
utilizing CAD-based rapid prototyping methods such as stereolithography. Chan et al. used a custom-
modified stereolithography apparatus to fabricate complex 3D structures from photopolymerization of
PEG by repetitive deposition and processing of individual layers (
Chan et al., 2010
). In addition, the
authors characterized the penetration depth and critical exposure energy parameters for ideal sequential
Search WWH ::
Custom Search