Biomedical Engineering Reference
In-Depth Information
cells are critical to nervous system function, but the intricacies of their interactions are not well char-
acterized. Schwann cell and oligodendrocyte myelination of axons is required for physiologically rel-
evant conduction of nerve impulses, and astrocyte-neuron communication influences both neuronal
differentiation and synapse formation (
Sherman and Brophy, 2005
;
Sofroniew and Vinters, 2010
). Mir-
roring the sentiments of previous applications, glia cells are both necessary for natural neuronal func-
tion and responsible for many pathogenic states. Implications in Alzheimer's, Parkinson's, multiple
sclerosis, neuropathy, and chronic pain have been tied to aberrant glial function (
Antony, 2014
;
Block
et al., 2007
;
Luongo et al., 2014
;
McMahon and Malcangio, 2009
). In order to study such interac-
tions, Park et al. constructed a microfluidic device to isolate axonal processes and enable coculture
with both oligodendrocyte precursor and astrocyte cells (
Park et al., 2012
). They then saw evidence
of healthy oligodendrocyte differentiation and myelination, alongside induced astrocytic and biomo-
lecular damage. Goudriaan et al. also demonstrated the reciprocal nature of genetic disturbances in
astrocyte-neuron interactions through a novel cellular isolation method (
Goudriaan et al., 2014
). Both
tools represent powerful examples of potentially high-throughput studies in neuron-glia interaction.
However, the speed and spatial resolution of laser direct write and CAD/CAM technology would allow
for the rapid manipulation of multiple-cell juxtaposition to define mechanisms for axon-glia com-
munication and interaction. The combination of throughput, flexibility, and accuracy would enable
experiments to define and explore contact- and signaling-related influences toward understanding both
healthy and pathological states.
4.5.1.4 Outlook
Through the examples given, it is clear that advances in technology have fundamentally increased our
understanding of the nervous system. By incrementally deconstructing the intricate milieu of factors
which govern the organization of the brain, both from a developmental and functional standpoint, re-
searchers are beginning to recognize and understand the consequences of particular biological mecha-
nisms. Engineered models utilizing laser direct write techniques would enable the manipulation of
molecular, cellular, and synaptic contributions from a single-cell level, representing the next advance-
ment required to decipher implication on emergent behavior and inform potential treatment strategies.
4.6
CONCLUSION
Laser bioprinting has become a proven method for biomaterial transfer and it is the only bioprinting
approach having single-cell resolution. Because of the unique combination of optical imaging and
CAD/CAM control, researchers have created a platform capable of fabricating complex constructs
from the bottom up with the potential for high-throughput biological construct fabrication, for example,
reproducible tissue constructs to the single-cell-level resolution to test different drugs with iterative
composition and/or spacing manipulations allowing unambiguous conclusions about the influence of
the cellular microenvironment. The MAPLE-DW platform, especially, has demonstrated greater than
5
m
m spatial precision with post-transfer cell viability consistently greater than 90%. Researchers
have achieved viable transfers with all types of cells enabling an even greater number of applications.
Moreover, the short time required to make constructs coupled with conventional cell culture protocol
and ease of printing make laser bioprinting with MAPLE-DW an efficient, feasible, and reliable way
to isolate and study cellular interactions and behaviors. Research models created by laser direct-write
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