Page 18 - IJB-7-4

Using Spheroids to build 3D Bioprinted Tumor Microenvironment
. Those notable reports also
cancer drug screening [161,162] spheroids will then gradually fuse together and achieve
detailed the challenges of current existing technologies the specified pattern over time. This manual processing
for assembling cell-favorable biomaterials with multiple has shed light on a great possibility of generating tissue
cell types in complex tissue microenvironment as we constructs by spheroidal modular assembly, despite its
summarized in Figure 3. limited control and low throughput. For overcoming such
Using spheroids as building blocks in facile challenge, several bioengineering strategies have been
macro-sized tissue construction has been proposed [163] , exploited for spheroid assembly, potentiating its large-
the most straightforward method in assembling these scale functional tissue manufacturing with improvements
spheroids is spontaneous fusion [164-167] . Fleming et al. in accuracy through a high-throughput manner.
had reported a spheroidal fusion between unilluminated Leveraging magnetic force, spheroids that are
vascular spheroids through liquid-like coalescence. functionalized with magnetic nano/microparticles
Specifically, 2 juxtaposed spheroids were fused when can be assembled into specific patterns by imposing
positioned close enough, forming a larger spheroid temporary magnetic fields [171-176] . An applied magnetic
with preserved composite structural characteristics [168] . field could accelerate the cell aggregation process, but
These features have legitimized a notion of suitability the topology of the constructs is highly dependent on the
for using spheroids as building modules in engineering magnetic template [172,173] . In addition, the association of
large-scale tissues for tissue regeneration and/or disease magnetic particles is inevitable, and the linker involved
modeling. Early studies have also demonstrated the may engender safety issues. The effects of magnetic
feasibility of assembling spheroids through directed nanoparticles on cell physiology and function, other
fusion, achieving microtissues with prescribed patterns than fundamental cell viability and proliferation, should
including honeycomb, rods, and tori [169,170] . Briefly, be considered before further involvement. Instead of
spheroids are manually placed in a pre-designed mold/ magnetically labeling cells, an alternative usage is
template containing the prescribed topography. These paramagnetizing the cells. Alahough a paramagnetic

Figure 3. Progress in establishing 3D tumor models via 3D bioprinting.

14 International Journal of Bioprinting (2021)–Volume 7, Issue 4