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International Journal of Bioprinting Precise fabrication of engineered vascular networks

Figure 1. Schematic diagram of swelling compensation of vasculature fabricated by additive manufacturing and sacrifice-based technique using
thermoresponsive hydrogel. (A) Hydrogel scaffold with vasculature at designed diameter d. (B) Fabrication of P/G hydrogel film. (C) 3D printing of
sacrificial material on the P/G hydrogel film. (D) Encapsulation of the sacrificial template in the P/G hydrogel. (E) Engineered vasculature within the P/G
hydrogel scaffold after swelling of the sacrificial template. Created with BioRender.com.

to generate micro-scale vasculature . The minimum of a smaller size than the swollen one and thus enhancing
[34]
vasculature diameter achieved is 50 μm. However, the the precision of the engineered vasculature, as shown in
study focused on fabricating micro-scale vasculature that Figure 1. Vasculature with the diameter at d in hydrogel
is as small as possible. Moreover, the wet-spun alginate scaffold was designed (Figure 1A). For the precise
fibers of the sacrificial template are arbitrarily distributed, fabrication of engineered vasculature, a PNIPAM/GelMA
which makes it difficult to control the shape of the target (P/G) hydrogel film was first generated, as shown in
vasculature. Figure 1B. As a proof of concept, PF-127 was used as the
Inspired by the volume shrinkage induced by the sacrificial material and printed on the P/G hydrogel film
thermoresponsive hydrogel in the cell culture environment to form the sacrificial template, as shown in Figure 1C.
and the scalability of combining additive manufacturing Subsequently, freshly prepared P/G hydrogel was utilized
and a sacrifice-based technique to fabricate engineered to cover the sacrificial template, and the whole hydrogel
vasculature, we hypothesize that the volume shrinkage scaffold was crosslinked under ultraviolet (UV) light to
can compensate for the deformation caused by swelling encapsulate the sacrificial template, as shown in Figure 1D.
of the sacrificial template. We established a molding Then, the hydrogel scaffold with the sacrificial template
mechanism for easy preparation of engineered vascular was placed at 4°C to remove the sacrificial template to
networks by varying the concentration of materials, form the engineered vasculature. The swelling of the
density of vessels, and other factors to achieve precise sacrificial template increased the engineered vasculature
preparation of engineered vasculature. Thus, the swollen diameter from d to D (Figure 1E). Finally, the scaffold
vasculature within the hydrogel constructs can be tuned to was placed at 37°C to induce the volume shrinkage of
the designed dimension to achieve precise manufacturing. the thermoresponsive P/G hydrogel. After shrinking, the
Here, 3D printing and the sacrifice-based technique were engineered vasculature with the targeted diameter at d was
combined to fabricate engineered vasculature through accomplished. The effects of different P/G concentrations
thermal post-treatment of the engineered vasculature at and various vasculature densities on the precise fabrication
the cell culture temperature (37°C), fabricating vasculature of engineered vasculature were quantitatively explored.

Volume 9 Issue 5 (2023) 36 https://doi.org/10.18063/ijb.749