posted on 2020-03-05, 14:41authored byTilman Ahlfeld, Nieves Cubo-Mateo, Silvia Cometta, Vera Guduric, Corina Vater, Anne Bernhardt, A. Rahul Akkineni, Anja Lode, Michael Gelinsky
Extrusion-based
bioprinting, also known as 3D bioplotting, is a powerful tool for
the fabrication of tissue equivalents with spatially defined cell
distribution. Even though considerable progress has been made in recent
years, there is still a lack of bioinks which enable a tissue-like
cell response and are plottable at the same time with good shape fidelity.
Herein, we report on the development of a bioink which includes fresh
frozen plasma from full human blood and thus a donor/patient-specific
protein mixture. By blending of the plasma with 3 w/v% alginate and
9 w/v% methylcellulose, a pasty bioink (plasma-alg-mc) was achieved,
which could be plotted with high accuracy and furthermore allowed
bioplotted mesenchymal stromal cells (MSC) and primary osteoprogenitor
cells to spread within the bioink. In a second step, the novel plasma-based
bioink was combined with a plottable self-setting calcium phosphate
cement (CPC) to fabricate bone-like tissue constructs. The CPC/plasma-alg-mc
biphasic constructs revealed open porosity over the entire time of
cell culture (35 d), which is crucial for bone tissue engineered grafts.
The biphasic structures could be plotted in volumetric and clinically
relevant dimensions and complex shapes could be also generated, as
demonstrated for a scaphoid bone model. The plasma bioink potentiated
that bioplotted MSC were not harmed by the setting process of the
CPC. Latest after 7 days, MSC migrated from the hydrogel to the CPC
surface, where they proliferated to 20-fold of the initial cell number
covering the entire plotted constructs with a dense cell layer. For
bioplotted and osteogenically stimulated osteoprogenitor cells, a
significantly increased alkaline phosphatase activity was observed
in CPC/plasma-alg-mc constructs in comparison to plasma-free controls.
In conclusion, the novel plasma-alg-mc bioink is a promising new ink
for several forms of bioprinted tissue equivalents and especially
gainful for the combination with CPC for enhanced, biofabricated bone-like
constructs.