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International Journal of Bioprinting 3D-bioprinted multicellular lung organoids

the printed constructs. However, the requirement for structures within the lung model. The inclusion of vascular
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photo-crosslinkable materials in SLA limits the range of networks not only improves cell viability but also enhances
usable bioinks. In addition, the high cost and complexity the overall functionality of the bioprinted lung tissue.
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of laser-based systems can be a barrier to widespread To facilitate widespread adoption and practical
adoption. The scalability of these methods for large-scale application, the bioprinting process must be both scalable
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tissue production also remains a challenge. 93 and reproducible. This entails standardizing bioink
3.4. Three-dimensional lung bioprinting and formulations, printing parameters, and post-processing
its considerations steps to ensure consistent and reliable results across
When developing a lung model using 3D bioprinting, different batches. Developing robust protocols for bioink
several critical considerations must be taken into account preparation, bioprinting, and subsequent tissue maturation
to ensure the model‘s functionality and relevance. One is crucial for achieving reproducibility. Additionally,
of the primary considerations is the selection of bioink, integrating automated systems and real-time monitoring
which must be carefully chosen to support cell viability, during the bioprinting process can further enhance the
proliferation, and differentiation. 19,73 The bioink should precision and consistency of the printed lung models. 75,96,97
closely mimic the ECM of lung tissue, providing the
necessary biochemical and mechanical cues for appropriate 4. Research on bioprinting-based 3D organ-
cell behavior, including attachment, migration, and oid and tissue modeling
differentiation into specific lung cell types. The bioink Recently, there has been significant progress in utilizing
composition often includes natural polymers like collagen, 3D bioprinting technology to replicate the structure and
gelatin, and hyaluronic acid, which are known for their function of lungs, thereby enhancing the ease of organoid
biocompatibility and ability to promote cell growth. creation. Krakos et al. used EBB to develop a lab-on-a-
The lung’s complex and hierarchical structure, with its chip device that simulates the mechanical and biological
branched airways and alveoli, poses a significant challenge environment of the lung. The researchers created six
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for bioprinting. Precise control over the bioprinting different hydrogel inks by varying the proportions of sodium
process is essential to ensure that the printed structures alginate, agar, chitosan, gelatin, and methylcellulose, and
accurately replicate the native tissue‘s intricate geometry optimized them with different bioprinting parameters.
and functionality. This involves optimizing the printing The hydrogel-based lab-on-chip composed of 3% sodium
resolution and layer thickness to create detailed and alginate, 7% gelatin, and 90% NaCl showed the highest
functional lung models. Techniques such as multi-material cell viability and had similar elasticity modulus values to
bioprinting can be employed to print different cell types biological tissues (0.060–0.512 MPa ) at 37°C conditions. 98
and ECM components in a spatially controlled manner,
closely mimicking the heterogeneous composition of While bioprinting has not yet fully simulated
lung tissue. 74,95 lung structure, scaffolds have been developed that are
conducive to cell culture for use in in vitro studies.
Another important consideration is the mechanical Gerbolés et al. created a hydrogel mixture by combining
properties of the printed lung model. The lung tissue Matrigel, porcine skin gelatin, and sodium alginate.
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is subjected to cyclic stretching and relaxation during To conduct 3D bioprinting of organoid-based scaffolds
respiration, so the printed structures must exhibit similar (OBST), the layered structure was based on 10% porcine
mechanical behavior to native lung tissue. This requires skin gelatin and 10% Matrigel, with variable proportions
careful tuning of the bioink formulation and scaffold of sodium alginate. Considering the viscosity to maintain
design to achieve the appropriate elasticity and strength. cell comfort, the sodium alginate concentration was fixed
Incorporating materials that can undergo dynamic at 2% at 35°C and the extrusion speed at 13 mm/s. The
mechanical stimulation can help in replicating the hydrogel mixture was then combined with Calu-3 cells, a
physiological conditions of the lung, thereby enhancing the human lung adenocarcinoma cell line, prior to bioprinting.
functionality and longevity of the bioprinted lung model. They reported that bioprinted Calu-3 cells treated with
Furthermore, vascularization is a critical aspect of lung colloidal toxic silver nanoparticles (AgNPs), known
tissue engineering. The printed lung model must include for their potential antitumor properties, exhibited half
a perfusable vascular network to ensure the delivery of maximal inhibitory concentration (IC ) values similar to
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toxicological studies conducted in mice.
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nutrients and oxygen to the cells, as well as the removal of
metabolic waste. This can be achieved through advanced Urciuolo et al. demonstrated that a photosensitive
bioprinting techniques that allow for the incorporation polymer, 7-hydroxycoumarin-3-carboxylic acid (HCCA)-
of endothelial cells and the creation of microvascular gelatin, can be added to Matrigel and subsequently
Volume 10 Issue 6 (2024) 7 doi: 10.36922/ijb.4092