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International Journal of Bioprinting 3D bioprinting for lung tissue

precise robotic control systems, macroscale bioprinting Micro lung structure refers to the detailed anatomical
facilitates the fabrication of scaffold-free isogenic artificial components and organization of the lung at the microscopic
[39]
tracheas, which can be utilized as tracheal grafts in rats . level. It involves the study and understanding of the intricate
Researchers have demonstrated the transplantation of a structures within the lung tissue, such as the alveoli,
[56]
macroscale 3D-printed trachea that mimics the natural bronchioles, capillaries, and various types of cells . The
trachea into a rabbit model to enhance the regeneration small airways also play a crucial role in the microstructure
of tracheal mucosa and cartilage . In another study, of the lung and distribute air to the alveoli and help regulate
[40]
a macroscopic structure composed of lung epithelial airflow within the lungs. The alveoli are surrounded by a
cells printed on the basis of primary lung fibroblasts and network of capillaries, allowing for efficient exchange of
monocyte cells was used to reconstruct alveolar model air between the alveoli and the blood (Figure 3A). In the
(about 7 mm long) in vitro to detect influenza virus blood–gas barrier, the proximity between an alveolus and a
infection . These constructs can be used to study lung capillary is approximately 0.5 μm, facilitating gas exchange
[41]
[57]
development, investigate disease mechanisms, and develop through the process of diffusion . Continued research
new therapies. and advancements in microscale bioprinting hold huge
promise for the advancements of functional lung tissues as
4. Microscale 3D bioprinting well as lung tissue recapitulation and application in future.

4.1. Microscale 3D bioprinting techniques 4.2. Microscale 3D bioprinting for lung tissue
Research on microscale systems to reconstruct local recapitulation and application
microenvironmental cues and microscale characteristics is Microscale bioprinting materials and strategies offer
also worthy of attention for realizing pulmonary structure precise control over the fabrication of lung tissue constructs
functions in vitro . Within the living organism, cells at a smaller scale, which enable the creation of intricate
[42]
reside in a complex microenvironment consisting of structures, mimic the native lung microenvironment, and
[58,59]
diverse biophysical and biochemical cues [43,44] . Microscale promote cell viability and functionality . Using 3D
bioprinter with a printing resolution in the micrometer
bioprinting refers to the fabrication of structures at a range, researchers printed a complex engineering microscale
smaller scale, typically in the range of micrometers [45,46] . 3D air–blood tissue barrier for safety assessment and drug
Microscale 3D bioprinting constructs aim to replicate efficacy testing (Figure 3B) . This development is expected
[60]
the complex biochemical and biophysical processes that to pave the way for high-throughput drug screening in
occur within and between cells in living tissues [47,48] . This vitro. Due to the impossibility of a single material ink to
approach offers several advantages, including enhanced establish a “synthetic” microenvironment that accurately
precision, increased resolution, and improved control simulates the in vivo conditions, there has been a growing
over cell placement, which are crucial for mimicking the emphasis on multimaterial bioprinting . Researchers
[61]
natural cellular composition and organization found in developed a groundbreaking material ink by combining
native tissues and organs [49,50] . Commonly used strategies alginate with dECM, showcasing its remarkable ability to
are laser-assisted bioprinting and inkjet-based bioprinting. maintain biological activity during the entire process of
Laser-assisted bioprinting realizes the printing of 3D-bioprinting intricate and mechanically resilient tissues,
photosensitive bioink by using plane projection, while both during and after printing (Figure 3C) . Through
[62]
inkjet-based bioprinting uses a piezoelectric printhead their research, it was discovered that the enhanced bioink,
to deposit droplets of bioink onto a substrate. Such enriched with lung dECM, exhibited remarkable potential
strategies enable us to create complex microscale tissue for 3D bioprinting of subsegmental human bronchus. This
structures. In microscale bioprinting, bioinks must possess bioink consisted of primary human lung smooth muscle
specific properties, such as shear-thinning behavior (to cells and primary airway epithelial progenitor cells, which
enable extrusion), biocompatibility, and appropriate possessed the capacity to differentiate into diverse cell
rheological properties (to simulate lung stretching) for types typically found in the airway.
precise printing. The bioprinted cells can interact with the The progress of microscale 3D bioprinting has
surrounding ECM or biomaterials [51,52] . By controlling the significantly advanced the simulation of lung diseases in vitro.
printing parameters and the composition of the bioink, In a recent and influential study, scientists made a significant
researchers can achieve desired mechanical properties, cell breakthrough by 3D bioprinting, which has proven to be a
densities, and functionalities within the printed microscale valuable model for investigating influenza infection within
constructs [53,54] . For example, hydrogels made from human the lung . Additionally, studies have demonstrated the
[63]
lung dECM can resemble the biophysical traits of native feasibility of bioprinting microscale lung using acellular
lung tissue . porcine lung hydrogel without external crosslinking, using
[55]
Volume 9 Issue 6 (2023) 440 https://doi.org/10.36922/ijb.1166