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Akter, et al.
complete the printing procedure and supply all the be an effective solution because of the high chance of
required components to the cells (culture media) must be mismatch. Another concern is antibody-mediated graft
chosen . Post-bioprinting is the third stage that includes rejection, which is life threatening to the host [104,105] .
[98]
all the post-processing steps to make a mature and fully 3D bioprinting is becoming a promising tool
functional bioprinting construct for in vivo usage . for reconstructing organs by utilizing specific issues
[97]
3D bioprinting has the capability of influencing stem and structures from patients for different purposes [106] .
cell differentiation throughout the printing procedure, A 3D-bioprinted lung that mimics the natural lung has
and this technique is capable of replicating supple and been constructed and transplanted into a New Zealand
tough textures de novo along with the precise control over rabbit model. Kim et al. demonstrated an efficient method
different cellular compositions, structural complexity, for creating a 3D-printed trachea with a functional,
distribution, and effective printing with accurate features cartilaginous, and epithelialized airway to improve host
that are reproducible and repeatable [97-100] . survivability [107] .
Recently, human alveolar lung model has been Regulatory considerations for customizable tissue-
successfully fabricated in vitro through 3D bioprinting engineered constructs are important for the approval
technique (microvalve bioprinting). The lung model of the 3D-bioprinted construct. Bioresin selection
had collagen matrix as well as alveolar lung epithelial, is a challenge as there are no approved bioresins.
endothelial, and fibroblast cells. This printed construct Moreover, there is no effective way to determine the
maintained high cell viability, proliferation, and printed construct’s toxicity and biocompatibility,
survivability. However, optimization of the cell printing making the whole procedure harder to complete. The
parameters was not easy. Thus, more investigations are absence of threshold process parameter limit and well-
warranted to optimize the fabrication of 3D bioprinted defined processing steps puts a constraint on process
organ that can be transplanted into human [101] . reproducibility. Thus, a reconsideration of all essential
Grigoryan et al. have created an air sac with a components is a prerequisite for simplifying the 3D
detailed internal structure including blood vessels and bioprinting process and increasing its application [93] .
airways, enabling air pump, and oxygen delivery to the 6. Evaluation techniques of irreversible lung
surrounding environment. Moreover, the lung analog
could withstand the inhalation and exhalation pressure. damage
Interestingly, the whole printing procedure took a Recovered COVID-19 patients who have associated risk
few minutes, which is superior over the conventional factors before the infection are vulnerable to irreversible
technique. Primary stem cells of mice were taken for lung injury, which necessitates a new lung for survival.
printing to treat the chronic liver damage of the mice and Before planning for replacement, accurate evaluation of
the printed construct’s details were inspected. The survival the existing lung is compulsory.
of liver cells in the mice indicates that the bioprinted The easiest evaluation can be carried out with a
blood vessels can deliver nutrients to the surrounding portable chest X-ray, which can determine infected or
cells [102,103] . 3D-bioprinted construct requires scaffolds damaged area in the patient’s lung and help with further
with controllable microstructures for the survival and decision-making [108] . A very common evaluation technique
growth of the printed cells following transplantation is 6MWT, which is utilized during the follow-up studies
in vivo. The porous scaffolds promote the diffusion of on recovered COVID-19 patients to estimate the extent
nutrients and oxygen, improve the mechanical stability of lung damage and the probability of irreversible lung
of the implant, and stimulate the formation of new damage [109] . A pulmonary function test can potentially
organizations. Rapid prototyping with computer-aided evaluate lung conditions and determine further treatment
design helps control the internal structure of the scaffold for individual patients [110,111] . A comprehensive CT
characterized by all the required features . examination will be advantageous in evaluating any
[96]
Risk factors, including age, pre-existing contiguous or overlapping thin section in the chest.
comorbidities, and critical laboratory findings, are The presence of cysts, emphysema, mosaic attenuation,
associated with long-term irreversible lung damage. The persistent air trapping, and acute or chronic pulmonary
severity determines whether the damage is reversible or thromboembolic disease can also be determined with
not . Moreover, some patients have already undergone the help of CT. Numerous features can be used to guide
[19]
lung transplantation due to COVID-19-mediated the transplantation decision, including interlobular
sudden and irreversible lung damage accompanied by septal thickening, abnormal ground-glass opacity, and/
numerous challenges [20,104] . Unfortunately, the number of or DLCO [112] . Moreover, any sequential change in
COVID-19 recovered patients requiring a lung transplant lung volumes and pulmonary opacity can be observed
will dramatically increase in the long run, leading to a through quantitative CT, and the disease progression
shortage of donors. However, having a donor would not can be determined by correlating lung fibrosis with

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