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International Journal of Bioprinting                                         3D bioprinting for lung tissue




            expansion of functional lung tissue production, enhancing   of artificial lung tissues or lung organs at the macroscale,
            vascularization  approaches,  and ensuring  sustained   precise tissue compositions at the microscale, and even cell
            long-term functionality [1,2] . Conditions such as chronic   and molecular compositions at the nanoscale. Although
            obstructive pulmonary disease (COPD), pulmonary    extensive work has been done on the 3D bioprinting
            fibrosis, and lung cancer pose significant challenges to   for LTE, there, to the best of our knowledge, appears no
            global health, severely impacting patients’ quality of life   review paper in this field. In this review, we present a
            and overall prognosis [3,4] . LTE is of paramount importance   comprehensive overview of the principles and recent
            in the context of lung diseases, as it holds great potential   advancements in 3D bioprinting for  LTE. We proceed
            for revolutionizing innovative strategies to replace or   to explore crucial elements such as the composition
            repair damaged lung tissue by leveraging the principles of   of bioink and the printing methodologies employed,
            biology, materials science, and engineering . The ultimate   and explore the potential of multiscale bioprinting to
                                              [5]
            goal is to provide effective treatments and potential cures   faithfully reproduce the intricate architecture of the lung,
            for regenerative medicine (RM), offering new possibilities   ranging  from  macrostructures  to  nanoscale  features.
            for patients requiring respiratory interventions. Especially,   Furthermore, we emphasized the current progress and
            LTE  combined  with  three-dimensional  (3D)  bioprinting   future perspectives in the in vitro reconstitution of lung
            holds great promise for advancing our understanding of   tissue, covering crucial considerations like cell sourcing,
            lung diseases, developing new therapies, and potentially   functionalization, and integration of physiological cues.
            providing transplantable lung tissue in the future.  With  these  groundbreaking  techniques,  a  new  era  is
               Bioprinting, as defined by the American Society for   dawning in the realm of lung tissue development, opening
            Testing Materials (ASTM), is a specific method used   doors to functional and biologically accurate constructs.
            to  3D-print  biomaterials into  various  structures.  3D   This remarkable progress promises to revolutionize disease
            bioprinting is a specific technique used within the broader   modeling, drug screening, and RM for lung conditions.
            field of tissue engineering (TE), to precisely deposit   2. Material inks for lung tissue fabrication
            cells, biomaterials, and growth factors in a 3D manner
            to create complex structures [6,7] . The common strategies   As the native extracellular matrix (ECM) can offer
            of  3D  bioprinting  include  inkjet-based  bioprinting,   structural support to tissues,  it is important to find an
            extrusion-based bioprinting, and laser-assisted (e.g.,   engineered ECM that can serve the same purpose. Material
            stereolithography) bioprinting (Figure 1) . Over the past   inks play a crucial role in TE as they provide scaffolds for
                                             [8]
            few decades, the field of 3D bioprinting has experienced   cell growth and differentiation, facilitating the formation
            significant advancements in terms of the types of tissue   of functional tissues . In the context of lung fabrication,
                                                                               [21]
            models that can be constructed, including cancer , blood   several biomaterials are being explored for creating lung
                                                   [9]
            vessels [10,11] , heart , and lungs [13,14] . Indeed, 3D bioprinting   tissue in vitro. For example, hydrogels (including alginate,
                         [12]
            has the potential to offer various benefits and applications   collagen, gelatin, and fibrin) are water-based materials
            beyond just lung transplantation. 3D bioprinting allows   that can mimic pulmonary ECM . They provide a 3D
                                                                                          [18]
            the creation of patient-specific tissues and organs, tailored   environment for cells to grow and can be engineered to
            to individual needs. Additionally, researchers can create   have  specific  mechanical  properties  and  biochemical
            disease-specific models using bioprinting, allowing   cues. Additionally, biocompatible and biodegradable
            them to study the effects of drugs on specific tissues or   synthetic polymers like poly(lactic-co-glycolic acid)
            organs without endangering patients [9,15,16] . Although this   (PLGA), polycaprolactone (PCL), and polyethylene glycol
            technology is still in its early stages, researchers have made   (PEG) are commonly used in 3D printing or melded into
            progress in generating small, simplified organs like liver   the scaffolds. In addition, decellularized ECM (dECM)
            patches, kidney tissues, and more . Therefore, the ability of   encompasses the characteristics of an ideal tissue scaffold:
                                      [17]
            3D bioplotting to recreate the lung tissue allows researchers   complex  composition,  vascular  networks,  and  unique
            to investigate disease progression, cellular interactions,   tissue-specific architecture [22,23] . Therefore, dECM has
            and responses to different drugs or treatments . 3D   emerged as a potential biomaterial ink with tissue-specific
                                                    [18]
            bioprinting has emerged as a transformative tool that   composition for  LTE . During the  fabrication process,
                                                                                [24]
            enables the creation of intricate 3D structures across   microcarrier inks, which are small, spherical particles,
            different  scales,  ranging  from macroscale  to microscale   play a role in carrying and protecting cells. Furthermore,
            and even nanoscale.                                the incorporation of nanofibers and nanoparticles can
                                                               enhance the mechanical properties and surface area
               Considering the complex structure and dynamic
            characteristics of lung, researchers have made various   of the nanoscale lung scaffolds. To achieve lung-like
                                                               structures with appropriate architecture and functionality,
            summaries [19,20] . 3D bioprinting enables the construction

            Volume 9 Issue 6 (2023)                        437                          https://doi.org/10.36922/ijb.1166
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