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International Journal of Bioprinting 3D bioprinting for organoid-derived EVs

inflammatory diseases like autoimmune uveitis because cellulose functionalized with carbon nanotubes has been
they provide a controlled environment to investigate how proposed to support neural cells, enhancing cell attachment
inflammation affects retinal cells. Sun et al. developed and conductivity for improved cell communication and
retinal organoids derived from human iPSCs using 3D neural network formation. These models offer a valuable
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printing technology on a polydimethylsiloxane (PDMS) platform for investigating the complex interplay between
microwell platform. This approach allows the creation inflammation and neurodegenerative diseases, which is
of uniform organoids with long sustained growth, fundamental for understanding the disease mechanisms
which exhibit proper differentiation into neural retina, and exploring potential therapeutic targets.
ciliary margin, and retinal pigment epithelium. The use These studies suggest that 3D bioprinting technology
of human platelet lysate as an alternative to fetal bovine plays a crucial role in the field of disease modeling by enabling
serum enhanced the clinical relevance of this model, the creation of complex organoid models that closely
offering a standardized platform for retinal development
research, disease modeling, and drug screening. These mimic the cellular interactions and microenvironments
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organoids can be used to model inflammatory responses observed in various inflammatory diseases.
by exposing them to pro-inflammatory cytokines or 2.5. Challenges and limitations in 3D bioprinting
other inflammatory stimuli, thereby mimicking the organoids for precision medicine
conditions seen in inflammatory retinal diseases like Although 3D bioprinting has shown significant progress
autoimmune uveitis. in organoid platforms, it still faces several challenges
Finally, neuroinflammation plays a crucial role in and limitations. 115,116 One major obstacle lies in the size
the pathogenesis of Alzheimer’s disease and Parkinson’s difference between organoids and real organs, which
disease, characterized by an imbalance in the “redox state” impacts the replication of organ complexity. Organoids
and chronic inflammation, leading to cell damage and are significantly smaller than actual organs, making
death. Research emphasizes the significant involvement it challenging to capture the intricate structural and
of microglial and astrocytes in neuroinflammation and functional details of human organs. This size discrepancy
neurodegeneration in these conditions. 105,106 Microglia can also lead to hypoxia-related damage due to inadequate
and astrocytes are recognized for inducing and releasing nutrient supply. 117,118
various inflammatory mediators in response to oxidative The long duration of the current manufacturing
stress, further amplifying the inflammatory response. 107,108 process can also contribute to hypoxia-related issues by
The use of cerebral organoids has emerged as a valuable interrupting the continuous nutrient and oxygen supply
tool for studying neuroinflammation, as the transcriptome required for optimal cell growth. Moreover, the absence
and responses of microglia in cerebral organoids closely of a functional vascular network in bioprinted tissues can
resemble those of adult microglia. 109,110 Thus, cerebral result in hypoxic conditions and hinder tissue development,
organoids have been pivotal in replicating disease necessitating improved vascularization techniques. 119
hallmarks and testing potential therapeutic interventions
for neurodegenerative diseases. For instance, in Alzheimer’s Researchers have explored various approaches to
disease, cerebral organoids derived from patient-specific address these challenges, For instance, the development of
iPSCs with a duplication in the APP gene exhibited 3D-printed bioreactors has shown promise in enhancing
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key disease features like amyloid β aggregation and tau vascularization in kidney organoids. Additionally,
phosphorylation, enabling the screening of inhibitors integrating vascular networks into organoids using
and reduction in aggregate formation. Similarly, in human pluripotent stem cells engineered to express
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Parkinson’s disease, brain organoids developed from iPSCs ETV2, a transcription factor essential for endothelial cell
containing the LRRK2 G2019S mutation highlighted development, has demonstrated potential in forming
synaptic dysfunction as a key altered pathway in PDOs, complex blood vessel-like networks within organoids.
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offering insights into disease mechanisms. 112 These strategies aim to replicate the vascularization seen in
native tissues, which is crucial for the long-term viability
Advancements in bioprinting techniques have further
enhanced our capacity to create 3D brain structures for and functionality of organoids.
neurodegenerative disease modeling. Novel printing Controlling the organization of multiple cell types
techniques using gellan gum modified with RGD peptides within complex 3D architectures is another significant
have been developed to encapsulate primary cortical challenge in 3D bioprinting. Although this technique
neural cells, which possess good viability and demonstrate allows precise cell arrangement, achieving precise
differentiated morphology of cortical neurons within the configurations remains difficult. Furthermore, the
printed constructs. Additionally, the use of nanofibrillated manipulation of cell organization within dynamic 3D
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Volume 10 Issue 5 (2024) 106 doi: 10.36922/ijb.4054