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

Table 5. Current research on organoids as promising models for studying extracellular vesicles in various inflammatory diseases.
Disease model Key findings Ref.
Inflammatory bowel disease EVs from human intestinal organoids modulated LPS-induced inflammatory response, with 138
various microRNA contributing to these effects.
Acute kidney injury EVs from 3D cultured MSC exhibited yield increase compared to those from 2D culture and 139
have superior anti-inflammatory effects, significantly reducing renal injury.
Osteochondral defects EVs derived from 3D cultured umbilical MSC positively affected chondrocyte proliferation, 140
migration, and stability, conferring chondroprotective effects and promoting osteochondral
regeneration activity.
Parkinson’s disease EVs from cerebral organoids reduced oxidative stress and apoptosis in astrocytes while 141
promoting neuronal differentiation.
Retinal development and disease EVs derived from retinal organoids regulate the expression of genes related to development, 142
functions, and disease in retinal progenitor cells.
Abbreviations: EVs, extracellular vesicles; LPS, lipopolysaccharide; 3D, three-dimensional; 2D, two-dimensional; and MSC, mesenchymal stem cell.

translation, as scalability and low yields hinder large- tissue regeneration, and disease treatment. Improving
scale therapeutic applications. 147 organoid models using 3D bioprinting technologies to
better represent the cellular and molecular environment
The application of 3D bioprinting technologies of human tissues is crucial to addressing the limitations
has shown significant advancements in enhancing the of current models and enhancing the efficacy of OEVs in
function and properties of OEVs, improving production various applications.
efficiency, and offering the potential for regenerative
medicine and immune-mediated treatment of chronic Research indicates that bioprinted EVs can
diseases. By utilizing automated ECM plating processes, significantly impact various medical fields by promoting
3D bioprinting enhances the speed, accuracy, and angiogenesis, osteogenesis, chondrogenesis, myogenesis,
performance of matrices, leading to improved organoid and carcinoprevention. The current review includes
production efficiency. The structural integrity, controlled a total of eight bioprinted EVs studies covering a
release, and targeted applications provided by 3D variety of medical applications (Table 6). The study
bioprinting offer a promising approach to maximize by Maiullari et al. specifically focuses on the use of
the therapeutic benefits of EVs, making them more 3D-bioprinted endothelial-derived EVs for promoting
effective in precision medicine applications, especially neovascularization, demonstrating the potential of
in inflammation. bioprinted EVs in enhancing vascularization and
tissue regeneration. Zhang et al. demonstrated that
148
Overall, the integration of 3D bioprinting in 3D-printed polylactic acid (PLA) scaffolds with MSC-
generating tissue structures, organoids, and EVs holds derived exosomes possess immunoregulatory potential
immense potential for personalized cancer treatment, and promote osteogenic differentiation, showing potential

Table 6. Current studies of 3D-bioprinted extracellular vesicles for various medical applications.

Medical application Key findings Ref.
Neovascularization 3D-bioprinted endothelial-derived EVs promoted vascularization and tissue regeneration. 148
Bone tissue regeneration 3D-printed PLA scaffolds with MSC-derived exosomes promoted osteogenic differentiation. 149
Osteogenesis and angiogenesis hADSCs-EVs promoted bone formation and angiogenesis in vitro and in vivo. 150
Improved migration and Bioceramic-induced macrophage-derived EVs enhanced migration, immune response, 151
osteogenesis osteogenesis, and angiogenesis.
Anti-cancer efficacy Exo-ssDNA-SA-FasL induced tumor cell apoptosis and modulated immune responses. 152
Cartilage and bone regeneration MSC-derived EVs in ECM/GelMA bioink induced cartilage and bone regeneration. 153
Myogenesis Bioprinted M2-EVs promoted myogenesis and myotube formation in vitro. 154
Cancer biomarker capture EVs antibody microarrays captured plasma tumor-specific EVs for early cancer detection. 155
Abbreviations: 3D, three-dimensional; ECM, extracellular matrix; EVs, extracellular vesicles; GelMA, gelatin methacryloyl; hADSCs, human adipose-
derived stem cells; MSC, mesenchymal stem cell; PLA, Polylactic acid; and M2, M2 type macrophage.

Volume 10 Issue 5 (2024) 109 doi: 10.36922/ijb.4054