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

Table 3. Application of studying inflammation with 3D-bioprinted organoid culture platforms.
Disease model Cell type used Key findings Ref.
Inflammatory bowel disease Caco-2 and HT29 (colon cancer cells) Development of 3D-bioprinted colitis-like condition model to 91
evaluate the barrier function of anti-inflammatory drugs
Rheumatoid arthritis EA.hy 926 (vascular endothelial Established 3D co-culture pannus model to screen anti- 92
cells); MH7A (synovial fibroblasts) rheumatoid arthritis drugs.
Intestine toxicity and Adult human intestinal Development of 3D-printed human intestinal tissues that 93
inflammation myofibroblasts; human intestinal mimic physiological barrier function to test compound-induced
epithelial cells; Caco-2 toxicity
Type 1 diabetes mellitus Murine islet β-cells Development of bioink comprising GelMA, ECM, and PRP to 94
enhance pro-angiogenic and immunoregulatory function for
3D-printed islet organoid
Type 1 diabetes mellitus Rat islet Incorporation of islets into HAMA/pECM hydrogel bioink to 95
study vascularization and inflammatory response of 3D-printed
islet organoids
Immune-driven brain aging Cortical organoid derived from Development of human brain organoid microphysiological 96
hESCs analysis platform that perfuses primary monocytes from
different age groups into human cortical organoids
Microglia-mediated Neuro-2a neuroblast cells; HMC3 3D printing tubular brain organoid platform co-cultured with 97
neuroinflammation human microglia microglia to test neuroinflammation after opioid exposure
Abbreviations: 3D, three-dimensional; dECM, cellularized extracellular matrix; GelMA, gelatin methacryloyl; hESCs, human embryonic stem cells;
pECM, pancreatic extracellular matrix; and PRP, platelet-rich plasma.

One of the notable applications of 3D bioprinting is the regenerative medicine research. Recent advancements
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creation of intestinal organoids for studying IBD. These in 3D bioprinting techniques, such as the development
organoids can model the impaired interaction between of the BATE technique by Jonathan et al., have enabled
epithelial cells and the microbiome, which is crucial for the creation of centimeter-sized gastrointestinal tissues
understanding IBD pathogenesis. By co-culturing these with self-organizing features, enhancing the scalability
organoids with immune cells and microbes, it is possible and applicability of bioprinted organoids in various
to identify the pathological mechanisms driving IBD, research areas. 83
including the contributions of microbial dysbiosis and Rheumatoid arthritis is characterized by inflammation
immune responses to disease progression. 98,99 Deng et al. in joint tissue, particularly by the formation of pannus,
developed an innovative intestinal organ culture system which is an inflamed fibroblastic tissue in the joint
designed to mimic the regenerative process of proliferative that leads to increased angiogenesis. Pannus plays a
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crypts following intestinal epithelial injury. Additionally, crucial role in RA pathogenesis by contributing to joint
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the researchers isolated crypt cells from patients to destruction through leukocyte infiltration, synovial
produce PDOs and compared the physiological differences membrane proliferation, and neovascularization. To better
between normal and disease states. PDOs derived from understand the 3D properties of pannus and explore
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disease states have shown reduced mRNA transcript levels potential treatments, 3D bioprinting technology has been
of tight junction markers, increased cell death, reduced adopted to fabricate 3D pannus tissue using synovial
proliferation, and impaired differentiation abilities. fibroblasts, vascular endothelial cells, and hydrogels, in
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Furthermore, organoids from Crohn’s disease patients order to replicate the complex structure of pannus. Such
exhibit unique transcriptomic and secretomic signatures, 3D-printed pannus models hold promise for future drug
revealing disease-specific mechanisms and responses. screening research, offering a more accurate representation
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To overcome the limitations of current 3D culture of the disease environment for testing and developing
systems, bioprinting techniques have been explored to new therapies. 92
create 3D intestinal tissues composed of human primary
intestinal epithelial cells and myofibroblasts. These Inflammatory diseases, such as autoimmune uveitis,
bioprinted tissues exhibit physiological barrier function involve complex interactions between immune responses
and responses to toxicity and inflammation, offering new and retinal tissues. The development of 3D-bioprinted
opportunities for drug discovery, disease diagnosis, and retinal organoids is particularly significant for studying

Volume 10 Issue 5 (2024) 105 doi: 10.36922/ijb.4054