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

applications in bone tissue regeneration. In one study, to affected tissues. This targeted strategy allows for the
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Kang et al. investigated the use of bioprinted human development of personalized treatment strategies, which
adipose-derived stem cell-derived EVs (hADSC-sEVs) for can lead to reduced side effects and increased intervention
bone and angiogenesis in vitro and in vivo, demonstrating efficacy tailored to individual patients. For instance,
their ability to promote osteogenesis and angiogenesis. incorporating EVs loaded with anti-inflammatory agents
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A study by Sun et al. demonstrated that bioceramic- into bioinks for printing organoids enables controlled
induced macrophage-derived EVs significantly and sustained release of these agents directly at the site
improved migration, attachment, immune response, and of inflammation. This method offers precise delivery
osteogenesis in human bone marrow-derived stem cells and sustained release, making it an effective strategy
(hBMSCs), and angiogenesis in human umbilical vein for managing chronic inflammatory diseases like RA
endothelial cells (HUVECs). Yerneni et al. investigated or IBD. 149,150,153
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bioprinted oligonucleotide-tethered macrophage-derived
small EVs (Exo-ssDNA-SA-FasL) for inducing tumor The application of OEVs in precision medicine
cell apoptosis and immunomodulation. Their study extends to various areas such as biomarker discovery,
triggered FasL/Fas-mediated apoptosis in squamous drug screening, and personalized treatment strategies.
cell carcinoma cells in vitro and reduced CD3+ and EVs have shown promise in identifying disease-specific
CD4+ T cells in vivo, demonstrating notable anti-cancer biomarkers, aiding in early diagnosis, and monitoring
efficacy and immunomodulation potential. Another disease progression. Proteomic analysis of EVs from
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study printed mesenchymal stem cell-derived small cancerous and healthy organoid cultures has improved the
extracellular vesicles (MSC-sEVs) in cartilage ECM and specificity and sensitivity of cancer diagnosis, enhancing
GelMA bioink, inducing cartilage and bone regeneration personalized medicine by providing specific biomarkers
in vivo. The 3D-printed ECM/GelMA/exosomes scaffold reflective of the individual’s microenvironment. 156–158
showed results in addressing chondrocyte mitochondrial Patient-derived exosomes have demonstrated therapeutic
dysfunction, enhancing chondrocyte migration, potential in cancer therapy by targeting specific molecular
and polarizing synovial macrophages toward an M2 pathways to mitigate aggressive cancer characteristics.
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phenotype. Yerneni et al. used bioprinted murine Additionally, EVs derived from intestinal organoids
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macrophage-derived EVs to manufacture an in vitro ECM have shown the ability to modulate immune responses,
microenvironment consisting of exosomes. EVs were suggesting therapeutic applications for inflammatory
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enriched from a murine macrophage cell line (J774A.1) conditions like colitis. 20
in M0 (non-activated), M1 (pro-inflammatory), and M2
(pro-regenerative) phenotypes and bioprinted in glycerol The use of 3D bioprinting to create patient-specific
bioink on collagen type-I-coated slides. Myogenesis organoids integrated with EVs represents an advanced
in murine myoblasts—C2C12 cells—was assessed, approach in regenerative medicine and personalized
showing that the bioprinted M1-EVs microenvironment therapy. This method utilizes patient-specific data
inhibited, while M2-EVs promoted, myogenesis by obtained through advanced imaging technologies
upregulating myosin heavy chain (MF20) expression and like computed tomography (CT) or X-ray scans to
myotube formation. These findings show the potential create precise models of tissue defects. By employing
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of bioprinted EVs in influencing cell bioactivity and personalized computer-aided design (CAD) modeling,
promoting myogenesis in vitro. Another study used a 3D-bioprinted constructs can be fabricated to replicate
bioprinting technique to print EV antibody microarrays the unique characteristics of the patient’s tissues.
to capture plasma tumor-specific stem cell-derived EVs Compared to traditional methods, incorporating EVs
(sEVs) from head and neck squamous cell carcinoma into these bioprinted models enhances their therapeutic
patients. These studies indicate the emerging interest potential by more accurately mimicking the complex
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in utilizing 3D-bioprinted sEVs for various applications. biological environment. 160,161
3.4. Applications of precision medicine Therefore, the combination of 3D-bioprinted
for inflammation organoids with EVs offers a promising avenue for
The integration of 3D-bioprinted organoids with EVs precision medicine in managing inflammatory conditions
presents a promising approach in the field of precision and advancing personalized treatment strategies. This
medicine, particularly for inflammatory conditions. approach enables targeted delivery of therapeutic
EVs derived from 3D-bioprinted organoids can carry agents and enhances disease monitoring, diagnosis, and
targeted therapeutic agents or genetic material, which treatment efficacy through the use of 3D-bioprinted
can modulate inflammatory responses when delivered OEVs (Figure 5).

Volume 10 Issue 5 (2024) 110 doi: 10.36922/ijb.4054