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International Journal of Bioprinting Printed organoids for medicine

with light-responsive bioinks (e.g., GelMA/poly[ethylene is crucial, and this can be accomplished by integrating
glycol] dimethacrylate) introduces temporal control over microfluidic bioprinting with two-photon polymerization
scaffold remodeling, enabling post-printing structural to replicate sub-10 µm ductal features.
anisotropy to support secretory epithelial polarization. Future applications should include patient-specific
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Such innovations bridge the gap between structural fidelity glandular models for autoimmune disease studies and
and functional integration. hormone replacement therapies. 98,99 As bioink formulations

2.5.3. Vascularization and nutrient transport and multi-omics validation evolve, bioprinted glands
Vascularization poses a key hurdle for glandular bioprinting, will likely transition from disease modeling to clinical
with strategies such as multi-material bioprinting transplantation, addressing critical shortages in organ
integrating endothelial cells with glandular parenchyma replacement therapies.
to establish perfusable networks. Evidence shows that
pancreatic constructs combining mouse insulinoma 6 3. Disease modeling based on three-dimen-
cells and vascular bioinks develop anastomosed capillaries sional bioprinted organoids
under bioreactor perfusion, enhancing nutrient delivery 3D bioprinted organoids offer a unique advantage in disease
and insulin secretion. A novel tissue-specific bioink was modeling due to their ability to replicate the heterotypic
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formulated by blending pancreatic ECM with hyaluronic organization of multicellular solid organs and the nanoscale
acid methacrylate. The 3D-printed islet organoids precision of pathological processes. It provides a platform
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created using this bioink can replicate the pancreatic for studying the complex microenvironments that regulate
microenvironment, preserving islet cell adhesion and cell behavior in various diseases, offering insights into
morphology via the Ras-related C3 botulinum toxin fundamental biological processes and potential therapeutic
substrate 1/rho-associated protein kinase/myosin light strategies. A significant advantage of organoids in disease
chain kinase signaling pathway (Figure 4A). This approach modeling and drug development is the ability to create
enhances islet function and activity. Moreover, the personalized models using patient-derived cells, which
3D-printed structures enhance the formation of vascular has been studied extensively. Early in 2015, Freedman
networks, while the hyaluronic acid methacrylate/ et al. developed kidney tubular organoids from human
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pancreatic ECM hydrogel supports the adhesion and pluripotent stem cells with drug responses similar to those
proliferation of new blood vessels, thereby augmenting found in clinical settings. The model was also amenable
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the density of vascular structures. Nanocellulose- to CRISPR/Cas9-based genome editing, which was used
alginate bioinks further improve mechanical stability to induce polycystic kidney disease characteristics in
and osteogenic differentiation, suggesting adaptability for the organoid. Votanopoulos et al. conducted a study
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vascularized glandular models. Emerging platforms like using patient-specific immune-enhanced tumor/node
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the Human Islet-like Cellular Aggregates and Vasculature organoids for immunotherapy screening. The responses
platform simulate native pancreatic vascular niches, of the organoids to various immunotherapy drugs were
promoting β-cell survival and functional maturation. 95 very similar to the clinical response, showing the feasibility
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of these organoids for patient-specific drug testing.
Traditional organoids lack precise structure and
scalability, whereas bioprinting overcomes these However, further studies are needed to fully understand
limitations by facilitating the efficient production of and widen the applications of organoids. This section
millimeter-scale constructs with specific geometries. discusses advancements in modeling inflammatory,
Bioprinted mammary tumor models incorporate cancer- genetic, metabolic, immune, and neurodegenerative
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disorders using bioprinted organoids.
associated fibroblasts (CAFs) and endothelial cells,
recapitulating chemoresistance mechanisms absent in 2D 3.1. Inflammatory-related disorders
cultures (Figure 4B & C). 96,97 Despite advancements, several Chronic inflammatory conditions like rheumatoid
challenges remain. Functional longevity is a concern as arthritis, inflammatory bowel disease, neuroinflammation,
printed glands often display temporary secretory activity liver inflammation, and osteoarthritis (OA) are intricate
due to inadequate innervation or vascular integration. Co- disorders characterized by persistent inflammation
printing with neuronal progenitors or utilizing optogenetic and tissue damage. 14,102,103 The pathophysiology of these
stimulation could potentially improve sustained ailments involves a blend of genetic, environmental,
functionality. Immunogenicity is another obstacle, and immunological factors, leading to diverse patient
which can be addressed by employing patient-specific responses to conventional therapies, necessitating a
iPSC-derived cells and dECM bioinks to reduce the risk more personalized treatment approach. 104,105 Recently,
of immune rejection. Achieving multi-scale resolution the fusion of 3D bioprinting technologies with patient-

Volume 11 Issue 4 (2025) 75 doi: 10.36922/IJB025190184