Page 106 - IJB-10-5

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

potential in modeling human diseases due to their high cultured organoids through 3D bioprinting may reveal the
culture success rate, close resemblance to primary tissue, complex mechanisms underlying chronic inflammatory
and short culture cycle. However, traditional organoid diseases, leading to more effective and personalized
3–5
culture methods rely on the self-organization of cells intervention strategies.
in a 3D environment, which can result in a variety of Here, we review recent advancements in 3D
morphologies, genetic drift, and the lack of endogenous bioprinting technologies for PDOs and the emerging
tumor-associated stromal components. These limitations field of 3D-bioprinted OEVs, focusing on their potential
6
hinder the reproducibility, scalability, and clinical applications in tackling immune-mediated chronic
applicability of organoid models. diseases. By analyzing current advancements, challenges,
3D bioprinting technology addresses these challenges and future prospects, this review underscores the potential
by enabling precise layer-by-layer positioning of biological of 3D-bioprinted PDOs and EVs in advancing precision
materials, living cells, and biochemical factors to create medicine strategies for inflammation-related conditions.
complex tissue structures that closely resemble in vivo
environments. This technology allows for the construction 2. 3D-bioprinted organoids: State-of-the-
7
of organoids with defined structures and spatial art in 3D bioprinting of organoids
arrangements, enhancing consistency across experimental
models and improving their utility in research and clinical 2.1. Organoids for novel model systems
applications. By incorporating vascular structures, Developing effective in vitro models to reflect the complexity
8,9
immune cells, achieving precise spatial architecture, and of immune interactions in chronic inflammation is crucial
scaling up to tissue sizes, 3D bioprinting plays a pivotal for deeply understanding inflammatory response. Studying
10
role in overcoming limitations in organoid construction. tissue biology in mammals presents challenges due to
The fabrication of 3D biological structures with multiple sample accessibility and ethical concerns. One innovative
functional, structural, and mechanical components through approach to overcome these challenges is organoid
3D bioprinting has facilitated drug development, toxicity technology, which utilizes the intrinsic ability of stem cells
studies, and the study of tissue and disease formation and to self-organize into 3D structures that resemble in vivo
progression. Moreover, 3D bioprinting technology offers organs (Figure 1).
11
novel opportunities for studying inflammatory diseases Compared to in vitro cell line models or in vivo animal
by incorporating immune cells, stromal cells, and other models, organoids offer several distinct advantages.
relevant cell types into organoid models. 12,13 Organoids have high culture success rates, which ensures
3
A significant advancement resulting from the reproducibility and reliability in experimental outcomes.
integration of 3D bioprinting and organoid cultures is the Additionally, their close resemblance to primary tissue
study of extracellular vesicles (EVs) released from these in three dimensions makes them more physiologically
organoids. EVs, including exosomes and microvesicles, are relevant for studying disease mechanisms and drug
5
nano-sized particles that play a crucial role in intercellular responses. The short culture cycle of organoids also
communication by transporting bioactive molecules such facilitates rapid experimentation and reduces the time
4
as proteins, lipids, and RNA. They emerge as important and costs associated with traditional models. Moreover,
14
mediators of immune regulation and are implicated in the organoids enable the establishment of low-malignancy
pathogenesis of various chronic inflammatory diseases. models, offering a safer and more ethical alternative for
23,24
Analysis of EVs facilitated by 3D bioprinting technology studying disease progression.
provides new insights into disease mechanisms at the Importantly, organoids can be derived from stem cells
molecular level, surpassing traditional biopsy methods. or tissue progenitors of the body, which in turn allows
15
Moreover, EVs from organoids have the potential to them to be used to establish patient-specific disease
identify essential biomarkers and therapeutic targets models for personalized precision medicine. Since the
for chronic inflammatory diseases like RA, IBD, and discovery in 2009 that adult tissue-resident stem cells can
neuroinflammation. 16–18 Chronic inflammatory conditions proliferate and self-organize into organoids in vitro, this
are particularly challenging to treat due to their complex methodology has been adapted to generate organoids
pathophysiology and the variability in patient responses from various epithelial tissues of major organs such as the
to treatments. Organoid-derived EVs (OEVs) offer a skin, kidney, liver, and intestines. These organoids have
5
novel perspective on cellular communication networks been used in physiological and disease-related studies on
and immune modulation mechanisms specific to these topics, including complex inflammation-related disorders
conditions, which may serve as potential biomarkers and such as IBD. The utilization of PDOs has paved the way
25
therapeutic targets. 19–22 Investigating EVs released from for the development of personalized therapy, enabling
Volume 10 Issue 5 (2024) 98 doi: 10.36922/ijb.4054