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crucial for drug responses and treatments. Furthermore, Hydrogels provide an environment that supports 3D
2
these models do not account for interactions between cell structures, mimicking the extracellular matrix (ECM)
matrix cells, microenvironmental factors, and cell-secreted in the body and allowing cells to grow and differentiate
cytokines, which are essential for accurate disease modeling. under conditions that resemble their natural physiology. 16,17
3
Complex organ models involving extensive intercellular and By adjusting their composition and structure, hydrogels
extracellular communication present significant challenges can alter their mechanical properties and degradation
for present research. Therefore, the demand for organoids has rates, making them suitable for different types of organoid
emerged to address these limitations. research. Compared to traditional 2D culture methods,

Organoids are three-dimensional (3D) tissue-like hydrogels support complex tissue structures and simulate
structures composed of stem cells, capable of unlimited intercellular communication and signal transduction. 18,19
in vitro expansion, and exhibit defined spatial organization. This characteristic gives them tremendous potential for
4
They are formed through stem cell differentiation, originating drug screening, disease modelling, and regenerative
from embryonic stem cells (ESCs), induced pluripotent stem medicine applications.
cells (iPSCs), or adult stem cells (AdSCs), and can simulate This review summarizes recent advancements
5
and exhibit specific functions of real organs. During in organoid development, highlighting biological
differentiation, these cells establish downstream populations, development models and organoid-promoting
allowing for the aggregation of organ-specific AdSCs into experimental techniques. In addition, it also discusses the
functional units, as seen in models for the intestine, lung, advantages of various hydrogels for culturing organoids
heart, bone, brain, retina, and other tissues. Early organoid across different human body systems. The review explores
6-8
culture models expressed limited organ functionalities, how these hydrogel-cultured organoids can mimic organ
primarily those created through cell separation and development, facilitate drug screening, and contribute
reaggregation techniques, while later models with a broader to translational research, with the potential for future
range of organ functions were created, making them more commercialization in clinical applications. In addition, it
feasible in accurately recapitulating physiological conditions. 9 addresses the present limitations and challenges in organoid
Present research emphasizes the connectivity of various research, while emphasizing the progress in biomaterial
systems and multi-organ functions, studying bidirectional fabrication and the convergence of bioengineering with
communication patterns, such as the bone-intestine axis, organoid studies. These developments offer expansive
bone-brain axis, and gut-brain axis. Inter-organ cell factor opportunities for simulating the development of various
10
interactions and signal transduction are often invisible and systems and organs.
challenging to monitor in vivo. However, organoid cultivation
facilitates the study of bidirectional organ connections. By 2. Organoids
utilizing the diverse cell composition of intestinal organoids, 2.1. Origin and development
which secrete neurotransmitters and mediate the connection
between gut microbiome signals to host changes, the limitations The earliest research on organoids dates back to 1907 when
of the traditional organ models can be addressed. 11,12 H. V. Wilson developed an artificial cultivation method for
sponges, laying the foundation for 3D cell growth. In the
20
In addition, the complexity of human organ systems 1980s, studies began utilizing Matrigel to simulate external
differs significantly from rabbit and rodent models, often environments for cell growth. The 1990s saw significant
21
leading to failed translations of successful drug treatments advancements in stem cell research, particularly with
from animals to humans. Organoids, by mimicking the the discovery and cultivation of ESCs and AdSCs, which
spatial morphology of normal tissues, provide an alternative provided essential cell sources for organoid research. A
22
for simulating drug resistance, drug screening, and the tumor significant breakthrough occurred by identifying leucine-
microenvironment. In the context of cancer, the individual rich repeat-containing G protein-coupled receptor 5
13
heterogeneity among tumor cells is a key reason for the failure (Lgr5)-positive stem cells, which were shown to form
of treatments. Patient-derived cancer organoid models have intestinal villi structures without mesenchymal cell
shown the ability to differentiate into various subcellular support. In 2013, the first brain organoids derived from
23
types. For example, gastric cancer organoids have been human pluripotent stem cells (hPSCs) were cultivated,
14
used to construct models with Ras and Wnt signalling demonstrating the potential for studying brain-related
pathway activation, and diffuse models, which enable diseases, such as microcephaly. 24
the assessment of drug sensitivity variations. Similarly,
15
organoids have shown success across various systems and Present research focuses on combining organoids with
organs, including cardiovascular, respiratory, digestive, gene editing technologies to engineer organs that express
urinary, and musculoskeletal systems, establishing a reliable specific genes and functions, enhancing their utility in
platform for developing novel therapeutic approaches. targeted cancer therapies. 25

Volume 1 Issue 2 (2025) 2 doi: 10.36922/or.8262