Page 41 - OR-1-2

Table 3. Clinical role and application of organoid hydrogels
System Organ Role of organoid hydrogels Examples of applications References
Circulatory Heart Good reproduction of the heart’s natural environment Hydrogels as scaffolds for 88
system morphology, structure, and function, as well as the endothelialized myocardial tissue as
complex microenvironment platforms
Vessels Ensure complex tubular structures and precise 3D 3D printing of blood vessels and 94,95
network distribution more using collagen hydrogels
Respiratory Lungs Provides a more consistent and adjustable culture microwell hydrogel 104
system environment
Digestive Gastrointestinal Intestinal organoid formation and functionalized CS/GelMA composite hydrogel 106
system tract substrates
Liver Controlled and stable 3D scaffolds for high-throughput Specific composite hydrogel capsules 145
and reproducible organoid generation
Urinary Kidney Constructing substrates for renal organoids that Ionic cross-linked alginate hydrogels 112
system encapsulate the complex structure and function of the
kidney
Nervous Brain For culturing and inducing the growth of cerebral Bioactive hydrogel with adjustable 124
system organoids stiffness
Spinal cord As a substrate for spinal cord organoid cultures of Alginate hydrogel 146
well-defined composition
Skeletal Bone As a long-term culture to mature large-scale bone Bone matrix analogue 134
system organoid matrices
Cartilage As a matrix to mimic the cartilage microenvironment Hydrogel microspheres 135
Abbreviations: 3D: Three-dimensional; CS: Calcium silicate; GelMA: Gelatin methacrylate.

mimic the microenvironment of natural cartilage or other or conducting drug screening. Secondly, organoids face
tissues. Moreover, Yang’s custom gelatine microcryogels can limitations in maturity and functionality. While some
self-assemble in vivo into a bone-cartilage-like structure, organoids (e.g., brain and liver organoids) have made
effectively inducing stem cell differentiation. In addition, strides in morphology and function, they still fall short
gelatine microcryogels can serve as drug delivery vehicles, of the maturity levels of in vivo organs. For instance, brain
encapsulating growth factors, cytokines, or other bioactive organoids, while simulating certain brain structures and
molecules within the microspheres, thereby promoting functions, still struggle with the complexity of neural
tissue repair and regeneration through controlled release. networks and functional representation. Similarly, liver
organoids, widely used in drug metabolism research, have
5. Limitations notable gaps in metabolic function compared to real livers.
The advent of organoid technology has ushered in a Moreover, organoids’ cellular heterogeneity is insufficient.
revolutionary transformation in biomedical research, Typically derived from a single type of stem cell, they
enabling the in vitro simulation of organ structures and lack the complex interactions of multiple cell types found
functions, hence, being widely applied in drug screening, in vivo organs. For example, intestinal organoids have
disease modelling, regenerative medicine, and other fields. a limited capacity to accommodate immune cells or
Despite the immense potential demonstrated by organoid neurons. Furthermore, organoids fail to fully replicate
technology, it encounters numerous non-negligible the biological microenvironment of the body, such as
limitations in specific applications across various tissues mechanical forces, electrical fields, and dynamic changes,
and organs. which may result in differences in cellular behaviour and
function.
Firstly, organoids exhibit significant shortcomings
in model complexity. Although they mimic certain Biocompatibility and transplantation issues also pose
structures and functions of specific organs, they cannot significant challenges. Transplanting organoids into
fully replicate the intricacy of in vivo organs, particularly host bodies may trigger immune rejection, necessitating
the absence of vascular networks and immune systems. further research to address this. In addition, organoids
The lack of complete vascular networks restricts oxygen face difficulties in long-term survival and functional
and nutrient supply, affecting cell survival and function. maintenance within the body. Standardization and
In addition, the absence of an immune system limits reproducibility issues are other limiting factors in organoid
organoids’ utility in researching immune-related diseases technology development. Differences in media, growth

Volume 1 Issue 2 (2025) 20 doi: 10.36922/or.8262