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factors, and cultivation conditions among various labs lead inadequate internal energy supply and developmental
to inconsistencies in organoid quality and functionality, delays. Methods, such as sectioning organoid spheroids
149
affecting the reproducibility of organoid studies and attempt to address these issues; however, organoids may still
limiting their application in clinical settings. Ethical struggle to replicate complex neuronal circuits and specific
issues are another major obstacle in organoid technology cell types, limiting studies on neurodegenerative diseases,
150
development. The generation of certain organoids requires such as Alzheimer’s disease. Similarly, in 3D bone
the use of hESCs or other ethically contentious cell sources, organoids, the lack of a replicable in vivo stress environment
138
potentially leading to ethical and legal controversies. hinders the modeling of bone formation. Vascularization
Lastly, the high cost and technical complexities of organoid remains a significant challenge, as continuous blood supply
technology pose significant barriers to its widespread is essential for organoid development.
application. These innovations enhance organoid development by
In summary, despite the immense potential of organoid mimicking human tissues, offering new opportunities
technology in various organ applications, it still faces for disease modeling and drug screening. As the field
numerous limitations in model complexity, maturity evolves, it promises to translate breakthroughs into clinical
and functionality, cellular heterogeneity, environmental applications that improve human health.
simulation, biocompatibility and transplantation,
standardization and reproducibility, and ethical issues. Acknowledgments
These limitations hinder the further development of None.
organoid technology and restrict its widespread application
in clinical and research settings. Future research must Funding
continuously improve cultivation conditions, optimize The work was supported by the National Natural Science
organoid structures, introduce new cell types, and enhance Foundation of China (No. 82472488), the Natural Science
organoid functionality to overcome these challenges and Foundation for Distinguished Young Scholars of Zhejiang
further advance organoid technology in various organ Province (No. LR25H060001), and High – level Innovation
applications. Team of Wenzhou’s “Ouyue Talent Plan” (No. 2024R3003).

6. Conclusion and perspectives Conflict of interest
Establishing in vitro disease models and cell culture systems The authors declare no conflicts of interest.
is crucial for investigating tissue and organ diseases. While
simple models yield favorable results in drug testing Author contributions
and clinical trials, their effectiveness is limited by the Conceptualization: Yuxin Jin, Qizhu Chen
complexity of diseases, species variability, and individual Visualization: Bo Li, Hao Zhou, Ouqiang Wu, Longhui
genetic differences, are impeding clinical research progress. Gong, Xinfeng Zheng, Linjie Chen
Organoid technology offers a solution by creating 3D cell Writing–original draft: Yuxin Jin, Qizhu Chen
models that mimic tissue architecture and replicate organ Writing–review & editing: Yuxin Jin, Qizhu Chen, Zitian
functions, making them a promising tool in contemporary Zheng, Yuting Huang, Dilhana S. Badurdeen, Kai
biomedical research. Chen, YikunChen, Sunren Sheng, Shengdan Jiang,
Organoids retain the genomic characteristics of their Aimin Wu
tissue progenitor cells and hold significant potential for
regenerative medicine, particularly for transplantation. Ethics approval and consent to participate
147
However, genetic variations among patients, such as tumor Not applicable.
heterogeneity, pose challenges to developing effective,
personalized treatments. In addition, organoid cultures Consent for publication
using engineered matrices often exhibit lower efficiency Not applicable.
than traditional extracellular matrices, limiting their
application in tumor organoid models. 148 Availability of data
The complexity of human tissues results in single stem Not applicable.
cell-derived organoids only partially replicating original
organ characteristics. For example, in 3D cultures of References
brain organoids, neural progenitor cells differentiate and 1. Nguyen NT, Shaegh SA, Kashaninejad N, Phan DT. Design,
proliferate on the surface, forming suspended spherical fabrication and characterization of drug delivery systems
structures. This enclosed environment can lead to based on lab-on-a-chip technology. Adv Drug Deliv Rev.

Volume 1 Issue 2 (2025) 21 doi: 10.36922/or.8262