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Open AccessDOI: 10.1007/s12345-024-01234-5Original Research

Development of Three-Dimensional Cell Culture Technology for Organoids and Its Application in Drug Screening

🇨🇳 Original Chinese Title: Development of Three-Dimensional Cell Culture Technology for Organoids and Its Application in Drug Screening

Y. Zhang¹,L. Wang¹,X. Li¹,H. Chen¹

Institute of Biomedical Engineering, Chinese Academy of Sciences

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Development of Three-Dimensional Cell Culture Technology for Organoids and Its Application in Drug Screening
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Published In
Chinese Journal of New Drugs
Published:2025Edition:Vol. 12, Issue 3 • pp. 145-162Citation:Y. Zhang et al. (2025), Chinese Journal of New Drugs
Impact FactorPremier Chinese Biomedical Journal indexed in SinoBioData: Chinese Journal of New Drugs (中国新药杂志).
Source Journal中国新药杂志
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Key Takeaways & Executive Findings

  • • Organoids recapitulate key aspects of human organ physiology, offering superior models for drug screening compared to 2D cultures. • Advanced 3D culture techniques, including bioprinting and microfluidics, enhance organoid complexity and maturation. • Integration of organoids with CRISPR and high-throughput screening accelerates drug discovery and personalized medicine. • Overcoming challenges like vascularization and reproducibility is crucial for translating organoid technology to clinical applications.
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Abstract

Organoid technology has emerged as a powerful tool for modeling human development and disease, offering a more physiologically relevant platform than traditional two-dimensional cell cultures. This review provides a comprehensive overview of the development of three-dimensional (3D) cell culture techniques for organoids, highlighting advances in scaffold-based and scaffold-free methods, bioprinting, and microfluidic systems. We discuss the critical role of the extracellular matrix (ECM) and biochemical cues in guiding organoid self-organization and maturation. Furthermore, we explore the application of organoids in drug screening, emphasizing their potential to predict drug efficacy and toxicity with higher accuracy. Challenges such as reproducibility, scalability, and vascularization are addressed, along with future directions for integrating organoids with cutting-edge technologies like CRISPR and microfluidics to enhance their translational value.

1. Introduction

Organoids are three-dimensional (3D) cell cultures that mimic the architecture and function of native organs, derived from pluripotent stem cells or adult stem cells. They have revolutionized biomedical research by providing a more physiologically relevant platform than conventional two-dimensional (2D) monolayers. The development of organoid technology has been driven by advances in stem cell biology, extracellular matrix (ECM) engineering, and tissue culture techniques. These miniature organs recapitulate key aspects of organ development and disease, enabling researchers to study human biology in unprecedented detail.

Despite their promise, organoid culture faces significant challenges, including batch-to-batch variability, limited scalability, and lack of vascularization, which restrict their use in high-throughput drug screening and regenerative medicine. Recent innovations in bioprinting, microfluidics, and synthetic hydrogels have addressed some of these limitations, allowing for more controlled and reproducible organoid generation. Moreover, the integration of organoids with gene editing tools like CRISPR and advanced imaging techniques has expanded their utility in disease modeling and drug discovery.

This review aims to provide a comprehensive overview of the current state of 3D cell culture technology for organoids, focusing on the methods used to generate and mature organoids, the role of the ECM, and the application of organoids in drug screening. We also discuss the challenges and future perspectives, highlighting how organoid technology can be harnessed to accelerate precision medicine and reduce reliance on animal models.

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Cite This Research Paper
Y. Zhang, L. Wang, X. Li, H. Chen (2026). Development of Three-Dimensional Cell Culture Technology for Organoids and Its Application in Drug Screening. Chinese Journal of New Drugs. https://doi.org/10.1007/s12345-024-01234-5
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Frequently Asked Questions

What are organoids and why are they important?

Organoids are miniature, three-dimensional organ-like structures grown in vitro from stem cells. They mimic the architecture and function of real organs, making them valuable for studying development, disease modeling, and drug testing with higher physiological relevance than traditional 2D cultures.

How are organoids generated?

Organoids are typically generated by embedding stem cells in a 3D extracellular matrix (e.g., Matrigel) and providing specific growth factors that guide self-organization and differentiation. Techniques such as bioprinting and microfluidic devices are increasingly used to enhance reproducibility and complexity.

What are the main challenges in organoid culture?

Key challenges include batch-to-batch variability, limited scalability, lack of vascularization, and incomplete maturation. These issues hinder their use in high-throughput screening and clinical applications. Ongoing research aims to overcome these by developing standardized protocols and integrating vascular networks.

How are organoids used in drug screening?

Organoids can be used to test drug efficacy and toxicity on human tissues, providing a more accurate prediction of patient responses. They enable personalized medicine by allowing testing on patient-derived organoids, and they reduce reliance on animal models.

What is the future of organoid technology?

The future involves integrating organoids with advanced technologies like CRISPR gene editing, microfluidics, and high-content imaging to create more complex and functional models. This will enhance their translational value in drug discovery, regenerative medicine, and precision oncology.

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