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Using Spheroids as Building Blocks Towards 3D Bioprinting of Tumor Microenvironment
Pei Zhuang1, Yi-Hua Chiang1, Maria Serafim Fernanda1
1Department of Pharmaceutics, University of Florida, Gainesville, Florida, 32610, USA.
Abstract:
Cancer still ranks as a leading cause of mortality worldwide. Although considerable efforts have been dedicated to anticancer therapeutics, progress is still slow, partially due to the absence of robust prediction models. Multicellular tumor spheroids, as a major three-dimensional (3D) culture model exhibiting features of avascular tumors, gained great popularity in pathophysiological studies and high throughput drug screening. However, limited control over cellular and structural organization is still the key challenge in achieving in vivo like tissue microenvironment. 3D bioprinting has made great strides toward tissue/organ mimicry, due to its outstanding spatial control through combining both cells and materials, scalability, and reproducibility. Prospectively, harnessing the power from both 3D bioprinting and multicellular spheroids would likely generate more faithful tumor models and advance our understanding on the mechanism of tumor progression. In this review, the emerging concept on using spheroids as a building block in 3D bioprinting for tumor modeling is illustrated. We begin by describing the context of the tumor microenvironment, followed by an introduction of various methodologies for tumor spheroid formation, with their specific merits and drawbacks. Thereafter, we present an overview of existing 3D printed tumor models using spheroids as a focus. We provide a compilation of the contemporary literature sources and summarize the overall advancements in technology and possibilities of using spheroids as building blocks in 3D printed tissue modeling, with a particular emphasis on tumor models. Future outlooks about the wonderous advancements of integrated 3D spheroidal printing conclude this review.
Insights
This review explores using multicellular tumor spheroids as building blocks in 3D bioprinting to create advanced tumor models. This integration aims to improve cancer research and drug screening by mimicking the in vivo tumor microenvironment more accurately.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Tissue Engineering
Background:
- Cancer remains a leading cause of death globally, with slow progress in therapeutics partly due to a lack of accurate prediction models.
- Multicellular tumor spheroids are valuable 3D culture models for studying avascular tumors and drug screening, but lack precise control over their microenvironment.
- Existing tumor models struggle to replicate the complex in vivo tissue microenvironment.
Purpose of the Study:
- To review the emerging concept of using multicellular spheroids as building blocks in 3D bioprinting for advanced tumor modeling.
- To discuss methodologies for spheroid formation and highlight the advantages and limitations of current 3D bioprinted tumor models.
- To summarize technological advancements and future possibilities in integrated 3D spheroidal printing for cancer research.
Main Methods:
- Literature review focusing on the integration of multicellular spheroids and 3D bioprinting for tumor modeling.
- Analysis of various spheroid formation techniques and their suitability for bioprinting.
- Examination of existing 3D bioprinted tumor models that utilize spheroids.
Main Results:
- 3D bioprinting offers enhanced spatial control, scalability, and reproducibility for creating complex tissue models.
- Combining spheroids with 3D bioprinting allows for more faithful recapitulation of the tumor microenvironment.
- Significant advancements have been made in developing 3D printed tumor models using spheroids as foundational units.
Conclusions:
- The integration of multicellular spheroids and 3D bioprinting presents a promising strategy for generating more accurate tumor models.
- This approach has the potential to significantly advance our understanding of tumor progression and improve anticancer drug development.
- Future developments in 3D spheroidal printing are expected to revolutionize cancer modeling and therapeutic strategies.

