3d bioprinting

Spheroids And Their Application In 3D Bioprinting

Spheroids are recognized as physiologically relevant three-dimensional models that could capture the major characteristics of both healthy and diseased tissues. Considering its high cell density, increased deposition of extracellular matrix and accelerated proliferation rates, spheroid-based tumour models can greatly reduce the tissue maturation time. These densely packed spheroids are thus proposed as building blocks for healthy or diseased tissue modelling. The spheroid growth and fusion are highly disorganized, which might affect the consistency in therapeutic conditions. Several strategies such as direct fusion and magnetic-driven assembly have been explored to impose spatial control and guide the spheroid fusion and arrangement (1).

Three-Dimensional Bioprinting

3D bioprinting possess superior flexibility and controllability on the spatial arrangements of biomaterials and cells, which have been expansively applied to tumour-related studies including tumour angiogenesis, tumour metastasis, and antitumour drug screening using individual cells and biomaterials.

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However, individually dispersed cells within the hydrogel matrix are insufficient in fully recapitulating specific diseases states. Spheroids could be a perfect alternative approach, despite the high potential in building tissue constructs by combining 3D bioprinting and spheroidal assembly. Given the capability of bioprinting in spatial control, several 3D printing strategies and its adaptations have been investigated for their potential in spheroid assembly (2,3).

Applications of Spheroid culture

Spheroids have found a great potential in anticancer pharmaceutical development, as they can be tailored to a specific application. In general, cellular types, seeding density and culture period are working synergistically in appropriating the size of spheroids generation.

Uniformity in spheroids is of utmost importance because of the relevant size and shape dictate therapeutic efficacy and clinical reproducibility. Numerous strategies have been reported in attempting to form spheroids with desired size and shape with hanging drop method, liquid overlay technique, hydrogel microwells, external-force driven techniques and microfluidics and 3D bioprinting (4,5,6).


1. Pei Zhuang, Yi-Hua Chiang, Maria Serafim Fernanda, and Mei He ,Using Spheroids as Building Blocks Towards 3D Bioprinting of Tumor Microenvironment, PubMet central , 2021

2. Ma X, Liu J, Zhu W, et al. 3D Bioprinting of Functional Tissue Models for Personalized Drug Screening and In Vitro Disease Modeling. Adv Drug Deliv Rev. 2018;132:235–51.

3. Albritton JL, Miller JS. 3D Bioprinting:Improving In Vitro Models of Metastasis with Heterogeneous Tumor Microenvironments. Dis Model Mech. 2017;10:3–14. https://doi.org/10.1242/dmm.025049.

4. Nunes AS, Barros AS, Costa EC, et al. 3D Tumor Spheroids as In Vitro Models to Mimic In Vivo Human Solid Tumors Resistance to Therapeutic Drugs. Biotechnol Bioeng. 2019;116:206–26.

5. Kingsley DM, Roberge CL, Rudkouskaya A, et al. Laser-based 3D Bioprinting for Spatial and Size Control of Tumor Spheroids and Embryoid Bodies. Acta Biomater. 2019;95:357–70.

6. Costa EC, de Melo-Diogo D, Moreira AF, et al. Spheroids Formation on Non-Adhesive Surfaces by Liquid Overlay Technique:Considerations and Practical Approaches. Biotechnol J. 2018;13:417.