Solid Tumor Micro-model 3D Printing Revolutionizing Cancer Research

Introduction

They're also a tough cancer to study and treat because of their complex microenvironment and a hostility to standard treatments. The 2D cell cultures and animal models we use often don't represent as well as they could the human tumour, so we need models that are better and reproducible. And then there's 3D printing, the new instrument that can print solid tumour micro-models — and it offers a new frontier in cancer studies. In this post, we will learn about the basics, technologies, and use cases of solid tumor micro-model 3D printing and how it could change oncology.

How to Use 3D Printing for Tumor Simulations?

3D printing (also known as additive manufacturing) constructs models, layer by layer and you can even fine-tune the shape and materials of the final product. In the case of tumour modelling, this technology allows the generation of three-dimensional models that very closely mimic the shape and cell heterogeneity of real tumours. It starts with the construction of a digital simulation (either from medical image data or computational models). It's biocompatible material (bioink) or living cell – which may include hydrogels, ECM components and living cells – that turn this model into a physical object.

Figure 1. Illustration of the biofabrication process. (Moghimi N, et al.; 2023)Figure 1. The schematic illustration of the biofabrication process. (Moghimi N, et al.; 2023)

How to Develop Solid Tumor Micro-models

1. Bioink Preparation and Selection

The bioink selected is key for the replication of the tumor microenvironment. Water content and cell encapsulation are properties of hydrogels, like alginate, gelatin, and collagen. They form a supportive scaffold, that can be modified to fit the stiffness and biochemistry of different tissues. Add ECM ingredients such as fibronectin or laminin, and the bioink is made to be even more adhesive and proliferative to cells.

2. Cell Sourcing and Culturing

The cell composition of the tumor model should be representative of the range of cell types found in solid tumours: cancer cells, stromal cells, immune cells. Primitive cells isolated from biopsies of patients or established cancer cell lines can be used. When they're co-culled together in the bioink, they can model the interactions between tumours and stroma and the immune response.

3. 3D Bioprinting Techniques

A few 3D bioprinting methods are used to create solid tumor micro-models:

  • Extrusion Bioprinting: In this process, the bioink is continually sprayed through a nozzle and the layers build up the final structure. It is good for large, high cell-density constructions.
  • Inkjet Bioprinting: Droplets of bioink are applied layer-by-layer and layered. It's highly printable and it can integrate different cell types in a specific design.
  • Stereolithography: By hardening photo-crosslinkable bioinks with light, this technique creates very fine and complex geometries, which can be useful for creating large tumor structures.

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Advantages of Solid Tumor Micro-models

1. Replicating Tumor Heterogeneity

Solid tumour micro-models can mimic the cell diversity and spatial dynamics of real tumors to give a better idea of tumor biology. That heterogeneity is crucial for studying the interplay between cell types and the tumour's response to therapy.

2. Microenvironmental Fidelity

These models can mimic the tumour microenvironment such as ECM, hypoxia and gradients of nutrients. That fidelity is key to seeing how tumours expand and engulf surrounding tissue, and testing the effectiveness of anti-cancer drugs realistically.

3. High-throughput Screening

The 3D printed tumour model is able to run drug tests at high throughput, which will minimise the use of animal models and help find better treatments faster. You can print a variety of models at once with various genetic backgrounds or drug histories, and it's quick and cheap to test.

Applications in Cancer Research

1. Drug Development and Testing

Solid tumour micro-models provide a solid basis for preclinical drug screening so that researchers can determine how effective and toxic new agents are in a well-regulated setting. These models can be used to look for resistance mechanisms of drugs and to detect combinations that are resistant to them.

2. Studying Tumor Biology

Because they emulate the tumour microenvironment closely, they reveal the processes of tumor growth, metastasis and angiogenesis. One can tinker with the model's parameters to see how microenvironmental changes alter tumor behaviour.

3. Personalized Medicine

Tissue-based tumor models of patients can be fabricated using the cells of individual patients to support individual drug testing and treatment. It's a technique that can be used to tailor treatments to the anatomy of a patient's tumour, for better outcomes.

Challenges and Future Directions

There is still a lot of work to be done in 3D printing solid tumor micro-models, however. There needs to be standardization of bioink compositions and printing methods to guarantee reproducibility and scale. What's more, adding vascular and immune parts to the models is key for investigating detailed tumor-immune dynamics and drug delivery. Bioprinting technology and materials science will continue to further refine these models for more accurate and useful use.

Conclusion

New possibilities for cancer research can be created thanks to 3D printing, which is now an increasingly powerful technology for creating solid tumor micro-models whose size resembles those of a real human tumour. They are new and remarkably promising models for the study of tumour biology, new therapies and personalized medicine. With a mature technology, oncology will transform from the bench to the bedside and, ultimately, better for patients.

Reference

  1. Moghimi N, et al.; Controlled tumor heterogeneity in a co-culture system by 3D bio-printed tumor-on-chip model. Sci Rep. 2023, 13(1):13648.
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