Rapid advances in 3D printing have changed everything from biomedical research to drug discovery. The best hope for 3D printing is the development of melanoma micromodels – three-dimensional, biologically valid models of malignant tumours. These models have many benefits over 2D (2D) cell cultures and animal models in that they better reflect the microenvironment of the tumor and can be used to study the biology and effectiveness of melanoma. In this post, I cover the major advantages of 3D printed melanoma micromodels and how they have changed melanoma research.

Figure 1. Method of production of the 3D microvascularized skin melanoma model. (Bourland J, et al.; 2018)

Enhanced Biological Relevance

Simple 2D cell cultures can't model the architecture and microenvironment of human tumours. Instead, 3D printed melanoma micromodels can mimic three-dimensional tumour architecture, such as the dynamics of cancer cells, stromal cells and extracellular matrix elements. This increased biological accuracy allows investigators to look at tumour behaviour, growth and therapy in a physiologically truer light.

• Tumor Microenvironment

Cancer development and treatment responses are also dependent on the microenvironment of the tumor. The 3D printed micromodel of melanoma could incorporate parts of the tumour microenvironment (fibroblasts, immune cells, blood vessels). This addition allows us to see the tum-stroma relationship, and how the microenvironment impacts drug resistance and progression.

• Heterogeneity

Melanoma is highly heterogenous – cells and molecules differ vastly in different tumours and even between tumours. This heterogeneity can be simulated through 3D printed models that add cells from different cell kinds, and create gradients of oxygen, nutrients, etc. That heterogeneity is hard to get in 2D cultures and 3D models are a better way to study the heterogeneity of melanoma.

• Improved Drug Testing and Development

Preclinical models that are representative are essential to the construction and validation of novel anticancer therapies. There are a number of benefits here that 3D printed melanoma micromodels can provide: they are a more predictive and effective tool for drug testing and diagnosis.

• Predictive Power

A few researches have reported that 3D models predict better clinical outcomes than 2D cultures. As they resemble closely the real world of a tumor, 3D printed micromodels can predict therapeutic effectiveness and toxicity. This predictive capacity can lower the drug failure rate in clinical trials, which saves time and resources when developing a drug.

• High-Throughput Screening

melanoma micromodels that are rapidly and reliably made using 3D printing for the high-throughput screening of potential drug candidates. Scientists print several models at a time, all with uniform size, shape and cell structure. This capability enables the rational testing of hundreds of compounds and treatments to determine therapies with the speed of light.

• Personalized Medicine

Personalised medicine has set out to design treatment programmes for patients who are genetically and molecularly distinct. 3D printed melanoma micromodels could be tailored to a patient's tumour, offering an individualised test bed for drugs. This way therapeutic strategies can be optimized for patient benefit and less adverse effect.

• Ethical and Practical Considerations

For decades, animal models were the foundation of cancer research but there are ethical issues and limitations. An option is 3D printed melanoma micromodels, which address some of these problems and are practical.

• Reduction in Animal Use

Animals are subject to ethical questions about their welfare and animal models for human disease. With 3D printed models, we can decrease animal testing and offer a humanised model for studying melanoma. This fewer animal uses goes along with the 3Rs (Replacement, Reduction, and Refinement) in animal studies and is responsible science at large.

• Cost and Time Efficiency

Research on animals is expensive and slow — taking up vast resources and gaining regulatory approval. 3D printed melanoma micromodels can be made and use to automate the research process for a much cheaper and faster solution. They can rapidly build and alter such models to experiment and iterate quickly, which speeds up the study of melanoma.

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Technological Advancements

3D printing technology is continuously developing more and more applications for melanoma micromodels. Innovations in printing material, techniques and bioprinting machines are increasing the accuracy and functionality of these models.

• Bioprinting

A type of 3D printing called bioprinting is made using bioinks, made of living cells and biomaterials. This approach allows highly detailed and functional tissue models such as vascularised tumour models to be produced. With the underlying anatomy of melanoma tumours — the assembly of blood vessels and multicellular intermixing — bioprinting can simulate even more fully the tumour microenvironment.

• Advanced Materials

New biomaterials are making 3D printed melanoma micromodels more realistic and functional. Hydrogels, for instance, could mimic the extracellular matrix, a supportive and biocompatible context in which cells could grow and communicate. These can be tailored to the mechanical and biochemical specifications of living tissues to make the models more realistic.

• Integration with Other Technologies

As 3D printed melanoma micromodels are integrated with other technologies, like microfluidics and imaging, they are being used more broadly. Microfluidics can model blood and nutrients circulating through them, giving us a more realistic tumour scene. Newer imaging methods – confocal microscopy and multiphoton imaging – enable the models to be viewed and analysed in fine detail to gain insights into the biology of the tumour and treatment response.

Future Directions

The 3D printed melanoma micromodels are in the pipeline with promising applications and upgrades coming out of research and technology development. Some potential future directions include:

Enhanced Personalization

Genomic technologies and personalized medicine will be able to produce ever more customisable micromodels of melanoma, which are derived from the genetic and molecular uniqueness of the individual tumour. That personalisation will yield better precision and effectiveness for cancer treatments.

Integration with Immunotherapy

Immunotherapy is a fast-evolving cancer therapy, and 3D printed melanoma micromodels can be essential to the development of it. If immune cells are incorporated into the models, scientists can analyse the relationship between the tumour and the immune system, tailoring immunotherapies and finding novel targets for treatment.

Collaborative Research

The manufacture and use of 3D printed melanoma micromodels will require collaboration among researchers, clinicians and industry. Collective studies can move these models from the bench to the clinic at a faster pace, with improved patient care and in the forefront of melanoma research.

Conclusion

Micromodels of melanoma that can be 3D printed are a revolution in cancer research with many advantages over standard models. They are biologically relevant, predictive and morally and practically useful – a real boon to research the biology of melanoma and the potential for new treatments. The advances in technology will make these models ever more valuable in personalized medicine and in the discovery of novel cancer therapies that ultimately will improve patient outcomes and help us to better understand this multifaceted disease.

Reference

1. Bourland J, et al.; Tissue-engineered 3D melanoma model with blood and lymphatic capillaries for drug development. Sci Rep. 2018, 8(1):13191.