Bioengineering in vitro tumor models with Dr Annalisa Tirella

Written by Annalisa Tirella

In this interview with Dr Annalisa Tirella (University of Manchester, UK), Dr Tirella discusses recent work involving 3D printing tumor in vitro models for breast and prostate cancer, as well as how this work could translate for the study of different diseases.

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I am Annalisa Tirella, Lecturer at the University of Manchester (UK). 

My current research focuses on the manufacturing of nano- and micro-technologies, an interest that started during my research in biomaterials and 3D manufacturing during my Masters at the University of Pisa (Italy). I continued this research throughout my PhD studies, during which I developed one of the first 3D printing systems. Within the PhD project, I investigated different ways to print soft matters – I was one of the pioneers working with bioinks and the 3D printing of living mammalian cells at that time. I received my PhD title in 2011 from the University of Rome Tor Vergata (Italy). 

In the last 5 years, I have been focusing on the manufacturing of microspheres rather than 3D constructs and basically still researching bioinks and their formulations for biomedical applications. The manufacturing of micro beads is the first step for the printing of more complex 3D shapes and scaffolds for biomedical applications and cancer research.

I moved to Manchester in 2014, when I also started to research nanoparticle formulations for drug delivery. My research team is now focusing on two areas of research: the manufacturing of nanotechnologies for targeted drug delivery using microfluidic systems and the development of engineered 3D in vitro systems. Within the latter research area, we are modifying hydrogels to mimic and control biophysical properties of the extracellular matrix of several tissues, both normal and diseased. 

Could you tell us about any current (or recent) projects?

As I previously mentioned, my team focuses on two areas of research. Currently, we are using microfluidic systems to manufacture nanoparticles and control their properties. The ultimate goal is to obtain nanotechnologies able to release and deliver a drug in a specific site of the body. 

Also, we are working on research projects focusing on the engineering of 3D in vitro tumor models, aligning with the University of Manchester beacons, ‘advanced materials’ and ‘cancer’. It is within these research projects that we optimising bioink formulations and using 3D printers to develop 3D in vitro models.

We are working to understand which are the physical and chemical properties of the tumour microenvironment to include in biomaterials in order to develop more relevant in vitro models”

The main interest within the cancer research area is to control the mechanical properties of hydrogels independently from the protein content, two factors known to direct tumor progression. The aim is to develop 3D in vitro models that are able to recapitulate the progression of cancer, from early to the latest stages of cancer when metastasis is formed.

How are 3D printing and bioprinting technologies involved with your group’s work? 

We are continuously working on the formulation of bioinks that can be printed in order to manufacture 3D scaffolds. As said earlier, these 3D models are engineered to combine several biophysical properties present in the tumor microenvironment.

I keep saying to my students that life is not flat and we are not static, so we need to raise the standard or the classic traditional tissue culture plate that are very stiff and flat and don’t move and try to engineer the system.”

We always investigate how to improve bioinks and are trying to mimic also the dynamic remodelling processes of the extracellular matrix.

An essential need for new developed bioinks is the possibility to include living cells that can be 3D printed in a 3D construct, then proliferate and secrete all the relevant and typical components of human extracellular matrix. 

3D printing technologies are essential for our research and within my group we believe they are key to bring our research to the next level. 

I think 3D models will then help in answering many relevant biological questions and fill the gaps in understanding early and late stages of diseases.”

What challenges with bioengineering tumor in vitro models do 3D printing and bioprinting technologies help to overcome? 

I think that as a bioengineer, it is important to influence and inform 3D printing technologies and identify new ways for printing biomaterials and cells.”

One of the main challenges in 3D printing of hydrogels is the control of size and shape of the final 3D printed structure, as well as the viability and functionality of printed cells.

Another challenge is the control over the material properties and their dynamical modification over time, mirroring what happens in biological systems.

When engineering 3D tumour models, we need to have control over materials properties and architecture – bioprinting and material science have to work side-by-side to find the sweet spot where we have better control over these models.”

We believe that with a greater control on both the material properties and 3D architecture we will be able to provide more relevant models to cancer biologists.

How do you see your work translating into the medical field? How long do you think it might be before we see personalized tumors for strategic treatment planning in practice? 

That’s a very hard question to answer.

What I can tell you is that we are currently planning some exciting research in this area and we have already achieved really promising results. Unfortunately, I cannot disclose any details of this project, performed in collaboration with research groups both in the UK and abroad. These projects hold really high potential to develop high throughput systems, informing the medical field and providing more personalized treatments for patients in the next (hopefully) 5 years. 

What’s next with your research? What should we be looking out for?  

As I mentioned, we are running really exciting research on solid tumors, focusing on breast and prostate cancers. We are about to start new research projects with emphasis on how these material-based nanoformulations are going to be used for 3D tumor models probably within the next 6 months. So that’s where we’re heading, with certainly a lot of 3D printing activities as well! 

We are researching on new strategies to mimic the metastatic process in vitro, recreating the primary tumor site and modelling how the secondary tumor (metastasis) is formed. I cannot disclose more than that!”

Where do you see bioprinting in the medical field in 5—10 years’ time? 

I don’t have a crystal ball to predict it unfortunately, but I can tell you that since I started my PhD, there has been so much improvement in terms of technology as well as material science and research. I believe the optimization of bioinks, biomaterials and printable biomaterials in general is key to this success. 

Translating 3D printing is essential to help in understanding biological processes, improving biomedical and clinical applications.”

I think it is necessary to learn from the past to build the success of 3D printing technology in biomedical applications. I think in the next 5–10 years we will hear about many successful models translated to the clinic. 

Do you have any final comments about medical 3D printing, bioprinting, bioengineering or tumor models you would like to share? 

Interdisciplinary research, working side-by-side with biologists, formulation scientists and bioengineering will develop more relevant and sophisticated 3D in vitro models.” 

I feel we are now at a stage of developing new ideas and bringing 3D printing to the next level. In doing this, we will be able to address many problems and gaps that are present in current research and in different areas. 

I think 3D printing is the technology that can help in directing this sort of research and boost outputs in the biomedical arena. The successful 3D printing of in vitro models including the remodelling of hydrogels that I was discussing before, will help and support improvement in personalized medicine and solving many healthcare problems.

The opinions expressed in this feature are those of the interviewee and do not necessarily reflect the views of 3DMedNet or Future Science Group.

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