Madhuri Dey, courtesy of the Ozbolat Lab/Penn State
A scanning electron microscopy image shows a breast cancer cell (cyan) being attacked by T cells (red), which were engineered to recognize the cancer cells.
Researchers at Pennsylvania State University have successfully 3D bioprinted breast cancer tumours and treated them in a new study to better understand the disease that is one of the biggest killers worldwide.
The university says that this is a scientific first and will lay the foundation for precision fabrication of tumour models.
The researchers believe the advancement will enable future study and development of anti-cancer therapies without the use of “in vivo” or “in animal” experimentation.
“This will help us understand how human immune cells interact with solid tumours,” said Ibrahim Ozbolat, Professor of Engineering Science and Mechanics, Biomedical Engineering and Neurosurgery at Penn State, senior author of the study. “We’ve developed a tool that serves as a clinical test platform to safety and accurately evaluate experimental therapies. It is also a research platform for immunologists and biologists to understand how the tumour grows, how it interacts with human cells, and how it metastasizes and spreads in the body.”
Ozbolat’s lab specialises in 3D printing to create a range of tissues for use in human health.
The researchers used a technique called aspiration-assisted bioprinting to precisely locate tumours in 3D and create the tissue. The tissue was then formed into a multi-scale vascularised breast tumour model with blood vessels, which they then discovered responded to chemotherapy and cell-based immunotherapeutics.
To validate the accuracy of the tumour model, the team treated it with doxorubicin, an anthracycline-based chemotherapeutic drug commonly used for treating breast cancer. After discovering the bioprinted tumour responded to chemotherapy, a cell-based immunotherapeutic treatment was tested on the tumour, working with Dr. Derya Unutmaz, an immunologist at Jackson Laboratory.
The researchers used human CAR-T cells that had been engineered via gene editing to recognise and fight an aggressive form of breast cancer cells. The CAR-T cells were circulated through the tumour for 72 hours, after which the researchers discovered that the cells with the bioprinted tumour had generated a positive immune response and were fighting off the cancer cells.
“Our model is made from human cells, but what we make is a very simplified version of the human body,” Ozbolat said. “There are many details that exist in the native microenvironment that we aren’t able to replicate, or even consider replicating. We are aiming for simplicity within complexity. We want to have a fundamental understanding of how these systems work – and we need the growth process to be streamlined, because we don’t have time to wait for tumours to grow at their natural pace.”
Patrick Mansell/Penn State / Penn State. Creative
According to Ozbolat, despite remarkable advances in cancer treatment, there are a lack of pre-clinical platforms for studying experimental anticancer agents. He explains that relying on clinical trials to test the efficacy of treatments limits the successful clinical transition of anti-cancer therapeutics. Ozbolat believes that developing bioprinted models could open the door to entirely new ways of understanding the tumour microenvironment and the body’s immune response.
Ozbolat and his colleagues are now working with tumours removed from actual breast cancer patients. The researchers will apply immunotherapeutics to patient-derived tumours to see how they respond.
“This is an important step in understanding the intricacies of the disease, which is essential if we are going to develop novel therapeutics and targeted therapies against cancer," said Ozbolat.
In August 2022, a team of researchers at Penn State developed a granular hydrogel bioink that was said could expand possibilities for tissue bioprinting, with a lead member of the team being recognised as the Advanced Materials' ‘Rising Star’ for the work. You can read about other uses of 3D printing at Penn State here.
Dr. Jia Min Lee and Dr. Wai Yee Yeong from Nanyang Technological University in Singapore wrote for TCT earlier this year, explaining 3D bioprinting and what could potentially be achieved in the future with the technology.
