Pioneering 3D printing to advance pediatric cancer research

In the race to solve the world’s most pressing health crises, innovation isn’t a luxury — it’s a necessity. Scientific breakthroughs emerge at the intersection where innovation meets urgent public health challenges because complex problems require unconventional solutions. Today’s biomedical researchers leverage technological capabilities in new and imaginative ways — just look at 3D printing.

3D printing originated in 1981 in Japan. Hideo Kodama developed the technique by creating a rapid prototyping machine that built objects by layering a light-sensitive polymer and curing it with ultraviolet (UV) light. Since then, 3D printing technology has evolved, with numerous innovations in techniques and materials that create physical objects directly from digital models. Now, it is widely used in fields such as prototyping, manufacturing and custom product design. While many 3D printer types exist, the most common models typically use materials such as plastic, steel, aluminum, ceramic and copper to construct solid objects.

3D printing has revolutionized the way we design and create. 3D printers use a simple starting material to produce everything from mundane objects to cutting-edge inventions. What began as a niche technology has evolved into a $20 billion industry, primarily focused on manufacturing products and creating product models across a wide range of industries.

At St. Jude, scientists are leveraging 3D printing technology for laboratory research by creating methods to print biomaterials, focusing on recreating pediatric solid tumors within their surrounding microenvironments.

Seeking a solution to a sophisticated struggle

Rhabdomyosarcoma (RMS) is a solid tumor that develops in soft tissue and mimics poorly differentiated muscle cells. RMS can occur in various locations, including the head and neck, urinary and reproductive organs, and limbs, and is highly malignant due to its rapid growth and potential to metastasize.

Anand Patel, MD, PhD, St. Jude Department of Oncology, is focused on treating challenging RMS solid tumors, particularly sarcomas that develop in soft tissue and bone, which then spread to the lungs. 

“One of the things that has always fascinated me about this class of tumors, called sarcomas, is that they develop in soft tissue or bone and tend to metastasize to the lungs,” said Patel. “These are two very different environments — bone and muscle are dense, rigid tissues, while the lungs are soft and compressible. I’ve always wondered how these tumor cells can adapt and survive such a dramatic environmental shift.” 

To date, most knowledge regarding the biology of RMS comes from cell lines cultured in two dimensions on flat, hard polymer surfaces called tissue culture flasks. While easily replicable and cheap, these conventional cell cultures have significant drawbacks. These methods may inadvertently push cells into an environment that doesn’t accurately reflect their natural conditions.

In contrast, animal models of RMS better replicate the heterogeneity of tumors but are slow, expensive and limited in how many models researchers can create. “Traditionally, we’ve studied this using animal models, but results can vary greatly and take a long time. I wanted a more controlled laboratory approach to examine how the density and stiffness of materials affect tumor cell growth,” said Patel. 

To overcome these limitations, the Patel lab is developing biomimetic 3D models that preserve the intratumoral heterogeneity of RMS. These models allow researchers to answer questions regarding the role of the physical properties of tissues and the microenvironment on tumor cell growth, resistance and migration. 

3D BIOprinting 

Using the Rastrum™ Instrument by Inventia Life Sciences, a technology company headquartered in Australia, the Patel lab has applied the concept of 3D printing to cancer biology research. The Rastrum™ is a commercially available “plug-and-play” instrument for implanting cells into a specialized matrix. It allows researchers to “print” tumors and cellular microenvironments and control the amount of mechanical stress on the cells by adjusting the cross-linking degree. 

“When people think of 3D printing, they often imagine cool shapes and designs, but that’s not how this instrument works,” explained Patel. “Instead, it combines cells and a matrix. This matrix contains peptides that mimic the microenvironment of real tissues, such as skin, muscle, liver or lung. When the cells contact the matrix, they coalesce together.

“We’ve collaborated closely with the company that makes this printer to develop protocols and understand how the instrument can be used in real lab settings — exploring applications that they hadn’t initially anticipated,” he said. 

Elisabet Olsen, PhD, Department of Oncology, a postdoc researcher in the Patel lab, has a background in biomedical engineering, and her previous expertise has contributed significantly to this project. “One of our first experiments focused on optimizing the parameters for our cells and experiments,” she said. “This printer offers high throughput with minimal user error, as it’s driven by the machine software rather than manual input.”

Out-of-the-box innovation 

When asked about his approach to innovation, Patel attributes his openness to new ideas to real-life challenges that he’s seen addressed through research, alternative approaches and, sometimes, a bit of serendipity. “It’s easy to keep thinking along the same lines as everyone else, but it’s important to take a step back and ask, ‘Why are we doing this? What are we missing? What assumptions are we making?’” said Patel. This questioning mindset has driven him to set ambitious goals for his research. 

Patel’s laboratory is working to create a lab-grown model of metastatic sarcoma. “We need to understand why these tumors often relapse. It’s heartbreaking to see patients respond well to treatment — only for their tumors to return weeks or months later,” he said. The innovative use of the Rastrum™ Instrument is bringing Patel’s team closer to their goal, advancing understanding of tumor relapse and metastasis.