Ailene Edwards fights cancer with a bioprinter.
Edwards, a third-year biomedical engineering student at the University of Virginia, does so as the recipient of a Harrison Undergraduate Research Fellowship. Harrison Grants pay up to $4,000 for a student to engage in a research project, with an additional $1,000 for a faculty mentor guiding the research.
“The human body is extremely complex, and the way cancer cells grow, divide and metastasize is regulated by several factors,” Edwards said. “In traditional 2D cell culture, in which cells are grown on plastic dishes, it is difficult to capture the influence of factors such as other cell types, the proximity of the tumor to blood vessels, and the extracellular matrix.
“Bioprinting offers a way to generate a 3D model of a tumor that is reproducible and better mimics the conditions found in the human body. Our model places cancer cells in a nucleus inside a shell of other cell types such as fibroblasts, a type of connective tissue cell, and endothelial cells, or blood vessels.
The model can be used as a platform for future cancer research, Edwards said, such as studying how low oxygenation or growth factors influence cancer cell migration in the 3D tumor.
Edwards, of Blacksburg, is currently bioprinting with a human pancreatic adenocarcinoma cell line.
“They are called HPAF-II cells and are classified as an immortalized cell line,” she said. “They can be purchased through the American Type Culture Collection. However, in the future and depending on the use of the model, it may be possible to print with cancer cells derived from patients. For example, if a tumor is biopsied, these cells could be used in the construct.Afterward, doctors could develop a personalized treatment plan for the patient based on how the cancer cells in the model behave in response to chemotherapy treatments.
Bioprinting can give doctors better insight into how cancer cells grow and respond.
“Bioprinting will allow us to create reproducible models of tumors where specific cell types can be positioned relative to each other in ways that mimic real tumors,” said Matthew J. Lazzara, associate professor of chemical engineering. , in whose lab Edwards works. “We believe that the architecture of the tumor may influence its progression.”
So how do these biological models work? Using nozzles or printing needles, the cells are extruded in the form of “bio-inks” which are a combination of the cells used and biomaterials such as gelatin and alginate. Gelatin comes from pork, while alginate comes from brown algae, usually biocompatible substances. The models are tiny – around 1 millimeter in radius and less than 1 millimeter in height.
“Tumors in the body have a wide range of sizes, but can be in the range of centimeters to inches,” Edwards said. “Our models are reduced in size compared to these tumors.”
The lab team is still working on achieving a stable core-shell construct, so they don’t yet have data on how the surrounding cells affect the cancer cell.
“One of the main goals of the project is to be able to consistently generate a stable, bioprinted construct of three cell types,” Edwards said. “To this end, we have identified cell types that are more resilient during the bioprinting process and the subsequent incubation period. We also optimized the consistency and composition of the bioprint ink, and evaluated how to visualize the location of cells in the construct.
During the research process, the team changed the types of cells used, the temperature at which the bio-ink is extruded, and added a step to cool it.
“The protocol changed in response to the instability of early builds,” Edwards said. “We changed the consistency of the ink to improve the immediate stability of the constructs after they are extruded. Originally, the ink was too liquid and the constructions degraded quickly. These changes have definitely improved the bioprints, but there is also more work to be done.
Lazzara said the student’s current work will have an impact as technology improves.
“She is working to develop a robust printing protocol that yields reproducible printed constructs so that we can start asking biological questions with the constructs,” he said. “We have benefited from collaborating with colleagues at other institutions who do, and we have unique applications in mind – for example, to study the role of epithelial-mesenchymal transition in tumor progression.”
“We started trying to develop our own protocols, but we are now working to replicate a result developed by colleagues elsewhere that is published,” Lazzara said. “However, just because the protocol is published doesn’t make it so easy to replicate the result.”
Despite the complexity of the research and the difficulties it encountered, Edwards developed the confidence to continue.
“At first I was intimidated by the scale of the project and the amount of information I needed to know,” she said. “I was afraid of making a mistake or failing in some way. Through this research, I learned that mistakes are inevitable and you can never know everything or anticipate everything. I have learned that it is absolutely necessary to ask for help and take advantage of the resources available to you.
Edwards’ interest in this technology began years ago at Blacksburg High School.
“I discovered bioprinting in high school and was fascinated by the potential of this emerging field to improve medical research and procedures,” she said. “I was extremely lucky that when I was considering joining a lab, the Lazzara lab had an opening.”
Edwards was also introduced to the complexity of research and the processes involved.
“While doing this research, I was surprised to learn of the magnitude of the work that even precedes the idea of publishing a scientific paper,” she said. “Research never goes as planned, and behind a section of finalized results are countless failed experiments and weeks spent troubleshooting.”
Lazzara said he liked having Edwards in his lab.
“Ailene is very driven and diligent,” he said. “She’s creative and she operates with ease in a lab full of graduate students. It is a real pleasure to work with her. »
A member of the Jefferson Literary and Debating Society, Edwards has worked on the Spectra Research Journal and volunteered at The Haven, a homeless day shelter in Charlottesville. A Rodman Scholar, she received an Academic Excellence Award for students who demonstrate leadership and character while overcoming personal challenges, and a Virginia Space Grant Consortium STEM Bridge Undergraduate Scholarship for sophomores.
Edwards plans to attend medical school or graduate school.