Becca Huber, a PhD candidate in Chemical Engineering, wants to make it easier to get accurate information about human health. Currently, most medical drugs are developed using 2D plastic models that are inexpensive but do not effectively mimic human tissue. Animal models are more accurate, but still are not human, and are much more expensive, preventing comprehensive use in drug development efforts.
Huber is working in Dr. Shelly Peyton’s lab to create an alternative 3D model system. This new testing material, depicted above, could adequately and inexpensively mimic human tissue.
Huber’s focus is mimicking the environment of the brain to culture human astrocytes, non-neuronal brain cells that are extremely sensitive to injury and disease. They are creating a new brain-mimicking biomaterial called a hydrogel that would house astrocytes within the microscopic polymer (long chain of repeating units to make one long molecule) matrix. A hydrogel must be able to replicate human brain stiffness and cell binding sites.
The brain-mimicking hydrogel is a combination of both animal models and tissue culture plastic as it contains components of each - synthetic polymers to make the system reproducible and cheap, and human protein segments within the hydrogel give the astrocytes the same cues they would see in the human brain, encouraging them to grow as they would naturally.
Hydrogels are droplet-shaped 10 microliter materials (smaller than a penny) swollen with water, with the polymer matrix giving it its 3D structure. Huber makes about 10-20 hydrogels in a sitting by mixing two chemical solutions. One solution has the long polymer molecules, cells, and cell culture supplements in water which allows cell growth with a defined set of conditions. The other is a saltwater solution which prevents cells from rupturing and includes a shorter polymer which acts as glue and binds the long polymer chains together, forming the matrix.
How quickly the polymers come together, or gel, is determined by acidity, salt, volume ratios, and temperature. Initially, Huber faced a significant challenge in making hydrogels, as the two solutions gelled so quickly upon interacting that the final hydrogel was not well mixed. This impeded Huber’s work; an uneven distribution of liquids meant that the cells did not receive all the cues that mimic human brain tissue.
Huber determined the cause of the mixture issue and identified a solution. The speed at which the solution solidified had to be slowed to allow enough time for the hydrogel to mix. Some of these variables (acidity and temperature) are restricted to the range where cells can grow. But experimenting with the other variables still left a large enough design space for Huber to find a combination that could work. Low salt concentration turned out to be crucial.
After having solved the mixture issue, they say they are one step closer to “creating a humanized cell culture system that gives us information accurate to human health and is cheap and reproducible…so that we can still process a lot of potential drug candidates.” Their work could potentially make drug development and testing more efficient and budget friendly.
Huber, an NSF Graduate Research Fellow, says they “love studying these invisible systems and understanding a little bit more each day about how they work.” This passion translates to several scales. They state that “...hydrogels, the human body, human cells, body systems. It's a privilege to be curious and have the resources to explore. It's so exciting!”
Huber plans to incorporate human astrocytes into the hydrogels and study the cells’ reactions to different stressors, using the humanized hydrogels to ask questions about brain injury. Huber says this phase is really exciting because “astrocytes are super interesting...they have very sensitive responses to different injuries…say inflammation, blood infiltration, crush injuries, even stress and aging…most studies so far have been either in 2D cell culture or in animal models”.
They are also interested in studying the impact of neurodegenerative diseases like Alzheimer's and Parkinson’s disease on astrocytes using these hydrogels. Huber’s hydrogel mimics brain tissue by incorporating human brain stiffness and cell binding sites from human proteins into the gel. However, these are just two characteristics of the human brain. They remark that no model is perfect, however, progress is possible as shown by Huber’s research and that of other labs all attempting to develop new, humanized drug testing materials. Other labs are working on different brain hydrogel designs using 3D bioprinters and other methods. Different research questions would require other characteristics and a different design.
Huber says the Peyton lab and the University of Massachusetts Amherst are the ideal place for this work, and their experiences there strongly influence their career aspirations. During their undergraduate studies at the University of Delaware, they worked with Dr. April Kloxin to use hydrogels to study breast cancer dormancy. When it came time to consider graduate school, they were interested in hydrogels and found Dr. Shelly Peyton, another expert in the field. They visited UMass Amherst and knew that they “just really loved the whole UMass vibe…people…atmosphere…it felt like home, so it was a pretty easy decision.”
This past summer, Huber interned at BioNTech working on cancer immunotherapy. While they did not work with biomaterials in this role, they say that the different experimental techniques and data analysis skills they have gained through this internship are already benefiting their graduate school research as well. These experiences align with their long-term career aspirations. Huber hopes to combine both their interests in “neuro[science] with astrocytes and immunology and do something in neuroimmunology [which] would just be so cool…” Huber’s research is an example of how solving puzzles could lead us to achieving the bigger picture of adequate, inexpensive, and efficient medicine testing materials.
Written by Timothy Nsubuga, PhD student in Civil Engineering, as part of the Graduate School's Public Writing Fellows Program.