A University of Virginia researcher has received a five-year, $2.1 million National Institutes of Health grant to develop advanced laboratory tissue models that could improve drug testing, deepen scientists’ understanding of disease and reduce the need for animal testing.
Steven R. Caliari, associate professor in UVA’s departments of Chemical Engineering and Biomedical Engineering, received the grant through the NIH’s Maximizing Investigators’ Research Award program.
Caliari’s lab develops hydrogels – water-rich materials designed to mimic the physical properties of living tissues. By re-creating key features of tissues in the laboratory, researchers can better understand how cells sense and respond to mechanical cues – such as the degree to which the tissue is stiff or soft or elastic – that affect health and disease.
Tissues have properties of both solids and liquids while displaying complicated time-dependent properties that are difficult to re-create in engineered materials. We’re leveraging a technology that allows us to use light to make versions of these hydrogels that mimic tissue mechanical heterogeneity.”
Steven R. Caliari, Associate Professor, UVA’s departments of Chemical Engineering and Biomedical Engineering
The research addresses a major challenge in biomedical science: understanding how cells behave within complex tissues without relying exclusively on animal studies. While animal models can capture the full complexity of a biological process, they can make it difficult to determine exactly which factors are driving cellular changes.
More realistic tissue models
Caliari’s hydrogels can be designed to zoom in on specific mechanical traits, like stiffness or softness, to study their effect on surrounding tissue.
“From an engineering perspective, we want to say, ‘This factor led to this change in cell behavior,'” Caliari said. “You need these simplified reductionist systems to do that.”
The project will focus on fibroblasts, connective-tissue cells that play a critical role in wound healing but can also drive harmful scarring. When fibroblasts become overactive they produce excessive scar tissue through a process, known as fibrosis, that can cause organs to stiffen and lose function. Fibrosis contributes to diseases affecting the lungs, kidneys, heart and other organs.
The grant supports three interconnected research themes aimed at building more realistic models of human tissues, Caliari said. The first will create hydrogels that more accurately reproduce the mechanical complexity and heterogeneity of living tissues. The second will examine how fibroblasts communicate with immune cells during the scarring process and how tissue mechanics influence those interactions. The third will combine the hydrogels with advanced light-based 3D bioprinting techniques to create tissue models that more closely resemble the architecture of human organs.
Caliari said UVA provides an ideal environment for the work, bringing together expertise in hydrogel design, fibrotic disease, cell interactions and emerging alternatives to animal testing. The project also funds graduate positions and includes collaborations with biomedical engineering faculty members Dan Abebayehu and Chris Highley.
“This is a good example of the type of research ecosystems that thrive at UVA,” Caliari said. “There are a lot of people working in this general area, and they are trying to get away from animal models to instead develop in vitro models that more accurately capture human disease. My work fits in nicely with that.
“If successful, the work could produce a versatile toolkit for building realistic laboratory models of human tissues. The team is also working to scale the technology using high-throughput formats that allow researchers to test many experimental conditions simultaneously.
Such a toolkit could allow researchers to evaluate therapies in laboratory models that more closely reflect individual patients, improving research while reducing dependence on animal testing.
“What we’re hoping to do is reduce that animal burden,” Caliari said. “If we design these materials in the right way, we can study therapeutic approaches in a patient-specific way.”
MIRA grants are different
The Maximizing Investigators’ Research Award is notable both for the nature of the funding and because it is Caliari’s second grant under the program. Rather than a single study, MIRAs support the recipient’s research program, providing steady funding and freedom to explore their scientific vision within a broader framework than a project-based grant allows. Caliari’s new MIRA builds on his first one, which recognized his potential as he was establishing his lab at UVA.
“The flexibility of a MIRA makes it uncommon, desirable to have, but also very competitive,” said Olsen Professor and chemical engineering chair Ayman Karim. “To get one is impressive. The second is truly a validation of the importance of Steven’s research and what the NIH thinks of its benefit to society.”
