Our laboratory research today is focused on cancer, biotribology, biofabrication, and biomedicine. A discussion of our past research and where we are today is below.
Cancer Engineering (www.CancerEngineering.org)
After a stage IV metastatic cancer diagnosis in 2013, I looked for opportunities to apply engineering approaches, in situ tools, and modeling to help in cancer research, treatment, diagnosis, and management; I eventually founded a cancer engineering laboratory, where we have developed the infrastructure need to print, perfuse, grow, collect, and study patient derived tumoroids in vitro. Our work with the National Institutes of Health and the National Cancer Institute is focused on glioblastoma multiforme (GBM). Our cancer engineering effort continues to expand, and we have a dynamic team of collaborators from astronomy to molecular biology working together to enable high through screening of drugs, immuno-therapy approaches, and combination therapy to treat this disease.
The importance for 3D in vitro assays is clear, but widespread adoption has been slow due to a lack of tools for 3D culture and the ubiquity of the 2D infrastructure. We are demonstrating the feasibility of in situ 3D studies of immuno-oncology with patient derived tumoroids, immune cells, and pharmacologic agents. Our goal is to accelerate discovery and complement existing high throughput screening of new agents, biologics, and compounds to treat cancer.
Printing Cancer’s End – UF Explore – by Cindy Spence
Tibology is a diverse field of study within Mechanical Engineering focused on surfaces, friction, adhesion, contact mechanics, and lubrication. Our laboratory is predominantly experimental, developing instrumentation to measure the forces, deformations, stresses, topography, contact areas, and surface degradation, with dynamic in situ measurements of the chemical, compositional, and structural evolution and heterogeneity occurring within these buried interfaces. Accessing these seemingly inaccessible interfaces requires creative design and precision engineering to bring complementary measurements into these experiments; we have built instruments with in situ spectroscopy, surface plasmon resonance spectroscopy, optical microscopy, digital image correlation, electron microscopy, interferometry, infrared thermal imaging, electrochemical probes and voltammetry, frustrated total internal reflection, and fluorescence microscopy. Our research is motivated by applications in engineering and biomedicine, with the goal of developing a fundamental understanding of the processes acting within these systems and applying this knowledge to develop new approaches, materials, and novel solutions, which has led to numerous patents on new materials, coatings, and technologies.
Surface Science – UF Explore – by Cindy Spence
The Contact Mechanics Challenge – Cutting Edge – by Tysoe and Spencer
Testing the da Vinci Codex – Cutting Edge – by Tysoe and Spencer
The Tribology of Jurassic Park – by Alisson Clark, Cindy Spence, and Dr. Gresham
How Many Licks? – Cutting Edge – by Tysoe and Spencer
Soft Matter Engineering
Soft matter engineering lies at the intersection of the fields of health and engineering. At the very frontier of healthcare today is the need for customized treatments tailored to the individual. The vision of this research is to establish a new field of engineering that enables the design, fabrication and use of precision 3-dimensional (3D) instrumented soft matter platforms for cancer research, treatments, therapeutic regimens and management. We envision that this convergence of health and engineering is poised to enable a transformation in the health industry within the next decade. The goals are to develop the foundational engineering and scientific principles around the design, realization, and use of complex, 3D, soft-matter systems. The recent breakthrough at UF in 3D fabrication using a liquid-like solid medium enables a scalable and economical approach to realize any conceived geometries with soft materials, including living cells, hydrogels, and silicones.
The significant engineering challenges in this research cross numerous boundaries and disciplines, and success requires an integrated approach and infrastructure to foster convergence across engineering, science, and medicine. Fundamental barriers include linking experiments and computation; managing transport in 3D cell culture; breaking the speed vs. precision barrier in fabrication; and the 3D integration of photonics and electronics in soft matter.
Nano-composites and Space
Our laboratory was among the first to demonstrate the potential of nanoparticles to dramatically improve the tribological properties of polymeric materials, a discovery that has led to a vibrant community of researchers across disciplines studying and developing polymeric nanocomposites for tribological applications. By 2004, this work led to an AFOSR MURI project (PI: Sawyer) with a multidisciplinary team of scientists and engineers focused on developing nanocomposites for air and space applications. At the conclusion of this program, we had a wide range of candidate materials and were given the opportunity to design, build, and remotely operate 8 tribology instruments on the International Space Station under exposure to Low Earth Orbit conditions for a year and half (STS129 11/2009 – STS134 6/2011). This unique opportunity allowed us to accelerate the adoption of these materials, by demonstrating their performance in space; ultimately, these data were used to qualify the materials for use on spacecraft and high-altitude aircraft. The cryogenic temperatures experienced in space represents a major obstacle to aerospace designers. Our discovery of thermally activated friction, as well as theoretical studies and nanoscale measurements demonstrating the phenomena provided the necessary fundamental understanding to change deployment and mission operational schedules to improve reliability and operation of moving mechanical assemblies on orbit.
Many of our ultra-low-wear polymer nanocomposites are based on fluoropolymers (PTFE/Teflon™), which provided a testbed in which we could explore the physics, chemistry, and mechanics of fragile interfaces that provided resilient low friction with nearly immeasurable wear. Using in situ techniques, molecular dynamics simulations, and over a decade of effort, we were able to unravel the fundamental processes leading to this exceptional behavior; unexpectedly, for a material considered among the world’s most inert plastics, the key was mechanochemistry. PTFE based composites could be made ultralow wear by stabilizing wear debris through the formation of carboxylic acid end-groups during chain scission and the subsequent chelation of these chains to the countersurfaces; the result was a soft polymeric film that was continuously fracturing (providing low friction) and self-healing (providing low wear). This fundamental understanding enabled a whole new range of high performance tribological materials to be developed using a wide range of functional nanoparticles.
Fighting Friction – Chemical and Engineering News
Ultralow Wear PTFE Experiments on the International Space Station – Space. com
Biotribology and Fragile Interfaces
These fragile resilient interfaces discovered in polymer nanocomposites, were nearly the perfect description of the mechanisms controlling lubricity of biological interfaces from cartilage to mucinated epithelial tissues. Using in vitro epithelial cell models, in situ fluorescence microscopy, rheology, and a suite of fluorescence assays, we developed a fundamental understanding of the biotribological mechanisms enabling gel spanning networks to provide lubrication and protection to the underlying cells. This work evolved into studies of cell mechanics that ultimately linked direct contact shear stresses to the production of pro-inflammatory cytokines, and at higher levels of shear stress, apoptosis (programmed cell death). In the context of ocular tribology this work has laid the foundation for understanding of the immunological tone and sterile inflammation in the eye. Our work in aqueous gels has demonstrated that the friction coefficient of self-mated (Gemini) gels scales inversely with polymer mesh-size and the shear stress scales inversely with mesh-size cubed. This fundamental understanding has led to patents on the development of hydrogels and solutions to control friction for bandages and contact lenses. This work in Biotribology has led to the development of numerous hydrogel-based contact lenses that have high water content surface gel layers to return shear stress to physiological levels and reduce contact lens discomfort.