Michelle Hernandez Immune Dysregulation During the Progression of Osteoarthritis
Osteoarthritis (OA) is a chronic and progressive degenerative joint disease. OA is characterized by the progressive loss of articular cartilage, changes in the subchondral bone, and inflammation of the synovium tissue. Currently, there are no curative therapeutics available for the disease, only ones to help manage the pain. According to the CDC, OA is the most common joint disorder, with millions of adults in the United States suffering. To understand the immune response during the progression of OA, our research focuses on identifying systemic inflammatory biomarkers concurrent with the progression of the disease in a rat model of OA. In this study, we surgically destabilized the knee via medial meniscal transection (MMT), which ultimately resulted in a degeneration of the cartilage and other tissues of the knee. We measured circulating levels of inflammatory cytokines and immune cells via longitudinal blood draws and characterized joint degeneration metrics via microcomputed tomography. We employed linear and nonlinear multivariate regression techniques to identify immune biomarkers that were correlated with the surface roughness of the articular cartilage at the end point. Early pilot studies demonstrated feasibility of longitudinal monitoring of immune responses in the MMT model of OA. By correlating joint degeneration with systemic immune responses, we hope to identify early immune biomarkers that may be indicative of disease status.
Ireland Johnson Design and Biocompatibility of Hyaluronic Acid Hydrogels for Bone Regeneration
Large bone defects and fractures caused by trauma or disease remain a serious challenge for orthopedic surgeons, and there is a need for more effective treatment strategies to repair injured bone. Bone autografts, a tissue graft from the same patient, are the ideal material to promote a healing response due to low host rejection; however, they can lead to donor site morbidity and are expensive to extract. To combat this problem, biomaterials, composed of the natural polymer hyaluronic acid (HA) can be used to deliver osteogenic (bone-forming) proteins that repair injured bone. This study describes the development of HA-based hydrogels for protein delivery for bone regeneration. HA hydrogels were formed by dynamic, covalent bonds between aldehyde functional groups on oxidized HA and HA functionalized with adipic acid hydrazide or carbohydrazide groups. Hydrogels were seeded with 3T3 fibroblast cells expressing green fluorescent protein to evaluate cell compatibility. Live and dead cells were evaluated using green fluorescence from GFP and red fluorescence from ethidium homodimer, respectively. A combination of oxidized HA and HA-carbohydrazide at 2.5% (w/v) maintained high cell viability (82.3% for all time points) and encouraged a rate of cell growth that surpassed all other conditions. Future expansions of this project could lead to the use of HA hydrogels as a biomaterial that rivals the healing response of bone autografts.
Sahana Krishna Kumaran Old Elastin Haploin sufficient Mice Have Impaired Memory, Motor Coordination and Endothelial Function
Large arteries stiffen due to advancing age and they are associated with cognitive impairment. However, the direct effects of long-term large artery stiffness require further investigation. Therefore, we studied cognitive and cerebral artery function in a model of greater large artery stiffness, the elastin haploin sufficient (Eln+/-) mouse, at old age.
We examined old wildtype (Eln+/+, n=8, 25 mo), old Eln+/- (n=8, 25 mo), and young wildtype (YC, n=9, 7 mo) mice. Memory was tested through the Morris Water Maze (MWM) test and motor coordination was measured through the accelerating Rotarod test. Endothelial function was measured in ex vivo pressurized posterior cerebral arteries (PCAs) by dilation to acetylcholine (ACh).
In the MWM test, old Eln+/- mice crossed the target area fewer times than old Eln+/+ mice (p<0.05), indicating impaired spatial memory. In the accelerating Rotarod test, old Eln+/- mice stayed on the rod for less time than the old Eln+/+ and young mice (p<0.05), suggesting poor motor coordination. Maximal PCA dilation to ACh was lower in old Eln+/- mice compared to old Eln+/+ and young mice (p<0.01), indicating impaired endothelial function.
These results indicate that long-term exposure to large artery stiffness leads to impaired spatial memory, motor coordination, and cerebral artery endothelial function. Future research is needed to study the cellular mechanisms resulting from large artery stiffness.
Albert Yim Wearable Microfluidic Colorimetric Sweat Sensors for Real-Time Personalized Hydration Monitoring
Continuous, real-time sweat analysis is an underdeveloped field with promising applications ranging from clinical health care to athletic performance. Currently, microfluidic devices allow for noninvasive collection and storage of sweat but lack a method to record continuous sweat rates. Sweat rate and biomarker composition are highly variant between individuals, requiring a personalized hydration feedback approach. The biomarker variance is significantly attributed to sweat rate, making rate normalized biomarker concentrations indicative of performance metrics. A low-cost and passive method to record the continuous sweat rate would enable real-time sweat loss measurement and hydration feedback. This proposed project will develop methods to accomplish this through microfluidics and colorimetric reagents. The colorimetric reagent will provide color gradients for physiologically sweat rates ranging from 3 to 34 μL/hour for a collection area of r = 3 mm. Then benchtop studies will create the colorimetric system that is capable of visually quantifying the collected sweat rate in microfluidic devices. This will provide a future opportunity to develop a smartphone app for immediate analysis. Eventually, on-body trials will test the accuracy of the sweat sensor’s analyzed rate. Attaining continuous sweat rates will normalize biomarker concentrations which correlate to health and performance metrics and are highly coveted in the biomedical and sports science communities.
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