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Biomaterials that mimic aspects of the extracellular matrix by presenting a 3D microenvironment that cells can locally degrade and remodel are finding increased applications as wound-healing matrices, tissue engineering scaffolds, and even substrates for stem cell expansion. In vivo, cells do not simply reside in a static microenvironment, but instead, they dynamically reengineer their surroundings. For example, cells secrete proteases that degrade extracellular components, attach to the matrix through adhesive sites, and can exert traction forces on the local matrix, causing its spatial reorganization. Although biomaterials scaffolds provide initially well-defined microenvironments for 3D culture of cells, less is known about the changes that occur over time, especially local matrix remodeling that can play an integral role in directing cell behavior. Here, we use microrheology as a quantitative tool to characterize dynamic cellular remodeling of peptide-functionalized poly(ethylene glycol) (PEG) hydrogels that degrade in response to cell-secreted matrix metalloproteinases (MMPs). This technique allows measurement of spatial changes in material properties during migration of encapsulated cells and has a sensitivity that identifies regions where cells simply adhere to the matrix, as well as the extent of local cell remodeling of the material through MMP-mediated degradation. Collectively, these microrheological measurements provide insight into microscopic, cellular manipulation of the pericellular region that gives rise to macroscopic tracks created in scaffolds by migrating cells. This quantitative and predictable information should benefit the design of improved biomaterial scaffolds for medically relevant applications.

During wound healing, human mesenchymal stem cells (hMSCs) migrate to injuries to regulate inflammation and coordinate tissue regeneration. To enable migration, hMSCs re-engineer the extracellular matrix rheology. Our work determines the correlation between cell-engineered rheology and motility. We encapsulate hMSCs in a cell-degradable peptide-polymeric hydrogel and characterize the change in rheological properties in the pericellular region using multiple particle tracking microrheology. Previous studies determined that pericellular rheology is correlated with motility. Additionally, hMSCs re-engineer their microenvironment by regulating cell-secreted enzyme, matrix metalloproteinases (MMPs), activity by also secreting their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). We independently inhibit TIMPs and measure two different degradation profiles, reaction-diffusion and reverse reaction-diffusion. These profiles are correlated with cell spreading, speed and motility type. We model scaffold degradation using Michaelis-Menten kinetics, finding a decrease in kinetics between joint and independent TIMP inhibition. hMSCs ability to regulate microenvironmental remodeling and motility could be exploited in design of new materials that deliver hMSCs to wounds to enhance healing.

PurposeMeasurement of the viscosity of concentrated protein solutions is vital for the manufacture and delivery of protein therapeutics. Conventional methods for viscosity measurements require large solution volumes, creating a severe limitation during the early stage of protein development. The goal of this work is to develop a robust technique that requires minimal sample.MethodsIn this work, a droplet-based microfluidic device is developed to quantify the viscosity of protein solutions while concentrating in micrometer-scale droplets. The technique requires only microliters of sample. The corresponding viscosity is characterized by multiple particle tracking microrheology (MPT).ResultsWe show that the viscosities quantified in the microfluidic device are consistent with macroscopic results measured by a conventional rheometer for poly(ethylene) glycol (PEG) solutions. The technique was further applied to quantify viscosities of well-studied lysozyme and bovine serum albumin (BSA) solutions. Comparison to both macroscopic measurements and models (Krieger-Dougherty model) demonstrate the validity of the approach.ConclusionThe droplet-based microfluidic device provides accurate quantitative values of viscosity over a range of concentrations for protein solutions with small sample volumes (~ μL) and high compositional resolution. This device will be extended to study the effect of different excipients and other additives on the viscosity of protein solutions.

As community veterinary clinics expand across the United States, there is a growing recognition that services need to be aligned with the specific needs of clients and their companion animals, which may vary from one community to the next. WisCARES Community Clinic, which has served low-income pet owners in Dane County, Wisconsin for over a decade, conducted a comprehensive needs assessment in the summer of 2024 to re-evaluate the support required by its clientele. Through an interviewer-administered survey of 51 clients, conducted either in person or by phone, the study identified key areas for assistance. Clients most frequently reported needing support with pet food, treats, pet cleaning supplies, and dental care items, as well as access to affordable grooming services. In addition, many clients expressed a need for help navigating social services and securing reliable transportation. These findings highlight that clients experiencing poverty require more than basic veterinary care to maintain the health and well-being of their pets. While local contexts vary, this assessment offers valuable insight for other community veterinary programs seeking to allocate limited resources to where they will have the greatest impact.

Service-learning, defined as integrating student education into academically relevant service activities to address a community need, is a way for students to learn and practice multiple skills. WisCARES (Wisconsin Companion Animal Resources, Education and Social Services) is a service-learning clinic in which veterinarians, veterinary nurses, and social workers form an interprofessional team providing a unique educational opportunity within a One Health access-to-care clinic with care for both the veterinary patient and the client. In addition to hands-on experiences in spectrum of care medicine, veterinary students learn about poverty, homelessness, and social determinants of health, and how these impact clients’ decision making and ability to adhere to treatment recommendations. They also work with social workers to understand how moral stress and perfectionism can impact their physical and mental health and develop a self-care plan to address their own stressors. WisCARES’ goal is to help students develop into veterinarians who will be positive additions the profession by recognizing and challenging their own biases, and by consciously integrating access-to-care medicine into their future practice for the wellbeing of their veterinary team and the community they serve.

In 1870, William Jackson Palmer founded the Denver & Rio Grande Railroad with the ambitious goal of constructing a line from Denver to Mexico. While Palmer had extensive engineering and business experience to draw on, he lacked capital. Up to this point, transcontinental railroads had relied on government funding, however, Palmer made the fateful decision to rely on private financing of investors from England, Holland, and elsewhere. This thesis explores the consequences of Palmer’s approach to funding the Denver & Rio Grande. On the one hand, Palmer’s approach allowed him to get his railroad off the ground quickly when the government was starting to curb support and American investors had become hesitant. Palmer’s approach allowed him to have the freedom to be ambitious and attempt to construct a line to Mexico. On the other hand, Palmer’s approach led to mismanagement, lack of funding, overextensions, and persistent construction stoppages. Palmer’s reliance on foreign investors allowed for Colorado to significantly change with the establishment of manufacturing in the region, and with his railroad. However, Palmer ultimately fell short of his main goal and would lose control of his railroad.

Choosing Materials for this Course When undertaking the review of the previous curriculum, staff polled former students regarding their AP experience, reviewed articles and blogs that discussed diversity in reading content, observed how other local groups and libraries made their reading selections, and explored local foundations and organizations that promote opportunities for social justice engagement for young people. What would help them engage in the process of determining how they contribute toward building community? Because the AP exams reflect the \"Canon,\" which is slowly evolving, certain traditional authors and texts, such as More's Utopia, would be kept in the curriculum to keep students competitive. Attending workshops or doing individual research on diversity, inclusion, and representation in the classroom; shadowing experienced teachers; and participating in classes and workshops that enable instructors to explore how to teach more inclusive texts and work through their own implicit bias may help with these issues. Instructors need to beware of dividing their classroom. Because we appear to have such a widely polarized and increasingly hostile political climate, making time to create a safe space to discuss the work, including the fact that some students will experience discomfort, is key.

Biomaterials that mimic aspects of the extracellular matrix by presenting a 3D microenvironment that cells can locally degrade and remodel are finding increased applications as wound-healing matrices, tissue engineering scaffolds, and even substrates for stem cell expansion. In vivo, cells do not simply reside in a static microenvironment, but instead, they dynamically reengineer their surroundings. For example, cells secrete proteases that degrade extracellular components, attach to the matrix through adhesive sites, and can exert traction forces on the local matrix, causing its spatial reorganization. Although biomaterials scaffolds provide initially well-defined microenvironments for 3D culture of cells, less is known about the changes that occur over time, especially local matrix remodeling that can play an integral role in directing cell behavior. Here, we use microrheology as a quantitative tool to characterize dynamic cellular remodeling of peptide-functionalized poly(ethylene glycol) (PEG) hydrogels that degrade in response to cell-secreted matrix metalloproteinases (MMPs). This technique allows measurement of spatial changes in material properties during migration of encapsulated cells and has a sensitivity that identifies regions where cells simply adhere to the matrix, as well as the extent of local cell remodeling of the material through MMP-mediated degradation. Collectively, these microrheological measurements provide insight into microscopic, cellular manipulation of the pericellular region that gives rise to macroscopic tracks created in scaffolds by migrating cells. This quantitative and predictable information should benefit the design of improved biomaterial scaffolds for medically relevant applications. Scaffolds that serve as synthetic mimics of the extracellular matrix have applications in wound healing, tissue engineering, and stem cell expansion. When cells are cultured in these tunable matrices, little is known about local microenvironmental changes during degradation and remodeling. Methods that provide quantitative and predictable information about cell-mediated remodeling could significantly improve the biomaterial design process. We use passive microrheology, a technique that measures rheological properties from Brownian motion of embedded particles, to characterize remodeling of a cell-laden peptide-functionalized poly(ethylene glycol) hydrogel that degrades in response to cell-secreted enzymes. Results show microenvironmental changes at multiple time and size scales, and reveal an interesting degradation gradient, as mesenchymal stem cells attach, spread, and move through these synthetic extracellular matrix mimics.

Canadian wild ginger (Asarum canadense L. [Aristolochiaceae]) is found in a variety of deciduous and moist coniferous forests throughout eastern Canada and the US. Because of the recalcitrant nature of Asarum seeds, we vegetatively propagate this species by divisions under natural shade at the Lake County Forest Preserve nursery in Illinois. This method yields plants suitable for outplanting in 3 y. We also use natural shade under established oak trees for native seed production, and an artificial shade bed system to produce 75 native woodland species found in the midwestern US.

Characterizing the rheological properties of hydrogels is critical in their development for therapeutic applications, such as wound healing and tissue regeneration. Such applications require materials that mimic biological microenvironments suitable for cell attachment, proliferation and motility. The goal of the present work is to develop characterization techniques to measure the rheological properties of biocompatible hydrogelators during gelation, degradation and after equilibration. An emphasis is made on maximizing the amount of rheological information collected while minimizing the sample preparation time and amount of material required. To achieve these goals, we use multiple particle tracking microrheology (MPT) to measure the hydrogel material properties. MPT relies on the thermal motion of probe particles to measure material properties and has emerged as a powerful technique for measuring the rheology of small samples. We begin by describing the characterization of the gelation reaction and composition dependence of gel formation in a poly(ethylene glycol)-high molecular weight heparin (PEG-HMWH) hydrogel. This covalently cross-linked hydrogel consists of a HMWH backbone functionalized with maleimide and a bis-thiol PEG cross-linker. The time dependent gelation reaction of the lowest HMWH functionality (f = 4) and three PEG molecular weights ( Mn 2000, 5000 and 10000) is characterized using MPT. Using time-cure superposition, the superposition of viscoelastic functions at different extents of reaction, the critical gelation time, tc, and critical relaxation exponent, n, are calculated. The critical relaxation exponent decreases as the molecular weight of PEG increases indicating a potential transition from a percolation to vulcanization universality class. The critical gelation time is non-monotonic with the shortest gelation kinetics observed for the 5000 molecular weight cross-linker. High-throughput microrheology is developed to characterize the hydrogel over a large parameter space, consisting of HMWH functionalities (f = 4 − 12), PEG cross-linker molecular weight and total polymer concentration (1 − 8 wt%). Gelation state diagrams are created from 219 rheological samples. The measured percolation transitions are accurately described with Flory-Stockmayer theory. To increase the throughput of the rheological characterization of the hydrogelator 2rheology, microrheology in a microfluidic device, is developed. A novel fabrication method for the device uses soft lithography techniques patterned over a stamp made by polymerization of an ultraviolet curing thiolene resin. The microfluidic device generates 5 L sample droplets in a continuous fluid using a T-junction. Each sample is made with a unique composition resulting in 50−100 samples per device. 2rheology is validated by measuring the rheology of glycerine. Discrete MPT measurements and tabulated data are compared to the 2rheology measurements with good agreement. This technique is used to measure the overlap concentration of HMWH. The measured overlap concentration of 8.1 ± 1.3 wt% agrees with the calculated value 6.5 wt%. A gelation state diagram is recreated with good agreement between MPT samples and Flory-Stockmayer gelation limits. A comparison of 2rheology to high-throughput microrheology shows that using 2rheology 20× more samples are made, 1/3 of the time is required for sample preparation and analysis and 18× less material is required. The PEG-HMWH hydrogel is processed using electrospinning. This highlights the utility of the gelation state diagrams by enabling identification of the appropriate material properties without trial and error experiments. Electrospinning uses electrostatic forces to create fibers that are nano- to micron sized in diameter. All hydrogel samples are spun using polyethylene oxide (PEO) as a carrier polymer. The hydrogel is spun first during the gelation reaction. Stable fiber formation is observed after a viscosity increase but prior to gelation. A weak hydrogel is chosen to spin after equilibration. This hydrogel spins continuously resulting in mats of disordered fibers. Upon dissolution of PEO, a unique porous microstructure is retained indicating that the cross-linking of the hydrogel material leads to a microstructure that is suitable for tissue engineering applications. Hydrogel degradation is monitored using MPT to enable the engineering of the material for tissue regeneration. This is the first investigation to monitor the evolving microstructure while simultaneously measuring material properties. The hydrogel is a poly(ethylene glycol)-low molecular weight heparin (PEG-LMWH) cross-linked with maleimide-thiol chemistry and degraded through hydrolysis. The hydrogel degrades homogeneously, which is quantified using van Hove correlation functions. Reverse time-cure superposition is used to extract the critical degradation time of tc ≈ 700 hours. A first-order kinetic model is derived to describe the relation of the measured steady-state creep compliance as a function of time using the first-order rate constant, mean-squared displacement dynamic scaling exponent and critical degradation time. In all, the present work develops characterization techniques that measure the rheological properties of a hydrogelator during gelation, degradation and after equilibration, facilitating engineering of this material for use in therapeutic applications.