Bi-disperse multiple particle tracking microrheology

Graduate students: Matthew Wehrman (PhD ’18) and John McGlynn (PhD, expected ’22)

Collaborator: Seth Lindberg (Procter & Gamble Co.)

Publication: M. D. Wehrman, S. Lindberg and K. M. Schultz*, “Multiple particle tracking microrheology measured using bi-disperse probe diameters,” Soft Matter, 14, 5811 – 5820, 2018.

This work develops a new technique to measure several length scales in a single sample using multiple particle tracking microrheology. Traditionally, MPT uses a single particle size to characterize rheological properties. But in complex systems, MPT measurements with a single size particle can characterize distinct properties that are linked to the materials length scale dependent structure. By varying the size of probes, MPT can measure the properties associated with different length scales within a material. We develop a technique to simultaneously track a bi-disperse population of probe particles. 0.5 and 2 μm particles are embedded in the same sample and these particle populations are tracked separately using a brightness- based squared radius of gyration, Rg2.

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Covalent adaptable hydrogel scaffolds pushed out of equilibrium

Graduate students: Francisco Escobar IV (M. Eng. ’16) and Nan Wu (PhD, expected ’21)

Collaborator: Prof. Kristi S. Anseth (University of Colorado at Boulder)

Publications: N. Wu and K. M. Schultz*, “Microrheological characterization of covalent adaptable hydrogels for applications in oral delivery,” submitted

F. S. Escobar IV, D. D. McKinnon, K. S. Anseth and K. M. Schultz*, “Dynamic Changes in Material Properties and Degradation of Poly(ethylene glycol)–Hydrazone Gels as a Function of pH,” Macromolecules, 50, 7351–7360, 2017.

Covalent adaptable hydrogels (CAHs) mimic aspects of the native extracellular matrix cells experience in vivo due to their ability to physically adapt to their environment. The goal of this work is to measure the evolution of covalent adaptable hydrogel scaffolds, including the rheological properties and microstructure, and quantitatively link this to material function to inform the design of these scaffolds for specific biological applications. This work characterizes a covalent adaptable hydrogel developed in the Anseth group, that mimics muscle and neuronal tissue. These CAHs are made from multi-arm poly(ethylene glycol) (PEG) molecules that form reversible bis-aliphatic hydrazone bonds. This unique chemistry creates a material that yields when stress is applied and reforms covalent bonds once stress is released creating an environment that cells can survive in and responds dynamically to cytoskeletal tension during basic cellular processes. The bonds ability to break and rearrange is not only dependent on applied shear but also depends on pH, elastic moduli and equilibrium constants.

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Understanding how mesenchymal stem cells controllably remodel their environment

Graduate students: Maryam Daviran (PhD, expected ’20) and John McGlynn (PhD, expected ’22)

M. Daviran and K. M. Schultz*, “Characterizing the dynamic rheology in the pericellular region by human mesenchymal stem cell re-engineering in PEG-peptide hydrogel scaffolds,” Rheologica Acta (Novel Trends in Rheology),, 2019.

M. Mazzeo, T. Chai, M. Daviran and K. M. Schultz*, “Characterization of the kinetics and mechanism of degradation of human mesenchymal stem cell-laden poly(ethylene glycol) hydrogels,” ACS Applied Bio Materials, 2, 81 – 92, 2019.

M. Daviran, S. M. Longwill, J. F. Casella and K. M. Schultz*, “Rheological characterization of dynamic remodeling of the pericellular region by human mesenchymal stem cell-secreted enzymes in well-defined synthetic hydrogel scaffolds,” Soft Matter, 14, 3078 – 3089, 2018.

M. Daviran, H. S. Caram andK. M. Schultz*, “Role of cell-mediated enzymatic degradation and cytoskeletal tension on remodeling of material microenvironments prior to motility,” ACS Biomaterials Science and Engineering,4, 468 – 472, 2018.

K. M. Schultz*, K. Kyburz and K. S. Anseth*, “Measuring dynamic cell–material interactions and remodeling during 3D human mesenchymal stem cell migration in hydrogels,” PNAS, 112, E3757-E3764, 2015.

Human mesenchymal stem cells (hMSCs) are critical players in wound healing. During wound healing, hMSCs are called to the wound by chemical cues in the environment. In response, they migrate out of their niche and traverse mechanically distinct microenvironments to reach the wound. At the injury, they are active in all phases of healing, regulating inflammation. hMSCs can also restart stalled healing in chronic wounds. To enhance wound healing, implantable synthetic hydrogels are designed to mimic in vivo microenvironments to deliver hMSCs and provide structural integrity to the surrounding tissue. It is still not understood how cells re-engineer their microenvironments during motility and how the microenvironment influences cellular degradation strategies. Our approach uses a combination of bulk rheology and passive microrheology to characterize the bulk material integrity and pericellular region during cellular remodeling and degradation in a synthetic hydrogel scaffold. The goal of this work is to identify the spatial and temporal rheological evolution of hydrogel scaffolds in response to cell-mediated degradation to determine the viability of these materials as implantable scaffolds that enhance wound healing.

Video created by Nicolle Fuller, Sayo Studio

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Characterization of heterogeneous colloidal gel systems

Graduate students: Matthew Wehrman (PhD ’18) and Shiqin He (PhD, expected ’22)

Collaborator: Seth Lindberg (Procter & Gamble Co.)

Publications: M. D. Wehrman, S. Lindberg and K. M. Schultz*, “Multiple particle tracking microrheology measured using bi-disperse probe diameters,” Soft Matter, 14, 5811 – 5820, 2018.

M. D. Wehrman, M. J. Milstrey, S. E. Lindberg and K. M. Schultz*, “Combining microfluidics and microrheology to determine rheological properties of soft matter during repeated phase transitions,” Journal of Visual Experiments, 134, e57429, 2018.

 M. D. Wehrman, S. E. Lindberg and K. M. Schultz*, “Impact of shear on the structure and rheological properties of a hydrogenated castor oil colloidal gel during dynamic phase transitions,” Journal of Rheology, 62, 437 – 446, 2018.

 M. D. Wehrman, M. S. Milstrey, S. Lindberg and K. M. Schultz*, “Using μ2rheology to quantify rheological properties during repeated reversible phase transitions of soft matter,” Lab on a Chip, 17, 2085-2094, 2017. Selected as a HOT article (top 10%)

 M. D. Wehrman, S. Lindberg and K. M. Schultz*, “Quantifying the dynamic transition of hydrogenated castor oil gels measured via multiple particle tracking microrheology,” Soft Matter, 12, 6463-6472, 2016.

Colloidal gels play a vital role in the stability of commercial products, such as shampoo and laundry detergent. The structure and properties of colloidal gels is dramatically changed by environmental conditions and these changes can cause decreases in shelf life and unexpected performance of the product. The goal of this work is to traverse the environmental parameter space creating a toolbox of measurement and analysis techniques that quantify dynamic colloidal gel rearrangement, degradation and heterogeneity to enhance product design, development and manufacturing.

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Polymeric gel characterization above the overlap concentration

Graduate student: Matthew Wehrman (PhD ’18)

Publications: H. Zhang, M. D. Wehrman and K. M. Schultz*, “Structural changes in polymeric gel scaffolds around the overlap concentration,” Frontiers in Chemistry (Rising Stars collection), doi: 10.3389/fchem.2019.00317, 2019.

M. D. Wehrman, A. Leduc, H. E. Callahan, M. S. Mazzeo, M. Schumm and K. M. Schultz*, “Rheological properties and structure of step- and chain-growth gels concentrated above the overlap concentration,” AIChE Journal (Futures series),64, 3168 – 3176, 2018.

Cross-linked gels have played a significant role in enhanced oil recovery. These materials are used to decrease permeability in high permeability zones near naturally fractured carbonates that require water shutoff but cannot be permanently plugged. The goal of this work is to establish a fundamental understanding of how the interplay between polymeric interactions and cross-linking changes assembly, final structure and properties and overall stability of the gel network. These history-dependent systems are monitored during gelation to establish a quantitative framework to understand how polymeric interactions, i.e. overlap and entanglement, within macromer solutions change the gelation reaction and influence final material properties in chain- and step-growth systems. A combination of bulk rheology and microrheology is used to determine the critical values of these gels during phase transitions and the final material properties.

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