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Human mesenchymal stem cells (hMSCs) are instrumental in the wound healing process. They migrate to wounds from their native niche in response to chemical signals released during the inflammatory phase of healing. At the wound, hMSCs downregulate inflammation and regulate tissue regeneration. Delivering additional hMSCs to wounds using cell-laden implantable hydrogels has the potential to improve healing outcomes and restart healing in chronic wounds. For these materials to be effective, cells must migrate from the scaffold into the native tissue. This requires cells to traverse a step-change in material properties at the implant-tissue interface. Migration of cells in material with highly varying properties is not well characterized. We measure 3D encapsulated hMSC migration and remodeling in a well-characterized hydrogel with a step-change in stiffness. This cell-degradable hydrogel is composed of 4-arm poly(ethylene glycol)-norbornene cross-linked with an enzymatically-degradable peptide. The scaffold is made with two halves of different stiffnesses separated by an interface where stiffness changes rapidly. We characterize changes in structure and rheology of the pericellular region using multiple particle tracking microrheology (MPT). MPT measures Brownian motion of embedded particles and relates it to material rheology. We measure more remodeling in the soft region of the hydrogel than the stiff region on day 1 post-encapsulation and similar remodeling everywhere on day 6. In the interface region, we measure hMSC-mediated remodeling along the interface and migration towards the stiff side of the scaffold. These results can improve materials designed for cell delivery from implants to a wound to enhance healing. 

Multiple particle tracking microrheology (MPT) is a powerful tool for quantitatively characterizing rheological properties of soft matter. 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, R g 2 . Bi-disperse MPT is validated by measuring the viscosity of glycerol samples at varying concentrations. Bi-disperse MPT measurements agree well with literature values. This technique then characterizes a homogeneous poly(ethylene glycol)-acrylate:poly(ethylene glycol)-dithiol gelation. The critical relaxation exponent and critical gelation time are consistent and agree with previous measurements using a single particle. Finally, degradation of a heterogeneous hydrogenated castor oil colloidal gel is characterized. The two particle sizes measure a different value of the critical relaxation exponent, indicating that they are probing different structures. Analysis of material heterogeneity shows measured heterogeneity is dependent on probe size indicating that each particle is measuring rheological evolution of a length scale dependent structure. Overall, bi-disperse MPT increases the amount of information gained in a single measurement, enabling more complete characterization of complex systems that range from consumer care products to biological materials.