Characterizing the dynamic rheology in the pericellular region by human mesenchymal stem cell re-engineering in PEG-peptide hydrogel scaffolds

Abstract

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.

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Acknowledgements

We thank Dr. Susan Perry from the Department of Bioengineering at Lehigh University for her useful discussion on Western blot experiments. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R15GM119065. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Daviran, M., Schultz, K.M. Characterizing the dynamic rheology in the pericellular region by human mesenchymal stem cell re-engineering in PEG-peptide hydrogel scaffolds. Rheol Acta 58, 421–437 (2019). https://doi.org/10.1007/s00397-019-01142-2

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Keywords

  • Multiple particle tracking microrheology
  • Cellular degradation
  • Polymeric hydrogel scaffold
  • Michaelis-Menten kinetics
  • Matrix metalloproteinases
  • Tissue inhibitor of metalloproteinases