Paper Number
BF4
Session
Biomaterials and Bio-fluid Dynamics
Title
Measuring human mesenchymal stem cells-mediated degradation in response to cytokines presented locally and, in the environment, using multiple particle tracking microrheology
Presentation Date and Time
October 10, 2022 (Monday) 4:45
Track / Room
Track 4 / Michigan AB
Authors
- O'Shea, Thomas C. (Lehigh University, Chemical and Biomolecular Engineering)
- Schultz, Kelly M. (Lehigh University, Chemical and Biomolecular Engineering)
Author and Affiliation Lines
Thomas C. O'Shea and Kelly M. Schultz
Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA 18015
Speaker / Presenter
O'Shea, Thomas C.
Keywords
biomaterials; gels
Text of Abstract
Human mesenchymal stem cell (hMSC)-laden hydrogels are being designed as implantable scaffolds that deliver additional cells to a wound, which enhance or restart the healing process. Once at the wound site hMSCs regulate inflammation, recruit single purposed cells to clean the wound and monocytes to produce new tissue. The hydrogel not only deliver additional cells to the wound it also provides structure to the damaged tissue. After implantation, hMSCs secrete matrix metalloproteinase degrading the gel and enabling them to move freely to the wound site following a gradient of cytokines. Tumor necrosis factor-a and transforming growth factor-ß1 are cytokines present at different concentrations in the wound. We tether these two cytokines into the network separately to characterize changes in cell-material interactions in an environment that more closely mimics the native wound. These two cytokines are chosen because they are present at different stages in the wound healing process. Our hydrogel scaffold uses thiol:ene chemistry to create a chemically cross-linked scaffold that is composed of four-arm poly(ethylene glycol)-norbornene, a degradable peptide cross-linker, a photoinitiator and a cell adhesion ligand, CRGDS. We also chemically cross-link each thiol functionalized cytokine into our hydrogel, which we confirm by antigen specific ELISAs. Next, we 3D encapsulate hMSCs into the hydrogel with cytokines locally tethered and in the surrounding environment. To investigate the relation between cytokines and hMSC migration we use multiple particle tracking microrheology (MPT) to measure hMSC-mediated degradation of the pericellular region. MPT uses video microscopy to measure the Brownian motion of embedded probe particles in a material which characterizes rheological properties. From these experiments, we determine a relation between the concentration and presentation of cytokines and the cellular response, which is a necessary step in future design of materials that using cytokines to direct hMSC motility.