Paper Number
BL10 My Program
Session
Biological, Living, Active, and Directed Systems
Title
Measuring human mesenchymal stem cell migration and remodeling in hydrogels with a gradient in elastic modulus
Presentation Date and Time
October 16, 2024 (Wednesday) 10:50
Track / Room
Track 3 / Waterloo 5
Authors
- Imran, Zaid (Purdue University, Davidson School of Chemical Engineering)
- Schultz, Kelly M. (Purdue University, Davidson School of Chemical Engineering)
Author and Affiliation Lines
Zaid Imran and Kelly M. Schultz
Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907
Speaker / Presenter
Imran, Zaid
Keywords
experimental methods; biological systems; directed systems; gels; living systems; particles; polymers; real-world rheology; techniques
Text of Abstract
Human mesenchymal stem cells (hMSCs) can be delivered by implanted hydrogels to wounded tissue to improve healing. To direct migration from the scaffold to the wounded tissue, physical and chemical cues can be presented to cells in the pericellular region. hMSCs undergo durotaxis a process where hMSCs migrate from softer to stiffer microenvironments. To spatially direct hMSC migration, we create a stiffness gradient in a well-defined hMSC-degradable hydrogel. This photopolymerized scaffold is composed of 4-arm poly(ethylene glycol)-norbornene cross-linked with a matrix metalloproteinases (MMPs)-degradable peptide where MMPs are cell-secreted enzymes. Hydrogels with a stiffness gradient are formed by moving a photomask at a constant speed across a sample, which varies UV exposure time and cross-link density. To characterize this stiffness gradient, we measure material autofluorescence spatially and use a calibration curve to calculate elastic modulus, G’. In this work, we characterize changes in the structure and rheology of the pericellular region in cell-laden hydrogel scaffolds with a stiffness gradient using multiple particle tracking microrheology (MPT). MPT measures the Brownian motion of embedded particles in a sample to characterize the structure and rheology of the material. On days 2 and 3 post-encapsulation, we measure that almost all hMSC remodeling is restricted to the soft (G’<319 Pa) and middle (319<G'<367 Pa) regions of the hydrogel due to the initial lower cross-link density in this part of the gel compared to the stiff region (367<G’<1014 Pa). By day 4 post-encapsulation, all regions of the hydrogel have been remodeled due to the cumulative effect of cell-secreted MMPs, which degrade the hydrogel cross-linker. We measure that hMSCs tend to migrate towards stiff regions of the hydrogel by durotaxis. These measurements can improve the design of implantable hydrogel scaffolds for wound healing and cell delivery by using the physical microenvironment to direct hMSCs to the patients wound site.