Paper Number
GN7   Keynote                         My Program 

Session
Gels and Networks

Title
Human mesenchymal stem cell response to hydrogel viscoelasticity

Presentation Date and Time
October 14, 2024 (Monday) 1:30

Track / Room
Track 1 / Waterloo 3

Authors (Click on name to view author profile)

1. Desai, Shivani (Lehigh University, Chemical and Biomolecular Engineering)
2. Carberry, Benjamin J. (University of Colorado at Boulder, Chemical and Biological Engineering)
3. Anseth, Kristi S. (University of Colorado at Boulder, Chemical and Biological Engineering)
4. Schultz, Kelly M. (Purdue University, Davidson School of Chemical Engineering)

Author and Affiliation Lines (in printed abstract book)
Shivani Desai¹, Benjamin J. Carberry², Kristi S. Anseth² and Kelly M. Schultz^3
1Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA 18015; ²Chemical and Biological Engineering, University of Colorado at Boulder, Boulder, CO 80309; ³Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907

Speaker / Presenter 
Schultz, Kelly M.

Keywords
biological systems; gels; polymers

Text of Abstract
Covalent adaptable networks (CANs) are self-healing materials that can be used for cell and drug delivery. These applications require network degradation at physiological conditions and timescales with microstructures that: (1) support, protect and deliver encapsulated cells or molecules and (2) provide structure to surrounding tissue. Due to this, the evolving microstructure and rheological properties during scaffold degradation must be characterized. In this work, we characterize degradation of photopolymerized networks composed of poly(ethylene glycol) (PEG)-thiol and PEG-thioester norbornene, which undergoes a thioester exchange reaction. We first measure degradation of PEG-thioester networks with varying amounts of excess thiol, which is directly related to adaptability, by incubation in L-cysteine using multiple particle tracking microrheology (MPT). MPT measures the Brownian motion of particles embedded in a material and relates this to rheological properties. We measure scaffold rearrangement during degradation and network elasticity increases non-monotonically with the amount of excess thiol. We then 3D encapsulate hMSCs in these networks and use MPT to measure cell-mediated degradation. hMSCs degrade these CANs ~4 days after encapsulation. We hypothesize that scaffold degradation is mainly due to cytoskeletal tension applied to the network triggering the exchange reaction. To test this, we measure degradation of thioester networks by hMSCs with cytoskeletal tension inhibited. We continue to measure a lower extent of degradation by treated hMSCs, which could be the result of the cell-secreted esterases that hydrolyze thioester bonds and initiate the exchange reaction. This work can be used to inform thioester network design for cell delivery. These scaffolds enable the material to be delivered by injection, the scaffold will protect the cells at the wound site and the properties cells engineer into the scaffold can be designed into the microenvironment to instruct cellular processes after injection.