Paper Number
GG52 

Session
Rheology of Gels, Glasses and Jammed Systems

Title
Rheological characterization of covalent adaptable thioester networks for delivery of human mesenchymal stem cells (hMSCs)

Presentation Date and Time
October 13, 2022 (Thursday) 8:45

Track / Room
Track 3 / Sheraton 5

Authors (Click on name to view author profile)

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

Author and Affiliation Lines (in printed abstract book)
Shivani Desai1, Benjamin Carberry2, Kristi Anseth2 and Kelly M. Schultz1
1Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA 18015; 2Chemical and Biological Engineering, University of Colorado at Boulder, Boulder, CO 80309

Speaker / Presenter 
Desai, Shivani

Keywords
biomaterials; gels

Text of Abstract
During wound healing, human mesenchymal stem cells (hMSCs) regulate inflammation and call other cells to the injury to repair tissue. Delivery of additional hMSCs can enhance natural repair processes and injectable hydrogels are being developed for this purpose. These hydrogels need to be pushed through a syringe, quickly recover to a gel and provide an environment that allows basic cellular functions. Covalent adaptable networks (CANs) can be used as injectable scaffolds due to their ability to break and reform cross-links under external forces. CANs also mimic aspects of the extracellular matrix and can be rearranged by cellularly applied forces allowing spreading, migration and proliferation. To design these networks for hMSC delivery, we characterize their properties when external forces are applied and measure remodeling by encapsulated hMSCs. We use bulk rheology and multiple particle tracking microrheology (MPT) to characterize a thioester CAN composed of 8-arm poly(ethylene glycol) (PEG)-thiol and PEG thioester norbornene. In bulk rheology experiments, we cyclically apply low and high strain to these CANs to assess injectability and measure that they return to their equilibrium properties. We then characterize network degradation due to thioester exchange using MPT. MPT measures the Brownian motion of fluorescent probes embedded in the sample, which is used to calculate material rheological properties. Using time-cure superposition to analyze MPT data, we calculate the critical relaxation exponent, n=0.53 ± 12, which indicates these CANs have structures similar to percolated networks. We then measure hMSC-mediated remodeling of the material. We evaluate whether this remodeling is due to cytoskeletal tension by treating cells with a myosin II inhibitor and measuring the resulting rheological properties. This work shows that thioester networks can be used as injectable scaffolds that hMSCs can remodel and can inform future design of these scaffolds for cell delivery.