Paper Number
BL5 My Program
Session
Biological, Living, Active, and Directed Systems
Title
Measurements of cell-mediated degradation of poly(ethylene glycol)-norbornene hydrogels with non-linear cytokine gradients using multiple particle tracking microrheology
Presentation Date and Time
October 15, 2024 (Tuesday) 5:05
Track / Room
Track 5 / Room 405
Authors
- O'Shea, Thomas C. (Purdue University, Davidson School of Chemical Engineering)
- Schultz, Kelly M. (Purdue University, Davidson School of Chemical Engineering)
Author and Affiliation Lines
Thomas C. O'Shea and Kelly M. Schultz
Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907
Speaker / Presenter
O'Shea, Thomas C.
Keywords
biological systems; gels; living systems
Text of Abstract
Degradable hydrogel scaffolds are being designed as implantable devices to additional deliver human mesenchymal stem cells (hMSCs) to treat wounds. hMSCs must migrate from the gel to the wounded tissue, which is complicated by physical and chemical cues present in the native niche. When a wound occurs, the tissue releases cytokines which form a concentration gradient causing directed stem cell migration from their native niche to the wound. Taking inspiration from this process, we create hydrogels with tethered cytokine concentration gradients to enhance and direct cell migration. The scaffold is composed of 4-arm poly (ethylene glycol)-norbornene, a cellular degradable peptide cross-linker, cellular adhesion ligand and hMSCs. This scaffold is degrade by encapsulated cells that secrete enzymes that cleave the peptide cross-linker inducing a gel-sol phase transition. The scaffold is photopolymerized in a custom microfluidic device that enables the formation of a cytokine concentration gradient. The device has two liquid sources: one is an inert liquid and the opposing source is a solution of thiol-functionalized cytokines either a pro-inflammatory cytokine, tumor necrosis factor-a (TNF- a), or an anti-inflammatory cytokine, transforming growth factor-ß (TGF-ß). The functionalized cytokines are clicked into placed after the concentration gradient is formed with a second UV light exposure. To characterize the system, we use a combination of multiple particle tracking microrheology (MPT) and live cell imaging. MPT characterized the pericellular remodeling around individual hMSCs by measuring embedded fluorescent probe particle motion and calculating their mean-squared displacements. We measure increased cell-mediated degradation, elongation and motility by isotropically tethering cytokines into our scaffolds. Building on this data, we hypothesize scaffolds with tethered cytokines gradients will increase directed cell delivery efficacy out the scaffolds to the wounded tissue.