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Terbatas Latifa Noor

Human mesenchymal stem cells (hMSCs) are motile cells that migrate from their native niche to wounded sites where they regulate in fl ammation during healing. New materials are being developed as hMSC delivery platforms to enhance wound healing. To act as an e ff ective wound healing material, the hydrogel must degrade at the same rate as tissue regeneration, while maintaining a high cell viability. This work determines the kinetics and mechanism of cell-mediated degradation in hMSC-laden poly(ethylene glycol) (PEG) hydrogels. We use a well-established hydrogel sca ff old that is composed of a backbone of four-arm star PEG functionalized with norbornene that is cross-linked with a matrix metalloproteinase (MMP) degradable peptide. This peptide sequence is cleaved by cell-secreted MMPs, which allow hMSCs to actively degrade the hydrogel during motility. Three mechanisms of degradation are characterized: hydrolytic, noncellular enzymatic and cell-mediated degradation. We use bulk rheology to characterize hydrogel material properties and quantify degradation throughout the entire reaction. Hydrolysis and noncellular enzymatic degradation are fi rst characterized in hydrogels without hMSCs, and follow fi rst-order and Michaelis ? Menten kinetics, respectively. A high cell viability is measured in hMSC-laden hydrogels, even after shearing on the rheometer. After con fi rming hMSC viability, bulk rheology characterizes cell-mediated degradation. When comparing cell-mediated degradation to noncellular degradation mechanisms, cell-mediated degradation is dominated by enzymatic degradation. This indicates hydrogels with hMSCs are degraded primarily due to cell- secreted MMPs and very little network structure is lost due to hydrolysis. Modeling cell-mediated degradation provides an estimate of the initial concentration of MMPs secreted by hMSCs. By changing the concentration of hMSCs, we determine the initial MMP concentration increases with increasing hMSC concentration. This work characterizes the rate and mechanism of sca ff old degradation, giving new insight into the design of these materials as implantable sca ff olds.