
2018_EJRNL_PP_Michelle_S__Mazzeo_1.pdf
Terbatas Latifa Noor
» ITB
Terbatas Latifa Noor
» ITB
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.