Three-dimensional hMSC Motility within Peptide-Functionalized PEG-Based Hydrogel of Varying Adhesivity and Crosslinking Density
Human mesenchymal stem cell (hMSC) migration and recruitment play a critical role during bone fracture healing. Within the complex 3D in vivo microenvironment, hMSC migration is regulated through a myriad of extracellular cues. Here, we use a thiol-ene photopolymerized hydrogel to recapitulate struc...
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Veröffentlicht in: | Acta biomaterialia 2013-02, Vol.9 (5), p.6381-6392 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Human mesenchymal stem cell (hMSC) migration and recruitment play a critical role during bone fracture healing. Within the complex 3D
in vivo
microenvironment, hMSC migration is regulated through a myriad of extracellular cues. Here, we use a thiol-ene photopolymerized hydrogel to recapitulate structural and bioactive inputs in a tunable manner to understand their role in regulating 3D hMSC migration. Specifically, peptide-functionalized poly(ethylene glycol) hydrogels were used to encapsulate hMSC while varying the crosslinking density, 0.18 ± 0.02 - 1.60 ± 0.04 mM, and the adhesive ligand density, 0.001 to 1.0 mM. Using live cell videomicroscopy migratory cell paths were tracked and fit to a persistent random walk model. It was shown that hMSC migrating through the lowest crosslinking density and highest adhesivity had more sustained polarization, higher migrating speeds (17.6 ± 0.9 μm/hr), and higher cell spreading (Elliptical Form Factor = 3.9 ± 0.2). However, manipulation of these material properties did not significantly affect migration persistence. Further, there was a monotonic increase in cell speed and spreading with increasing adhesivity showing a lack of the biphasic trend seen in two dimensional cell migration. Immunohistochemistry showed well-formed actin fibers and β1 integrin staining at the ends of stress fibers. This thiol-ene platform provides a highly tunable substrate to characterize 3D hMSC migration with application as an implantable cell carrier platform or for the recruitment of endogenous hMSC
in vivo. |
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ISSN: | 1742-7061 1878-7568 |
DOI: | 10.1016/j.actbio.2013.01.026 |