Mediating the Migration of Mesenchymal Stem Cells by Dynamically Changing the Density of Cell-selective Peptides Immobilized on β -Cyclodextrin-modified Cell-resisting Polymer Brushes

Dynamic control of mesenchymal stem cell (MSC) behaviors on biomaterial surface is critically involved in regulating the cell fate and tissue regeneration. Herein, a stimuli-responsive surface based on host-guest interaction with cell selectivity was developed to regulate migration of MSCs in situ by dynamic display of cell-specific peptides. Azobenzene-grafted MSC-affinitive peptides (EPLQLKM, Azo-E7) were grafted to β -cyclodextran ( β -CD)-modified poly(2-hydroxyethyl methacrylate)- b -poly(2-hydroxyethyl methacrylate- co -glycidyl methacrylate) (PHG) brushes, which were prepared by using surface-initiated atom transfer radical polymerization (SI-ATRP). X-ray photoelectron spectroscopy (XPS), quartz crystal microbalance (QCM), and water contact angle were used to characterize their structure and property. Cell adhesion assay showed that the combination effect of resisting property of PHG and MSC-affinity of E7 could promote the selective adhesion of MSCs over other types of cells such as RAW264.7 macrophages and NIH3T3 fibroblasts to some extent. UV-Vis spectroscopy proved that the competing guest molecules, amantadine hydrochloride (Ama), could release Azo-E7 peptides from the CD surface to different extents, and the effect was enhanced when UV irradiation was employed simultaneously. As a result, the decrease of cell adhesion density and migration rate could be achieved in situ . The cell density and migration rate could be reduced by over 40% by adding 20 μmol/L Ama, suggesting that this type of surface is a new platform for dynamic regulation of stem cell behaviors in situ .