Modulation of Osteogenic Differentiation of Stromal Cells by the BMP-2 Protein-Derived Peptide Grafted to a Hydrogel Substrate

摘要

Osteogenic differentiation and mineralization of bone marrow stromal (BMS) cells depends on the cells’ interactions with bioactive peptides associated with the matrix proteins. Multiple bioactive peptides in the bone ECM, interact with progenitor BMS cells to initiate the cascade of chemotaxis, differentiation, and mineralization. Among these peptides, RGD sequences associated with ECM matrix proteins interact with BMS cells through integrin cell surface receptors to facilitate cell spreading and focal-point adhesion to the ECM. The peptide KIPKASSVPTELSAISTLYL (hereafter referred to as the BMP peptide), corresponding to residues 73-92 of the knuckle epitope of recombinant human bone morphogenetic protein (rhBMP-2), is implicated in osteogenic differentiation of BMS cells. We have recently synthesized a novel poly(lactide-co-ethylene oxide fumarate) (PLEOF) macromer that can be crosslinked in aqueous environment to produce biodegradable inert hydrogels. The objective of this work was to determine the synergistic effect of RGD and BMP-2 protein-derived peptides, grafted to the inert PLEOF hydrogel, on osteogenic differentiation and mineralization of BMS cells. RGD peptide was conjugated to the hydrogel by the reaction of acrylamide terminated RGD with PLEOF fumarate. The BMP peptide was grafted to the hydrogel surface by “click chemistry”, as shown in Figure 1.