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Published online by Cambridge University Press: 23 April 2012
Recombinant human bone morphogenetic protein (rhBMP-2) plays a major role in differentiation of marrow stromal cells (MSCs). Peptides based on the active domains of rhBMP- 2, like the LYLTSIASLETPVSSAKPIK (BMP peptide), have been proposed as an alternative to reduce the side effects associated with high doses of rhBMP-2. The objective of this work was to determine the osteogenic activity of the BMP peptide grafted to poly(lactide fumarate) nanoparticles (PLAF NPs). A cysteine-terminated BMP peptide was grafted to PLAF NPs by linking the cysteine residue to the fumarate groups. Groups included blank NPs, free BMP peptide, free BMP-2 protein, and BMP-grafted NPs. The decrease in cell numbers after 21 days was consistent with an increase in mineral content and decrease in proliferation with osteogenic differentiation of MSCs. Alkaline phosphatase (ALPase) activity peaked at 14 days, consistent with the start of the osteogenic cascade. A slightly higher mineral content was observed in the BMP-grafted NP group after 14 days. m-RNA and immunostaining showed that cells in the BMP-grafted NP group had a higher content of osteocalcin protein after 21 days. Results suggest that the BMP-grafted NPs have a greater affinity to BMP cell surface receptors, leading to a stronger activation of the pathways leading to osteogenesis.