During the first year of the OsteNano project biomimetic platforms have been characterized with surface sensitive techniques, used to obtain information on the exact amount of HS and on BMP-2 present on the surface. The control over BMP-2 surface molecular density is necessary to interpret cellular responses once interacting with the platforms.
Indeed, these surfaces have been used as support for cellular studies. In particular, murine cell model, which responds to BMP-2 (C2C12) and human mesenchymal stem cells, have been plated on these surfaces and their responses analyzed.
One of the earlier events of BMP-2 signaling pathway is the phosphorylation of SMAD protein, which is transported into cellular nucleus and activates genes responsible for osteogenic differentiation.
Cells plated on the biomimetic platforms show an enhanced SMAD phosphorylation level, only when BMP-2 is presented via HS.
Moreover, HS prevents BMP-2 recognition by noggin, one of the known BMPs antagonists. This result demonstrates that grafted HS improves the biological effect of BMP-2 and suggests that grafted HS can be a good candidate for future regenerative medicine applications.
In the last period I proved the versatility of these biomimetic platforms, which can be functionalized by multiple ligands, such as BMP-2 and Integrin ligands (RGD peptides).
During OsteoNano project I first wrote a review titled “Tuning cellular responses to BMP-2 with material surfaces” published in Cytokine & Growth Factor Reviews in 2015, which shows the open questions and the new challenges on BMP-2 presentation through engineered surfaces. The main results of the OsteoNano project have been published in a paper titled “Enhanced biological activity of BMP-2 bound to surface-grafted heparan sulfate” published in Advanced Biosystems in 2017.
This project has been also presented to several international conferences such as:
1st ERC BIOMIM Meeting, Grenoble, April 10-12, 2015; FEBS-MPST, Rhodes, September 24-29, 2015 and 11th international BMP Conference, Boston, October 26-30, 2016.
