(352c) Construction of Polysaccharide-Based Polyelectrolyte Multilayer for the Delivery of Growth Factor to Induce Mesenchymal Stem Cell (MSC) Response
It is generally accepted that both surface chemistry and biochemical cues affect mesenchymal stem cell (MSC) proliferation and differentiation. Several growth factors that have strong influences on MSC behavior, belonging to the FGF family and the TGF-beta superfamily, bind to glycosaminoglycans in interactions that affect their stability and their biochemical activity with respect to MSCs. The goal of this work was to develop polysaccharide-based polyelectrolyte multilayers (PEMs) to stabilize and deliver therapeutic growth factors to MSCs. Using the naturally derived polysaccharides chitosan and heparin, PEMs were constructed on gold-coated glass chips, tissue-culture polystyrene (TCPS), and titanium. PEM construction and basic fibroblast growth factor (FGF-2) adsorption to these PEMs were evaluated by Fourier transform surface plasmon resonance, X-ray photoelectron spectroscopy, and polarization modulation infrared reflection adsorption spectroscopy. The functional response of bone marrow-derived ovine MSCs to FGF-2 on PEM-coated TCPS and titanium was evaluated in vitro. The effect of FGF-2 dose and presentation on MSC proliferation was evaluated using serum-deprived media, over four days. On TCPS, we found that FGF-2 adsorbed to heparin-terminated PEMs induces a stronger proliferative response of ovine MSCs than any of the other conditions tested, including delivery of the FGF-2 in solution, at an optimally mitogenic dose. Cell densities on day four were 1.8 times higher when FGF-2 was delivered by adsorption to the PEM, than when FGF-2 was delivered in solution. Interestingly, the same effects were not observed when FGF-2 was delivered by adsorption to PEMs on titanium. When the polysaccharide-based PEMs were formed on titanium the proliferative response of ovine MSCs to adsorbed FGF-2 was not as strong as the response to FGF-2 delivered in solution. Overall, MSCs attached and proliferated better on heparin-terminated PEMs than they did on chitosan-terminated PEMs.