Page 157 - Physico-Chemical Niche Conditions for Bone Cells

culturing on SLBs induces signaling that stimulates COL1a1 expression even after the SLBs have started to degrade. To further elucidate the long-term effect of SLBs on cells, SLBs exhibiting higher stability are required. This can be achieved by for example, polymerization of diacetylene-containing lipids introduced within the SLB [45]. An important consideration while targeting SLB stability is preserving SLB fluidity, that is, its biomimicry as desired for certain biomedical applications [45,46].
Future perspectives for SLBs as coating for biomaterials in bone
Taken together, the results of this study are a first indication that SLBs may be promising as coating for biomaterials in bone, although SLBs have to be further developed to optimize adhesion and differentiation of osteoprogenitors. Changing fatty acid composition and thereby the lateral mobility of SLBs and attached ligands likely affects osteoprogenitor adhesion and differentiation. Osteoprogenitors adhere and differentiate better on substrates with higher rigidity [36]. Preparing SLBs of lipids with a higher melting transition temperature and thereby lower lateral mobility (e.g., 1-myristol-2-palmityol-sn-glycero-3-phosphocholine [MPPC], melting transition temperature 37°C) may provide an environment where cells experience slightly more resistance when pulling on their attachments, increasing focal adhesion formation and thereby adhesion strength and probably also osteogenic differentiation.
Another way to optimize SLBs for osteoprogenitor adhesion and differentiation may be SLB functionalization with more than one peptide. Immobilization of the short peptide GFOGER, the major binding locus for integrins on collagen type I, to nonfouling substrates induces adhesion of osteoblasts to a level comparable to adhesion on full collagen type I- coated substrates [47]. Furthermore, immobilization of RGD together with its synergy sequence PHSRN to poly(ethylene glycol) hydrogels improves osteoblast adhesion compared to RGD alone [48]. Osteoprogenitors also adhere with a higher affinity to RGD-peptides with a cyclic conformation than to RGD-peptides with a linear conformation [7]. The current study used a peptide with a linear conformation and therefore adhesion can likely be improved by functionalizing SLBs with a cyclic RGD peptide. Furthermore, peptides derived from growth factors or cytokines can be incorporated into the SLBs to optimize cellular function, for example, vascular endothelial growth factor (VEGF) to stimulate vascularization.
An advantage of SLBs is their nonfouling nature. This intrinsic resistance of SLBs to the adsorption of proteins and cellular adhesion likely prevents bacteria from attaching to the surface, lowering the risk of infection when SLBs are used as a coating for biomaterials. To further reduce the infection risk, antimicrobial proteins/ peptides can be incorporated into the SLBs as well [49]. Future research will have to elucidate how changing fatty acid composition of the SLBs and functionalization with other peptides can be used to develop innovative coatings for biomaterials in bone regeneration.
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