Effect of Co-presentation of Adhesive Ligands and Short Hyaluronan on Lymphendothelial Cells

Abstract

Controlled activation of lymphangiogenesis through functional biomaterials represents a promising approach to support wound healing after surgical procedures, yet remains a challenge. In a synthetic biological approach, we therefore set out to mimic the basal microenvironment of human primary dermal lymphatic endothelial cells (LECs) during lymphangiogenesis. As the extracellular matrix component hyaluronan (HA) regulates lymphangiogenesis, we designed a bifunctional surface in which adhesive peptide ligands and short HA oligosaccharides (sHA) tethered to nanoparticles are copresented to the basal side of LECs in a controlled, concentration-dependent manner. Exposure of LECs to sHA in solution to mimic luminal stimulation of the cells did not result in modified metabolic activity. However, LECs grown on the bifunctional adhesive surfaces showed a biphasic change in metabolic activity, with increased metabolic activity being observed in response to increasing nanoparticle densities up to a maximum of 540 particles/μm2. Thus, interfaces that concomitantly present adhesive ligands and sHA can stimulate LEC metabolism and might be able to trigger lymphangiogenesis.

Mimicking the endothelial glycocalyx through the supramolecular presentation of hyaluronan on patterned surfaces

“…The effect of HA length on culture of endothelial cells has been investigated in several studies, 51,52 but mainly using HA in solution (added to the culture medium). Covalent immobilization of HA on solid surfaces 53,54 has also been investigated, but the methods used require chemical modification of HA. Using the Pep-1 SAM described in the previous sections, we have studied the effect of HA molecular weight on HUVECs, where HA is presented at surfaces in its native form without covalent immobization.…”

“…These results were consistent with the literature reporting that low molecular weight HA can stimulate cell motility while high molecular weight HA inhibits. 53 In the cell viability assay, cells seeded on bare Au were used as control cells, and the percentage difference between treated (seeded on peptide SAMs with and without HA) and control cells was calculated (Fig. 5C).…”

Synthetic hyaluronic acid coating preserves the phenotypes of lymphatic endothelial cells

“…Indeed, it was shown in several studies that LMW HA induces lymphangiogenesis through LYVE-1 mediated signaling pathways. [46][47][48] One recent study also shows that HA-binding peptide modulates EC spreading and migration through focal adhesion kinase (FAK). 49 Despite the unique expression of HA receptors by LECs, the effect of HA on the regulation of lymphatic characteristic markers has not been explored yet.…”