High-throughput hyaluronic acid hydrogel arrays for cell selective adhesion screening

As a component of extracellular matrix (ECM), hyaluronic acid (HA) has plenty of applications in the biomedical field such as tissue engineering. Due to its non-adhesive nature, HA requires further grafting of functional molecules for cell related study. RGD and YIGSR are two kinds of cell adhesion peptides. YIGSR enhances endothelial cell (EC) adhesion, which is important for endothelialization after implantation of stents to prevent in-stent restenosis. However, the effect of combined densities of these peptides for EC and smooth muscle cell (SMC) adhesion has not been explored in a quantitative and high-throughput manner. In this work, single or orthogonal gradient densities of RGD and YIGSR were grafted onto the HA hydrogel array surfaces using thiol-norbornene click chemistry. Optimized peptide combinations for EC preponderant adhesion were found in hydrogel arrays and confirmed by scaling samples.