Combinational Effect of Cell Adhesion Biomolecules and Their Immobilized Polymer Property to Enhance Cell-Selective Adhesion

Abstract

Although surface immobilization of medical devices with bioactive molecules is one of the most widely used strategies to improve biocompatibility, the physicochemical properties of the biomaterials significantly impact the activity of the immobilized molecules. Herein we investigate the combinational effects of cell-selective biomolecules and the hydrophobicity/hydrophilicity of the polymeric substrate on selective adhesion of endothelial cells (ECs), fibroblasts (FBs), and smooth muscle cells (SMCs). To control the polymeric substrate, biomolecules are immobilized on thermoresponsive poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide) (poly(NIPAAm-co-CIPAAm))-grafted glass surfaces. By switching the molecular conformation of the biomolecule-immobilized polymers, the cell-selective adhesion performances are evaluated. In case of RGDS (Arg-Gly-Asp-Ser) peptide-immobilized surfaces, all cell types adhere well regardless of the surface hydrophobicity. On the other hand, a tri-Arg-immobilized surface exhibits FB-selectivity when the surface is hydrophilic. Additionally, a tri-Ile-immobilized surface exhibits EC-selective cell adhesion when the surface is hydrophobic. We believe that the proposed concept, which is used to investigate the biomolecule-immobilized surface combination, is important to produce new biomaterials, which are highly demanded for medical implants and tissue engineering.

Combinational Effects of Polymer Viscoelasticity and Immobilized Peptides on Cell Adhesion to Cell-selective Scaffolds

“…The ATK (SMC-selective adhesion in Fig. S6, Supporting Information), and RRR (FB-selective adhesion in previous report) 12,18 also retained their function on some polymers, however changed (or even inversed) the function on other polymers. Also from our previous studies, such combinational effect of peptide and polymer, which change the original peptide function, had been also found with III, another EC-selective adhesion peptide.…”

“…Also from our previous studies, such combinational effect of peptide and polymer, which change the original peptide function, had been also found with III, another EC-selective adhesion peptide. 18 This also suggests that this cell-selective adhesion performance was supported by the peptide sequence/polymer itself, and their combinations. Therefore, this shows the risk that some functional peptides obtained from screening on different solid platforms can easily be changed (enhanced or strengthened) by polymer properties, and their optimum condition should be carefully determined by systematic analyses, such as our data.…”

“…18 However, recently, it was determined that the physicochemical properties (e.g. wettability) were not only the critical factor changing the scaffold performance.…”

“…These results indicated that the cell adhesion with RGDS could be diminished only on some cell types by the combination of polymer properties. Therefore, although RGDS was not evaluated as a cell-selective peptide, 18 RGDS showed FB-selectivity by the combination with the P4 polymer property.…”

“…We reported that cell-selective adhesion is significantly influenced by combining the physicochemical properties of peptides and polymers. 18 To further enhance the understanding of the combinational effects on cell-selective adhesion, the combinational effect of cell-selective adhesion peptides on viscoelastic and biodegradable scaffolds was investigated in the present study. We fabricated six types of poly(ε-caprolactoneco-D,L-lactide) (poly(CL-co-DLLA)) plates with a variety of thermal, mechanical, physicochemical, and topological properties by changing the CL/DLLA ratio and unit numbers.…”