Peptide Interfacial Biomaterials Improve Endothelial Cell Adhesion and Spreading on Synthetic Polyglycolic Acid Materials

Abstract

Resorbable scaffolds such as polyglycolic acid (PGA) are employed in a number of clinical and tissue engineering applications owing to their desirable property of allowing remodeling to form native tissue over time. However, native PGA does not promote endothelial cell adhesion. Here we describe a novel treatment with hetero-bifunctional peptide linkers, termed "interfacial biomaterials" (IFBMs), which are used to alter the surface of PGA to provide appropriate biological cues. IFBMs couple an affinity peptide for the material with a biologically active peptide that promotes desired cellular responses. One such PGA affinity peptide was coupled to the integrin binding domain, Arg-Gly-Asp (RGD), to build a chemically synthesized bimodular 27 amino acid peptide that mediated interactions between PGA and integrin receptors on endothelial cells. Quartz crystal microbalance with dissipation monitoring (QCMD) was used to determine the association constant (K (A) 1 x 10(7) M(-1)) and surface thickness (~3.5 nm). Cell binding studies indicated that IFBM efficiently mediated adhesion, spreading, and cytoskeletal organization of endothelial cells on PGA in an integrin-dependent manner. We show that the IFBM peptide promotes a 200% increase in endothelial cell binding to PGA as well as 70-120% increase in cell spreading from 30 to 60 minutes after plating.

Biocompatible and Bioactive Surface Modifications for Prolonged In Vivo Efficacy

“…83 PGA was selected because this biodegradable polymer has been used as a scaffolding material to engineer vascular grafts. 84 However, re-endothelialization of the inner PGA lining of these engineered vascular grafts remains a significant challenge.…”

Staphylococcus aureus resistance on titanium coated with multivalent PEGylated-peptides

“…Furthermore, the modular nature of this platform presents a general approach for the directed assembly and organization of various other biological and chemical mediators on any target material, from metal to plastic to ceramic [29,51-53]. …”

Repetitive Gly-Leu-Lys-Gly-Glu-Asn-Arg-Gly-Asp Peptide Derived from Collagen and Fibronectin for Improving Cell–Scaffold Interaction

“…Thus, whole fibronectin or collagen proteins were reported to biofunctionalize the scaffold via various means, e.g., infiltration, blending, and grafting [13,[21][22][23][24][25][26][27][28][29]. Interestingly, collagen and fibronectin contain short motifs to activate integrin receptors and stimulate cellular responses [30]: Gly-Leu-Lys-Gly-GluAsn (GLKGEN) motif of collagen [31,32] and Arg-Gly-Asp (RGD) motif of fibronectin [21,[32][33][34]. In this work, we are interested in producing a single peptide that contains both motifs as the ECM-mimicking peptide for improving cell-scaffold interaction, especially in the biologically inert PCL scaffold.…”