The inhibition of platelet adhesion and activation on collagen during balloon angioplasty by collagen-binding peptidoglycans.

Abstract

Collagen is a potent stimulator for platelet adhesion, activation, and thrombus formation, and provides a means for controlling blood loss due to injury, and recruiting inflammatory cells for fighting infection. Platelet activation is not desirable however, during balloon angioplasty/stent procedures in which balloon expansion inside an artery exposes collagen, initiating thrombosis, and inflammation. We have developed biomimetic polymers, termed peptidoglycans, composed of a dermatan sulfate backbone with covalently attached collagen-binding peptides. The peptidoglycan binds to collagen, effectively masking it from platelet activation. The lead peptidoglycan binds to collagen with high affinity (K(D) = 24 nm) and inhibits platelet binding and activation on collagen in both static studies and under flow, while promoting endothelial regrowth on collagen. Application for angioplasty is demonstrated in the Ossabaw miniature pig by fast delivery to the vessel wall through a therapeutic infusion catheter with a proprietary PTFE porous balloon. The peptidoglycan is an approach for locally preventing platelet deposition and activation on collagen. It can be used during angioplasty to prevent platelet deposition on target vessels and could be used in any vessel, including those not amenable to stent deployment.