Time-Dependent UV/Ozone Treatment Modulates Platelet Adhesion on Polystyrene and Cyclo-Olefin Polymer through Fibrinogen Orientation

Abstract UV/ozone (UVO) treatment is a versatile, solvent-free approach for modifying polymer surfaces in biomedical applications. Although its effects on RGD-dependent cell adhesion have been extensively studied, the mechanisms underlying non-RGD-dependent interactions, specifically platelet adhesion, remain poorly understood. In this study, we investigated the adhesion and activation of human platelets on polystyrene (PS) and cyclo-olefin polymer (COP) surfaces modified with 172 nm vacuum ultraviolet (VUV) light-induced UVO treatment. A distinctive non-monotonic relationship between UVO irradiation time and platelet response was observed: short-term treatment (1–2 min) maximized platelet density, with a substrate-dependent increase in platelet activation that was most pronounced on PS, whereas prolonged treatment (>10 min) slightly reduced platelet density compared to short-term treatment. Surface analyses by X-ray photoelectron spectroscopy (XPS), water contact angle (WCA), and atomic force microscopy (AFM) showed monotonic increases in oxygen content, hydrophilicity, and nanoscale roughness, and were accompanied by a two-orders-of-magnitude decrease in Young’s modulus (from approximately 1500 MPa to 10 MPa). Quartz Crystal Microbalance with Dissipation (QCM-D) measurements of fibrinogen (Fg) adsorption indicated that short-term treatment promotes a “side-on” orientation of Fg, maximizing the exposure of γ-chain binding sites relevant to platelet integrin recognition. In contrast, long-term treatment leads to a crowded interfacial environment, likely disrupting stable protein presentation. Furthermore, excessive surface softening may impair platelet mechanosensing. These findings provide mechanistic insight into time-dependent UVO surface modification and offer a rational framework for optimizing the hemocompatibility of polymer-based medical devices.