Bidentate Click-Functionalized Thermoplastic Polyurethane for Modular Immobilization of PEGylated Compounds: Mirabegron as a Proof-of-Concept

Abstract Thermoplastic polyurethane (TPU) is widely used in the development of biomedical devices, due to its excellent physicochemical properties; however, its chemical inertness limits its application in drug-immobilization systems. Here, we report the development of a postfabrication “TPU-click platform” utilizing a novel bidentate polyethylene glycol (PEG) linker [N-(aminooxy-PEG2)-N-bis(PEG3-propargyl)]. To ensure biomedical suitability, surface activation was achieved using a nontoxic bismuth-based catalyst. The bidentate architecture provides dual orthogonal alkyne sites, enabling the copper-catalyzed azide–alkyne cycloaddition (CuAAC) of complex molecules with enhanced theoretical payload capacity and versatility. Mirabegron was selected as a representative molecule to demonstrate the platform’s versatility. Surface modification was confirmed using multiple characterization techniques. ATR-FTIR spectroscopy revealed characteristic bands associated with isocyanates (2260–2270 cm−1), alkyne groups (2200–2500 cm−1), and ether bonds (1000–1100 cm−1). XPS (C 1s, N 1s, and O 1s) showed changes in surface elemental composition consistent with successful functionalization. SEM revealed variations in surface topography, while water contact angle values increased from 75.6° ± 1.04 to 122.58° ± 5.17, indicating a transition in wettability behavior attributable to changes in surface chemistry. Finally, the antioxidant capacity (59.67 ± 4.46 Trolox equivalents) supported the chemical feasibility of immobilizing PEGylated mirabegron and a broad range of PEGylated therapeutic molecules on TPU. To the best of our knowledge, this is the first report describing a TPU-click platform employing a bidentate PEG linker and Mirabegron PEGylation. This platform opens new opportunities for the development of drug-functionalized biomedical devices.