One‐Step Covalent Biofunctionalization of Tubular Constructs Enabled by Surface‐Embedded Radicals

Tubular constructs are fundamental in tissue engineering and implant applications across vascular, renal, and urethral systems. Covalent attachment of biomolecules to their internal surfaces is often needed to create biofunctional structures, yet achieving uniform biofunctionalization within these confined geometries remains challenging. Surface‐embedded radicals generated via plasma immersion ion implantation (PIII) enable single‐step, reagent‐free covalent biofunctionalization without requiring multi‐step processing. However, uniform plasma treatment of 3D tubular structures is hindered by limited plasma penetration into confined geometries. To address this, a novel tubular dielectric barrier discharge (DBD) configuration is introduced for PIII treatment to achieve uniform internal PIII surface activation and biofunctionalization. By optimizing electric field distribution, informed by numerical modeling, PIII activation is selectively confined to either inside or outside of expanded polytetrafluoroethylene (ePTFE) tubes. Electron paramagnetic resonance spectroscopy data confirmed surface radicals remained detectable after six months, far exceeding the reactivity lifespan of conventional plasma treatments. Covalent immobilization of tropoelastin and fibronectin was validated using fluorescence imaging, ELISA, and time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS). Endothelialization studies using human coronary artery endothelial cells demonstrated enhanced cell attachment and proliferation in biofunctionalized submillimetre‐scale tubes. This industrially scalable, radical‐based, solvent‐free technology enables the fabrication of biofunctional tubular constructs, advancing tissue engineering, regenerative medicine, and beyond.