3D‐Printed Piezoionic/Bioelectronic Hydrogel for Electro‐Metabolic Regulation of Osteogenic Differentiation

ABSTRACT Bone regeneration is often hindered by large defects caused by trauma, tumors, or infection, necessitating advanced biomaterials beyond conventional grafts. Piezoelectric biomaterials have emerged as promising scaffolds due to their extracellular matrix‐mimicking properties, with long‐term conductivity offering additional advantages through electroactive interactions with cells. In this study, we present a direct ink writing 3D‐printable, biodegradable, adhesive, and piezoionic‐conductive nanocomposite hydrogel (GPM x ) based on polypyrrole‐grafted gelatin methacrylate (GelMA‐PPy) and Ti 3 C 2 T x (MXene) nanoflakes. The incorporation of MXene into the GelMA‐PPy matrix enhanced the viscoelasticity, showcasing its excellent printability. The GPM x hydrogel demonstrates superior mechanical strength (∼450 ± 32.36 kPa), long‐term conductivity (∼30.41 ± 3.21 S/cm), and strong adhesiveness (∼64.55 ± 13.17 kPa). Furthermore, the 3D‐printed and dual‐crosslinked GPM x ‐1% hydrogel functions as a piezoionic nanogenerator (PING), converting mechanical stress into electrical signals (∼8.29 ± 1.26 mV) upon varying strain. The macroporous PING hydrogel shows superior biocompatibility (>99%) with human bone mesenchymal stem cells (hBMSCs) and promotes osteogenic differentiation via bioelectric modulation. Additionally, antibody‐functionalized GPM x enables label‐free electrochemical sensing of alkaline phosphatase under various conditions (e.g., healthy or diseased), offering clinical potential for monitoring bone health and regenerative therapies.