Bioelectric ink bridge: An electroactive casein bioink for cartilage regeneration by actively restoring the...

The development of bioinks that recapitulate key physiological cues remains a central challenge in 3D bioprinting. Although endogenous bioelectric signals are crucial regulators of cell migration, proliferation, and matrix assembly, they are rarely incorporated into bioink design. Here we present a filler-free electroactive bioink, quaternized-methacrylated casein (QCMA), that integrates intrinsic ionic conductivity with high-resolution digital light processing (DLP) bioprinting. Quaternization markedly improves casein solubility and optical clarity (>90% solubility) while introducing permanent cationic moieties that, together with mobile counterions, enhance charge transport in hydrated constructs; subsequent methacrylation enables rapid photocrosslinking and high-fidelity DLP printing (>95% dimensional accuracy in X-Y and Z). With an optimized cationic density, QCMA maintains chondrocyte viability, promotes cell adhesion and recruitment, and provides broad-spectrum antibacterial activity. Under a physiologically relevant pulsed electric field (150 mV/mm), QCMA-laden constructs activate MAPK-associated signaling, enhance chondrocyte migration and proliferation, and upregulate key chondrogenic markers (ACAN, SOX9, COL2A1, and TGF-β1), leading to increased cartilage matrix deposition. In a rat osteochondral defect model, QCMA implantation reduces local impedance and improves voltage recovery within the defect region, accompanied by increased Cx43 expression, suggesting enhanced gap-junctional communication and improved cartilage repair. Collectively, QCMA establishes a bioelectric niche-oriented strategy for next-generation regenerative bioinks by coupling filler-free electroactivity with DLP printability and therapeutic functionality.