Cu‐Enhanced Medium‐Entropy TiZrCoCrMo Alloys: Balancing Superior Antibacterial and Osteogenic Properties for Orthopedic Implants

ABSTRACT This study introduces novel nonequiatomic TiZrCoCrMoCu x ( x = 0, 5, 10; at%) medium‐entropy alloys (MEA x ) tailored for orthopedic implants, synergistically combining the biocompatibility of Ti‐based alloys, the wear resistance of CoCrMo alloys, and the antibacterial/osteogenic attributes of Cu. The alloy's microstructure, mechanical properties, corrosion behavior, antibacterial efficacy, biocompatibility, and osteogenic mechanisms were systematically investigated. MEA10 featured nanoscale Cu‐rich precipitates (mean diameter of 32.4 nm), reducing Young's modulus by 31 GPa and increasing microhardness by 2.07 GPa compared to commercially pure Ti (CP‐Ti), while conferring superior wear resistance through mitigation of plastic deformation. Although increasing Cu content marginally impaired corrosion resistance, MEA10 still maintained a lower corrosion current density than CP‐Ti; notably, MEA0 and MEA5 displayed enhanced corrosion stability alongside moderate antibacterial efficacy. Antibacterial assays demonstrated a 97.7% reduction in Escherichia coli viability for MEA10, mediated by contact‐killing from the Cu‐rich nanoprecipitates. In vitro, MEA10 promoted osteoblast viability to 122% relative to CP‐Ti, and in vivo rat femoral implantation yielded a 33.4% higher bone volume fraction, signifying robust osseointegration. RNA sequencing revealed upregulated gene sets in extracellular matrix organization and Wnt signaling pathways, with periostin emerging as a pivotal mediator, ostensibly stimulated by galvanic effects from the Cu precipitates. These attributes underscore MEA10's multifaceted superiority in mechanical, antimicrobial, and osteoinductive performance, establishing it as a compelling candidate for next‐generation orthopedic implants.