Ultrafine-grained Nb-Cu immiscible alloy implants for hard tissue repair: Fabrication, characterization, and in vitro and in vivo evaluation

Abstract

The biocompatible metallic implants with strong osteointegration often lack the ability of anti-infection. The biocompatible niobium (Nb) containing the antibacterial copper (Cu), the obtained Nb-Cu alloy, could be a potential candidate to solve this issue. To test this hypothesis, ultrafine-grained Nb-Cu immiscible alloys were fabricated via mechanical alloying and spark plasma sintering. The aim of this study was to investigate the microstructure, mechanical properties, magnetic susceptibility, corrosion behavior, ion release, and the bactericidal activity, biocompatibility and osteogenic potential of the Nb-Cu alloys in vitro and their osteogenesis and osteointegration ability in vivo with a comparison with pure Nb. The rat cranial defect model and the bone screws insertion in rabbit femoral bone were used to evaluate the osteogenesis and osteointegration ability, respectively. The results showed that after the addition of 3 wt.% of Cu, the compressive strength was significantly improved from 1.57 GPa to 2.21 GPa and the magnetic susceptibility slightly decreased. The Nb-3 wt.% Cu (Nb-3Cu) alloy exhibited higher corrosion resistance than pure Nb in Hank's solution and strong bactericidal activity against both E. coli and S. aureus. In vitro, the Nb-3Cu alloy showed comparable biocompatibility with pure Nb. The addition of 3 wt.% Cu also significantly enhanced the expression of osteogenesis-related genes (RUNX2, ALP, COLA1 and OCN) of pre-osteoblasts. In vivo, the Nb-3Cu alloy promoted bone regeneration at the defect sites and showed enhanced osteointegration after 12 weeks of implantation. Such a good combination of high mechanical strength and corrosion resistance, strong antibacterial activity and improved osteogenesis and osseointegration ability enables the present Nb-3Cu alloy a promising candidate for heavy load-bearing hard tissue repair.