Porous agarose/Gd-hydroxyapatite composite bone fillers with promoted osteogenesis and antibacterial activity

Artificial bone fillers are essentially required for repairing bone defects, and developing the fillers with synergistic biocompatibility and anti-bacterial activity persists as one of the critical challenges. In this work, a new agarose/gadolinium-doped hydroxyapatite filler with three-dimensional porous structures was fabricated. For the composite filler, agarose provides three-dimensional skeleton and endows porosity, workability, and high specific surface area, hydroxyapatite (HA) offers the biocompatibility, and the rare earth element gadolinium (Gd) acts as the antibacterial agent. X-ray photoelectron spectroscopy detection showed the doping of Gd in HA lattice with the formation of Gd-HA interstitial solid solution. Attenuated total reflection Fourier transform infrared spectroscopy imaging suggested chemical interactions between agarose and Gd-HA, and the physical structure of agarose was tuned by the Gd-doped HA. Cytotoxicity testing and alizarin red staining experiments using mouse pro-osteoblasts (MC3T3-E1) revealed remarkable bioactivity and osteogenic properties of the composite fillers, and proliferation and growth rates of the cells increased in proportion to Gd content in the composites. Antibacterial testing using the gram-positive bacteria S. aureus and the gram-negative bacteria E. coli indicated promising antibacterial properties of the fillers. Meanwhile, the antibacterial properties of composite filles were enhanced with the increase of Gd content. The antibacterial fillers with porous structure and excellent physicomechanical properties show inspiring potential for bone defect repair.