Magnesium dopped Calcium-Fluoride/Icaritin composite multi-layer coating functionalized 3D printed β-TCP scaffold induces sustained bone regeneration in a rabbit model

Osteonecrosis of femoral head (ONFH) requires bone grafts to fill bone defects and provide braced force after hip preservation surgery. Scaffolds functionalized with osteogenic factors may solve problems above. Icaritin (ICT) nanofilm and Magnesium dopped Calcium-Fluoride (Mg-CaF) nanofilm were loaded on β-TCP scaffolds by plasma coating technology and two new scaffolds were fabricated, namely ICT/β-TCP (IT) scaffold and Mg-CaF/ICT/β-TCP (MFIT) scaffold. In vitro, physical characterization, cytotoxicity, osteogenic ability and ICT release of scaffolds were assessed. Furthermore, osteogenic and angiogenic abilities of IT scaffolds and MFIT scaffolds, as well as their biocompatibility after implantation, were determined in ONFH rabbits. Results showed both scaffolds remained well-designed in structure and mechanical properties after coating. ICT release on MFIT scaffold was more sustained than on IT scaffold. Analysis of calcium nodules at 28 days indicated that degradation of Mg-CaF film promoted bone formation. Correspondingly, Micro-CT and histological staining suggested MFIT scaffold possessed similar osteogenic and angiogenic abilities compared with IT scaffold at 6 weeks and significantly better at 12,18 weeks. In addition, MFIT scaffold supported the weight-bearing area effectively throughout the observation period. Therefore, MFIT scaffolds provided stable support along with persistent osteogenesis and angiogenesis, which had potential applications in ONFH.