Effect of Fe-Mg Co-Doping on the Comprehensive Properties of 3D-Printed Biphasic Calcium Phosphate Ceramics

Incorporating functional elements into biomaterials is an effective strategy to enhance their biological performance. Compared with single-element doping, one advantage of multi-element co-doping is that it can improve the bioactivity of bioceramics at relatively low doping concentrations. Lower doping concentrations generally correspond to better biocompatibility. Recently, Professor Haijun Su and his team from Northwestern Polytechnical University published a study in Ceramics International entitled “Effect of Fe-Mg co-incorporation on the mechanical properties, biodegradation, osteogenesis and immunoregulation in vitro of 3D printed biphasic calcium phosphate bioceramics”. In this work, they proposed co-incorporating iron (Fe) and magnesium oxide (MgO) into biphasic calcium phosphate (BCP) bioceramics fabricated via vat polymerization (VPP) 3D printing, aiming to regulate their microstructure, mechanical properties, biodegradability, biocompatibility, and bioactivity.

Original link: https://doi.org/10.1016/j.ceramint.2025.02.146
AdventureTech website: https://www.adventuretech.cn

Research Content
In this study, a series of BCP slurries containing Fe and Mg were prepared by adjusting the amounts of Fe powder and MgO powder. Fe-Mg co-doped BCP bioceramics and porous scaffolds were then fabricated using a stereolithography (SLA) 3D printer and sintered at 1250 °C for 2 hours. The effects of the Fe/Mg ratio on the microstructure, mechanical properties, biodegradability, and bioactivity of the BCP bioceramics were systematically investigated.

The following are the research methods and data of the article:

Figure 1 (a) Bioceramic sample and (b) Porous scaffold model


Figure 2 Curing depth under different exposure energies


Figure 3 (a) Bulk density of BCP and Fe-Mg co-doped BCP bioceramics, (b) Porosity of BCP and Fe-Mg co-doped BCP scaffolds, (c) Dimensions


Figure 4 XRD spectra of pure BCP and Fe-Mg co-doped BCP bioceramics


Figure 5 FTIR spectra of pure BCP and Fe-Mg co-doped BCP bioceramics


Figure 6 Appearance and SEM images of pure BCP and Fe-Mg co-doped BCP scaffolds


Figure 7 Microstructural morphology and grain size distribution of bioceramics after polishing and thermal etching: (a,f) BCP, (b,g) 0.5Fe-BCP, (c,h) 0.5Fe1Mg-BCP, (d,i) 0.5Fe2Mg-BCP, (e,j) 0.5Fe3Mg-BCP


Figure 8 Compressive strength of pure BCP and Fe-Mg co-doped BCP (a) bioceramics and (b) scaffolds, (c) Hardness of pure BCP and Fe-Mg co-doped BCP bioceramics


Figure 9 Cumulative release concentrations of (a) Ca, (b) P, (c) Fe, and (d) Mg ions from BCP and Fe-Mg co-doped BCP scaffolds at different time points in SBF solution


Figure 10 Surface morphologies of BCP and Fe-Mg co-doped BCP scaffolds after soaking in SBF for different time periods. (a) BCP, (b) 0.5Fe-BCP, (c) 0.5Fe1Mg-BCP, (d) 0.5Fe2Mg-BCP, (e) 0.5Fe3Mg-BCP; (a1-e1) 1 day, (a2-e2) 3 days, (a3-e3) 7 days, (a4-e4) 14 days, (a5-e5) 21 days, (a6-e6) 28 days. Yellow arrows: micropores formed by biodegradation; red arrows: flake-like bioactive hydroxyapatite; blue arrows: spherical bioactive hydroxyapatite


Figure 11 Concentrations of Ca²⁺, Mg²⁺, and Fe²⁺ions in the original extracts used for culturing (a) MC3T3-E1 cells and (b) RAW 264.7 cells


Figure 12. Fluorescence images of MC3T3-E1 cells cultured in different extracts for 1, 3, and 5 days. (a) α-MEM, (b) BCP, (c) 0.5Fe-BCP, (d) 0.5Fe1Mg-BCP, (e) 0.5Fe2Mg-BCP, (f) 0.5Fe3Mg-BCP; (a1-f1) 1 day, (a2-f2) 3 days, (a3-f3) 5 days. Green staining: live cells; red staining: dead cells


Figure 13 Expression of macrophage polarization and inflammation-related genes on day 3 and day 7: (a) iNOS, (b) Arg-1, (c) TNF-α, (d) TGF-β. ∗, ∗∗, and ∗∗∗ indicate statistically significant differences at P < 0.05, 0.01, and 0.001, respectively

Conclusion:
This study, for the first time, investigated the effect of Fe-Mg co-doping on the physicobiological properties of BCP bioceramics prepared by VPP. The results revealed that the introduction of Fe reduced the curing ability of BCP slurry. Single-element Fe doping enhanced the compressive strength of BCP bioceramics and slowed their biodegradation in SBF solution. In contrast, compared with Fe doping alone, Fe-Mg co-doping decreased the compressive strength of BCP bioceramics but accelerated their biodegradation.

In vitro experiments showed that Fe-Mg co-doped BCP exhibited good biocompatibility and promoted the proliferation of MC3T3-E1 cells. The Fe-Mg co-doped BCP bioceramics induced RAW 264.7 cells to polarize toward the M1 phenotype at day 3 and toward the M2 phenotype at day 7, promoting an inflammatory response at day 3, which began to subside by day 7, with a significant enhancement of anti-inflammatory effects. The 0.5Fe2Mg-BCP significantly upregulated the expression of osteogenesis-related genes, including OPN, OCN, BMP-2, and RUNX-2. These results indicate that Fe-Mg co-doped BCP bioceramics have promising potential as bone regeneration biomaterials, offering suitable strength, good biocompatibility, and excellent bioactivity.