Cu‐doped magnesium phosphate supraparticles: A promising material for bone tissue regeneration

Calcium phosphate (CaP) minerals have been widely studied as bone substitutes due to their excellent osteoconductivity and biocompatibility. However, their limited biodegradability remains a challenge. Magnesium phosphates (MgPs) are promising alternatives; offering similar properties to CaP while exhibiting enhanced bioresorption due to their higher solubility. To advance the relatively unexplored field of MgP research, this study investigated Cu-doped MgP supraparticles with enhanced biodegradability as potential bone substitute materials. For this purpose, MgP nanoparticles (NPs) were synthesized using a modified sol-gel process with different parameter variations to tailor the crystal structure and particle size. The NPs were then spray-dried with Cu ions (5.0 wt%) to produce antibacterial supraparticles whose unique properties were demonstrated in previous studies on CaP supraparticles. Subsequent calcination was used to study the impact of the crystal structure on Cu release experiments over 14 days as well as its efficacy against the gram-positive bacterium Staphylococcus aureus. In particular, uncalcined, amorphous MgP supraparticles exhibited high Cu release in bi-distilled water and antibacterial activity when tested as eluates. Interestingly, all MgP particle systems, with or without Cu, achieved a significant bactericidal effect against S. aureus at a particle concentration of 100 mg/mL in Mueller Hinton Broth, thereby demonstrating the antibacterial effect of Mg2+ ions. The cell viability of the supraparticles was also investigated using human telomerase–immortalized mesenchymal stromal cells (hMSC-TERT), which exhibited high biocompatibility at particle concentrations of 0.01-0.1 mg/L over 72 h. Uncalcined Cu-doped MgP supraparticles induced the expression of proinflammatory markers (interleukin 1 beta, interleukin 6, interleukin 8, and serum amyloid A1), whereas the expression of osteogenic markers (alkaline phosphatase, bone gamma-carboxyglutamate protein, and secreted phosphoprotein 1) was only slightly affected. However, the osteogenic differentiation of hMSC-TERT showed a positive effect on mineralization when exposed to uncalcined MgP supraparticles. Overall, the results indicate that MgP supraparticles, both with and without Cu, exhibit high biocompatibility and hold promise for applications in bone tissue regeneration.