Precipitation of doped hydroxyapatite nanoparticles in a Y-shaped 3D-printed continuous millireactor

This paper demonstrates the continuous synthesis of magnesium-, zinc-, copper-, cobalt-, or strontium-doped hydroxyapatite nanoparticles (nHAp) using a 3D-printed Y-shaped millireactor, emphasizing process intensification. Continuous precipitation provided precise control over particle morphology and size (below 40 nm), yielding spherical nanoparticles that retain key hydroxyapatite functional groups. Uniquely, the continuous system yielded predominantly amorphous structures compared to conventional batch methods, potentially enhancing solubility and bioactivity. Doping efficiencies varied by ion: cobalt and strontium incorporation were compared favorably to values reported in the batch precipitation literature under comparable stoichiometries; magnesium doping was comparable; zinc doping was comparable at similar initial concentrations but lower at higher initial concentrations; and copper doping was lower. The intensified mass- and heat-transfer kinetics of the continuous system contribute to enhanced doping efficiency and product homogeneity. Nanoparticles demonstrated limited colloidal stability in aqueous suspensions, with zeta potential values indicating strong agglomeration regardless of doping. This study highlights the advantages of continuous precipitation in achieving scalable and reproducible synthesis of multifunctional doped nHAp, offering added angiogenic and enhanced osteogenic potential critical for bone tissue engineering. Future work should focus on biological evaluations, ion-release kinetics, and process optimization to fully leverage the intensified continuous production for industrial applications.