Copper (Cu) ions have a variety of advantageous biological functionalities, such as proangiogenic and bactericidal activities. Given the intrinsic biodegradability and biocompatibility, silicate-based mesoporous bioactive glass nanoparticles (MBGNs) are considered as promising platforms for the delivery of Cu ions. However, effective incorporation of Cu into MBGNs still faces challenges, e.g., particle aggregation, the formation of insoluble crystalline Cu-based nanoparticles, and a low loading amount of Cu. We report a novel method to synthesize chemically homogenous and highly dispersed Cu-containing MBGNs (Cu-MBGNs) with tunable Cu concentration by using ascorbic acid/Cu complexes as the precursor of Cu in a microemulsion-assisted sol-gel approach. Cu-MBGNs exhibited a sphere-like shape with a particle size between 100 and 300 nm while their pore size varied from 2 to 10 nm. The inclusion of Cu, regardless of the incorporated concentration, did not significantly affect the morphology of particles. ICP-AES results indicated that the concentration of Cu in the particles could be conveniently tuned from 0 to ~6 mol% by controlling the amount of ascorbic acid/Cu complexes added, while the formation of crystalline Cu-based nanoparticles was avoided. The amorphous feature of Cu-MBGNs was proved by XRD, while the predominant oxidation state of Cu was evidenced to be Cu²⁺ by XPS. The incorporation of Cu did not inhibit the apatite-forming ability (bioactivity) of the particles in contact with simulated body fluid. Cu-MBGNs exhibited the capability of releasing Cu, Si, and Ca ions over time in the physiological fluid. The concentration of released Cu ions could be controlled by selecting specific Cu-MBGNs of different Cu contents. The dissolution products of most Cu-MBGNs at the dosage of 1, 0.1, and 0.01 mg/mL did not exhibit cytotoxicity, while only 7Cu-MBGN was cytotoxic at the dosage of 1 mg/mL. This study provided a feasible strategy to synthesize highly dispersed amorphous Cu-MBGNs with high Cu concentrations for biomedical applications. The particles exhibit great potential as building blocks for developing composite 3D scaffolds, coatings, and drug carriers, particularly when a large amount of particles incorporated may compromise the properties of (polymer) matrix materials while a relatively high concentration of released Cu ions is still required.

Zinc (Zn)-containing materials have osteogenic and antibacterial activities while bioactive glass nanoparticles (BGN) show bone-bonding ability, as well as osteoconductive and osteoinductive properties. Zn-containing BGN are therefore considered to be promising materials for various biomedical applications, particularly in bone regeneration. In this study, we report a convenient method to prepare Zn-containing BGN by coating ZnO quantum dots (QDs) on BGN via electrostatic interactions. The synthesized ZnO–BGN nanocomposite particles are spherical and highly dispersed, and exhibit a unique fluorescence behavior under UV excitation, emitting three wavelengths in the violet, blue and green range. ZnO–BGN showed apatite-forming ability upon immersion in simulated body fluid, but their apatite formation was delayed compared to BGN. Interestingly, ZnO–BGN showed a rapid release of Zn ions at pH 4 but a far slower release at pH 7.4. ZnO–BGN also exhibited antibacterial effects on both Gram-positive and Gram-negative bacteria at the concentrations of 1, 0.1, and 0.01 mg mL⁻¹. Higher concentrations could lead to stronger antibacterial effects. The LDH and live/dead assays indicated that ZnO–BGN had no significant cytotoxicity towards human mesenchymal stem cells (hMSC) at concentration of 0.1 and 0.01 mg mL⁻¹, but ZnO–BGN inhibited the relative proliferation of hMSC compared to BGN and the control according to the MTT assay. Notably ZnO–BGN improved the osteogenic differentiation of hMSC as indicated by the determination of the alkaline phosphatase activity. In conclusion, coating quantum dots on BGN is a promising strategy to produce Zn-containing BGN. The synthesized ZnO–BGN are potential materials for bone regeneration, considering their apatite-forming ability, unique ion-release behavior, effective antibacterial activity, non-cytotoxicity, and osteogenic potential.