Evaluation of magnetic hyperthermia, drug delivery and biocompatibility (bone cell adhesion and zebrafish assays) of trace element co-doped hydroxyapatite combined with Mn–Zn ferrite for bone tissue applications

Abstract

The treatment and regeneration of bone defects, especially tumor-induced defects, is an issue in clinical practice and remains a major challenge for bone substitute material invention. In this research, a composite material of biomimetic bone-like apatite based on trace element co-doped apatite (Ca_10−δM_δ(PO₄)_5.5(CO₃)_0.5(OH)₂; M = trace elements of Mg, Fe, Zn, Mn, Cu, Ni, Mo, Sr and BO₃³⁻; THA)-integrated-biocompatible magnetic Mn–Zn ferrite ((Mn, Zn)Fe₂O₄ nanoparticles, BioMags) called THAiBioMags was prepared via a co-precipitation method. Its characteristics, i.e., physical properties, hyperthermia performance, ion/drug delivery, were investigated in vitro using osteoblasts (bone-forming cells) and in vivo using zebrafish. The synthesized THAiBioMags particles revealed superparamagnetic behaviour at room temperature. Under the influence of an alternating magnetic field, THAiBioMags particles demonstrated a change in temperature, indicating their potential for magnetic hyperthermia, in which THAiBioMags further exhibited a specific absorption rate (SAR) value of 9.44 W g⁻¹ (I = 44 A, H = 6.03 kA m⁻¹ and f = 130 kHz). In addition, the as-prepared particles demonstrated sustained ion/drug (doxorubicin (DOX)) release under physiological pH conditions. Biological assay analysis revealed that THAiBioMags exhibited no toxicity towards osteoblast cells and demonstrated excellent cell adhesion properties. In vivo studies employing an embryonic zebrafish model showed the non-toxic nature of the synthesized THAiBioMags particles, as revealed by evaluation of the survivability, hatching rate, and embryonic morphology. These results could potentially lead to the design and fabrication of magnetic scaffolds to be used in therapeutic treatment and bone regeneration.