The potential of external ions doped biomaterials has been extensively explored; however, the co-doped biomaterials remain typically unexplored for their biological properties for precise biomedical applications. The current study was aimed to explore the impact of structural features of Sr/Fe co-doped hydroxyapatite (HAp) bionanomaterial on osteoblastic proliferation and osteogenic differentiation for its application as a bone substitute. A 10 mol% isomorphous co-doping of strontium and iron with respect to calcium was carried into HAp in the solid solution. Raman spectroscopy verified the presence of major functional groups of apatite structure together with the carbonate peaks. The Sr/Fe co-doped HAp bionanomaterials showed slightly negative zeta potential (at neutral pH), versatile DLS particle size (140–205 nm), high BET surface area (186 m²/g), and narrow width pore size (13–19 nm). TG/DTA analysis showed low thermal stability of the Sr/Fe co-doped HAp groups. The nanoparticles showed an initial burst release of amoxicillin for 15 h followed by extended-release up to 81 h and demonstrated an excellent antibacterial activity by producing inhibition zones of 17.6 ± 0.3 mm and 19.5 mm ± 0.4 mm for Escherichia coli and Staphylococcus aureus. Live/dead cell staining and MTT assay confirmed the non-toxic nature of Sr/Fe co-doped HAp bionanomaterial towards MC3T3-E1 cells. Further, an improved ALP activity, increased calcium deposition, enhanced RUNX2 expression, and regulated OPN and OCN expression levels suggest in MC3T3-E1 cells demonstrate the maturation of osteoblasts. This study provides the unique advantages of the co-doping approach for the applications Sr/Fe co-doped HAp bionanomaterials as a bone substitute.

外部离子掺杂生物材料的潜力已被广泛探索；然而，共掺杂​​生物材料在精确生物医学应用中的生物特性通常尚未得到探索。本研究旨在探讨Sr/Fe共掺杂羟基磷灰石（HAp）生物纳米材料的结构特征对成骨细胞增殖和成骨分化的影响，及其作为骨替代物的应用。相对于钙，锶和铁的 10 mol% 同晶共掺杂被带入固溶体中的 HAp 中。拉曼光谱证实了磷灰石结构的主要官能团以及碳酸盐峰的存在。Sr/Fe 共掺杂 HAp 生物纳米材料表现出轻微的负 zeta 电位（在中性 pH 下）、多种 DLS 粒径（140–205 nm）、高 BET 表面积（186 m 2 /g）和窄宽度孔径^（ 13 –19 纳米）。TG/DTA 分析表明 Sr/Fe 共掺杂 HAp 基团的热稳定性较低。该纳米颗粒首先突释阿莫西林 15 小时，然后延长释放长达 81 小时，并通过对大肠杆菌和金黄色葡萄球菌产生 17.6 ± 0.3 mm 和 19.5 mm ± 0.4 mm 的抑制区而表现出优异的抗菌活性。活/死细胞染色和 MTT 测定证实了 Sr/Fe 共掺杂 HAp 生物纳米材料对 MC3T3-E1 细胞的无毒性质。此外，MC3T3-E1 细胞中 ALP 活性的改善、钙沉积的增加、RUNX2 表达的增强以及 OPN 和 OCN 表达水平的调节表明成骨细胞的成熟。这项研究为Sr/Fe共掺杂HAp生物纳米材料作为骨替代品的应用提供了共掺杂方法的独特优势。