仿生学因其多种功能优势正逐渐深入到生物陶瓷的领域。自然界中的羟基磷灰石（HA）除了原初的纳米结构外，还具有各种离子置换。将这些关键元素纳入HA晶格的容易程度已知会增强生物陶瓷的骨愈合性能。本文采用仿生方法合成羟基磷灰石，并通过单独和多种阳离子置换来用于骨修复。首次使用在定义的生物矿化培养基中培养的实验杆菌进行Sr，Mg和Zn HA的离子置换。对不同浓度的单独离子置换在Serratia HA（Sr SHA，Mg SHA和Zn SHA）中进行了晶体性，功能组，形态和晶体尺寸的分析。所有三种情况下，晶体性降低，相位纯度下降，大量聚集成团，呈针状形态。傅里叶变换红外光谱（FTIR）显示碳酸盐含量增加了5.8％，类似于天然骨骼。此外，减少的羟基（O-H）强度清晰表明HA晶格受到了破坏和随后的离子置换。本研究的创新之处主要在于调查1％Sr，Zn和Mg的组合共置换在SHA中的作用，以及与之相关的骨参数的变化。扫描电镜（SEM）和透射电镜（TEM）图像清晰地展示了Sr SHA的均匀纳米级成团的平均尺寸为20-50 nm长，8-15 nm宽；在Zn SHA和Mg SHA的情况下，它们的尺寸分别为10-40 nm长，8-10 nm宽；在1％Sr，Zn，Mg SHA的情况下，它们的尺寸为40-70 nm长，4-10 nm宽。在单独或共置换中，由于浓度较低，未观察到明显的峰移。但由于Sr2+的存在，细胞体积在两种情况下均有所增加，验证了它在SHA晶格中的占主导地位。能量分散X射线光谱（EDS）和电感耦合等离子体光谱法（ICP-OES）定量评价了富含痕量离子沉积。在三个细胞系（NIH / 3T3成纤维细胞，MG-63骨肉瘤细胞和RAW 264.7巨噬细胞）中进行的体外细胞毒性研究表明，1％Sr，Zn和Mg在SHA中的生物相容性超过90％。Serratia的微生物生物矿化产生了羟基磷灰石的纳米晶体，其与骨骼类似，纯净度高，含有碳酸基团，晶体性降低，纳米成团，细胞参数变化，痕量离子沉积丰富，不具有毒性。因此，离子置换和共置换的生物韵律纳米SHA似乎是用于生物医学中骨伤的治疗和愈合的适当候选物，因为其特性与人类骨骼相近。 © 2023年 原作者

Biomimicry is becoming deep-rooted as part of bioceramics owing to its numerous functional advantages. Naturally occurring hydroxyapatite (HA) apart from primary nano structures are also characterised by various ionic substitutions. The ease of accommodating such key elements into the HA lattice is known to enhance bone healing properties of bioceramics. In this work, hydroxyapatite synthesized via biomimetic approach was substituted with individual as well as multiple cations for potential applications in bone repair. Ion substitutions of Sr, Mg and Zn was carried out on HA for the first time by using Serratia grown in a defined biomineralization medium. The individual ions of varying concentration substituted in Serratia HA (SHA) (Sr SHA, Mg SHA and Zn SHA) were analysed for crystallinity, functional groups, morphology and crystal size. All three showed decreased crystallinity, phase purity, large agglomerated aggregates and needle-shaped morphologies. Fourier transform infrared spectroscopy (FTIR) spectra indicated increased carbonate content of 5.8% resembling that of natural bone. Additionally, the reduced O-H intensities clearly portrayed disruption of HA lattice and subsequent ion-substitution. The novelty of this study lies primarily in investigating the co-substitution of a combination of 1% Sr, Zn and Mg in SHA and establishing the associated change in bone parameters. Scanning electron microscope (SEM) and transmission electron microscope (TEM) images clearly illustrated uniform nano-sized agglomerates of average dimensions of 20-50 nm length and 8-15 nm width for Sr SHA; 10-40 nm length and 8-10 nm width for both Zn SHA and Mg SHA and 40-70 nm length and 4-10 nm width in the case of 1% Sr, Zn, Mg SHA. In both individual as well as co-substitutions, significant peak shifts were not observed possibly due to the lower concentrations. However, cell volumes increased in both cases due to presence of Sr2+ validating its dominant integration into the SHA lattice. Rich trace ion deposition was presented by energy dispersive X-ray spectroscopy (EDS) and quantified using inductively coupled plasma optical emission spectrometer (ICP-OES). In vitro cytotoxicity studies in three cell lines viz. NIH/3T3 fibroblast cells, MG-63 osteosarcoma cells and RAW 264.7 macrophages showed more than 90% cell viability proving the biocompatible nature of 1% Sr, Zn and Mg in SHA. Microbial biomineralization by Serratia produced nanocrystals of HA that mimicked "bone-like apatite" as evidenced by pure phase, carbonated groups, reduced crystallinity, nano agglomerates, variations in cell parameters, rich ion deposition and non-toxic nature. Therefore ion-substituted and co-substituted biomineralized nano SHA appears to be a suitable candidate for applications in biomedicine addressing bone injuries and aiding regeneration as a result of its characteristics close to that of the human bone.© 2023. The Author(s).