Aberdeen Centre for Arthritis and Musculoskeletal Health, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
Aberdeen Centre for Arthritis and Musculoskeletal Health, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK; Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen AB24 3UE, UK.
Biomater Adv. 2022 Sep;140:213068. doi: 10.1016/j.bioadv.2022.213068. Epub 2022 Aug 3.
Hydroxyapatite is a commonly researched biomaterial for bone regeneration applications. To augment performance, hydroxyapatite can be substituted with functional ions to promote repair. Here, co-substituted lithium ion (Li) and carbonate ion hydroxyapatite compositions were synthesised by an aqueous precipitation method. The co-substitution of Li and CO is a novel approach that accounts for charge balance, which has been ignored in the synthesis of Li doped calcium phosphates to date. Three compositions were synthesised: Li-free (Li 0), low Li (Li 0.25), and high Li (Li 1). Synthesised samples were sintered as microporous discs (70-75 % theoretical sintered density) prior to being ground and fractionated to produce granules and powders, which were then characterised and evaluated in vitro. Physical and chemical characterisation demonstrated that lithium incorporation in Li 0.25 and Li 1 samples approached design levels (0.25 and 1 mol%), containing 0.253 and 0.881 mol% Li ions, respectively. The maximum CO ion content was observed in the Li 1 sample, with ~8 wt% CO, with the carbonate ions located on both phosphate and hydroxyl sites in the crystal structure. Measurement of dissolution products following incubation experiments indicated a Li burst release profile in DMEM, with incubation of 30 mg/ml sample resulting in a Li ion concentration of approximately 140 mM after 24 h. For all compositions evaluated, sintered discs allowed for favourable attachment and proliferation of C2C12 cells, human osteoblast (hOB) cells, and human mesenchymal stem cells (hMSCs). An increase in alkaline phosphatase (ALP) activity with Li doping was demonstrated in C2C12 cells and hMSCs seeded onto sintered discs, whilst the inverse was observed in hOB cells. Furthermore, an increase in ALP activity was observed in C2C12 cells and hMSCs in response to dissolution products from Li 1 samples which related to Li release. Complementary experiments to further investigate the findings from hOB cells confirmed an osteogenic role of the surface topography of the discs. This research has shown successful synthesis of Li doped carbonated hydroxyapatite which demonstrated cytocompatibility and enhanced osteogenesis in vitro, compared to Li-free controls.
羟基磷灰石是一种常用于骨再生应用的研究生物材料。为了提高性能，可以用功能离子替代羟基磷灰石以促进修复。在这里，通过水相沉淀法合成了锂离子（Li）和碳酸根离子共取代的羟基磷灰石组合物。Li 和 CO 的共取代是一种新方法，考虑到了电荷平衡，这在迄今为止的 Li 掺杂磷酸钙合成中被忽略了。合成了三种组成：无 Li（Li 0）、低 Li（Li 0.25）和高 Li（Li 1）。合成的样品被烧结成微孔圆盘（理论烧结密度的 70-75%），然后研磨并分级以产生颗粒和粉末，然后对其进行体外特性和评估。物理化学特性表明，Li 0.25 和 Li 1 样品中的 Li 掺入接近设计水平（0.25 和 1mol%），分别含有 0.253 和 0.881mol%的 Li 离子。Li 1 样品中观察到最大的 CO 离子含量，约为 8wt%的 CO，碳酸根离子位于晶体结构中的磷酸根和羟基位置上。孵育实验后测量溶解产物表明，在 DMEM 中存在 Li 突释释放，30mg/ml 样品孵育 24 小时后，Li 离子浓度约为 140mM。对于所有评估的组成，烧结圆盘允许 C2C12 细胞、人成骨细胞（hOB）细胞和人间充质干细胞（hMSC）良好地附着和增殖。在 C2C12 细胞和接种到烧结圆盘上的 hMSC 中，随着 Li 掺杂的增加，碱性磷酸酶（ALP）活性增加，而在 hOB 细胞中则相反。此外，C2C12 细胞和 hMSC 对 Li 1 样品溶解产物的反应中观察到 ALP 活性增加，这与 Li 释放有关。进一步研究 hOB 细胞结果的补充实验证实了圆盘表面形貌在成骨中的作用。这项研究成功合成了 Li 掺杂碳酸化羟基磷灰石，与 Li 自由对照相比，其在体外具有细胞相容性和增强的成骨作用。
