The role of fluorine in bioactive glasses is of interest due to the potential of precipitating fluorapatite, a phase with higher chemical resistance than the typical hydroxyapatite precipitated from oxide bioactive glasses. However, the introduction of fluorine in silicate bioactive glasses was found deleterious to the bioactivity of the glass. Here, phosphate glasses with the composition 75NaPO₃-(25-x) CaO-xCaF₂ (in mol%), with x = 0–20 and glass-ceramics were investigated to evaluate their potential as substitutes to the traditional silicate bioactive glass. An increase in CaF₂ substitution for CaO led to an increase in the glass solubility, due to an increase in highly soluble F(M)n species (where M is a cation) and to an increased polymerization of the phosphate network. Structural analysis reveals the formation of FP bonds, in addition to the F(M)n species, in the glass with the higher CaF₂ content. Furthermore, with heat treatment, CaF₂ crystals precipitate within the bulk in the newly developed glass, when x = 20. This bulk crystallization reduces the glass dissolution without compromising the precipitation of a reactive layer at the glass surface. Finally, in vitro cell tests were performed using MC3T3 pre-osteoblastic cells. While the substitution of CaF₂ for CaO led to an increased cytotoxicity, the controlled crystallization of the fluorine containing glasses decreased such cytotoxicity to similar values than traditional bioactive phosphate glass (x0). This study reports on new oxyfluorophosphate glass and glass-ceramics able, not only, to precipitate a Ca-P reactive layer but also to be processed into glass-ceramics with controlled crystal size, density and cellular activity.

Statement of significance

Uncontrolled crystallization of bioactive glasses has negative effect on the materials' bioactivity. While in silicate glass the bioactivity is solely reduced, in phosphate glasses it is often completely suppressed. Furthermore, the need for fluorine containing bioactive glasses, not only for use in bone reconstruction but also in toothpaste as emerged. The addition of F in both silicate and phosphate has led to challenges due the lack of Si-F or P-F bonds, generally leading to a decrease in bioactivity. Here, we developed a bioactive invert phosphate glass where up to 20 mol% of CaO was replaced with CaF₂. In the new developed glasses, NMR demonstrated formation of P-F bonds. The content of fluorine was tailored to induce CaF₂ bulk crystallization. Overall an increase in F was associated with an increase network connectivity. In turns it led to an increased dissolution rate which was linked to a higher cytotoxicity. Upon (partial to full) surface crystallization of the F-free glass, the bioactivity (ability to form a reactive layer) was loss and the cytotoxicity again increased due to the rapid dissolution of one crystal phase and of the remaining amorphous phase. On another hand, the controlled bulk precipitation of CaF₂ crystals, in the F-containing glass, was associated with a reduced cytotoxicity. The new oxyfluorophosphate glass-ceramic developed is promising for application in the biomedical field.

中文翻译：

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磷酸盐/氧氟磷酸盐玻璃的结晶及其对溶解和细胞毒性的影响。

氟在生物活性玻璃中的作用是令人感兴趣的，这是因为有可能使氟磷灰石沉淀，该相具有比从氧化物生物活性玻璃中沉淀的典型羟基磷灰石更高的耐化学性。然而，发现在硅酸盐生物活性玻璃中引入氟对玻璃的生物活性有害。在这里，对组成为75NaPO _3-（25-x）CaO-xCaF ₂（以摩尔％计），x = 0-20的磷酸盐玻璃和玻璃陶瓷进行了研究，以评估其替代传统硅酸盐生物活性玻璃的潜力。CaF ₂替代CaO的增加导致玻璃溶解度的增加，这是由于高可溶性F（Mn个物种（其中M为阳离子）并增强磷酸盐网络的聚合。结构分析表明，在具有较高CaF ₂含量的玻璃中，除了F（M）n物种外，还形成了F P键。此外，通过热处理，当x = 20时，CaF ₂晶体会沉淀在新开发的玻璃中的块体内。这种块状结晶减少了玻璃的溶解，而不会损害玻璃表面反应层的沉淀。最后，使用MC3T3骨成骨前细胞进行体外细胞测试。而CaF ₂的替代由于CaO导致细胞毒性增加，含氟玻璃的受控结晶将这种细胞毒性降低到与传统生物活性磷酸盐玻璃（x0）相似的值。这项研究报道了新的含氧氟磷酸盐玻璃和玻璃陶瓷，它们不仅能够沉淀Ca-P反应层，而且能够加工成具有受控晶体尺寸，密度和细胞活性的玻璃陶瓷。

重要声明

生物活性玻璃的不受控制的结晶会对材料的生物活性产生负面影响。虽然在硅酸盐玻璃中仅降低了生物活性，但在磷酸盐玻璃中通常却被完全抑制了。此外，出现了对不仅用于骨骼重建而且还用于牙膏中的含氟生物活性玻璃的需求。由于缺乏Si-F或PF键，在硅酸盐和磷酸盐中都添加了F导致了挑战，通常导致生物活性降低。在这里，我们开发了一种生物活性的可逆磷酸盐玻璃，其中多达20 mol％的CaO被CaF ₂代替。在新开发的玻璃中，NMR证实了PF键的形成。调整氟含量以诱导CaF ₂大量结晶。总体而言，F的增加与网络连接性的增加有关。继而导致溶解速率增加，这与更高的细胞毒性有关。在无氟玻璃的表面结晶（部分或全部）时，由于一种晶相和其余无定形相的快速溶解，生物活性（形成反应层的能力）丧失，细胞毒性再次提高。另一方面，在含氟玻璃中控制的CaF ₂晶体的大量沉淀与降低的细胞毒性有关。开发的新型氧氟磷酸盐玻璃陶瓷有望在生物医学领域中应用。