Modelling Ion Migration in Bioactive Glasses

生物活性玻璃被广泛应用于生物医学中，作为修复和再生植入物，它们在暴露于身体生理环境后不久就能与硬组织(骨、牙齿)和软组织(肌腱、韧带)粘合。这种能力反映了材料对接触生理液体的反应，涉及一系列物理化学过程，导致植入后几小时或几天内在玻璃表面形成一层类骨磷灰石(AP)。AP层提供了一个强大的界面，有效地将材料和活组织结合在一起：这种稳定的生物材料-组织链接促进了植入物的整合，因此是其成功的关键。自20世纪80年代以来，许多研究在这一领域取得了重大进展：玻璃的生物活性，即其与骨结合和/或诱导组织修复和再生的能力，通常通过测量体内或体外AP的形成速度来评估，玻璃成分、颗粒形态、表面纹理和热处理的重要性现在已经得到证实。进一步技术进步的一个主要障碍是，尽管它们很重要，但生物玻璃的结构-生物活性关系仍然很大程度上是未知的，主要是由于缺乏准确的结构数据。这些材料的无序和多组分的性质阻碍了标准实验探针的应用来获取它们的结构，结果是对组成效应的预测和测试主要依赖于低效和昂贵的试错方法：虽然已经确定了典型熔体衍生组合物的生物活性的范围和水平，但没有提出合理的解释来解释生物活性随组合物的急剧变化。任何这样的解释都需要详细了解原子结构，至少是最常见的熔体衍生生物玻璃。传统的熔体衍生生物玻璃的结构研究仍然非常必要：由于许多熔体衍生成分的生物活性水平已经被准确测量，这些结构研究可以提供对结构-活性影响的直接洞察，并且由此产生的知识应该可以转移到不同组成的玻璃和/或通过不同的途径获得。原子计算机模拟可以提供这些材料的结构和动力学特征的高分辨率图像，从而支持一种更合理的方法来确定这些玻璃的组成、结构和生物活性之间的联系。至于标准的实验技术，生物活性玻璃对建模方法也是一个重大挑战。我们最近的计算研究解决了生物玻璃的整体结构：通过对不同已知生物活性的成分进行模拟，我们确定了标记生物活性或生物非活性成分的特定结构特征；这些大量结构数据和获得的相应见解代表了基本的基线，可以在此基础上进行进一步的具体研究。一个很大程度上仍未被探索的领域是Na和Ca离子的扩散动力学：它们在体相结构中的迁移在生物活性机制中起着关键作用，因为钠离子最初浸出到生理溶液中，以及随后从玻璃中释放钙都是生物活性机制中的关键步骤。关于钠和钙迁移的数据很少；本项目旨在利用分子动力学模拟来研究修饰阳离子在生物玻璃中的扩散机制。最终目的是确定玻璃组成、局部配位/结构和修饰阳离子的运输之间的可能相关性，这些可能与生物活性有关，从而改善我们目前对这些材料工作原理的有限理解。

Bioactive glasses (bioglasses) are widely used in biomedicine as restorative and regenerative implants, which exploit their ability to bond to hard (bone, teeth) and soft (tendons, ligaments) tissues shortly after exposure to the body physiological environment. This ability reflects a reactive response of the material to the contact with physiological fluids, involving a series of physico-chemical processes, leading to the formation of a layer of bone-like apatite (Ap) on the glass surface within a few hours or days after implantation. The Ap layer provides a strong interface effectively bonding the material and the living tissues: this stable biomaterial-tissue link promotes the integration of the implant and is therefore central for its success. Since the 1980s many studies have led to significant developments in this field: the glass bioactivity, i.e., its ability to bond to bone and/or to induce tissue repair and regeneration, is usually assessed by measuring the rate of Ap formation in-vitro or in-vivo, and the importance of glass composition, particle morphology, surface texture, and thermal treatment is now well established. One major obstacle to further technological progress is that, despite their importance, structure-bioactivity relationships are still largely unknown for bioglasses, mostly due to lack of accurate structural data. The disordered and multicomponent nature of these materials hinders the application of standard experimental probes to access their structure, with the result that prediction and test of compositional effects mostly relies on inefficient and expensive trial-and-error approaches: while the range and level of bioactivity of typical melt-derived compositions has been determined, no rational interpretation of the sharp changes in bioactivity with the composition has been proposed. Any such interpretation requires a detailed knowledge of the atomistic structure, at least of the most common melt-derived bioglasses. Structural investigations of the traditional, melt-derived bioglasses are still highly needed: since the bioactivity level of many melt-derived compositions has been exactly measured, these structural investigations can provide direct insight into structure-activity effects, and the resulting knowledge should be transferable to glasses of different composition and/or obtained through different routes. Atomistic computer simulations can provide a high-resolution picture of structural and dynamical features of these materials, thus supporting a more rational approach to identify the links between the composition, the structure, and the bioactivity of these glasses. As for standard experimental techniques, bioactive glasses represent a significant challenge also to modelling approaches. Our recent computational studies have tackled the bulk structure of bioglasses: by modelling compositions of different, known bioactivity, we identified specific structural features marking bioactive or bio-inactive compositions; these bulk structural data and the corresponding insight obtained represent the essential baseline, upon which further specific investigations can be based. A still largely unexplored field is the diffusive dynamics of Na and Ca cations: their migration within the bulk structure plays a critical role in the bioactive mechanism, because the initial leaching of sodium ions into the physiological solution, and the subsequent release of Ca from the glass are both key steps in the bioactive mechanism. Very few data are available on the Na and Ca transport; the present project aims at investigating the diffusive mechanism of modifier cations in bioglasses, using Molecular Dynamics simulations. The final purpose is to identify possible correlations between the glass composition, the local coordination/structure and the transport of modifier cations, which can be linked to the bioactive properties, and therefore improve our current limited understanding of how these materials work.