Laboratoire de Biomécanique & Bioingénierie, CNRS, Université de Technologie de Compiègne, BP 20529, F-60205 Compiègne Cedex, France.
Institute of Condensed Matter and Nanosciences, Bio & Soft Matter, Université catholique de Louvain, Croix du Sud 1 (L7.04.02), 1348, Louvain-la-Neuve, Belgium.
Nanoscale. 2020 May 14;12(18):10051-10064. doi: 10.1039/d0nr01638a.
In hard tissues of vertebrates, calcium phosphate (CaP) biomineralization is a fascinating process that combines specific physicochemical and biochemical reactions, resulting in the formation of extracellular matrices with elegant nanoarchitectures. Although several "biomimetic" strategies have been developed for the design of mineralized nanostructured biointerfaces, the control of the crystallization process remains complex. Herein, we report an innovative approach to overcome this challenge by generating, in situ, CaP precursors in a confined medium. For this purpose, we explore a combination of (i) the layer-by-layer assembly, (ii) the template-based method and (iii) the heterogeneous enzymatic catalysis. We show the possibility of embedding active alkaline phosphatase in a nanostructured multilayered film and inducing the nucleation and growth of CaP compounds under different conditions. Importantly, we demonstrate that the modulation of the crystal phase from spheroid-shaped amorphous CaP to crystalline platelet-shaped hydroxyapatite depends on the degree of confinement of active enzymes. This leads to the synthesis of highly anisotropic mineralized nanostructures that are mechanically stable and with controlled dimensions, composition and crystal phase. The present study provides a straightforward, yet powerful, way to design anisotropic nanostructured materials, including a self-supported framework, which may be used in broad biomedical applications.
在脊椎动物的硬组织中，磷酸钙（CaP）生物矿化是一个引人入胜的过程，它结合了特定的物理化学和生化反应，导致具有优雅纳米结构的细胞外基质的形成。尽管已经开发了几种“仿生”策略来设计矿化纳米结构的生物界面，但结晶过程的控制仍然很复杂。在这里，我们报告了一种通过在受限介质中就地生成 CaP 前体来克服这一挑战的创新方法。为此，我们探索了（i）层层组装、（ii）基于模板的方法和（iii）异相酶催化的结合。我们展示了在纳米结构化多层膜中嵌入活性碱性磷酸酶并在不同条件下诱导 CaP 化合物成核和生长的可能性。重要的是，我们证明了从球形无定形 CaP 到结晶板状羟基磷灰石的晶体相的调制取决于活性酶的受限程度。这导致了具有各向异性的高度矿化纳米结构的合成，这些纳米结构具有机械稳定性和可控的尺寸、组成和晶体相。本研究提供了一种简单而强大的设计各向异性纳米结构材料的方法，包括自支撑框架，可广泛应用于生物医学应用。
