Mineralized tissues

The evolution of mineralized tissues has been puzzling for more than a century. It has been hypothesized that the first mechanism of animal tissue mineralization began either in the oral skeleton of conodont or the dermal skeleton of early agnathans. The dermal skeleton is just surface dentin and basal bone, which is sometimes overlaid by enameloid. It is thought that the dermal skeleton eventually became scales, which are homologous to teeth. Teeth were first seen in chondrichthyans and were made from all three components of the dermal skeleton, namely dentin, basal bone and enameloid. The mineralization mechanism of mammalian tissue was later elaborated in actinopterygians and sarcopterygians during bony fish evolution. It is expected that genetic analysis of agnathans will provide more insight into the evolution of mineralized tissues and clarify evidence from early fossil records. ==Hierarchical structure==

Hierarchical structures are distinct features seen throughout different length scales. Hierarchical structures are characteristic of biology and are seen in all structural materials in biology such as bone and nacre from seashells Nacre Nacre has several hierarchical structural levels. The types of mechanisms that operate at different structural length scales are yet to be properly defined. Five hierarchical structures of bone are presented below. The macroscale Compact bone and spongy bone are on a scale of several millimetres to 1 or more centimetres. The microscale There are two hierarchical structures on the microscale. The first, at a scale of 100 μm to 1 mm, is inside the compact bone where cylindrical units called osteons and small struts can be distinguished. The second hierarchical structure, the ultrastructure, at a scale of 5 to 10 μm, is the actual structure of the osteons and small struts. The nanoscale There are also two hierarchical structures on the nanoscale. The first being the structure inside the ultrastructure that are fibrils and extrafibrillar space, at a scale of several hundred nanometres. The second are the elementary components of mineralized tissues at a scale of tens of nanometres. The components are the mineral crystals of hydroxyapatite, cylindrical collagen molecules, organic molecules such as lipids and proteins, and finally water. The hierarchical structure common to all mineralized tissues is the key to their mechanical performance. ==Mineral component==

The mineral is the inorganic component of mineralized tissues. This constituent is what makes the tissues harder and stiffer. In bone, studies have shown that calcium phosphate nucleates within the hole area of the collagen fibrils and then grows in these zones until it occupies the maximum space. ==Organic component==

The organic part of mineralized tissues is made of proteins. However, without this organic portion, the biological material would be brittle and break easily. Moreover, many proteins are regulators in the mineralization process. They act in the nucleation or inhibition of hydroxyapatite formation. For example, the organic component in nacre is known to restrict the growth of aragonite. Some of the regulatory proteins in mineralized tissues are osteonectin, osteopontin, osteocalcin, bone sialoprotein and dentin phosphophoryn. In nacre, the organic component is porous, which allows the formation of mineral bridges responsible for the growth and order of the nacreous tablets. ==Formation of minerals==

Understanding the formation of biological tissues is inevitable in order to properly reconstruct them artificially. Even if questions remain in some aspects and the mechanism of mineralization of many mineralized tissues need yet to be determined, there are some ideas about those of mollusc shell, bone and sea urchin. ==Organic-inorganic interface==

The mineral-protein interface with its underlying adhesion forces is involved in the toughening properties of mineralized tissues. The interaction in the organic-inorganic interface is important to understand these toughening properties. At the interface, a very large force (>6-5 nN) is needed to pull the protein molecules away from the aragonite mineral in nacre, despite the fact that the molecular interactions are non-bonded. A model has shown that during tension, the back stress that is induced during the plastic stretch of the material plays a big role in the hardening of the mineralized tissue. As well, the nanoscale asperities that is on the tablet surfaces provide resistance to interlamellar sliding and so strengthen the material. A surface topology study has shown that progressive tablet locking and hardening, which are needed for spreading large deformations over large volumes, occurred because of the waviness of the tablets. ==Diseased mineralized tissues==

In vertebrates, mineralized tissues not only develop through normal physiological processes, but can also be involved in pathological processes. Some diseased areas that include the appearance of mineralized tissues include atherosclerotic plaques, tumoral calcinosis, juvenile dermatomyositis, kidney and salivary stones. All physiologic deposits contain the mineral hydroxyapatite or one analogous to it. Imaging techniques such as infrared spectroscopy are used to provide information on the type of mineral phase and changes in mineral and matrix composition involved in the disease. The causes and cures of these conditions can possibly be found from further studies on the role of the mineralized tissues involved. ==Bioinspired materials==

Natural structural materials comprising hard and soft phases arranged in elegant hierarchical multiscale architectures, usually exhibit a combination of superior mechanical properties. For instance, many natural mechanical materials (Bone, Nacre, Teeth, Silk, and Bamboo) are lightweight, strong, flexible, tough, fracture-resistant, and self-repair. The general underlying mechanism behind such advanced materials is that the highly oriented stiff components give the materials great mechanical strength and stiffness, while the soft matrix "glues" the stiff components and transfer the stress to them. Moreover, the controlled plastic deformation of the soft matrix during fracture provides an additional toughening mechanism. Such a common strategy was perfected by nature itself over millions of years of evolution, giving us the inspiration for building the next generation of structural materials. There are several techniques used to mimic these tissues. Some of the current techniques are described here. Large scale model materials The large scale model of materials is based on the fact that crack deflection is an important toughening mechanism of nacre. This deflection happens because of the weak interfaces between the aragonite tiles. Systems on the macroscopic scales are used to imitate these week interfaces with layered composite ceramic tablets that are held together by weak interface "glue". Hence, these large scale models can overcome the brittleness of ceramics. Since other mechanisms like tablet locking and damage spreading also play a role in the toughness of nacre, other models assemblies inspired by the waviness of microstructure of nacre have also been devised on the large scale. metal/ceramic, and polymer/ceramic hybrid biomimetic materials with fine lamellar or brick-and-mortar architectures. The "brick" layer is extremely strong but brittle and the soft "mortar" layer between the bricks generates limited deformation, thereby allowing for the relief of locally high stresses while also providing ductility without too much loss in strength. Additive manufacturing Additive manufacturing encompasses a family of technologies that draw on computer designs to build structures layer by layer. Recently, a lot of bioinspired materials with elegant hierarchical motifs have been built with features ranging in size from tens of micrometers to one submicrometer. Therefore, the crack of materials only can happen and propagate on the microscopic scale, which wouldn't lead to the fracture of the whole structure. However, the time-consuming of manufacturing the hierarchical mechanical materials, especially on the nano- and micro-scale limited the further application of this technique in large-scale manufacturing. Layer-by-layer deposition Layer-by-layer deposition is a technique that as suggested by its name consists of a layer-by-layer assembly to make multilayered composites like nacre. Some examples of efforts in this direction include alternating layers of hard and soft components of TiN/Pt with an ion beam system. The composites made by this sequential deposition technique do not have a segmented layered microstructure. Thus, sequential adsorption has been proposed to overcome this limitation and consists of repeatedly adsorbing electrolytes and rinsing the tablets, which results in multilayers. Thin film deposition: microfabricated structures Thin film deposition focuses on reproducing the cross-lamellar microstructure of conch instead of mimicking the layered structure of nacre using micro-electro mechanical systems (MEMS). Among mollusk shells, the conch shell has the highest degree of structural organization. The mineral aragonite and organic matrix are replaced by polysilicon and photoresist. The MEMS technology repeatedly deposits a thin silicon film. The interfaces are etched by reactive ion etching and then filled with photoresist. There are three films deposited consecutively. Although the MEMS technology is expensive and more time-consuming, there is a high degree of control over the morphology and large numbers of specimens can be made. Self-assembly The method of self-assembly tries to reproduce not only the properties, but also the processing of bioceramics. In this process, raw materials readily available in nature are used to achieve stringent control of nucleation and growth. This nucleation occurs on a synthetic surface with some success. The technique occurs at low temperature and in an aqueous environment. Self-assembling films form templates that effect the nucleation of ceramic phases. The downside with this technique is its inability to form a segmented layered microstructure. Segmentation is an important property of nacre used for crack deflection of the ceramic phase without fracturing it. As a consequence, this technique does not mimic microstructural characteristics of nacre beyond the layered organic/inorganic layered structure and requires further investigation. ==The future==

The various studies have increased progress towards understanding mineralized tissues. However, it is still unclear which micro/nanostructural features are essential to the material performance of these tissues. Also constitutive laws along various loading paths of the materials are currently unavailable. For nacre, the role of some nanograins and mineral bridges requires further studies to be fully defined. Successful biomimicking of mollusk shells will depend will on gaining further knowledge of all these factors, especially the selection of influential materials in the performance of mineralized tissues. Also the final technique used for artificial reproduction must be both cost effective and scalable industrially. ==See also==