High toughness bioresorbable ceramics for bone regeneration

拟议研究计划的目标：*高韧性材料因其大量的应用而走在材料科学的前沿。例如，在生物医学领域，需要高韧性陶瓷来治疗颌面部和骨科应用中的骨重建。然而，现有的生物材料要么太脆，要么植入后不能吸收并被体内的活骨取代，这是实现最佳骨再生的关键特征。因此，本研究计划的最终目标是创造具有类骨生物吸收特性的高韧性骨替代材料。这些材料将是由两种可吸收材料组成的仿生复合材料：可吸收生物陶瓷(即刷石，芒硝酸盐)和骨蛋白(即胶原，骨非胶原蛋白)。为了实现这一目标，我们将致力于两个主要目标：(I)晶体组织(Ii)蛋白质的掺入。*对于第一个目标，我们将研究使用手性纯对映体来控制晶体生长的选择，为了解决第二个目标，我们将专注于探索使用骨非胶原蛋白来调节矿物形成和胶原在生物陶瓷上的掺入。科学方法概述：*目标1)生物陶瓷中的晶体组织*晶体组织对于天然生物矿物(即骨和牙齿)中发现的高韧性特性至关重要，这就是为什么本目标侧重于模拟合成生物陶瓷中的这些结构。在天然生物矿物的形成过程中，与特定生物分子的直接接触调控着生物矿物的成核、生长、形态、组织乃至功能。有趣的是，这些功能生物分子是完全由L-氨基酸和生物分子的对映体组成的同手性。我们将探索使用对映体纯晶体生长抑制剂来制备具有有序晶体结构和高韧性的生物陶瓷。*目的2)骨有机ECM在组织和增强骨矿结构以及调节其与周围细胞的相互作用方面发挥着关键作用。这就是为什么骨衍生材料比合成的磷酸钙骨水泥表现出更好的机械性能和生物活性。因此，该研究计划的第二个目标将集中在研究如何将骨蛋白结合到磷酸二钙生物陶瓷中，以提高生物和机械性能。

Objectives of proposed research program:***High toughness materials are on the forefront of materials science due to their immense number of applications. For instance, in the biomedical field, high toughness ceramics are needed to treat bone reconstructions in maxillofacial and orthopedic applications. However, available biomaterials are either too brittle, or do not get resorb and replaced by living bone in vivo upon implantation, which are critical characteristics for optimal bone regeneration. Accordingly, the ultimate goal of this research program is to create high-toughness bone substitutes with bone-like bioresorption properties. These material will be biomimetic composites made of two bioresorbable materials: a resorbable bioceramic (i.e. brushite, monetite) and bone proteins (i.e. collagen, bone non-collagenous proteins). To achieve this goal, two main objectives will be addressed: (i) Crystals organization (ii) Proteins incorporation.***For the first objective we will study the previously unexplored option of using chiraly pure enantiomers to control crystal growth, to address the second objective we will focus on exploring the use of bone non-collagenous proteins to regulate mineral formation and collagen incorporation onto bioceramics. Summary of scientific approach:***Aim 1) Crystal organization in bioceramics***Crystal organization is critical for the high toughness properties found in naturally occurring biominerals (i.e. bone and teeth), and this is why this objective focuses on mimicking theses structure in synthetic bioceramics. During the formation of natural biominerals, direct contact with specific biomolecules regulates the nucleation, growth, morphology, organization and even function of the biominerals. Interestingly, these functional biomolecules are homochiral composed exclusively L-enantiomers of amino acids and biomolecules. We will explore the use of enantiomerically pure crystal growth inhibitors to fabricate bioceramics with organized crystallographic structure and subsequently, high toughness.***Aim 2) Bone organic ECM plays a crucial role in organizing and reinforcing bone mineral structure, and regulating its interactions with the surrounding cells. This is why bone-derived materials present much better mechanical properties and bioactivity than synthetic calcium phosphate cements. Accordingly, the second aim of the research program will focus on investigating how to incorporate bone proteins into di-calcium phosphate bioceramics to improve both the biological and the mechanical properties.