High toughness bioresorbable ceramics for bone regeneration

高韧性材料是材料科学的前沿，因为它们的应用范围从土木工程到牙科和整形外科的骨重建。然而，可用于骨再生的生物陶瓷要么太脆，要么不能再吸收，并且在植入后在体内被活骨替代，这对于最佳骨再生至关重要。天然生物矿物，如贝壳和骨头，比大多数生物陶瓷更坚韧和坚固。这些独特性质的主要原因是，第一，它们的超微结构在不同水平上的层次组织，即晶体组织，第二，增加抗断裂性的结构蛋白的掺入。Tamimi博士发现某些磷酸钙骨陶瓷，如无水磷酸二钙（DCP），虽然它们相对较脆，但它们具有最佳的生物吸收和骨再生特性。* 本研究计划的总体长期目标是开发能够替代骨源性生物材料用于骨再生的新型合成材料。在这种情况下，未来5年的研究计划的短期目标是创造高韧性的生物陶瓷，由生物可吸收的磷酸二钙制成，使用天然生物矿物的启发策略，有两个主要目标：* 目标1）生物陶瓷中的超微结构组织 * 天然生物矿物的形成受到控制晶体成核，生长，形态，组织甚至功能的特定生物分子的调节。这些功能性生物分子是纯手性的，仅由氨基酸的L-对映体组成。因此，在这一目标中，我们将研究以前未探索的选择，即使用手性纯晶体生长抑制剂在纳米级水平上控制晶体生长，以制造具有有序超微结构和高韧性的生物陶瓷。目的2）蛋白质对生物骨的强化骨蛋白在组织和强化骨矿物质结构以及调节其与周围细胞的相互作用中起着至关重要的作用。在我已发表的工作中，我表明胶原蛋白可以改善透钙磷石生物陶瓷的生物学性能，在我未发表的初步工作中，我发现非胶原骨蛋白可用于调节体外胶原矿化和增加透钙磷石生物陶瓷的体内骨整合。在这些发现的基础上，该目标将集中于研究如何通过使用骨蛋白制造磷酸钙生物陶瓷来改善其机械和生物性能。新奇和预期意义：* 该研究计划将通过揭示对映体分子和骨蛋白对生物陶瓷的影响，在生物矿化领域取得重大进展，并提供新一代高韧性陶瓷材料，其应用范围广泛，从骨再生到建筑和土木工程。

High toughness materials are on the forefront of materials science due to their immense number of applications ranging from civil engineer to bone reconstructions in dental and orthopedic surgery. However, bioceramics available for bone regeneration are either too brittle, or do not resorb and to be replaced by living bone in vivo upon implantation, which is critical for optimal bone regeneration. Natural biominerals, such as seashells and bone, are much tougher and stronger than most bioceramics. The main reason for these unique properties is, first, the hierarchal organization of their ultrastructure at different levels, namely the crystal organization, and second, the incorporation of structural proteins that increase fracture resistance. Dr Tamimi has discovered that certain calcium phosphate bone ceramics such as dicalcium phosphate anhydrous (DCP), though they are relatively brittle, they have optimal bioresorption and bone regeneration properties. ***The overall long -term goal of this research program is to develop new synthetic materials able to replace bone derived biomaterials for bone regeneration. In this context the short term goal of the research program for the next 5 years is to create high toughness bioceramics, made of bioresorbable dicalcium phosphates, using strategies inspired by natural biominerals in two main aims:***Aim 1) Ultrastructural organization in bioceramics***The formation of natural biominerals is regulated by specific biomolecules that control crystal nucleation, growth, morphology, organization and even function. These functional biomolecules are homochiral composed exclusively L-enantiomers of amino acids. Accordingly, in this aim we will study the previously unexplored option of using chiraly pure crystal growth inhibitors to control crystal growth at the nanoscale level to fabricate bioceramics with organized ultrastructure and high toughness.***Aim 2) Proteins reinforcement of bioceramics***Bone proteins serve a crucial role in organizing and reinforcing bone mineral structure, and regulating its interactions with the surrounding cells. In my published work, I showed that collagen can improve the biological performance of brushite bioceramics, and in my preliminary unpublished work, I discovered that noncollagenous bone proteins could be used to regulate collagen mineralization in vitro and increase osseointegration of brushite bioceramics in vivo. Building on these findings, this aim will focus on investigating how to improve the mechanical and biological properties of calcium phosphate bioceramics by fabricating them using bone proteins.***Novelty and expected significance:***This research program will trigger significant advancements in the field of biomineralization by unraveling the effect of enantiomeric molecules and bone proteins on bioceramic, and deliver a new generation of high toughness ceramic materials with a wide range of applications ranging bone regeneration to even construction and civil engineering.*****