High toughness bioresorbable ceramics for bone regeneration

高韧性材料因其广泛的应用范围，从土木工程到牙科和整形外科中的骨重建，一直走在材料科学的前沿。然而，可用于骨再生的生物陶瓷要么太脆，要么不能吸收，植入后被体内的活骨取代，这是实现最佳骨再生的关键。天然生物矿物质，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等级组织，即晶体组织，第二，结构蛋白的结合，提高了抗断裂性。Tamimi博士发现，某些磷酸钙骨陶瓷，如无水磷酸氢钙(DCP)，虽然相对易碎，但它们具有最佳的生物吸收和骨再生性能。 这项研究计划的总体长期目标是开发新的合成材料，能够取代骨衍生生物材料用于骨再生。在此背景下，未来5年研究计划的短期目标是利用受自然生物矿物质启发的策略，在两个主要目标中创造高韧性生物陶瓷，由生物可再吸收磷酸氢钙制成： 目的1)生物陶瓷中的超微结构 天然生物矿物的形成受到特定生物分子的调控，这些生物分子控制着晶体的成核、生长、形态、组织甚至功能。这些功能生物分子是完全由氨基酸的L对映体组成的同手性分子。因此，在这一目标中，我们将研究以前未曾探索过的选择，即使用手性纯晶体生长抑制剂在纳米级控制晶体生长，以制备具有有序超微结构和高韧性的生物陶瓷。 目的2)生物陶瓷的蛋白质增强 骨蛋白在组织和加强骨矿结构以及调节其与周围细胞的相互作用方面起着至关重要的作用。在我发表的工作中，我发现胶原可以改善刷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以在体外调节胶原的矿化，并在体内增加刷石生物陶瓷的骨整合。在这些发现的基础上，这个目标将集中在研究如何通过使用骨蛋白来制造磷酸钙生物陶瓷来改善其机械和生物性能。 新颖性和预期意义： 这项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，推动生物矿化领域的重大进展，并提供新一代高韧性陶瓷材料，其应用范围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.