High toughness bioresorbable ceramics for bone regeneration

用于骨再生的高韧性生物可吸收陶瓷

• 批准号: RGPIN-2019-04340
• 负责人: Tamimi, Faleh
• 金额: $ 2.84万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=687343
• 关键词: toughness; bioresorbable; ceramics; bone; regeneration

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.*****

高韧性材料因其广泛的应用而处于材料科学的前沿，从土木工程师到牙科和骨科手术中的骨骼重建。然而，可用于骨再生的生物陶瓷要么太脆，要么在植入后不能吸收并在体内被活骨取代，这对于最佳骨再生至关重要。天然生物矿物质，如贝壳和骨头，比大多数生物陶瓷更坚韧、更坚固。这些独特性能的主要原因是，首先，其超微结构在​​不同层次上的分层组织，即晶体组织，其次，掺入了增加断裂抗力的结构蛋白。 Tamimi 博士发现，某些磷酸钙骨陶瓷，例如无水磷酸二钙 (DCP)，虽然相对较脆，但具有最佳的生物吸收和骨再生特性。 ***该研究计划的总体长期目标是开发能够替代骨源生物材料进行骨再生的新型合成材料。在这种背景下，未来 5 年研究计划的短期目标是使用受天然生物矿物质启发的策略来制造由可生物吸收的磷酸二钙制成的高韧性生物陶瓷，其主要目标有两个：***目标 1) 生物陶瓷中的超微结构组织***天然生物矿物质的形成受到特定生物分子的调节，这些生物分子控制晶体成核、生长、形态、组织甚至功能。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，在此目标中，我们将研究以前未探索过的选择，即使用手性纯晶体生长抑制剂来控制纳米级晶体生长，以制造具有有序超微结构和高韧性的生物陶瓷。***目标 2) 生物陶瓷的蛋白质强化***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方面发挥着至关重要的作用。在我已发表的工作中，我证明了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在体外调节胶原蛋白矿化并增加透钙磷石生物陶瓷在体内的骨整合。基于这些发现，该目标将重点研究如何通过使用骨蛋白制造磷酸钙生物陶瓷来提高其机械和生物性能。***新颖性和预期意义：***该研究计划将引发该领域的重大进展。通过揭示对映体分子和骨蛋白对生物陶瓷的影响，开发出具有广泛应用的新一代高韧性陶瓷材料，从骨再生到建筑和土木工程。 *****