"Nanostructured Block-copolymer Reinforced Calcium Phosphate Composites

描述（由申请人提供）：本提案的主要目标是开发下一代牙科修复复合材料的合成方法，该复合材料具有无机和有机成分的纳米结构排列，类似于牙本质和牙釉质中发现的结构。作为这项工作的一部分，合成的自硬化复合材料将在龋齿引起的牙齿空洞的修复中应用。我们的方法是将联合收割机磷酸钙矿物与两亲性（疏水/亲水）嵌段共聚物的公认能力结合，以引导无机材料组装成介观结构的杂化物（例如，圆柱形、层状或双连续形态）。我们将从作为前体相的无定形磷酸钙颗粒开始，其在与嵌段共聚物形成结构后，将结晶以形成具有磷灰石（Ca 10（PO 4，CO 3）6（OH）2）纳米晶体作为无机组分的坚固的复合材料。材料的合成将完成四个具体目标：1）稳定的无定形磷酸钙（ACP）颗粒（< 100 nm）的合成和表征，能够在水溶液和有机溶剂中形成稳定的悬浮液。2)使用两亲性二嵌段共聚物来引导ACP颗粒组装成具有限定的1-D、2-D和3-D纳米结构的材料。3)纳米结构复合材料的无定形无机相的受控结晶。4)通过将在目标2和3中开发的纳米结构复合材料的粉末与含水液相混合以诱导二次结晶来开发自硬化复合材料。这些用于牙科修复的新型复合材料的设计代表了从具有嵌入连续聚合物基质中的孤立无机颗粒的传统材料到具有被聚合物渗透的连续无机相的复合材料的范式转变。连续无机相的益处包括减少（或甚至消除）复合材料在硬化时的收缩、改进的耐磨性和更强的材料。在机械上，作为有机组分的两亲性嵌段共聚物将为复合材料提供韧性和抗断裂性。这些自硬化复合材料对天然牙齿的粘附力应该比传统树脂更好，因为我们使用的是能够渗透水合牙本质的水基系统。嵌段共聚物体系的灵活性将使我们在未来能够定制复合材料的介观结构，以形成机械性能最佳匹配牙齿部分的材料（例如，牙本质或牙釉质）被修复。这项研究是一致的R21的理念，即两亲性嵌段共聚物的能力相分离成纳米结构的膜从来没有被应用到磷酸钙矿化的结构。

DESCRIPTION (provided by applicant): The broad objective of this proposal is to develop synthetic methodologies towards next generation dental restorative composites that have a nanostructured arrangement of the inorganic and organic components, similar to the structures found in dentin and enamel. The self-hardening composites synthesized as part of this proposed work will have applications in the repair of dental cavities caused by caries. Our approach is to combine calcium phosphate minerals with the well-established ability of amphiphilic (hydrophobic/hydrophilic) block copolymers to direct the assembly of inorganic materials into mesostructured hybrids (with e.g., cylindrical, lamellar, or bicontinuous morphologies). We will start from amorphous calcium phosphate particles as a precursor phase, which, after structure formation with the block copolymers, will be crystallized to form robust composites with apatite (Ca10(PO4,CO3)6(OH)2) nanocrystals as the inorganic component. The synthesis of the materials will be completed with four specific aims: 1) Synthesis and characterization of stable amorphous calcium phosphate (ACP) particles (< 100 nm) capable of forming stable suspensions in both aqueous and organic solvents. 2) Use of amphiphilic diblock copolymers to direct the assembly of ACP particles into materials with defined 1-D, 2-D, and 3-D nanostructures. 3) Controlled crystallization of the amorphous, inorganic phase of the nanostructured composites. 4) Development of self-hardening composites by mixing powders of the nanostructured composites developed in Aims 2 and 3 with an aqueous liquid phase to induce secondary crystallization. The design of these new composites for dental restoration represents a paradigm shift away from traditional materials with isolated inorganic particles embedded within a continuous polymer matrix to composites with a continuous inorganic phase penetrated by polymer. The benefits of a continuous inorganic phase include a reduction (or even elimination) of shrinkage of the composites as they harden, improved abrasion (wear) resistance, and stronger materials. Mechanically, the amphiphilic blockcopolymer as the organic component will provide toughness and fracture resistance to the composite. The adhesion of these self-hardening composites to the natural tooth should be better than the traditional resins since we are using a water-based system that will be able to infiltrate the hydrated dentin. The flexibility of the block copolymer system will allow us in the future to tailor the mesostructure of the composites to form materials whose mechanical properties best match the part of the tooth (e.g., dentin or enamel) being repaired. This research is consistent with the R21 philosophy in that the ability of amphiphilic block copolymers to phase segregate into nanostructured films has never been applied to the structuring of calcium phosphate mineralization.