Silica-protein Nanocomposites for Dental Repair

描述（由申请人提供）：无机材料如生物活性玻璃和复合材料用于牙科应用，但存在许多缺点，包括脆性，机械性能与周围组织不匹配以及界面稳定性差。在目前的建议中，我们描述了一种新的仿生纳米复合材料方法来解决这些限制。重要的是，我们利用材料科学和工程的两个关键经验，纳米级蛋白质结构和有机-无机界面的控制，来优化材料的特性。我们描述了由生物工程融合蛋白形成的新型生物材料纳米复合材料，由两部分组成：(a)基于模仿蜘蛛丝的一致重复的蛋白质自组装结构域-由于形成具有令人印象深刻的机械性能的高度稳定的二级结构（β -sheet），以及(b)源自硅藻的硅蛋白的硅形成结构域，该结构域在控制生成二氧化硅和不同形态的反应方面提供了多功能性。这些融合蛋白提供了一种纳米级材料组装和控制的新方法，可以在体外（植入前）或体内（保形填充，界面键合，避免因复合特性而收缩）形成组织良好的复合材料结构。该研究的假设是，纳米复合材料的特征（结构、形态、机械）可以通过适当设计嵌合（融合）蛋白来优化和控制（在不同的长度尺度上），其中自组装结构域和功能（二氧化硅形成）域在分子水平上连接。我们的目标是阐明这两个领域的化学变化将如何导致复合材料性能（结构、形态、力学）的可预测变化（目标1），优化基于生物相容性反应条件的原位材料形成的特征（目标2），并评估体外和体内牙本质修复的新材料（目标3）。我们的初步数据证明了所提出方法的可行性，并为原位二氧化硅形成提供了一个新的平台，具有前所未有的材料设计和功能特性控制。二氧化硅形成结构域也可以进一步修饰以形成其他无机相（例如，羟基磷灰石，二氧化钛），因此可以用这种嵌合仿生蛋白质设计策略探索的多功能性和机会是广泛的。

DESCRIPTION (provided by applicant): Inorganic materials such as bioactive glasses and composites are used in dental applications but suffer from a number of drawbacks including brittleness, mismatch in mechanical properties with surrounding tissues and poor interfacial stability. In the present proposal we describe a novel biomimetic nanocomposite approach to address these limitations. Importantly, we exploit two critical lessons in materials science and engineering from Nature, nanoscale protein structures and control of organic-inorganic interfaces, to optimize material features. We describe new biomaterial nanocomposites formed from bioengineered fusion proteins that consist of two components: (a) a protein self-assembling domain based on mimicking the consensus repeat in spider dragline silk - due to the formation of highly stable (beta-sheet) secondary structures with impressive mechanical properties, and (b) a silica-forming domain derived from the silicatin protein of a diatom that offers versatility in control of the reactions that generate silica and different morphologies. These fusion proteins provide a novel approach to nanoscale materials assembly and control, leading to well-organized composite material structures that can be formed either in vitro (prior to implantation) or in vivo (conformal fill ins, interfacial bonding, avoid shrinkage due to the composite features) in biocompatible approaches. The hypothesis for the proposed study is that nanocomposite material features (structure, morphology, mechanical) can be optimized and controlled (at different length scales) through appropriate design of chimeric (fusion) proteins in which the self-assembling structural domains and functional (silica forming) domains are linked at the molecular level. Our goal is to elucidate how alterations in the chemistry of the two domains will lead to predictable changes in composite material properties (structure, morphology, mechanics) (Aim #1), to optimize features for in situ materials formation based on biocompatible reaction conditions (Aim #2), and to assess the new materials for dentinogenic restoration in vitro and in vivo (Aim #3). Our preliminary data demonstrate the feasibility of the proposed approach and offers a new platform for in situ silica formation with unprecedented control of materials design and functional properties. The silica-forming domain can also be further modified to form other inorganic phases (e.g., hydroxyapatite, titanium dioxide), thus the versatility and opportunities that can be explored with this chimeric biomimetic protein design strategy are expansive.