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。在本提案中，我们描述了一种新的仿生纳米复合材料的方法来解决这些限制。重要的是，我们利用自然界材料科学和工程的两个关键教训，纳米级蛋白质结构和有机-无机界面的控制，以优化材料特性。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，其由两种组分组成：（a）基于模拟蜘蛛拖丝中的共有重复序列的蛋白质自组装结构域-由于形成高度稳定的具有令人印象深刻的机械性能的（β-片层）二级结构，和（B）衍生自硅藻的硅化蛋白质的二氧化硅形成结构域，其在控制产生二氧化硅和不同形态的反应中提供多功能性。这些融合蛋白为纳米级材料组装和控制提供了一种新的方法，从而导致可以在生物相容性方法中在体外（植入前）或体内（共形填充，界面结合，避免由于复合特征而导致的收缩）形成组织良好的复合材料结构。所提出的研究的假设是，纳米复合材料的功能（结构，形态，机械）可以优化和控制（在不同的长度尺度）通过适当的设计嵌合（融合）蛋白，其中自组装结构域和功能（二氧化硅形成）域连接在分子水平。我们的目标是阐明这两个领域的化学变化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），基于生物相容性反应条件优化原位材料形成的特征（目标2），并评估用于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的方法的可行性，并提供了一个新的平台，原位二氧化硅的形成与前所未有的控制材料的设计和功能特性。二氧化硅形成域还可进一步改性以形成其它无机相（例如，羟基磷灰石、二氧化钛），因此可以用这种嵌合仿生蛋白设计策略探索的多功能性和机会是广阔的。

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.