Developing a technological platform based on the fundamental understanding of peptide self-assembly for the design of novel biomaterials

利用非共价自组装来构建材料已经成为材料科学中的一项重要战略，为构建功能日益增强的生物材料提供了可行的途径。为此，可以使用各种分子构建块；其中一个这样的构建块是从头设计的多肽。多肽为材料科学家提供了许多优势。多肽合成已经成为一种常规程序，使它们很容易获得。由20个天然氨基酸组成的库提供了利用多肽的内在属性的能力，如结构、疏水性、电荷和功能，从而允许设计具有广泛属性的材料。这一领域的科学家面临的主要挑战是能够合理地设计这些多肽，以获得对所产生的自组装材料的物理性质的控制。这不仅需要深入了解所有长度范围内的自组装过程，而且还需要详细了解每个目标应用的具体要求。使实际技术平台的开发变得至关重要的一个关键点是，对材料的要求根据目标应用的不同而变化。例如，需要开发用于细胞输送的可注射材料，而对于药物输送，可能需要口腔喷雾系统。对于细胞培养和组织工程来说，材料特性的适应性问题更加关键，因为根据细胞类型、来源和预期行为，细胞在其放置的环境(即：材料特性和功能)方面有非常不同的要求。最后，另一个关键因素是这些材料的成本。当用作结构材料时，例如在水凝胶中，所需的多肽的数量是很大的。在这方面，开发一种基于同一系列“简单”和“廉价”的技术平台，以生产可用于多种应用的多肽，是一个重大优势(见影响摘要)。通过这项合作，我的团队将通过以下方式开发这样一个技术平台：-对我们的材料在所有长度范围内的自组装和凝胶化特性有一个基本的了解。特别是，我们将扩大材料和材料性能(例如：机械、触发机制、注入性)的范围，使其能够设计和开发新的功能和响应材料-与学术和工业最终用户发展强有力的合作。这将使我们能够让最终用户参与开发过程，确保我们设计的材料相关并得到使用，同时我们还将最大限度地探索新的潜在应用领域--为开发产生的知识产权制定综合战略，以最大限度地提高各级工作的影响。这将与曼彻斯特大学知识产权(UMIP)密切合作完成，将包括协调和有效地管理现有和未来与工业和学术合作伙伴的协议，以及开发一个有效的程序来识别新的知识产权及其保护和开发。该项目将有助于EPSRC职权范围中心的一些优先事项和重大挑战。它完全被置于EPSRC医疗技术挑战主题中，并将直接为生物材料和组织工程战略研究主题做出贡献。此外，这项工作还将为EPSRC再生医学重大挑战和化学科学与工程重大挑战做出贡献：具有目标特性的扩展结构的定向组装，我是其中的一员。

The use of non-covalent self-assembly to construct materials has become a prominent strategy in material science offering practical routes for the construction of increasingly functional biomaterials. A variety of molecular building blocks can be used for this purpose; one such block is de-novo designed peptides. Peptides offer a number of advantages to materials scientists. Peptide synthesis has become a routine procedure making them easily accessible. The library of 20 natural amino acids offers the ability to play with the intrinsic properties of the peptide such as structure, hydrophobicity, charge and functionality allowing the design of materials with a wide range of properties. The main challenge facing scientists in this field is being able to rationally design these peptides to gain control over the physical properties of the resulting self-assembled materials. This requires not only an in depth knowledge of the self-assembling processes at all length scales, but also a detailed understanding of the specific requirements of each application targeted. A key point that makes the development of an actual technological platform crucial is the variability of the requirements placed on the materials depending on the application targeted. For example, injectable materials need to be developed for cell delivery, while for drug delivery oral cavity sprayable systems could be required. For cell culture and tissue engineering the issue of adaptability of material properties is even more critical as depending on cell type, origin and intended behaviour, cells have very different requirements in term of their environment, (i.e.: material properties and functionality) in which they are placed. Finally, one other key element is the cost of these materials. When used as structural materials such as in hydrogels the quantity of peptide required is significant. In this context the development of a technological platform based on the same family of "simple" and "cheap" to produce peptides that can be used across a number of applications is a significant advantage (see impact summary). Through this fellowship my group will develop such a technological platform by:- Developing a fundamental understanding of the self assembly and gelation properties of our materials at all length scales. In particular we will broaden the range of materials and materials properties (e.g.: mechanical, triggering mechanism, injectability) available to be in a position to design and develop new functional and responsive materials- Develop strong collaborations with academic and industrial end-users. This will allow us to engage end-users with the development process ensuring that the materials we design are relevant and used, and also that we maximise exploration of new potential fields of application- Develop a comprehensive strategy for the exploitation of the IP generated to maximise the impact of the work at all levels. This will be done in close collaboration with University of Manchester Intellectual Properties (UMIP) and will include the coherent and efficient management of existing and future agreements with industrial and academic partners as well as the development of an efficient process for the identification of novel IPs and their protection and exploitation.This project will contribute to a number of priorities and Grand Challenges at the centre of EPSRC's remit. It is fully placed within the EPSRC Healthcare Technologies Challenge theme and will directly contribute to the Biomaterials and Tissue Engineering strategic research theme. In addition the work will also contribute towards the EPSRC Regenerative Medicine Grand Challenge and the Chemical sciences and engineering Grand Challenge: Directed Assembly of Extended Structures with Targeted Properties, of which I am a member.