Topological Design of Novel Foldamer-Polymer Scaffolds for Applications in Drug Delivery and to Probe New Agents with Biological Activity

该项目将设计和生产新的分子，自组装，创造新的混合折叠聚合物支架能够多样化的拓扑结构。这些新的高阶杂化结构将具有可调的物理和生物学性质，并作为潜在的药物递送载体、伤口愈合生物材料和/或作为具有生物活性的新试剂（例如，抗癌或抗微生物）用于潜在的疾病治疗。背景：折叠体是合成的螺旋低聚物，其通过模仿生物系统的折叠模式来采用稳定的二级结构，以产生具有明确定义的大小和形状的仿生结构。1近年来，各种各样的折叠体作为潜在的抗微生物剂和抗菌剂的生物活性引起了人们的极大兴趣。1b然而，尽管折叠体具有有效的抗微生物性质，这使它们成为局部伤口愈合治疗的优良候选物，但它们作为伤口愈合生物材料的潜在应用尚未被探索。此外，由折叠体的超分子组装获得的3D支架通常缺乏作为生物医学设备的最佳性能所需的机械性能。聚合物由于其易于合成和可调的机械性能，最近成为一类有前途的生物医学应用材料。这些有吸引力的特征鼓励了它们在一系列应用中的广泛使用，包括药物递送、组织再生，并且对它们的伤口愈合性质的初步研究已经被证实。2然而，聚合物材料用于伤口愈合应用的有效使用受到它们诱导生物反应的无效性的严重限制，这又导致促进原位组织愈合和生长的失败。在该项目中，我们将通过创建一类新的仿生混合折叠体-聚合物材料，其联合收割机组合并优化两种单独支架的期望特征。这些混合支架将形成受控的双网络水凝胶，其中支架的机械和生物相容性可以通过聚合物或折叠体组分的改性进行正交调节。此外，仿生折叠体组分的存在允许支架不仅用作局部伤口护理装置，而且还表现出抗微生物活性，这对增加患者恢复具有长期意义。在该项目的过程中，将创建各种各样的折叠体-聚合物支架库，以优化这些混合生物材料的生物性能，作为具有内置抗菌活性的新一代局部伤口愈合器械，也作为潜在的药物递送载体。这些生物材料的细胞相容性和组织愈合和生长特性将在2D和3D体外细胞培养中进行评估。a）S. J. Pike等人，欧洲化学品J.，2014，20，15981; B）C. Adam，Chem. Eur. J.，2018年，24，2249.2。M. Mir，生物材料进展，2018，7，1。

: This project will design and produce new molecules that self-assemble to create novel hybrid foldamer-polymers scaffolds capable of a diverse range of topologies. These new higher order hybrid structures will possess tuneable physical and biological properties and find wide-reaching applications as potential drug delivery vehicles, wound healing biomaterials and/or as new agents with biological activity (e.g., anti-cancer or anti-microbial) for the potential treatment of diseases.Background: Foldamers are synthetic helical oligomers that adopt stable secondary structures through mimicking the folding patterns of biological systems to generate biomimetic structures of well-defined size and shape.1 In recent years, the biological activity of a diverse array of foldamers as potential antimicrobial and antibacterial agents has excited much interest.1b However, despite the potent antimicrobial properties of foldamers, which make them excellent candidates for topical wound healing treatment, their potential application as wound healing biomaterials has not yet been explored. Moreover, 3D scaffolds obtained from the supramolecular assembly of foldamers often lack the mechanical properties required for their optimal performance as biomedical devices.Polymers have recently emerged as a promising class of materials for biomedical applications, due to their ease of synthesis and tunable mechanical properties. These attractive features have encouraged their widespread use in a range of applications, including drug delivery, tissue regeneration, and initial studies into their wound healing properties have been reported.2 However, the effective use of polymeric materials for wound healing applications is severely limited by their inefficacy to induce a biological response, which in turn leads to a failure in promoting in situ tissue healing and growth.In this project, we will address the current limitations associated with the use of individual foldamers and polymers scaffolds as topical wound healing treatments by creating a new class of biomimetic hybrid foldamer-polymer materials which combine and optimize the desirable features of both individual scaffolds. These hybrid scaffolds will form controlled double-network hydrogels in which the mechanical and biocompatibility properties of the scaffold can be orthogonally tuned through modification of either the polymer or foldamer components. Furthermore, the presence of the biomimetic foldamer component allows the scaffold to not only function as a topical wound care device but also to exhibit antimicrobial activity, which has long term implications for increased patient recovery. During the course of the project, a diverse range of libraries of foldamer-polymer scaffolds will be created in order to permit optimization of the biological performance of these hybrid biomaterials as a new generation of topical wound healing devices with in-built antimicrobial activity and also as potential drug delivery vehicles. The cytocompatibility and the tissue healing and growth properties of these biomaterials will be assessed in 2D and 3D in vitro cell culture.References: 1. a) S. J. Pike et al., Chem. Eur. J., 2014, 20, 15981; b) C. Adam, Chem. Eur. J., 2018, 24, 2249.2. M. Mir, Progress in Biomaterials, 2018, 7, 1.