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能够自组装的新分子，以创建具有多种拓扑结构的新型杂化折叠聚合物支架。这些新的高阶杂化结构将具有可调谐的物理和生物特性，并作为潜在的药物输送载体、伤口愈合生物材料和/或具有生物活性的新制剂（例如抗癌或抗微生物）广泛应用于潜在的疾病治疗。背景：折叠物是一种合成的螺旋状低聚物，通过模仿生物系统的折叠模式，采用稳定的二级结构，产生具有明确大小和形状的仿生结构近年来，多种折叠材料作为潜在的抗微生物和抗菌药物的生物活性引起了人们的极大兴趣。然而，尽管折叠膜具有有效的抗菌特性，这使它们成为局部伤口愈合治疗的优秀候选者，但它们作为伤口愈合生物材料的潜在应用尚未得到探索。此外，由文件夹的超分子组装获得的3D支架往往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，最近成为生物医学应用的有前途的一类材料。这些吸引人的特性促使其在一系列应用中广泛使用，包括药物输送，组织再生，以及对其伤口愈合特性的初步研究已经报道然而，聚合物材料在伤口愈合应用中的有效使用受到严重限制，因为它们不能诱导生物反应，这反过来导致未能促进原位组织愈合和生长。在这个项目中，我们将通过创建一类新的仿生混合折叠聚合物-聚合物材料来解决当前使用单个折叠材料和聚合物支架作为局部伤口愈合治疗的局限性，该材料结合并优化了这两种支架的理想特征。这些杂化支架将形成可控的双网络水凝胶，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修饰来正交调节。此外，仿生折叠组件的存在使得支架不仅可以作为局部伤口护理装置，而且还具有抗菌活性，这对增加患者的康复具有长期意义。在项目过程中，为了优化这些混合生物材料的生物性能，将创建各种各样的折叠聚合物支架库，作为具有内置抗菌活性的新一代局部伤口愈合装置，也作为潜在的药物输送载体。这些生物材料的细胞相容性、组织愈合和生长特性将在体外2D和3D细胞培养中进行评估。引用:1。a) S. J. Pike等人，化学。欧元。[J] .生物医学工程学报，2014,20,15981；b) C.亚当，化学。欧元。[J] ., 2018, 24, 2249.2.]张建军，张建军，张建军，等。生物材料研究进展，2018,31(1):1 - 4。

: 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.