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

: 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.