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Hybrid Foldamer-Polymer Scaffolds as Novel Biomaterials for Wound Healing Applications

Primary Supervisor: Dr Sarah Pike, School of Chemistry

Secondary supervisor: Dr Maria Chiara Arno

PhD project title: Hybrid Foldamer-Polymer Scaffolds as Novel Biomaterials for Wound Healing Applications

University of Registration: University of Birmingham

Project outline:

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. The cytocompatibility and the tissue healing and growth properties of these biomaterials will be assessed in 2D and 3D in vitro cell culture.

Objectives

  1. i) To create a new generation of biomaterials based on hybrid foldamer-polymer scaffolds and fully characterize them using well-established analytical techniques. Systematically rationally designed libraries of compounds will be generated wherein fundamental structural features (e.g. foldamer and/or polymer length, nature of the foldamer and/or polymer side chains and terminal groups) will be varied to provide a broad scope of substrates for subsequent structure-activity relationship studies.
  2. ii) To determine the mechanical properties of the biomimetic foldamer-polymer scaffolds and establish structure-activity relationships on the influence of key structural features (e.g. oligomer length, terminal group, polymer molecular weight and composition) on their water content, mechanical strength, and cytocompatibility.

iii) To optimize the biological performance of the foldamer-polymer scaffolds as effective wound healing materials with potential antibacterial activity through investigation of the structure-activity relationship, with rationally designed libraries of compounds, to determine the effect of important structural features on their biological activity and their ability to promote tissue healing and growth.

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.

BBSRC Strategic Research Priority: Integrated Understanding of Health: Regenerative Biology

    Techniques that will be undertaken during the project:

    The student will receive in-depth training and will gain extensive experience in a wide range of standard and advanced synthetic organic chemistry techniques as well as receiving training in a wide range of polymerisation techniques (ring-opening, step-growth, and free radical polymerisations) and size exclusion chromatography for polymer analysis. The student will also receive training and gain in-depth knowledge of a diverse range of analytical techniques in order to fully characterise the novel hybrid foldamer-polymer scaffolds, including NMR spectroscopy, mass spectrometry, IR spectroscopy, fluorescence spectroscopy, UV/Vis spectroscopy, circular dichroism spectroscopy, single crystal X-ray diffraction and powder X-ray diffraction.

    The student will also be trained in a wide range of material characterisation techniques in order to determine the mechanical properties of the new hybrid scaffolds including rheology, mechanical analysis (e.g. tensile analysis and compression tests), and adhesive property assays.

    Finally, in order to determine the wound healing ability and properties of the new hybrid scaffolds, the student will gain extensive training in a diverse array of biological assays including executing 2D and 3D cell cultures, live/dead assays to determine cytocompatibility, confocal fluorescence microscopy, live cell imaging, and cell proliferation assays.

    Contact: Dr Sarah Pike, University of Birmingham