Polyamide plastics—the same family that includes nylons and the proteins in your body—are getting a molecular makeover that could give them built-in self-healing and drug-releasing abilities. The researcher will thread ring-shaped molecules onto polyamide chains, creating mechanically interlocked materials that combine the strength of permanent bonds with the flexibility of temporary ones. This is a synthetic chemistry challenge: no one has yet found a general way to install these mechanical bonds into polyamides, despite their widespread use in drug delivery, tissue engineering, and regenerative medicine. If successful, the work will produce new biomaterials whose surface structure can be tuned to control how stem cells differentiate—for example, steering mesenchymal stem cells toward bone-forming or fat-forming cells depending on the polyrotaxane design. The same materials could also be used for photopatternable hydrogels that regulate cell adhesion, or for delivering model anti-cancer drugs. This is fundamental science: the immediate payoff is a new synthetic toolkit and a deeper understanding of how mechanical bonds alter polymer properties, not a finished medical device. But similar fundamental work on interlocked molecules has already spawned artificial molecular machines and responsive materials.
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The mechanical bond is an interlocking linkage between molecular components that combines the robustness of the covalent bond with dynamics of supramolecular interactions. Mechanical bonds have broad applications in fields such as sensing, catalysis and artificial molecular machines, but perhaps the most promising venue for these units is in mechanically interlocked materials (MIMats). When mechanical bonds are incorporated into polymers, it often results in drastically improved materials properties and new features like stimuli-responsiveness and self-healing Surprisingly, the use of MIMats for biological materials applications is highly underdeveloped, despite the constant need for disruptive technology and innovative approaches in the biomedical sciences. The reason for this is mainly the synthetic difficulty in obtaining biocompatible interlocked systems, which limits the range of accessible polymeric interlocked architectures. In this fellowship, I will use state-of-the-art methods for mechanical bond synthesis to access an entirely new category of MIMats based on polyamide backbones. Polyamides (and its sub-categories polypeptides and nylons) are ubiquitously used as biomaterials for applications in drug delivery, tissue engineering and regenerative medicine, to name just a few examples. However, there are no general ways to install and hence make use of the mechanical bond in these systems. With access to mechanically interlocked polyamides, the mechanical bond could be used to efficiently modify physical materials properties such as solubility, improve mechanical performance and add functionality such as stimuli-responsiveness, adaptability and self-healing. I will use kinetically controlled active template synthesis to make linear and cross-linked polyamides and polypeptides that are encircles by rings - compounds known as polyrotaxane materials. The fellowship will (1) explore multiple synthetic approaches to create novel mechanically interlocked polypeptide biomaterials and mechanically interlocked nylons, (2) study the properties of these materials and (3) demonstrate their application in fields such as drug delivery and tissue engineering. Synthetically, I will explore both discrete approaches where pre-made rotaxanes are incorporated into materials and integrated approaches to linear interlocked polymers and crosslinked slide-ring networks where the mechanical bond is established during the polymerisation process. These interlocked biomaterials will then be tested for applications in for example small molecule drug delivery (with a model anti-cancer drug), photopatternable hydrogels (where the mechanical bond controls cell adhesion at the materials/cell biointerface), and to control parameters such as migration and differentiation for stem cells. In particular, I want to use the variations in surface structure between different polyrotaxanes to change the mechanotransduction efficiency at the biointerface, which will lead to differentiation of mesenchymal stem cells to either osteogenic or adipogenic cells depending on the polyrotaxane structure. This strategic merging of supramolecular chemistry, organic synthesis, polymer chemistry, peptides and cell biology is perfectly adapted for my research background. This makes me the optimal candidate to execute this groundbreaking research, which will greatly expand use of polyamide biomaterials and hence have wide societal and economic impact. Successful completion of this project will realise the full potential of the mechanical bond for biomaterials applications, and open a wealth of new opportunities in a range of areas associated to bioengineering, biotechnology and chemical biology (all focus areas in the UK research landscape). The award of a prestigious and flexible EPSRC Open Fellowship will be crucial to establish me as a global scientific leader in this highly important field, and is integral to realise the vision in this highly ambitious program.
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