Scaffolds designed to regrow damaged tissues often fail because they cannot hold onto the right cells or mimic the complex structure of real body parts. This project builds a "design toolkit" to fix that, creating bespoke, cell-friendly scaffolds for three very different applications: cardiovascular implants, skin grafts, and nerve repair guides. The core technology uses ice-templated collagen scaffolds—essentially, freezing collagen into a porous, three-dimensional structure. The researchers will then engineer the scaffold surfaces with specific peptide sequences that act like docking stations, latching onto only the desired cell types and steering them toward repair. They will also vary the scaffold’s internal chemistry to create zones with different cell-binding properties, matching the heterogeneity of real tissues. If successful, the toolkit would allow clinicians to order a personalised scaffold tailored to a patient’s specific injury—a heart patch that attracts only cardiac muscle cells, for instance, or a nerve guide that pulls in regenerating neurons while excluding scar-forming cells. This is fundamental science with a clear translational path: it directly addresses why current scaffolds underperform, and the three demonstrator applications show how the same platform could treat diseases ranging from heart failure to severe burns to spinal cord injury.
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Although there has been an explosion of interest in the development of biomedical scaffolds over the past 15 - 20 years, the repair and regeneration of tissues is not always successful. The ability of the scaffolds to deliver cells to aid and guide the repair process, is limited their capacity to retain and encourage the appropriate cell types for optimised repair. Furthermore, the structural complexity and heterogeneity of many soft tissues demand matching scaffold architectures, which current technologies cannot produce. We believe that is it possible to develop a "design Toolkit" for bespoke, personalised cell-based therapies to ensure optimised treatment of a range of different diseases. In order to test our hypothesis, we aim to address the specific issues in scaffold development for three contrasting, demonstrator applications: cardiovascular devices, dermal grafting and nerve guidance. Each of these applications presents different structural and biochemical challenges, which we aim to address using specifically designed three dimensional biomacromolecular environments. The underlying technology will be based on ice-templated collagen-based scaffolds. The pathway through the project is the acquisition of knowledge, first about the three dimensional architectures required for optimised cell infiltration through the scaffold, then about the nature of the specific cell binding interactions with the scaffold surfaces. We will create cell-selective surfaces, by the incorporation of receptor-reactive collagen-derived triple helical peptide sequences to control cell reactivity and direct them towards specific regulatory receptors. We will investigate heterogeneity in scaffold architectures and then consider the creation of structures with spatially varying cell binding characteristics based on variations in the intrinsic chemistry of the scaffold struts. By considering optimised properties specific to each application, we will demonstrate the potential of the Toolkit for developing refined and targeted scaffolds with increasing levels of complexity. The mechanism for this Fellowship is novel: for the first time, an EPSRC Fellowship will be based on a "job share" style arrangement with two PIs. For about 10 years the PIs have jointly run the Cambridge Centre for Medical Materials, both having part time contracts based on their family commitments. This joint which would be a 60% FTE fellowship split evenly between Professors Best and Cameron and reflects a forward-thinking approach by EPSRC based on Equality and Diversity considerations.
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