Self-assembling peptide-based materials for 3D-printed tissue engineering constructsTools Hill, Jordan Oliver (2025) Self-assembling peptide-based materials for 3D-printed tissue engineering constructs. PhD thesis, University of Nottingham.
AbstractThere is a growing unmet global need for the transplant and repair of tissues and organs in humans. In some cases, such as those for traumatic spinal cord injury, current therapies focus on relieving pain and improving quality of life, and the chance of a full recovery of motor function is slim. Beyond personal impact, the inability to repair or replace tissues and organs has a profound economic impact. In this thesis, biological self-assembly is presented as a pathway towards future biomedical innovation in tissue engineering, regenerative medicine, and tissue modelling. The growth and development of biological systems is guided and underpinned by non-covalent interactions, yielding shapes, forms, and functions which combine to facilitate life. By exploiting the fundamentals of biological self-assembly, it is possible to create materials which closely recreate cellular milieus, mimicking the components and properties of the ECM. Here, peptide-based supramolecules are adapted for use in 3D printing systems, yielding precision control from the molecular to macroscopic scale. A heparin-mimetic peptide amphiphile is used to exploit the paracrine effect and is demonstrated to have the potential to improve neurite outgrowth in damaged neural cells. This system is then integrated into additive manufacturing by means of two-photon polymerisation, being combined with a photopolymerisable gelatin. Additive manufacturing is then used to aid the fabrication of peptide-based co-assembled supramolecular tubular membranes with a thickness in the range of native basement membranes. These membranes are demonstrated to support endothelial cell adhesion for up to 7 days post-seeding. By demonstrating the incorporation of additive manufacturing with molecular self-assembly in this manner, it is hoped that this work contributes to the growing body of research for tissue engineering and regenerative medicine which utilise peptide-based supramolecules as their foundation.
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