Preparation and Characterisation of Peptide-Decorated Nanomaterials

Peptide-based nanomaterials offer exceptional tunability through sequence control and chemical modification. Within the NanoReMedi framework, this work establishes a structure–property paradigm wherein the hydrophobic domain—aliphatic lipidation, amphiphilic β‑sheet extension, or AIE conjugation—deterministically governs assembly, mechanics, and bioactivity across three complementary strategies. Strategy I established that stearic acid (C18) conjugation dominates morphological outcome, overriding peptide sequence to drive spherical or vesicular architectures. Under physiological ionic strength, colloidal stability was dictated by net electrostatic charge rather than β‑sheet propensity. Strategy II extended these findings to macroscopic hydrogel formation using the GFOGER epitope functionalised with three distinct domains: an amphiphilic hexapeptide (FQFQFK), its lipidated analogue, and the AIE luminogen TPE. Spectroscopic and rheological studies revealed that lipidation acts as a conformational switch, yielding high modulus β‑sheet networks with enhanced early adhesion but poor shear recovery. In contrast, AIE conjugation produced softer, intrinsically fluorescent matrices, with hydroxyproline content being a critical determinant of supramolecular packing density. Strategy III, conducted with the University of Pavia, demonstrated that, following covalent immobilisation of bioactive peptides onto electrospun PLGA scaffolds via thiol-maleimide chemistry, the peptide hydropathy index exerts greater control over surface wettability and endothelial selectivity than grafting density. Collectively, this thesis establishes a predictive framework for the rational design of peptide-decorated biomaterials, balancing mechanical robustness against dynamic reversibility. It also demonstrates that subtle sequence modifications—like proline hydroxylation—offer control over supramolecular architecture, providing a molecular roadmap for targeted regenerative therapies.