Designing soft material exploiting peptide-PEG conjugates for biomedical applications

Abstract

Soft hydrogels based on self-assembling peptides are widely used in tissue engineering because they can mimic different environments of extracellular matrix. Commonly in these hydrogels, the peptide chains mainly contain at least 10 amino acids. It is also found that peptides with short chains (i.e. less than 10 amino acids) can form fibrous hydrogels with secondary structures, α-helical coiled-coil and β-sheet structures. However, such short peptide-based hydrogels normally suffer from the relatively low stiffness, i.e. relatively storage modulus (lower than 100 Pa), limiting their applications. One strategy to address this issue is to employ synthetic polymer to be crosslinked with the peptide chains to prepare the hybrid hydrogels with the improved storage modulus. In this PhD project, β-sheet structure peptide FKFEFKFK (FK) was first explored to form the hydrogel by adjusting the system pH value. Then, the FK peptide was crosslinked with polyethylene glycol (PEG) via non-covalent bonding to give the hybrid hydrogels with tuneable mechanical property, which can be varied by changing the ratios of FK to PEG. Also, natural amino acid (i.e. cysteine) modified peptides of CFKFEFKFK (CFK) and CFKFEFKFKC (CFKC) were crosslinked with maleimide PEG via covalent bonding. PEG with molecular weight 2 kDa, 5 kDa were used to synthesis with peptides to study the effect of chain length of conjugates on the properties including solubility and gel formation ability. It was found that the resulting conjugate, i.e. CFK-PEG5k-CFK (TRI), can form the stiff hydrogel on its own due to its approximate hydrophobicity. Furthermore, hybrid hydrogels with tuneable viscoelasticity can be obtained simply by mixing FK and TRI with different ratios of FK to TRI. Peptide CFKC was crosslinked with PEG with high molecular weight, i.e. PEG 20 kDa, to prepare the conjugate of BC-20k, which can form not only hydrogel but also dry film. We demonstrated that the BC-20k hydrogel has a remarkably enhanced viscoelasticity (200 Pa with peptide concentration 5 mg/ml) and the relevant BC-20k film has a good elasticity, i.e. the strain can reach until 15%.

Date of Award	31 Aug 2021
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Alberto Saiani (Supervisor) & Robin Curtis (Supervisor)