The ionic complementary oligo peptide FEFKFEFK (F8) is known to self-assemble into β-sheet rich fibrillary network hydrogel at the concentration of ~8mg/ml at pH. The fragile nature of the F8 hydrogel (which is also related to rheological performance) is one of the major drawback which limits its use in force bearing tissue regeneration and long term controlled drug delivery applications. Though, the mechanical property such as shear modulus (Gâ²) of F8 can be improved by increasing the concentration of peptide they unfortunately remain fragile i.e. easily breakdown at lower strain. Therefore, as an initial method to improve the rheological properties of F8 a series of pH responsive poly (ethylene glycol)/peptide (PEG/F8) hybrid hydrogels were prepared by physical mixing of polymer and peptide. The Gâ² of hybrid gels was found to be a function of the number of EO units, which were controlled either by varying the molecular weight or concentration of PEG. FTIR showed that the secondary structure adopted by F8 was not disturbed in the presence of different number of EO units. Though the strategy of physical mixing of polymer with peptide allowed the freedom to control the Gâ² of F8 hydrogels, it remained fragile (easily break down at lower strain) in the presence of different numbers of EO units. To overcome this issue, a one-pot double network (DN) design strategy was employed to fabricate physically-chemically cross-linked F8/poly (ethylene glycol) diacrylate hydrogels. In the prepared DN hydrogel, the first network is comprised of a physically cross-linked network of F8, while the second network is a chemically cross-linked network of PEGDA. Mechanical properties such as Gâ², viscoelasticity and compressive stress of DN hydrogels increased compared to the control single peptide network hydrogel. Moreover, F8/pPEGDA DN hydrogel could be produced in different complex shapes, by using the first fibrous network as a âskeletonâ, which is a desirable property in biomedical applications where patient-tailored scaffolds are required. The biocompatibility of the DN hydrogels was also demonstrated using murine 3T3 cells, which were cultured under two-dimensional (2D) and three-dimensional (3D) cell culture conditions. In later to prepare the covalently interconnected peptide/polymer DN hydrogels, F8 was modified by incorporating a photo reactive alloxycarbonyl (alloc) functional group at lysine to provide vinyl groups to react with double bonds in PEGDA via free radical polymerization. F8 with two alloc functional group at the termini was named F10. In this approach, F10 was firstly self-assembled to form a fibrous network of peptide in the presence of precursors of the second network, PEGDA. Due to the available double bond on F10 peptide it was anticipated that during free radical polymerization, F10 would be covalently link with the PEGDA. Moreover, the injectable nature of F10 gel made it possible to produce covalently connected F10/PEGDA double network hydrogel that can be shaped using a one pot method in a short preparation time of 1hr. Lastly, the sustained controlled release of a model anti-cancer drug doxorubicin (Dox) from DN hydrogel was studied.
Date of Award | 1 Aug 2019 |
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Original language | English |
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Awarding Institution | - The University of Manchester
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Supervisor | Aline Saiani (Supervisor) & Alberto Saiani (Supervisor) |
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- Polymer, drug delivery, self-assembly, double network hydrogel, peptide, two components, mechanical
- Tissue engineering
Designing Of Polymer/Peptide Hydrogels For Biomedical Applications
Siddique, B. (Author). 1 Aug 2019
Student thesis: Phd