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Title: Production and properties of fibre webs containing self-assembling peptides for promotion of hard tissue repair
Author: Gharaei, Robabeh
ISNI:       0000 0004 6347 6962
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2017
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Self-assembling peptides (SAPs) have attracted interest due to their potential value in therapeutics. The 11-residue family of peptides (P11-X), are able to self-assemble hierarchically into β-sheet tapes with higher order structures (ribbons, fibrils and fibres) being produced depending on peptide concentration. Previous studies of P11-X peptides aimed at tissue repair focused on hydrogel formats where their potential for deposition of hard tissue minerals in vivo was demonstrated due in part to their ability to mimic the physiochemical properties of natural extracellular matrix (ECM) of bone. However, SAP hydrogels are often associated with inherently weak and transient mechanical properties, which make their handling and fixation challenging in large load-bearing tissue defects. Accordingly, to engineer a more robust scaffold, the present research demonstrates the feasibility of producing electrospun webs composed of a biodegradable polymer, poly (e-caprolactone) (PCL) commixed with either P11-4 (Ac-QQRFEWEFEQQ-Am) or P11-8 (Ac QQRFOWOFEQQ-Am) self-assembling peptides. Morphological features of the electrospun webs investigated via scanning and transmission electron microscopies (SEM and TEM) revealed that PCL/P11-4 and PCL/P11-8 electrospun webs contain fibres in both nano- (10–100 nm) and submicron ranges (100–700 nm), whereas PCL fibre webs, produce a predominantly submicron fibre distribution. Homogeneous distribution of SAPs within the electrospun fibres was revealed via confocal microscopy. . Furthermore, it was discovered by spectroscopic analysis that SAPs exist entirely in their monomeric state in the electrospinning solution, and convert from monomeric form to β-sheet secondary conformation when converted into fibres. PCL/SAP fibres were shown to exhibit enhanced hydrophilicity compared to PCL-only fibres, and induce no cytotoxic response when cultured with L929 mouse fibroblasts. A study of the release kinetics of SAP from PCL fibres II in simulated conditions of biological pH (neutral pH of 7.4) after 7 days revealed at least 75% of P11-4 and 45% of P11-8 still remained, suggesting potential for long-term therapeutic delivery. Finally the ability of SAP embedded PCL fibrous scaffold to nucleate and support growth of bone minerals was investigated using two in vitro assays, specifically the simulated body fluid (SBF) method and the in vitro nucleation (IVN) tank method. PCL/SAP fibres were found to nucleate and support spheroidal growth of hydroxyapatite crystals and were capable of comparable mineral nucleation performance as SAP hydrogels.
Supervisor: Russell, Stephen ; Parikshit, Goswami Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available