Thesis
Supramolecular assemblies : a new route to controlled drug delivery and scaffold for tissue engineering
- Creator
- Awarding institution
- University of Strathclyde
- Date of award
- 2014
- Thesis identifier
- T13899
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Ionic self-complementary peptides can self-assemble into hydrogels similar in properties to the natural extracellular matrix. Hydrogels can be exploited as drug carriers and scaffolds for tissue engineering due to many reasons including their biocompatibility, biodegradability and physico-chemical properties. RADA16-I, for instance, is characterised by its ability to form stable β-sheet nanostructures. The main focus of this project is to study the effect of anionic salts (Hofmeister series) on the self-assembly of RADA16-I hydrogel which could be used as a drug vehicle and as a scaffold to induce the differentiation of mesenchymal stem cells into adipogenic and osteogenic linages. Hydrogels were prepared using different concentrations (e.g. 100, 300, 600 and 900 mM) of sulphate, citrate, phosphate monobasic, chloride, perchlorate, nitrate, thiocyanate and iodide sodium salts, and characterised by CD and FT-IR. The 600 mM concentration was chosen as the minimum effective concentration which induces self-assembly in order to avoid cytotoxicity of the salts upon the cells. The prepared hydrogels in the presence of sulphate and iodide sodium salts were further characterised by circular dichroism (CD), FT-IR spectroscopy and atomic force microscopy (AFM). The stability of RADA16-I under physiological conditions (pH around 7, temperature of 37°C) was explored. The release of quinine from the self-assembling hydrogels was measured using UV-spectroscopy. Finally, the impact of the hydrogels on murine mesenchymal (C3H10T1/2) stem cells was assessed in order to provide a non-invasive strategy to manipulate the differentiation of stem cells in the absence of chemical treatment with potential for tissue engineering applications. The peptide (RADA16-I) was shown to assemble into β-sheet nanofibres with a diameter of 23.4 ±2.1 nm, 40.8±3.7 nm in the presence of sodium sulphate, and 32.8±2.2 nm with sodium iodide. The CD and FT-IR results revealed that sulphate anion exhibited kosmotropic (gel maker) properties while and iodide acted as a chaotrope (gel breaker). The stability experiment showed that RADA16-I lost its β-nanostructures at a pH around 7 and formed irregular aggregates indicating that the self-assembly of this peptide occurs in acidic environments rather than the physiological pH. Quinine release decreased with the kosmotropic sulphate system compared with the chaotropic iodide indicating that salt-induced self-assembling peptides can be used as vehicles for controlled drug release. Fibronectin (FN) was used to enhance the cell attachment on the hydrogel. The cell culture findings suggested that inducing the self-assembly of peptide hydrogels by ionic salts might not be a suitable strategy for using hydrogels in the biomedical applications of murine C3H10T1/2 stem cells due to the cytotoxicity of the sulphate and iodide ions on the cells.
- Resource Type
- DOI
- Date Created
- 2014
- Former identifier
- 1041915
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