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DESIGNING NANO-STRUCTURED HYDROGEL FOR CARTILAGE TISSUE ENGINEERING
[Thesis]. Manchester, UK: The University of Manchester; 2019.
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Abstract
As the natural turnover level of cartilage and its ability to repair itself are both relatively slow, minor injuries or lesions may lead to progressive damage of cartilage. Unlike other types of tissues that can heal intrinsically, cartilage, being avascular, has a confined supply of nutrients. For the past 25 years, researchers have turned to tissue engineering (TE) in treating cartilage injury. Cells, matrix and signalling molecules are three essential ingredients in TE. An ideal matrix such as biomaterial scaffold would support the cells at the primitive stage of tissue development, in terms of promoting desired phenotype and regeneration of neo-tissues. Physiologically, ~80% of the extracellular matrix of healthy cartilage comprises of water. This makes hydrogels, which are composed of >90% water, the best scaffold candidate to support the cells during cartilage regeneration. Self-assembling peptide hydrogels (SAPH) are designed by embracing the nature of self-assembly in protein folding. SAPHs are seen to have great potential in TE applications; as the properties of peptide fibrils can be controlled by changing peptide sequences, concentration and pH. Other advantages of using SAPH in TE are their biocompatibility, biodegradability, tunability for desired mechanical properties, injectability and they can be functionalised. The primary objective of this thesis was to develop fully chemically and physically defined peptide-based hydrogels that can be used as three dimensional (3D) scaffolds for TE applications. In the present study, we have shown that these peptide hydrogels have different storage moduli depending on the concentration and the pH of the hydrogels. This thesis also discusses the effects of charge in peptide hydrogels on cell viability, proliferation and production of GAGs. It was seen that bovine and human chondrocytes were viable for the duration of the study (21 days). In addition, these charged peptide hydrogels, when cultured without chondrogenic media, were observed to inhibit the production of GAG and type II collagen. In addition, cells were also found to respond differentially to the dynamic mechanical properties of the peptide hydrogels. Cell - material interaction has been shown to play a vital role in cartilage engineering. Different biomaterial properties significantly influence the initial cell attachment to the substrate, which is crucial for chondrogenesis. The interaction of chondrocytes with the SAPH has been explored in this project. We show the effects of using different peptide hydrogels on the attachment, proliferation and spreading of immortalised human chondrocytes. Cell adhesion rate on SAPH was comparable to those on collagen hydrogels. Arginine was seen to induce cells’ elongated morphology. This thesis shows that modifying the peptide sequence changes the gelation and degradation behaviour of the SAPH, which affects the cells bio-response due to cells’ mechanosensitivity. The work also contributes to the knowledge of substituting phenylalanine with arginine to the pioneering peptide sequence, FEFKFEFK. The study led an inaugural investigation on the interaction between the cells and SAPH.