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Title: Bioactive hydrogels for tissue engineering
Author: Place, Elsie Sarah
ISNI:       0000 0004 2709 8677
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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Modern tissue engineering (TE) scaffolds are expected to actively promote tissue repair as well as meeting the traditional requirements of non-toxicity, degradability and structural integrity. This thesis presents two novel bioactive hydrogel systems for bone and cartilage TE. A series of alginate hydrogels were developed in which all or a fraction of the calcium normally used for crosslinking alginate was replaced by bioactive strontium and/or zinc ions. Strontium was chosen for its ability to stimulate bone formation, while zinc is essential for alkaline phosphatase activity. Due to an interaction between the crosslinking ion and alginate type, the hydrogel properties could be tailored independently of the crosslinking ion used – meaning that varying biological and materials requirements can be accommodated. Strontium release from alginate gels was of a physiologically relevant magnitude, and alkaline phosphatase protein activity in Saos-2 cells was highest in strontium gels. Secondly, a biomimetic strategy for transforming growth factor beta (TGF-β) presentation and release was evaluated. TGF-β in vivo is secreted as part of an inactive latent complex, which is sequestered in a stable form within extracellular matrix until released by cells. TGF-β was therefore incorporated into poly(ethylene glycol)-hyaluronic acid hydrogels in its latent form. When compared to free TGF-β, advantages were demonstrated in terms of lower protein adsorption to tissue culture plastic and relative biological inactivity. The latter implies that high doses may be loaded into TE scaffolds without exposing cells to excessive quantities of active growth factor, with TGF-β bioavailability then being controlled by gradual activation by cells. Increased metabolic activity and ECM deposition by bovine chondrocytes were seen after almost five weeks in culture with a single initial loading of LTGF-β. These innovations correspond to current TE trends, which seek to use biomimetic principles to evoke regenerative responses from transplanted or host cells, but to do so using technically and commercially feasible means.
Supervisor: Stevens, Molly Sponsor: EPSRC ; RepRegen Ltd
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral