Silicon is an essential element in human nutrition, with the symptoms of a silicon-deficient diet being abnormal bone development (Carlisle, 1972). Similarly, animals and bone forming osteoblast-like cells in vitro show an increase in bone growth when supplemented with the soluble, bioavailable form of silicon, orthosilicic acid [Si(OH4)] (Carlisle, 1988). Certain bioactive glass compositions can form a strong chemical bond with bone, doing so by dissolving to form a solution that includes orthosilicic acid which re-polymerises to form a hydrated silica gel layer that adsorbs growth factors, supports cell growth and acts a nucleation bed for bone mineral (Hench, 1980). Bioactive glass degradation products alone have also been shown to significantly enhance the activity of osteoblasts in vitro (Xynos et al, 2001). Pure, crystalline silicon is not soluble in water or body fluids, but when electrochemically etched with hydrofluoric acid, nanoscale silicon hydride-lined pores are formed through the material which render it soluble in aqueous solutions, yielding orthosilicic acid (Canham, 1996). Porous silicon has therefore been proposed as a novel orthopaedic biomaterial, acting in a similar way to bioactive glasses. In addition, the long, narrow pores can be filled with pharmaceuticals, creating a dissolvable drug delivery material with release kinetics that are easily controllable by adjusting the pore morphology and drug loading density (Anglin et al, 2008). This research aims to evaluate porous silicon (pSi) as a therapeutic biomaterial for bone tissue engineering applications in the form of a composite with the biodegradable polymer, polycaprolactone (PCL). pSi microparticles were incorporated into a polycaprolactone matrix and the composites characterised in terms of the ability to generate orthosilicic acids under various conditions. It was found that the composites released silicic acids at a rate proportional to the loading proportion of pSi, with 8% composites (20mg pSi in 230mg PCL) eluting ~400 ng.ml-1 Si per day. At this composition, pSi increased the amount of calcium phosphate formed on the composite in a simulated body fluid and this had the morphology and molar ratio of biological apatite (Ca:P ≈ 1.5). The addition of 8% pSi to polymers enhanced the electroconductivity of hydrogels by two orders of magnitude and did not significantly affect mechanical strength. The release profiles of small molecules such as gentamicin and large hydrophobic proteins such as alkaline phosphatase were enhanced by pre-loading sample drugs into pSi rather than directly loading drugs into PCL. Crucially, the molecules retained their activity following release. Other proteins such as bovine serum albumin were adsorbed onto the surface silica gel layer, suggesting a method for localising growth factors onto biomaterial surfaces. Osteoblasts responded well to 8% pSi-PCL composites, producing significantly more collagen and glycosaminoglycans in vitro. Collagen in the extracellular matrix (ECM) was also significantly more highly crosslinked as determined by the pyridinium content of ECM lysates and was more mineralised than the ECM on PCL alone. The breakdown products of pSi also significantly enhanced the osteoblastic phenotype of cells in vitro. This research demonstrates that porous silicon can be added to polymer-based materials to enhance their effectiveness as biomaterials for orthopaedic tissue engineering.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:514884 |
| Date | January 2009 |
| Creators | Henstock, James Rolleston |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://eprints.nottingham.ac.uk/11022/ |
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