Papers by Author: Julian R. Jones

Abstract: Different ratios of a resorbable phosphate glass (ICEL) and a bioactive silicate glass (CEL2) were co-sintered to obtain 3D porous scaffolds by gel-cast foaming method. The scaffold morphology, crystalline phases and compressive strength were studied. All the scaffolds showed a 3D structure with highly interconnected pores. The ICEL/CEL2 co-sintering resulted in a lower shrinkage leading to higher scaffold porosity (more than 70 vol%) compared to pure ICEL and CEL2 (about 65 vol%). Tuning ICEL/CEL2 ratio allowed the modulation of the scaffold resorption rate, with weight loss ranging from 20% to 75% after soaking for 3 months in simulated body fluid. Scaffolds containing higher amount of CEL2 silicate glass, resulted in a very high bioactivity. In vitro biological test showed no toxic effect of the scaffolds on human osteoblast-like cells.

Abstract: Materials for bone defect filling should have 3D macroporous structure and be flexible to be packed into complex defects with limited entrance space. Tissue engineering scaffolds should also mimic the structure and morphology of the host tissue. Electrospinning is a versatile technique to produce materials with micro/nanofibrous structure, large surface area and high porosity. Electrospun materials are very promising for tissue engineering due to the possibility of mimicking the fibrous structure of natural extra cellular matrix (ECM). Siloxane-containing vaterite (SiV)/poly (_L-lactic acid) (PLLA) hybrids (SiPVH) with controlled silicate and calcium ions releasing ability has been produced in our group. They have also demonstrated good cell infiltration into the electrospun hybrid materials that had fiber diameters greater than 10 μm. However, these electrospun hybrid materials were planar (2D) and are not suitable for large defect regeneration. In this work, the development of a fabrication technique for the production of 3D cotton wool-like structures with fiber diameter in the range of 10 μm was performed. SiPVH cotton wool-like structure containing 0, 30 and 60 wt % SiV were prepared by blowing air in the direction perpendicular to fiber spinning. Si-vaterite particles and small pores were found on the surface of the fibers. The fiber diameter of the samples were found to be in the range of 10 ~ 20 μm. Stretch tests showed more than 50 % extension for the SiPVH cotton wool-like material containing 30 wt % SiV (SiPVH30). This extension was similar to that observed for the PLLA cotton wool-like material. The results suggest that the SiPVH30 cotton wool-like material are good candidates for bone tissue engineering scaffolds.

Abstract: Siloxane-containing vaterite (SiV) / poly (lactic acid) hybrid (SiPVH) beads with the releasability of silicate and calcium ions were prepared with an electrospraying method. According to the increase in the silicon content of the SiV, the amount of silicate ion released from the resulting beads also increased. When the beads were soaked in a cell culture medium, proteins derived from fetal bovine serum were adsorbed on their surfaces. Cell adhesion tests were also performed on the beads with using mouse osteoblast-like cell line (MC3T3-E1) in vitro. After 5 days of culturing, the cells adhered and spread well to cover the surface of the beads. In the localized area, agglomerated cells were observed to combine with cauliflower-shaped calcium phosphate deposits.

Abstract: Bone tissue has evolved into hierarchical three-dimensional structures with dimensions ranging from nanometres to metres. The structure varies depending on the site in the body, which is dictated by the loading environment. Medically, bone is one of the most replaced body parts (second only to blood) but replicating these complex living hierarchical structures for the purpose of regenerating defective bone is a challenge that has yet to be overcome. A temporary template (scaffold) is needed that matches the hierarchical structure of native bone as closely as possible that is available ‘off the shelf’ for surgeons to use. After implantation the scaffold must bond to bone and stimulate not only three dimensional (3D) bone growth, but also vascularisation to feed the new bone. There are many engineering design criteria for a successful bone scaffold and bioactive glass foam scaffolds have been developed that can fulfil most of them, as they have a hierarchical porous structure, they can bond to bone, and they release soluble silica species and calcium ions that have been found to up-regulate seven families of genes in osteogenic cells. Other ions have also been incorporated to combat infection and to counteract osteoporosis. Their tailorable hierarchical structure consists of highly interconnected open spherical macropores, further, because the glass is sol-gel derived, the entire structure is nanoporous. The macropores are critical for bone and blood vessel growth, the nanopores for tailoring degradation rates and protein adsorption and for cell attachment. This chapter describes the optimised sol-gel foaming process and how bone cells respond to them. Whatever type of scaffold is used for bone regeneration, it is critically important to be able to quantify the hierarchial pore structure. The nanopore size can be quantified using gas sorption, but to obtain full information of the macropore structure, imaging must be done using X-ray microtomography and the resulting images must be quantified via 3D image analysis. These techniques are reviewed.

Abstract: Bioactive glass scaffolds have been developed with interconnected macropore networks, with pore diameters in excess of 500µm and apertures in excess of 100µm, by foaming sol-gel derived bioactive glasses. Bioactive glasses bond to bone by forming a hydroxycarbonate apatite (HCA) layer on their surface on contact with body fluid, which is similar to the composition of the apatite in bone. The aim of this work was to investigate the how changing the atomic structure of the glass affects HCA layer formation. Scaffolds were synthesised at 3 sintering temperatures and were characterised using 29Si and proton MAS-NMR, from which the silica network connectivity and Si-OH groups were quantified. The rate of HCA layer formation decreased as the number of Si-OH groups decreased, confirming the role of Si-OH groups in HCA layer formation.

Abstract: The possibility of enhancing mechanical properties by incorporation of polymeric components to sol-gel derived materials is extremely attractive to prepare macroporous scaffolds, leading to materials with potential applications in both hard and soft tissue regeneration. In this work bioactive glass-polyvinyl alcohol hybrids were developed and their mechanical behavior was evaluated. Hybrids were synthesized by adding polyvinyl alcohol to a sol-gel precursor solution, which was then foamed with the addition of a surfactant and vigorous agitation. The foams were cast, aged and dried at 40°C. A cleaning step to decrease the acidic character of the obtained hybrids was undertaken by immersion in a NH4OH solution. The mechanical behavior of the hybrids was evaluated in compression using both stress and strain control tests. Hybrid foams had a high porosity varying from 60-90% and the macropore diameter ranged from 10 to 600 µm. The modal macropore diameter varied with the inorganic phase composition and with the polymer content in the hybrid. The strain at fracture of the as prepared hybrid foams was substantially greater than pure gel-glass foams. The cleaned hybrids presented a slightly higher strength and lower deformation than the as prepared foams.

Abstract: Septal cartilage is widely used for the repair of soft tissue defects in the head, neck and nose. Tissue Engineering techniques are being investigated to create cartilage in vitro by seeding appropriate cells on resorbable scaffolds. In this study, human chondrocytes were cultured on macroporous bioactive glass foam scaffolds. The aim was to investigate how Raman spectroscopy could be used as a non-invasive technique to monitor the response of chondrocytes to a 3D scaffold in real time. The spectra were compared to scanning electron microscope (SEM) micrographs and immunohistochemistry results.

Abstract: Bioactive glass scaffolds with interconnected macroporous networks have been developed by foaming sol-gel derived bioactive glass of the 70S30C (70 mol% SiO2, 30 mol% CaO) composition. The effect of sintering temperature on the dissolution of the scaffolds in simulated body fluid (SBF) was investigated in 3D using x-ray micro-computer tomography (micro CT) and inductive coupled plasma (ICP) analysis. Micro-CT is non-destructive and allows observation of specific parts of the scaffold at various stages of degradation. However, data analysis is complex at present. Percentage porosity data obtained by micro-CT was compared to physical data and pore size distributions obtained from mercury intrusion porosimetry were compared to the interconnected pore diameters observed from the micro CT images.

Abstract: In dentistry, chronic periodontitis often leads to bone resorption together with an increasing risk of bacteremia. Bioactive glass has found extensive application as dental graft material. A successful antimicrobial bactericidal effect has been shown from the introduction of Ag2O into the glass composition. In this study, the cytotoxicity of soluble silver, calcium and silica ions on primary human osteoblasts was investigated by measurements of mitochondrial activity and neutral red dye uptake. Silver concentrations of 4 - 6 ppm (1 mg/ml conc.) and 6 - 9 ppm (2 mg/ml conc.) have been measured in complete culture medium. It was found that the bioactive gel-glass extract with an initial concentration of 1 mg/ml (1mg glass per ml of culture medium) has no negative effect, whereas increased gel-glass concentration of 2 mg/ml seemed to have a toxic effect on the cell viability of human osteoblasts. It might be concluded that a reduction of the rate of silver dissolution from the bioactive gel-glass might preserve a maximum cell viability.

Abstract: Bioactive gel-glasses, such as the silver-doped Ag-S70C30 glass, can be used to modify the inflammatory response in a local body compartment such as in acne lesions and in nonhealing dermal wounds. In this study, the cytotoxicity of soluble silver, calcium and silica ions on human epidermal keratinocytes was investigated by measurements of mitochondrial activity (MTT assay) and neutral red dye uptake (NR assay). Ag-S70C30 extracts were prepared by soaking glass powder in complete culture medium at concentrations of 1 mg/ml and 2 mg/ml (mg of glass powder per ml of culture medium). Silver concentrations for both concentrations of approximately 1 ppm were detected by inductive coupled plasma analysis (ICP). No negative effect on the cell viability was measured for an initial gel-glass concentration of 1 mg/ml and for the two shortest extraction times at a concentration of 2 mg/ml. Based on the results from MTT/ NR assays, a pH rise of approximately one unit had no negative effect on the NHEK-A cell viability. This preliminary study on keratinocyte viability merits future investigations on silver bioglass as a novel antimicrobial wound healing agent.