Sheng Yue

Bone is the second most widely transplanted tissue after blood. Synthetic alternatives are needed that can reduce the need for transplants and regenerate bone by acting as active temporary templates for bone growth. Bioactive glasses are one of the most promising bone replacement/regeneration materials because they bond to existing bone, are degradable and stimulate new bone growth by the action of their dissolution products on cells. Sol–gel-derived bioactive glasses can be foamed to produce… Show more

Bone is the second most widely transplanted tissue after blood. Synthetic alternatives are needed that can reduce the need for transplants and regenerate bone by acting as active temporary templates for bone growth. Bioactive glasses are one of the most promising bone replacement/regeneration materials because they bond to existing bone, are degradable and stimulate new bone growth by the action of their dissolution products on cells. Sol–gel-derived bioactive glasses can be foamed to produce interconnected macropores suitable for tissue ingrowth, particularly cell migration and vascularization and cell penetration. The scaffolds fulfil many of the criteria of an ideal synthetic bone graft, but are not suitable for all bone defect sites because they are brittle. One strategy for improving toughness of the scaffolds without losing their other beneficial properties is to synthesize inorganic/organic hybrids. These hybrids have polymers introduced into the sol–gel process so that the organic and inorganic components interact at the molecular level, providing control over mechanical properties and degradation rates. However, a full understanding of how each feature or property of the glass and hybrid scaffolds affects cellular response is needed to optimize the materials and ensure long-term success and clinical products. This review focuses on the techniques that have been developed for characterizing the hierarchical structures of sol–gel glasses and hybrids, from atomic-scale amorphous networks, through the covalent bonding between components in hybrids and nanoporosity, to quantifying open macroporous networks of the scaffolds. Methods for non-destructive in situ monitoring of degradation and bioactivity mechanisms of the materials are also included. Show less

Bioactive glass has high potential for bone regeneration due to its ability to bond to bone and stimulate osteogenesis whilst dissolving in the body. Although three-dimensional (3-D) bioactive glass scaffolds with favorable pore networks can be made from the sol–gel process, compositional and structural evolutions in their porous structures during degradation in vivo, or in vitro, have not been quantified. In this study, bioactive glass scaffolds were put in a simulated body fluid flow… Show more

Bioactive glass has high potential for bone regeneration due to its ability to bond to bone and stimulate osteogenesis whilst dissolving in the body. Although three-dimensional (3-D) bioactive glass scaffolds with favorable pore networks can be made from the sol–gel process, compositional and structural evolutions in their porous structures during degradation in vivo, or in vitro, have not been quantified. In this study, bioactive glass scaffolds were put in a simulated body fluid flow environment through a perfusion bioreactor. X-ray microtomography (μCT) was used to non-destructively image the scaffolds at different degradation stages. A new 3-D image processing methodology was developed to quantify the scaffold’s pore size, interconnect size and connectivity from μCT images. The accurate measurement of individual interconnect size was made possible by a principal component analysis-based algorithm. During 28 days of dissolution, the modal interconnect size in the scaffold was reduced from 254 to 206 μm due to the deposition of mineral phases. However, the pore size remained unchanged, with a mode of 682 μm. The data presented are important for making bioactive glass scaffolds into clinical products. The technique described for imaging and quantifying scaffold pore structures as a function of degradation time is applicable to most scaffold systems. Show less

PhD thesis in quantifictaion of porous scaffolds from 3D micro-CT images.
I was awarded Larry Hench Biomaterials Prize for excellence in a PhD in a Biomaterials related Subject.

Porous melt-derived bioactive glass scaffolds with interconnected pore networks suitable for bone regeneration were produced without the glass crystallizing. ICIE 16 (49.46% SiO2, 36.27% CaO, 6.6% Na2O, 1.07% P2O5 and 6.6% K2O, in mol.%) was used as it is a composition designed not to crystallize during sintering. Glass powder was made into porous scaffolds by using the gel-cast foaming technique. All variables in the process were investigated systematically to devise an optimal process… Show more

Porous melt-derived bioactive glass scaffolds with interconnected pore networks suitable for bone regeneration were produced without the glass crystallizing. ICIE 16 (49.46% SiO2, 36.27% CaO, 6.6% Na2O, 1.07% P2O5 and 6.6% K2O, in mol.%) was used as it is a composition designed not to crystallize during sintering. Glass powder was made into porous scaffolds by using the gel-cast foaming technique. All variables in the process were investigated systematically to devise an optimal process. Interconnect size was quantified using mercury porosimetry and X-ray microtomography (μCT). The reagents, their relative quantities and thermal processing protocols were all critical to obtain a successful scaffold. Particularly important were particle size (a modal size of 8 μm was optimal); water and catalyst content; initiator vitality and content; as well as the thermal processing protocol. Once an optimal process was chosen, the scaffolds were tested in simulated body fluid (SBF) solution. Amorphous calcium phosphate formed in 8 h and crystallized hydroxycarbonate apatite (HCA) formed in 3 days. The compressive strength was approximately 2 MPa for a mean interconnect size of 140 μm between the pores with a mean diameter of 379 μm, which is thought to be a suitable porous network for vascularized bone regeneration. This material has the potential to bond to bone more rapidly and stimulate more bone growth than current porous artificial bone grafts. Show less

Scaffolds are needed that can act as temporary templates for bone regeneration and actively stimulate vascularized bone growth so that bone grafting is no longer necessary. To achieve this, the scaffold must have a suitable interconnected pore network and be made of an osteogenic material. Bioactive glass is an ideal material because it rapidly bonds to bone and degrades over time, releasing soluble silica and calcium ions that are thought to stimulate osteoprogenitor cells. Melt-derived… Show more

Scaffolds are needed that can act as temporary templates for bone regeneration and actively stimulate vascularized bone growth so that bone grafting is no longer necessary. To achieve this, the scaffold must have a suitable interconnected pore network and be made of an osteogenic material. Bioactive glass is an ideal material because it rapidly bonds to bone and degrades over time, releasing soluble silica and calcium ions that are thought to stimulate osteoprogenitor cells. Melt-derived bioactive glasses, such as the original Bioglass® composition, are available commercially, but porous scaffolds have been difficult to produce because Bioglass and similar compositions crystallize on sintering. Sol-gel foam scaffolds have been developed that avoid this problem. They have a hierarchical pore structure comprising interconnected macropores, with interconnect diameters in excess of the 100 μm that is thought to be needed for vascularized bone ingrowth, and an inherent nanoporosity of interconnected mesopores (2–50 nm) which is beneficial for the attachment of osteoprogenitor cells. They also have a compressive strength in the range of cancellous bone. This paper describes the optimized sol-gel foaming process and illustrates the importance of optimizing the hierarchical structure from the atomic through nano, to the macro scale with respect to biological response. Show less

X-ray microtomography (μCT) is a popular tool for imaging scaffolds designed for tissue engineering applications. The ability of synchrotron μCT to monitor tissue response and changes in a bioactive glass scaffold ex vivo were assessed. It was possible to observe the morphology of the bone; soft tissue ingrowth and the calcium distribution within the scaffold. A second aim was to use two newly developed compression rigs, one designed for use inside a laboratory based μCT machine for continual… Show more

X-ray microtomography (μCT) is a popular tool for imaging scaffolds designed for tissue engineering applications. The ability of synchrotron μCT to monitor tissue response and changes in a bioactive glass scaffold ex vivo were assessed. It was possible to observe the morphology of the bone; soft tissue ingrowth and the calcium distribution within the scaffold. A second aim was to use two newly developed compression rigs, one designed for use inside a laboratory based μCT machine for continual monitoring of the pore structure and crack formation and another designed for use in the synchrotron facility. Both rigs allowed imaging of the failure mechanism while obtaining stress–strain data. Failure mechanisms of the bioactive glass scaffolds were found not to follow classical predictions for the failure of brittle foams. Compression strengths were found to be 4.5–6 MPa while maintaining an interconnected pore network suitable for tissue engineering applications. Show less