Bioactive glasses are known to stimulate bone healing, and the incorporation of strontium has the potential to increase their potency. In this study, calcium oxide in the 45S5 bioactive glass composition was partially (50%, Sr50) or fully (100%, Sr100) substituted with strontium oxide on a molar basis. The effects of the substitution on bioactive glass properties were studied, including density, solubility, and in vitro cytotoxicity. Stimulation of osteogenic differentiation was investigated using mesenchymal stromal cells obtained from rat bone marrow. Strontium substitution resulted in altered physical properties including increased solubility. Statistically significant reductions in cell viability were observed with the addition of bioactive glass powders to culture medium. Specifically, addition of ≥ 13.3 mg/ml of 45S5 bioactive glass or Sr50, or ≥ 6.7 mg/ml of Sr100, resulted in significant inhibition. Real‐time PCR analyses detected the upregulation of genes associated with osteoblastic differentiation in the presence of all bioactive glass compositions. Some genes, including Alpl and Bglap, were further stimulated in the presence of Sr50 and Sr100. It was concluded that strontium‐substituted bioactive glasses promoted osteogenesis in a differentiating bone cell culture model and, therefore, have considerable potential for use as improved bioactive glasses for bone tissue regeneration. © 2015 The Authors. Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

Healthy cells are required in large numbers to form a tissue-engineered construct and primary cells must therefore be increased in number in a process termed 'expansion'. There are significant problems with existing procedures, including cell injury and an associated loss of phenotype, but three-dimensional culture has been reported to offer a solution. Reversible gels, which allow for the recovery of cells after expansion would therefore have great value in the expansion of chondrocytes for tissue engineering applications, but they have received relatively little attention to date. In this study, we examined the synthesis and use of thermoresponsive polymers that form reversible three-dimensional gels for chondrocyte cell culture. A series of polymers comprising N-isopropylacrylamide (NIPAM) and styrene was synthesized before studying their thermoresponsive solution behaviour and gelation. A poly(NIPAM-co-styrene-graft-N-vinylpyrrolidone) variant was also synthesized in order to provide increased water content. Both random-and graft-copolymers formed particulate gels above the lower critical solution temperature and, on cooling, re-dissolved to allow enzyme-free cell recovery. Chondrocytes remained viable in all of these materials for 24 days, increased in number and produced collagen type II and glycosaminoglycans.

Nanocrystalline hydroxyapatite (HA) has good biocompatibility and the potential to support bone formation. It represents a promising alternative to autologous bone grafting, which is considered the current gold standard for the treatment of low weight bearing bone defects. The purpose of this study was to compare three bone substitute pastes of different HA content and particle size with autologous bone and empty defects, at two time points (6 and 12 months) in an ovine scapula drillhole model using micro-CT, histology and histomorphometry evaluation. The nHA-LC (38% HA content) paste supported bone formation with a high defect bridging-rate. Compared to nHA-LC, Ostim® (35% HA content) showed less and smaller particle agglomerates but also a reduced defect bridging-rate due to its fast degradation The highly concentrated nHA-HC paste (48% HA content) formed oversized particle agglomerates which supported the defect bridging but left little space for bone formation in the defect site. Interestingly, the gold standard treatment of the defect site with autologous bone tissue did not improve bone formation or defect bridging compared to the empty control. We concluded that the material resorption and bone formation was highly impacted by the particle-specific agglomeration behaviour in this study.

Barrier membranes used for the treatment of bone tissue defects caused by periodontitis lack the ability to promote new bone tissue regeneration. However, the addition of an osteogenic component to membranes may enhance their regenerative potential. Here the manufacturing of composite membranes made of poly(caprolactone) and strontium‐substituted bioactive glass is described using the solution‐electrospinning technique, with particles located both inside and on the surface of the fibers. All membranes are characterized using scanning electron microscopy and energy dispersive X‐ray spectroscopy, and glass dissolution from within the fibers is investigated in water. In vitro material cytotoxicity is determined using a rat osteosarcoma cell line. Electrospun fibers exhibit porous surfaces and regions of increased diameter where the particles are accumulated. The glass dissolves after immersion in water, releasing dissolution products that are associated with increased pH. Further evidence suggests accelerated polymer degradation due to interactions between both components, which may provide the additional benefit of reducing the pH changes associated with glass dissolution. All compositions are biocompatible in vitro, with the exception of membranes with >50 μg of glass on their surface. In conclusion, these membranes show great potential for bone healing applications, including guided bone regeneration and scaffolds for musculoskeletal tissue engineering.

Biomaterials composed of hydroxyapatite (HA) are currently used for the treatment of bone defects resulting from trauma or surgery. However, hydroxyapatite supplied in the form of a paste is considered a very convenient medical device compared to the materials where HA powder and liquid need to be mixed immediately prior to the bone treatment during surgery. In this study we have tested a series of hydroxyapatite (HA) pastes with varying microstructure and different rheological behaviour to evaluate their injectability and biocompatibility. The particle morphology and chemical composition were evaluated using HRTEM, XRD and FTIR. Two paste-types were compared, with the HA particles of both types being rod shaped with a range of sizes between 20 and 80nm while differing in the particle aspect ratio and the degree of roundness or sharpness. The pastes were composed of pure HA phase with low crystallinity. The rheological properties were evaluated and it was determined that the pastes behaved as shear-thinning, non-Newtonian liquids. The difference in viscosity and yield stress between the two pastes was investigated. Surprisingly, mixing of these pastes at different ratios did not alter viscosity in a linear manner, providing an opportunity to produce a specific viscosity by mixing the two materials with different characteristics. Biocompatibility studies suggested that there was no difference in vitro cell response to either paste for primary osteoblasts, bone marrow mesenchymal stromal cells, osteoblast-like cells, and fibroblast-like cells. This class of nanostructured biomaterial has significant potential for use as an injectable bone graft substitute where the properties may be tailored for different clinical indications.