Effects Of Ionic Dissolution Products Research Articles

Biodegradable Si3N4 bioceramic sintered with Sr, Mg and Si for spinal fusion: Surface characterization and biological evaluation

Silicon nitride (Si3N4) is an industrial ceramic used in spinal fusion and maxillofacial reconstruction because of its excellent mechanical properties and good biocompatibility. This study compares the surface properties, apatite formation ability, bacterial infection, cell-biomaterial interactions, and in vivo toxicity (zebrafish) of newly developed Si3N4 bioceramics (sintered with bioactive sintering additives SrO, MgO and SiO2) with two standard biomaterials; titanium (Ti) and traditional Si3N4 bioceramics (sintered with standard sintering additives Al2O3 and Y2O3). In general, Si3N4 bioceramics (both the newly developed and the traditional) displayed less in vitro bacterial affinity than Ti, which may arise from differences in the surface properties between these two types of material. The newly developed Si3N4 bioceramics developed lower biofilm coverage and thinner biofilm, compared to traditional Si3N4 bioceramics. The effects of ionic dissolution products (leach) on proliferation and differentiation of MC3T3-E1 cell were also investigated. Ionic dissolution products containing moderate amount of Sr, Mg and Si ions (approximately 4.72mg/L, 3.26mg/L and 3.67mg/L, respectively) stimulated osteoblast proliferation during the first 2 days in culture. Interestingly, ionic dissolution products from the traditional Si3N4 bioceramics that contained small amount of Si and Y ions achieved the greatest stimulatory effect for alkaline phosphatase activity after 7 days culture. The toxicity of ionic dissolution products was investigated in a putative developmental biology model: zebrafish (Danio rerio). No toxicity, or developmental abnormalities, was observed in zebrafish embryos exposed to ionic dissolution products, for up to 144h post fertilization. These newly developed Si3N4 bioceramics with bioactive sintering additives show great potential as orthopedic implants, for applications such as spinal fusion cages. Future work will focus on evaluation of the newly developed Si3N4 bioceramics using a large animal model.

Angiogenic effects of ionic dissolution products released from a boron-doped 45S5 bioactive glass.

In regenerative medicine of vascularized tissues, there is a great interest in the use of biomaterials that are able to stimulate angiogenesis, a process necessary for rapid revascularization to allow the transport and exchange of oxygen, nutrients, growth factors and cells that take part in tissue repair and/or regeneration. An increasing number of publications have shown that bioactive glasses stimulate angiogenesis. Because it has been established that boron (B) may play a role in angiogenesis, the aim of this study was to assess the in vivo angiogenic effects of the ionic dissolution products that from a bioactive glass (BG) in the 45S5 system doped with 2 wt% B2O3 (45S5.2B). The pro-angiogenic capacity of 45S5.2B BG was assessed on the vasculature of the embryonic quail chorioallantoic membrane (CAM). Ionic dissolution products from 45S5.2B BG increased angiogenesis. This is quantitatively evidenced by the greater expression of integrin αvβ3 and higher vascular density in the embryonic quail CAM. The response observed at 2 and 5 days post-treatment was equivalent to that achieved by applying 10 µg mL-1 of basic fibroblast growth factor. These results show that the ionic dissolution products released from the bioactive glass 45S5.2B stimulate angiogenesis in vivo. The effects observed are attributed to the presence the ionic dissolution products, which contained 160 ± 10 µM borate.

Biological Impact of Bioactive Glasses and Their Dissolution Products.

For many years, bioactive glasses (BGs) have been widely considered for bone tissue engineering applications due to their ability to bond to hard as well as soft tissue (a property termed bioactivity) and for their stimulating effects on bone formation. Ionic dissolution products released during the degradation of the BG matrix induce osteogenic gene expression leading to enhanced bone regeneration. Recently, adding bioactive metallic ions (e.g. boron, copper, cobalt, silver, zinc and strontium) to silicate (or phosphate and borate) glasses has emerged as a promising route for developing novel BG formulations with specific therapeutic functionalities, including antibacterial, angiogenic and osteogenic properties. The degradation behaviour of BGs can be tailored by adjusting the glass chemistry making these glass matrices potential carrier systems for controlled therapeutic ion release. This book chapter summarises the fundamental aspects of the effect of ionic dissolution products from BGs on osteogenesis and angiogenesis, whilst discussing novel BG compositions with controlled therapeutic ion release.

Effects of Dicalcium Silicate Coating Ionic Dissolution Products on Human Mesenchymal Stem-Cell Proliferation and Osteogenic Differentiation

This study investigated the effects of ionic dissolution products released from dicalcium silicate (DS) coatings on human mesenchymal stem cells (hMSC), cultured in the presence or absence of the dissolution products, with or without osteogenic supplements (OS). DS(+) medium promoted cell proliferation during the first 4 days, but then inhibited proliferation. DS(+)OS(-) medium increased alkaline phosphatase (ALP) activity on day 14, and upregulated runt-related transcription factor 2 and osteonectin mRNA on days 7 and 14, respectively. The addition of osteogenic supplements (DS(+)OS(+)) led to a significant increase in ALP activity from days 7 to 21, upregulation of osteogenic markers on day 14, and formation of more mineralized nodules on day 28. The results demonstrated that the ionic dissolution products from DS coating alone can partly induce osteogenic differentiation of hMSC, and that the addition of osteogenic supplements further enhances osteoblast-specific gene expression and mineralization in hMSC.

The effect of ionic dissolution products of Ca–Sr–Na–Zn–Si bioactive glass on in vitro cytocompatibility

Many commercial bone grafts cannot regenerate healthy bone in place of diseased bone. Bioactive glasses have received much attention in this regard due to the ability of their ionic dissolution products to promote cell proliferation, cell differentiation and activate gene expression. Through the incorporation of certain ions, bioactive glasses can become therapeutic for specific pathological situations. Calcium-strontium-sodium-zinc-silicate glass bone grafts have been shown to release therapeutic levels of zinc and strontium, however the in vitro compatibility of these materials is yet to be reported. In this study, the in vitro cytocompatibility of three different calcium-strontium-sodium-zinc-silicate glasses was examined as a function of their ion release profiles, using Novabone® bioglass as a commercial comparison. Experimental compositions were shown to release Si(4+) ranging from 1 to 81 ppm over 30 days; comparable or enhanced release in comparison to Novabone. The maximum Ca(2+) release detected for experimental compositions was 9.1 ppm, below that reported to stimulate osteoblasts. Sr(2+) release was within known therapeutic ranges, and Zn(2+) release ranged from 0.5 to 1.4 ppm, below reported cytotoxic levels. All examined glass compositions show equivalent or enhanced in vitro compatibility in comparison to Novabone. Cells exposed to BT112 ionic products showed enhanced cell viabilities indicating cell proliferation was induced. The ion release profiles suggest this effect was due to a synergistic interaction between certain combinations and concentrations of ions. Overall, results indicate that the calcium-strontium-sodium-zinc-silicate glass compositions show equivalent or even enhanced in vitro compatibility compared to Novabone®.