Strontium-substituted Bioactive Glass Research Articles

Roles of strontium and hierarchy structure on the in vitro biological response and drug release mechanism of the strontium-substituted bioactive glass microspheres.

The strontium (Sr) substituted bioactive glasses (BGs) have inimitable advantages for bone generation, but the influences of Sr substitution on bioactivity and biocompatibility are still in debate. A brand novel porous microstructure of Sr-substituted BG microspheres was prepared by an electro-spraying technique combined with phase inversion, in which in vitro biological response (bioactivity, cell viability, alkaline phosphatase (ALP) activity and extracellular matrix (ECM) mineralization) and drug release were clarified in view of physical chemistry and ionic release behavior. The electro sprayed bioactive glass (ESBG) microspheres involved three characteristic pores: <100 nm, 100-1000 nm and >1000 nm. The Sr substitution on molar basis hindered the bioactivity of the samples in some extent but the cell behavior of the MC3T3-E1 cells was not significantly discouraged. The drug release profile was also controlled by amount of Sr substitution. However, the porous structure of the microspheres conferred improvement in bioactivity and provided a distinct three-stage drug release mode. Therefore, the Sr substituted ESBG microspheres may provide an effective way to deliver a steady supply of therapeutic ions and drugs in bone implantation patients.

Rheological Characterization of Biomaterials Directs Additive Manufacturing of Strontium-Substituted Bioactive Glass/Polycaprolactone Microfibers.

Additive manufacturing via melt electrowriting (MEW) can create ordered microfiber scaffolds relevant for bone tissue engineering; however, there remain limitations in the adoption of new printing materials, especially in MEW of biomaterials. For example, while promising composite formulations of polycaprolactone with strontium-substituted bioactive glass have been processed into large or disordered fibres, from what is known, biologically-relevant concentrations (>10 wt%) have never been printed into ordered microfibers using MEW. In this study, rheological characterization is used in combination with a predictive mathematical model to optimize biomaterial formulations and MEW conditions required to extrude various PCL and PCL/SrBG biomaterials to create ordered scaffolds. Previously, MEW printing of PCL/SrBG composites with 33 wt% glass required unachievable extrusion pressures. The composite formulation is modified using an evaporable solvent to reduce viscosity 100-fold to fall within the predicted MEW pressure, temperature, and voltage tolerances, which enabled printing. This study reports the first fabrication of reproducible, ordered high-content bioactive glass microfiber scaffolds by applying predictive modeling.

The effects of strontium incorporation on a novel gelatin/bioactive glass bone graft: In vitro and in vivo characterization

Growing evidence indicates that biomaterials that contain bioactive glass (BG) exert positive effects on bone tissue repair. Strontium-substituted BGs have been demonstrated to promote bone formation while inhibiting bone resorption by osteoclasts. In this study, we fabricated composites containing gelatin combined with different concentrations of strontium (Sr)-delivering glasses. We then investigated the in vitro effect of the presence of Sr in the polymer matrix on proliferation and differentiation of bone marrow mesenchymal stem cells (BMMSCs). The potential angiogenic effect of Sr was assessed by subcutaneous implantation in mice. Scanning electron microscopy (SEM) of prepared scaffolds showed an interconnected porous structure with an average diameter of 100–300 µm; increasing the percentage of Sr decreased the average pore size. The stiffness of scaffolds containing Sr was about five times greater than that of scaffolds containing BG with no Sr. Cytocompatibility of the prepared scaffolds, assessed using BMMSCs, was confirmed with MTT assay. Secretion of alkaline phosphatase was significantly enhanced in cells cultured on Sr-containing scaffolds, compared with other samples, after 14 days. Imunohistofluorescence analysis indicated that the addition of Sr increased perivascular localization and cell migration, and stimulated sprouting angiogenesis. The results of this study highlight the enhanced mechanical and biological properties of our polymer matrix after the addition of Sr. Our results indicate that Sr-containing bioactive glasses could exert beneficial effects on bone tissue engineering.

Data for accelerated degradation of calcium phosphate surface-coated polycaprolactone and polycaprolactone/bioactive glass composite scaffolds.

Polycaprolactone (PCL)-based composite scaffolds containing 50 wt% of 45S5 bioactive glass (45S5) or strontium-substituted bioactive glass (SrBG) particles were fabricated into scaffolds using melt-extrusion based additive manufacturing technique. Additionally, the PCL scaffolds were surface coated with a layer of calcium phosphate (CaP). For a comparison of the scaffold degradation, the scaffolds were then subjected to in vitro accelerated degradation by immersion in 5 M sodium hydroxide (NaOH) solution for up to 7 days. The scaffold׳s morphology was observed by means of SEM imaging and scaffold mass loss was recorded over the experimental period.

In vitro and in vivo bone formation potential of surface calcium phosphate-coated polycaprolactone and polycaprolactone/bioactive glass composite scaffolds

In this study, polycaprolactone (PCL)-based composite scaffolds containing 50wt% of 45S5 Bioglass® (45S5) or strontium-substituted bioactive glass (SrBG) particles were fabricated into scaffolds using an additive manufacturing technique for bone tissue engineering purposes. The PCL scaffolds were surface coated with calcium phosphate (CaP) to enable further comparison of the osteoinductive potential of different scaffolds: PCL (control), PCL/CaP-coated, PCL/50-45S5 and PCL/50-SrBG scaffolds. The PCL/50-45S5 and PCL/50-SrBG composite scaffolds were reproducibly manufactured with a morphology highly resembling that of PCL only scaffolds. However, 50wt% loading of the bioactive glass (BG) particles into the PCL bulk decreased the scaffold’s compressive Young’s modulus. Coating of PCL scaffolds with CaP had a negligible effect on the scaffold’s porosity and compressive Young’s modulus. When immersed in culture media, BG dissolution ions (Si and Sr) were detected for up to 10weeks in the immersion media and surface precipitates were formed on both PCL/50-45S5 and PCL/50-SrBG scaffolds’ surfaces, indicating good in vitro bioactivity. In vitro cell studies were conducted using sheep bone marrow stromal cells (BMSCs) under non-osteogenic or osteogenic conditioned media, and under static or dynamic culture environments. All scaffolds were able to support cell adhesion, growth and proliferation. However, when cultured in non-osteogenic media, only PCL/CaP, PCL/50-45S5 and PCL/50-SrBG scaffolds showed an up-regulation of osteogenic gene expression. Additionally, under a dynamic culture environment, the rate of cell growth, proliferation and osteoblast-related gene expression was enhanced across all scaffold groups. Subsequently, PCL/CaP, PCL/50-45S5 and PCL/50-SrBG scaffolds, with or without seeded cells, were implanted subcutaneously into nude rats for the evaluation of osteoinductivity potential. After 8 and 16weeks, host tissue infiltrated well into the scaffolds, but no mature bone formation was observed in any scaffolds groups. Statement of significanceThis novelty of this research work is that it provide a comprehensive comparison, both in vitro and in vivo, between 3 different composite materials widely used in the field of bone tissue engineering for their bone regeneration capabilities. The materials used in this study include polycaprolactone, 45S5 Bioglass, strontium-substituted bioactive glass and calcium phosphate. Additionally, the composite materials were fabricated into the form of 3D scaffolds using additive manufacturing technique, a widely used technique in tissue engineering.

Enhanced Osseous Implant Fixation with Strontium-Substituted Bioactive Glass Coating

The use of endosseous implants is firmly established in skeletal reconstructive surgery, with rapid and permanent fixation of prostheses being a highly desirable feature. Implant coatings composed of hydroxyapatite (HA) have become the standard and have been used with some success in prolonging the time to revision surgery, but aseptic loosening remains a significant issue. The development of a new generation of more biologically active coatings is a promising approach for tackling this problem. Bioactive glasses are an ideal candidate material due to the osteostimulative properties of their dissolution products. However, to date, they have not been formulated with stability to devitrification or thermal expansion coefficients (TECs) that are suitable for stable coating onto metal implants while still retaining their bioactive properties. Here, we present a strontium-substituted bioactive glass (SrBG) implant coating which has been designed to encourage peri-implant bone formation and with a TEC similar to that of HA. The coating can be successfully applied to roughened Ti6Al4V and after implantation into the distal femur and proximal tibia of twenty-seven New Zealand White rabbits for 6, 12, or 24 weeks, it produced no adverse tissue reaction. The glass dissolved over a 6 week period, stimulating enhanced peri-implant bone formation compared with matched HA coated implants in the contralateral limb. Furthermore, superior mechanical fixation was evident in the SrBG group after 24 weeks of implantation. We propose that this coating has the potential to enhance implant fixation in a variety of orthopedic reconstructive surgery applications.

Fabrication and in vitro characterization of bioactive glass composite scaffolds for bone regeneration

Here we fabricate and characterize bioactive composite scaffolds for bone tissue engineering applications. 45S5 Bioglass® (45S5) or strontium-substituted bioactive glass (SrBG) were incorporated into polycaprolactone (PCL) and fabricated into 3D bioactive composite scaffolds utilizing additive manufacturing technology. We show that composite scaffolds (PCL/45S5 and PCL/SrBG) can be reproducibly manufactured with a scaffold morphology highly resembling that of PCL scaffolds. Additionally, micro-CT analysis reveals BG particles were homogeneously distributed throughout the scaffolds. Mechanical data suggested that PCL/45S5 and PCL/SrBG composite scaffolds have higher compressive Young's modulus compared to PCL scaffolds at similar porosity (∼75%). After 1 day in accelerated degradation conditions using 5M NaOH, PCL/SrBG, PCL/45S5 and PCL lost 48.6 ± 3.8%, 12.1 ± 1% and 1.6 ± 1% of the original mass, respectively. In vitro studies were conducted using MC3T3 cells under normal and osteogenic conditions. All scaffolds were shown to be non-cytotoxic, and supported cell attachment and proliferation. Our results also indicate that the inclusion of bioactive glass (BG) promotes precipitation of calcium phosphate on the scaffold surfaces which leads to earlier cell differentiation and matrix mineralization when compared to PCL scaffolds. However, as indicated by alkaline phosphatase activity, no significant difference in osteoblast differentiation was found between PCL/45S5 and PCL/SrBG scaffolds. These results suggest that PCL/45S5 and PCL/SrBG composite scaffolds show potential as next generation bone scaffolds.

Melt‐electrospun polycaprolactone strontium‐substituted bioactive glass scaffolds for bone regeneration

Polycaprolactone (PCL) is a resorbable polymer used extensively in bone tissue engineering owing to good structural properties and processability. Strontium-substituted bioactive glass (SrBG) has the ability to promote osteogenesis and may be incorporated into scaffolds intended for bone repair. Here, we describe for the first time, the development of a PCL-SrBG composite scaffold incorporating 10% (weight) of SrBG particles into PCL bulk, produced by the technique of melt electrospinning. We show that we are able to reproducibly manufacture composite scaffolds with an interconnected porous structure and, furthermore, these scaffolds were demonstrated to be noncytotoxic in vitro. Ions present in the SrBG component were shown to dissolve into cell culture media and promoted precipitation of a calcium phosphate layer on the scaffold surface which in turn led to noticeably enhanced alkaline phosphatase activity in MC3T3-E1 cells compared to PLC-only scaffolds. These results suggest that melt-electrospun PCL-SrBG composite scaffolds show potential to become effective bone graft substitutes.

Strontium-substituted bioactive glass coatings for bone tissue engineering

control 0%Sr 10%Sr 50%Sr % Strontium Substitution N or m al is ed M TT A ct iv ity Day1 Day 7 Day14    Strontiumsubstituted Bioactive Glass Coatings for Bone Tissue Engineering Nasrin Lotfibakhshaiesh , Eileen Gentleman, Robert G Hill, Molly M Stevens Corresponding Author: m.stevens@imperial.ac.uk Department of Materials & Institute of Biomedical Engineering, Imperial College, London, UK Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, UK Introduction Metallic prosthetic implants are widely used to treat joint and skeletal injuries. However, some implants can fail because the metal alloys used do not bond with bone. Bioactive glass (BG) coatings may offer a solution to this problem as they form a strong bond with living tissue and have the added benefit that their dissolution ions stimulate cell activity. Strontium ranelate, a drug used to treat and prevent osteoporosis works via the action of Sr ions which stimulate the formation of new bone and prevent osteoclast-mediated resorbtion. Sr can be substituted for calcium in BGs creating a material that may combine the bone remodelling benefits of Sr ions with the well-established bone stimulatory action of bioactive glass. The aim of this study is to develop Sr containing BG coatings on metallic surfaces to bond to an implant as an effective biomaterial choice for a range of bone regeneration therapies. Materials and Methods Bioactive glasses in the system: SiO2-MgONa2O-K2O-ZnO-P2O5-CaO with 0, 10, and 50 of the Ca being replaced by Sr were prepared by a melt-quench route. A degradation study was carried out on <38μm glass powders in simulated body fluids. Silicon [Si], Phosphorus [P], Calcium [Ca] and Sr were checked at different time periods: 10, 30, 60, 120, 240 and 480 min. Produced glasses were combined with RPMI media on a roller for 4 hours at 37°C and then passed through a 0.2 μm filter. This media was then supplemented with 10% foetal bovine serum, 2mM L-glutamine and 1% penicillin/ streptomycin. The human osteosarcoma cell line, Saos-2, was seeded (30,000 cells/cm) in Sr substituted medium and cultured for up to 28 days. On days 1, 7 and 14 post-planting cell metabolic activity was measured using the tetrazole MTT. BGs were coated on to the surface of Ti6AL4V coupons and were sterilised under UV light both side. 10,000 Saos-2 cells/cm2 were seeded on BG coatings and viability was assessed after 1, 7 and 14 days with a Live/Dead stain. Results Glass dissolution leads to a rise of all the ion concentrations in solution. When [Si] hits the solubility limit, [P] declines. At this point a silica gel layer will start to form on the surface and this might be expected to promote nucleation of HCA consuming the P.[Ca] follows the [P] decrease in low Ca content glasses but decreases then rises in high Ca content glasses. Finally, Sr increases the overall concentration of ions in solution. MTT activity (Fig.1) increased in all samples with time in culture until 14 days. Saos2 cultured treated with Sr-substituted BGs had higher MTT activities than controls. Live/Dead staining showed that cells were alive on all coating materials.