Nowadays, S53P4 bioactive glass is indicated as a bone graft substitute in various clinical applications. This review provides an overview of the current published clinical results on indications such as craniofacial procedures, grafting of benign bone tumour defects, instrumental spondylodesis, and the treatment of osteomyelitis. Given the reported results that are based on examinations, such as clinical examinations by the surgeons, radiographs, CT, and MRI images, S53P4 bioactive glass may be beneficial in the various reported applications. Especially in craniofacial reconstructions like mastoid obliteration and orbital floor reconstructions, in grafting bone tumour defects, and in the treatment of osteomyelitis very promising results are obtained. Randomized clinical trials need to be performed in order to determine whether bioactive glass would be able to replace the current golden standard of autologous bone usage or with the use of antibiotic containing PMMA beads (in the case of osteomyelitis).
Calcium phosphate cements (CPCs) are commonly used as bone substitute materials. However, their slow degradation rate and lack of macroporosity hinders new bone formation. Poly(dl-lactic-co-glycolic acid) (PLGA) incorporation is of great interest as, upon degradation, produces acidic by-products that enhance CPC degradation. Yet, new bone formation is delayed until PLGA degradation occurs a few weeks after implantation. Therefore, the aim of this study was to accelerate the early stage pore formation within CPCs in vitro. With that purpose, we incorporated the water-soluble porogen sucrose at different weight percentages (10 or 20 wt %) to CPC and CPC/PLGA composites. The results revealed that incorporation of sucrose porogens increased mass loss within the first week of in vitro degradation in groups containing sucrose compared to control groups. After week 1, a further mass loss was observed related to PLGA and CPC degradation. Macroporosity analysis confirmed that macroporosity formation is influenced by the dissolution of sucrose at an early stage and by the degradation of PLGA and CPC at a later stage. We concluded that the combination of sucrose and PLGA porogens in CPC is a promising approach to promote early stage bone tissue ingrowth and complete replacement of CPC through multimodal pore formation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 500-509, 2018.
Clinically, S53P4 bioactive glass (BAG) has shown very promising results in bone infection treatment, but it is also known to degrade very slowly in vivo. To evaluate which mechanisms (cellular or dissolution) can play a role in the degradation of S53P4 BAG and S53P4 BAG putty, in vitro degradation experiments at different pH (7.4 and 4.6) were performed. Micro computed tomography showed a rapid dissolution of the synthetic binder in the putty formulation, within 12 h is simulated body fluid (pH = 7.4), leaving behind only loose granules. Therefore the degradation of the loose granules was investigated further. Significant weight loss was observed and ion chromatography showed that Ca 2+ , Na + and PO 4 3− ions were released from S54P4 BAG granules in the two fluids. It was observed that the weight loss and ion release were increased when the pH of the fluid was decreased to 4.6. Osteoclasts are known to create such a low pH when resorbing bone and therefore their capacity to degrade S53P4 surfaces were studied as well. Scanning electron microscopy and energy-dispersive X-ray spectroscopy confirmed that osteoclasts were able to create resorption pits in the calcium phosphate layer on S53P4 BAG surfaces. The silica of the BAG, located underneath the calcium phosphate, seemed to hinder further osteclastic resorption of the material. To our knowledge we were the first to observe actively resorbing osteoclasts on S53P4 bioactive glass surfaces, in vitro. Future research is needed to define the specific role osteoclasts play in the degradation of BAG in vivo.
To improve the handling properties of S53P4 bioactive glass granules for clinical applications, bioactive glass putty formulations were developed. These formulations contain both granules and a synthetic binder to form an injectable material that is easy to shape. To explore its applicability in load-bearing bone defect grafting, the relation between the putty composition and its mechanical behaviour was assessed in this study. Five putty formulations with variations in synthetic binder and granule content were mechanically tested in confined compression. The results showed that the impaction strains significantly decreased and the residual strains significantly increased with an increasing binder content. The stiffness of all tested formulations was found to be in the same range as the reported stiffness of cancellous bone. The measured creep strains were low and no significant differences between formulations were observed. The stiffness significantly increased when the samples were subjected to a second loading stage. The residual strains calculated from this second loading stage were also significantly different from the first loading stage, showing an increasing difference with an increasing binder content. Since residual strains are detrimental for graft layer stability in load-bearing defects, putty compositions with a low binder content would be most beneficial for confined, load-bearing bone defect grafting.
The one-stage treatment of chronic osteomyelitis with S53P4 bioactive glass (BAG) granules has shown excellent results. However, these granules possess suboptimal handling properties. Therefore, new injectable S53P4 putty materials have been developed by the incorporation of a synthetic binder to contain glass granules. The goal of the current study was to assess their potential to eradicate five clinically relevant pathogens: methicillin sensitive Staphylococcus aureus (MSSA), methicillin resistant Staphylococcus aureus (MRSA), Enterococcus coli (E. coli), Enterococcus faecalis (E. faecalis), and Pseudomonas aeruginosa (P. aeruginosa). As a control, S53P4 granules (500-800 µm) and S66 glass (< 45 µm) were used. To evaluate the antimicrobial properties, the materials were cultured with the pathogens in a Müller-Hinton II broth for a week with daily colony forming unit (CFU) counting. One of the tested putty formulations was observed to reduce the number of CFU/mL compared to a negative control (no material, only pathogen in broth) for E. coli, E. faecalis and P. aeruginosa. However, none of the tested putty formulations was able to completely eradicate the pathogens in the broths, which would be needed for safe infection treatment. The results obtained for the control materials were unexpected. S66 glass showed full eradication of P. aeruginosa and reduced the number of CFUs of other pathogens, while the S53P4 granules did not show eradication. The observations on the loose S53P4 granules in this study contradict available literature, which needs further investigation. The results obtained in this study also stretch the importance for a better understanding of the underlying antimicrobial mechanism of S53P4 BAG and how this is related to the dosage. In addition, it should be elucidated how these antimicrobial properties are affected by changes in the material formulation, for example by addition of binders to improve the handling properties or by changing the surface area.
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