S53P4 bioactive glass

Bioactive glasses (BAGs) are synthetic bone graft substitutes that have been investigated by various orthopedic research groups in the past decades. These bone-bonding, osteoconductive materials can be used for various clinical applications. S53P4 is a specific composition of BAG, which is the main topic of this chapter, with the focus on granular S53P4. First, the working mechanism of S53P4 BAG is explained extensively on the basis of surface reactions, the bond to bone, osteostimulation, and bone proliferation around the material. S53P4 BAG has an antibacterial effect that is unique among bone graft materials, which makes the material useful in (suspected) septic bone defects. This antibacterial effect is discussed in detail. Additionally, its degradation and effect on angiogenesis are addressed. The chapter concludes with the current clinical applications of the material that are known in the literature

Mechanical behaviour of Bioactive Glass granules and morselized cancellous bone allograft in load bearing defects

Bioactive Glass (BAG) granules are osteoconductive and possess unique antibacterial properties for a synthetic biomaterial. To assess the applicability of BAG granules in load-bearing defects, the aim was to compare mechanical behaviour of graft layers consisting of BAG granules and morselized cancellous bone allograft in different volume mixtures under clinically relevant conditions.The graft layers were mechanically tested, using two mechanical testing modalities with simulated physiological loading conditions: highly controllable confined compression tests (CCT) and more clinically realistic in situ compression tests (ISCT) in cadaveric porcine bone defects. Graft layer impaction strain, residual strain, aggregate modulus, and creep strain were determined in CCT. Graft layer porosity was determined using micro computed tomography. The ISCT was used to determine graft layer subsidence in bone environment.ANOVA showed significant differences (p<0.001) between different graft layer compositions. True strains absolutely decreased for increasing BAG content: impaction strain −0.92 (allograft) to −0.39 (BAG), residual strain −0.12 to−0.01, and creep strain −0.09 to 0.00 respectively. Aggregate modulus increased with increasing BAG content from 116 to 653 MPa. Porosity ranged from 66% (pure allograft) to 15% (pure BAG). Subsidence was highest for allograft, and remarkably low for a 1:1 BAG-allograft volume mixture.Both BAG granules and allograft morsels as stand-alone materials exhibit suboptimal mechanical behaviour for load-bearing purpose. BAG granules are difficult to handle and less porous, whereas allograft subsides and creeps. A 1:1 volume mixture of BAG and allograft is therefore proposed as the best graft material in load-bearing defects. Bioactive Glass (BAG) granules are osteoconductive and possess unique antibacterial properties for a synthetic biomaterial. To assess the applicability of BAG granules in load-bearing defects, the aim was to compare mechanical behaviour of graft layers consisting of BAG granules and morselized cancellous bone allograft in different volume mixtures under clinically relevant conditions.The graft layers were mechanically tested, using two mechanical testing modalities with simulated physiological loading conditions: highly controllable confined compression tests (CCT) and more clinically realistic in situ compression tests (ISCT) in cadaveric porcine bone defects. Graft layer impaction strain, residual strain, aggregate modulus, and creep strain were determined in CCT. Graft layer porosity was determined using micro computed tomography. The ISCT was used to determine graft layer subsidence in bone environment.ANOVA showed significant differences (p<0.001) between different graft layer compositions. True strains absolutely decreased for increasing BAG content: impaction strain −0.92 (allograft) to −0.39 (BAG), residual strain −0.12 to−0.01, and creep strain −0.09 to 0.00 respectively. Aggregate modulus increased with increasing BAG content from 116 to 653 MPa. Porosity ranged from 66% (pure allograft) to 15% (pure BAG). Subsidence was highest for allograft, and remarkably low for a 1:1 BAG-allograft volume mixture.Both BAG granules and allograft morsels as stand-alone materials exhibit suboptimal mechanical behaviour for load-bearing purpose. BAG granules are difficult to handle and less porous, whereas allograft subsides and creeps. A 1:1 volume mixture of BAG and allograft is therefore proposed as the best graft material in load-bearing defects

Composition dependent mechanical behaviour of S53P4 bioactive glass putty for bone defect grafting

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. 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

Resorption of the calcium phosphate layer on S53P4 bioactive glass by osteoclasts

\u3cp\u3eClinically, 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 \u3csup\u3e2+\u3c/sup\u3e, Na \u3csup\u3e+\u3c/sup\u3e and PO \u3csub\u3e4\u3c/sub\u3e \u3csup\u3e3−\u3c/sup\u3e 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. [Figure not available: see fulltext.]. \u3c/p\u3

The implantation of bioactive glass granules can contribute the load-bearing capacity of bones weakened by large cortical defects

\u3cp\u3eBioactive glass (BAG) granules (S53P4) have shown good clinical results in one-stage treatment of osteomyelitis. During this treatment, a cortical window is created, and infected bone is debrided, which results in large defects that affect the mechanical properties of the bone. This study aimed to evaluate the role of BAG granules in load-bearing bone defect grafting. First, the influence of the geometry of the cortical window on the bone bending stiffness and estimated failure moments was evaluated using micro finite element analysis (μFE). This resulted in significant differences between the variations in width and length. In addition, μFE analysis showed that BAG granules contribute to bearing loads in simulated compression of a tibia with a defect grafted with BAG and a BAG and bone morsel mixture. These mixtures potentially can unload the cortical bone that is weakened by a large defect directly after the operation by up to approximately 25%, but only in case of optimal load transfer through the mixture.\u3c/p\u3

Multimodal pore formation in calcium phosphate cements

\u3cp\u3eCalcium 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.\u3c/p\u3

Bioactive glass particles as multi‐functional therapeutic carriers against antibiotic‐resistant bacteria

The development of antibiotic resistance in pathogenic bacteria like Staphylococcus aureus calls for novel approaches to cope with the limited availability of effective antibacterial options. This work aims to develop a site- specific drug- delivery multifunctional vehicle with the ability to clear resistant bacteria while promoting the healing of the surrounding damaged tissue. The use of silver- doped microparticles (Ag- BG) is proposed as a platform to deliver vancomycin against MRSA, which under growth- arrested conditions exhibits resistance to vancomycin. Ag- BG caged vancomycin within the Ca- P deposits resulted from the ion exchange between surface and medium, with a loading efficiency higher than 50% after 6 h of uptake. The drug was always released above the minimum inhibitory concentration against MRSA. The Ag- BG@vanc conjugate presented strong antibacterial properties against metabolically impaired bacteria, which can tolerate high concentrations of vancomycin. Ag- BG@vanc was more lethal for MRSA than Ag- BG alone, due to its capability to synergize with antibiotics. The presence of Ca- P deposits and antibiotics at the Ag- BG surface did not compromise its biological properties since the Ag- BG@vanc conjugate still promoted the cell proliferation of human pre- osteoblast cells. These properties of multifunctional Ag- BG@vanc can provide new hope to fight antibiotic resistance and simultaneously promote bone regeneration holding great potential.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171517/1/jace17923_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171517/2/jace17923.pd