Band 3, Heft 1

Bioactive glasses, invented by Prof. Larry L. Hench in the late 1960s, have revolutionized the field of biomaterials as they were shown to tightly bond to both hard and soft living tissues and to stimulate cells towards a path of regeneration and self-repair. However, due to their relatively poor mechanical properties (brittleness, low bending strength and fracture toughness), they are generally unsuitable for load-bearing applications. On the other hand, bioactive glasses have been successfully applied as coatings on the surface of stronger/tougher substrates to combine adequate mechanical properties with high bioactivity and, in some cases, additional extrafunctionalities (e.g. antibacterial properties, drug release). After giving a short overview of the main issues concerning the fabrication of glass coatings, this review provides a state-of-the-art picture in the field and specifically discusses the development of bioactive and hierarchical coatings on 3D porous scaffolds, joint prostheses, metallic substrates (e.g. wires or nails) for orthopedic fixation, polymeric meshes and sutures for wound healing, ocular implants and percutaneous devices.

The effect of increasing substitutions of Ga 2 O 3 :Na 2 O on the structure and contingent properties, of six quaternary high borate glasses was evaluated. Component ion release and particularly gallium ion release was studied post extraction, under simulated physiological conditions. Increasing substitutions of Ga 2 O 3 :Na 2 O (i.e. 0:1 - 6:4) resulted in destabilization of the glass network, observed by increases in component ion release and half-life of release. However, at ≥ 6:4 Ga 2 O 3 :Na 2 O ratio, network stabilization appeared to occur, resulting in a decrease in ion release half-life and total ion release for B, Sr, and Ga at 720 h of extraction. A linear release profile for strontium was provided by each glass composition, and for gallium by composition GB202 (70B 2 O 3 -20SrO-6Na 2 O-4Ga 2 O 3 ) and GB203 (70B 2 O 3 -20SrO-4Na 2 O-6Ga 2 O 3 ) for up to 720 h. 11B MAS NMR reveals that the replacement of Na 2 O with Ga 2 O 3 (in the studied composition range) causesa linear increase of three-fold coordinated B[3] groups at the expense of B[4] groups. The data indicates the potential formation of GaO 4 -tetrahedra, associated with network stabilization.

Bioactive glass (BAG) S53P4 granules represent a bone augmentation biomaterial for the surgical treatment of bony defects, even in challenging conditions such as osteomyelitis. The aim of this eight-week rabbit implantation study was to evaluate the biocompatibility and bone regeneration performance of a BAG S53P4 putty formulation following its implantation into the proximal tibia bone of twenty-eight New Zealand white rabbits. BAG S53P4 putty was compared to BAG S53P4 granules (0.5-0.8 mm) to evaluate whether the synthetic putty binder influences the bone regeneration of the osteostimulative granules. The putty formulation facilitates clinical use because of its mouldability, injectability and ease of mixing with autograft. Implantation of putty and granules into proximal tibia defects resulted in good osseointegration of the two groups. Both biomaterials were biocompatible, showed high new bone formation, high vascularization and periosteal growth. No signs of disturbed bone formation were observed due to the PEG-glycerol binder in the BAG S53P4 putty. Instead, intramedullary ossification and stromal cell reaction were more advanced in the putty group compared to the control group (p = 0.001 and p < 0.001). In conclusion, the novel mouldable BAG S53P4 putty showed reliable bone regeneration in bony defects without adverse tissue or cell reactions.

An alkali niobate-silicate veneer ceramic for ZrO 2 -based dental restoration was developed and characterized for its physical properties and structure. The properties were adjusted for dental applications. The new lithium disilicate glass-ceramic VBK (sold as cerafusion or LiSi) can easily be applied by spray coating to any individually formed ZrO 2 -matrix and needs only one final tempering treatment. The surface of the glass-ceramic is very smooth. The color of the already translucent glass-ceramic can be adjusted to that of individual natural teeth. The structure of the glass-ceramicwas studied by XRD and Ramanspectroscopy as a function of heat-treatment and of spatial variations within the material and at its interfaces. ToF SIMS, SEM and thermal analysis techniques were applied to investigate the crystallization behavior and surface-interface reactions. XRD and Raman spectroscopy identified different crystalline phases in the amorphous glass matrix including Li 2 Si 2 O 5 , Li 2 SiO 3 , Na x Li (1−x) NbO 3 and Na 3 NbO 4 . The Raman spectrum of the amorphous matrix is dominated by the vibrational activity of the highly polarizable niobate units with a prominent feature at 865 cm −1 , assigned to Nb-O stretching in NbO 6 octahedra, which have non-bridging oxygen atoms and are connected to the silicate matrix rather than to other niobate polyhedra.

Bioactive glass particles andweak scaffolds have been used to heal small contained bone defects but an unmet challenge is the development of bioactive glass implants with the requisite mechanical reliability and in vivo performance to heal structural bone defects. Inadequate mechanical strength and a brittle mechanical response have been key concerns in the use of bioactive glass scaffolds in structural bone repair. Recent research has shown the capacity to create strong porous bioactive glass scaffolds and the ability of these scaffolds to heal segmental bone defects in small and large rodents at a rate comparable to autogenous bone grafts. Loading these strong porous scaffolds with bone morphogenetic protein-2 can significantly enhance their ability to regenerate bone. Recentwork has also shown that coating the external surface of strong porous scaffolds with an adherent biodegradable polymer can dramatically improve their load-bearing capacity in flexural loading and their work of fracture (a measure of toughness). These tough and strong bioactive glass-polymer composites with an internal architecture conducive to bone infiltration could provide optimal synthetic implants for structural bone repair.

To improve bone cell cytocompatibility properties of porous anodic alumina (PAA) and implement anti-bacterial properties, amorphous CaO-SiO 2 -CuO materials were loaded into PAA nano-pores (termed CaO-SiO 2 - CuO/PAA) by a facile ultrasonic-assisted sol-dipping strategy. The surface features and chemistry of the obtained CaO-SiO 2 -CuO/PAA were investigated by a field emission scanning microscope (FESEM), an energy-dispersive Xray spectrometer (EDS) and an X-ray photoelectron spectroscopy (XPS). The ability of the CaO-SiO 2 -CuO/PAA specimens to form apatite via a bio-mineralization processwas evaluated by soaking them in simulated body fluid (SBF) in vitro. The surface microstructure and chemical properties after soaking in SBFwere characterized. The release of ions into the SBF was also measured. In addition, rat osteoblasts and two types of bacterial were cultured on the samples to determine their cytocompatibility and antibacterial properties. The results showed that the amorphous CaO-SiO 2 -CuO materials were successfully decorated into PAA nano-pores and at the same time maintained their nano-featured surfaces. The CaO-SiO 2 -CuO/PAA samples induced apatite-mineralization in SBF. Meanwhile, the CaO-SiO 2 -CuO/PAA samples demonstrated great potential for promoting the proliferation of osteoblasts and inhibiting Escherichia coli (E. coli) as well as Staphylococcus. aureus (S. aureus) growth. Specifically, there was an 86.5±4.1% reduction in E. coli, an 88.0 ± 2.2% reduction in S. aureus for the CaO-SiO 2 -CuO/PAA surfaces compared to PAA controls. The capability to promote osteoblast proliferation and better antibacterial activity of CaO-SiO 2 - CuO/PAA may be attributed to the fact that Cu ions can be slowly and constantly released from the samples. Importantly, this was achieved without the use of antibiotics or any pharmaceutical agent. Ultimately, these results suggest that the CaO-SiO 2 -CuO/PAA substrates possessed improved bone cell cytocompatibility and high antibacterial properties leading to a promising bioactive coating candidate for enhanced orthopedic applications.

Bacterial infection of bone tissue and bone marrow, referred to as osteomyelitis, is a challenging clinical problem. In this study we analysed the influence of the granule size of the bone substitute bioactive glass (BAG) S53P4 and the novel putty material containing BAG S53P4 on four clinically important bacteria associated with osteomyelitis; Staphylococcus aureus, methicillin resistant Staphylococuus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa. Reference materials were the frequently used biomaterial in surgical bone grafting procedures; tricalcium phosphate and an inert glass. Powder of BAG S53P4 was used as a positive control. The materials were incubated with bacterial suspension and the viability of the microbeswas determined as colony forming units after cultivation on agar plates. All pathogens lost their viability in contact with the BAG S53P4 granules and the powder of the BAG S53P4. The reference materials tricalcium phosphate and the inert glass had no effect on the viability of the bacteria. The BAG S53P4 putty containing 0.5-0.8 mm granules did not show any antibacterial effect on any of the tested bacteria. New putty compositions need to be investigated to obtain antibacterial properties for this novel bone regeneration biomaterial.

Bioactive glasses have attractive characteristics as a scaffold material for healing bone defects but their brittle mechanical response, particularly in bending, is a concern. Recent studies have shown that coating the external surface of strong porous bioactive glass (13-93) scaffolds with an adherent biodegradable polymer layer can significantly improve their load-bearing capacity andwork of fracture, resulting in a non-brittle mechanical response. In the present study, finite element modeling (FEM) was used to analyze the mechanical response in four-point bending of composites composed of a porous glass scaffold and an adherent polymer surface layer. The glass scaffold with a cylindrical geometry (diameter = 4.2 mm; porosity = 20%) was composed of randomly arranged unidirectional fibers (diameter 200-700 μm) thatwere bonded at their contact points. The thickness of the polymer layer was 500 μm. By analyzing the stresses in the individual glass fibers, the simulations can account for the main trends in the observed mechanical response of practical composites with a similar architecture composed of a bioactive glass (13-93) scaffold and an adherent polylactic acid surface layer. These FEM simulations could play a useful role in designing bioactive glass composites with improved mechanical properties.

Bioactive glasses (BG) are known for their ability to induce bone formation by the action of their dissolution products. Glasses can deliver active ions at a sustained rate, determined by their composition and surface area. Nanoporous sol-gel derived BGs can biodegrade rapidly, which can lead to a detrimental burst release of ions and a pHrise. The addition of phosphate into the glass can buffer the pH during dissolution. Here, dissolution of BG with composition 60 mol% SiO 2 , 28 mol% CaO and 12 mol% P 2 O 5 at 600 μg/ml were investigated. Initially, the dissolution and apatite formation of the BG particulates were examined in simulated body fluid using FTIR and XRD. BG particulates were indirectly exposed to dental pulp stem cells, and the effect of 14 days continuous ion release on human dental pulp stem cells (hDPSC) viability and differentiation was evaluated. Alamar blue assay showed that cell proliferation was not inhibited by the continuous release of Ca, P and soluble silica. In fact, hDPSC in the presence of BG particulate displayed a higher density of mineralized nodules than untreated cells, as assessed by Alizarin red. The results will have a great contribution to the in vivo application of this particular BG.

This study evaluated the influence of ionic dissolution products of a novel Ca-enriched silicate bioactive glass compared to commercial available hydroxyapaptite samples (Endobonr) on cell activity and vascular endothelial growth factor (VEGF) release in vitro. Bone marrow stromal cells (ST-2) were cultivated with the supernatant of granules of different sizes and at different concentrations (0-1 wt/vol % of granules) for 48 h. In addition to in vitro studies, Ca-ion release from all as cell morphology observation revealed no cytotoxic effect of the released products from all tested materials. It was found that supernatants from granules in concentrations of 1 wt/vol %enhanced the VEGF release from ST2 cells, which is important as a marker of the vascularisation ability of the glass during the bone healing process.