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The study aimed at preparing Ag-doped bioactive glass (BG) nanoparticles containing 5 wt% Ag2O using a new modified Stober method (Ag-BGm) and the conventional sol-gel method (Ag-BGsg). The aim of employing the new Ag-doping mechanism is to implement a relatively short process to incorporate higher concentration of silver (Ag+) ions in an attempt to combine the antibacterial activity of silver with the bioactivity of BG. SEM and TEM micrographs showed that Ag-BGm nanoparticles were mondispersed, and spherical, while Ag-BGsg nanoparticles were formed of highly porous irregular agglomerated particles. A significantly higher silicon, calcium and silver ions release from the Ag-BGsg was evident, as compared to Ag-BGm, in deionized water (DIW). In vitro bioactivity test showed rapid bioactive properties of Ag-BGsg in simulated body fluid (SBF), as compared to Ag-BGm. Both BGs showed antibacterial effect against E. coli O157: H7 wild type strain 93111 and S. aureus ATCC 25923 as evident by the disc diffusion assay, but Ag-BGsg showed significantly higher mean inhibition zone compared to Ag-BGm. It may be concluded that both Ag-BGsg and Ag-BGm has the potential to be used as bone substitute materials with the Ag-BGsg being more promising due to its high bioactivity and antibacterial effect.

Three dimensional TiO2 scaffolds are receiving renewed attention for bone tissue engineering (TE) due to their biocompatibility and attractive mechanical properties. However the bioactivity of these scaffolds is comparatively lower than that of bioactive glass or hydroxyapatite (HA) scaffolds. One strategy to improve bioactivity is to functionalize the surface of the scaffolds using biomolecules. Alkaline phosphatase (ALP) was chosen in this study due to its important role in the bone mineralization process. The current study investigated the ALP functionalization of 3D titanium dioxide scaffolds using self-polymerization of dopamine. Robust titanium scaffolds (compressive strength∼2.7 ± 0.3 MPa) were produced via foam replica method. Enzyme grafting was performed by dip-coating in polydopamine/ALP solution. The presence of ALP was indirectly confirmed by contact angle measurements and enzymatic activity study. The influence of the enzyme on the bioactivity, e.g. hydroxyapatite formation on the scaffold surface, was measured in simulated body fluid (SBF). After 28 days in SBF, 5 mg ALP coated titania scaffolds exhibited increased hydroxyapatite formation. It was thus confirmed that ALP enhances the bioactivity of titania scaffolds, converting an inert bioceramic in an attractive bioactive system for bone TE., Graphical abstract Image 1, Highlights • TiO2 scaffolds of competent mechanical properties fabricated by foam replica method. • Bioactivity enhanced by functionalization with alkaline phosphatase (ALP). • ALP functionalization achieved by self-polymerization of dopamine.

We report the development and characterization of boron-releasing highly porous three-dimensional bioactive glass (BG) scaffolds fabricated by the foam replica technique. Three types of bioactive glasses with (wt%) 0.2%, 12.5%, 25% B2O3, and related varying SiO2 contents (wt%): 50%, 37.5%, and 25%, were investigated. The well-known 13-93 (silicate) and 13-93B3 (borate) (in wt% – 56.6% B2O3, 5.5% Na2O, 11.1% K2O, 4.6% MgO, 18.5% CaO, 3.7% P2O5) BGs were used as controls to study the influence of the presence of boron on the mechanical properties, surface reactivity, and cytotoxicity of scaffolds. Surface morphology and surface properties of the BG scaffolds were measured. X-ray diffraction (XRD) analyses showed that the scaffolds of all five compositions were amorphous. The scaffolds with 12.5 wt% B2O3 exhibited satisfactory compressive strength in the range of 1–2 MPa. A dissolution study in cell culture medium was carried out, and ion release profiles, and apatite formation of the scaffolds were assessed. The cytotoxicity of the scaffolds was evaluated using a stromal cell line (ST2). Cells were found to attach and spread well on the scaffolds' surfaces. We conclude that borosilicate scaffolds containing 12.5 wt% B2O3 provide the best combination of properties, including relatively high mechanical strength, apatite formation, and cytocompatibility, and thus, they are promising candidates for bone tissue engineering.

Mesoporous bioactive glass nanoparticles (MBG) are multifunctional building blocks for tissue regeneration and nanomedicine applications. Incorporation of biologically active ions can endow MBG with additional functionalities toward promoted therapeutic effects. Here, boron is incorporated into MBG by using a sol–gel approach. The concentration of boron incorporated is controllable by tuning the amount of boron precursor. Two types of boron‐doped MBG, namely 10B‐ and 15B‐MBG (5.8 and 6.5 mol% of B2O3, respectively) are synthesized. Boron incorporation does not significantly influence the particle morphology. All synthesized particles exhibit a sphere‐like shape with a size ranging from 100 to 300 nm. 10B‐ and 15B‐MBG show large specific surface area (346 and 320 m² g−1, respectively) and pore volume. Both boron‐doped MBG exhibit remarkable in vitro bioactivity and noncytotoxicity. Boron incorporation is shown to reduce the inflammatory response linked to macrophages as indicated by downregulated expression of pro‐inflammatory genes. However, boron incorporation delays the osteogenic differentiation in osteoblasts as indicated by the downregulated expression of pro‐osteogenic genes. The results demonstrate the promising potential of using boron‐doped MBG to modulate inflammatory response for bone regeneration under inflammatory conditions, as shown in this study for the first time.

Certain biomaterials are capable of inducing the secretion of Vascular Endothelial Growth Factor (VEGF) from cells exposed to their biochemical influence, which plays a vital role in stimulating angiogenesis. Looking for this capacity, in this study three porous glasses were synthesized and characterized. The objective of this study was to determine the concentration of the glass particles that, being out of the cytotoxic range, could increase VEGF secretion. The viability of cultivated bone marrow stromal cells (ST-2) was assessed. The samples were examined with light microscopy (LM) after the histochemical staining for haematoxylin and eosin (HE). The biological activity of glasses was evaluated in terms of the influence of the Cu2+ and Sr2+ ions on the cells. The dissolution products of CuSr-1 and CuSr-2.5 produced the highest secretion of VEGF from ST-2 cells after 48 h of incubation. The combination of Cu2+ and Sr2+ lays the foundation for engineering a bioactive glass than can lead to vascularized, functional bone tissue when used in bone regeneration applications., Comment: 21 pages, 7 figures

We report for the first time on the combination of polymer replication method and flock technology to produce 45S5 bioactive glass (45S5 BG) scaffolds with a fibrous surface morphology suitable for tissue engineering (TE). In order to develop a fibrous morphology on the surface of the scaffolds, electroflocking was used with BG scaffolds serving as the substrate. Gelatin was used as the adhesive and short polyamide (PA) fibers were electroflocked on the top surface to produce scaffolds with anisotropic properties. In order to improve the stability of the adhesive (gelatin) and to create a better bonding between the fibers and the adhesive, a crosslinking step was carried out. The porosity on the surface could be tailored by varying the flocking time which, in turn, was shown to influence the packing density of the fibers. In vitro bioactivity study in simulated body fluid (SBF) was carried out and complete mineralization of the scaffold, including on the PA fibers, was detected and characterized using various techniques.

A simple yet promising approach to construct bi-layered scaffolds using bioactive ceramics and biodegradable polymers is presented. This method involves two versatile fabrication techniques used in the field of TE: foam replication process and electrospinning. By the foam replication method, three-dimensional 45S5 bioactive glass (BG)-based scaffolds with high porosity, in the range of 95.8 ± 0.9 %, were produced. To improve the mechanical properties of the BG scaffolds, dip-coating using polycaprolactone (PCL) was performed, which led to a significant increase in the compressive strength of the scaffolds. In order to develop a bi-layered construct, bead-less submicrometric fibers of collagen-PCL were electrospun over the PCL-coated BG scaffolds. Surface morphology, surface properties and mechanical strength of the bi-layered construct were evaluated using scanning electron microscopy analysis, contact angle measurements and compressive strength testing, respectively. In vitro degradation of the collagen-PCL fibers in phosphate buffered saline and in vitro bioactivity of the bi-layered constructs in simulated body fluid were investigated. Formation of hydroxyapatite on the PCL-coated BG and along the morphology of the collagen-PCL fibers was ascertained using different characterization techniques. The bi-layered construct is intended for interface tissue engineering applications where the PCL-coated BG scaffold, which is highly bioactive, can serve as a support for the bone side and the composite collagen-PCL submicrometric fibers are intended for the cartilage side.

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.

Three-dimensional 45S5 bioactive glass (BG)-based scaffolds are being investigated for bone regeneration. Besides structural properties, controlled time-dependent alteration of scaffold morphology is crucial to achieve optimal scaffold characteristics for successful bone repair. There is no in vitro evidence concerning the dependence between structural characteristics and dissolution behavior of 45S5 BG-based scaffolds of different morphology. In this study, the dissolution behavior of scaffolds fabricated by the foam replica method using polyurethane foam (Group A) and maritime sponge Spongia Agaricina (Group B) as sacrificial templates was analyzed by micro-computed-tomography (µCT). The scaffolds were immersed in Dulbecco’s Modified Eagle Medium for 56 days under static cell culture conditions and underwent µCT-analysis initially, and after 7, 14, and 56 days. Group A showed high porosity (91%) and trabecular structure formed by macro-pores (average diameter 692 µm ± 72 µm). Group-B-scaffolds were less porous (51%), revealing an optimal pore size distribution within the window of 110–500 µm pore size diameter, combined with superior mechanical stability. Both groups showed similar structural alteration upon immersion. Surface area and scaffold volume increased whilst density decreased, reflecting initial dissolution followed by hydroxycarbonate-apatite-layer-formation on the scaffold surfaces. In vitro- and/or in vivo-testing of cell-seeded BG-scaffolds used in this study should be performed to evaluate the BG-scaffolds’ time-dependent osteogenic properties in relation to the measured in vitro structural changes.

Bioactive glasses (BG) are versatile materials for various biomedical applications, including bone regeneration and wound healing, due to their bone bonding, antibacterial, osteogenic, and angiogenic properties. In this study, we aimed to enhance the antibacterial activity of SiO2-CaO mesoporous bioactive glass nanoparticles (MBGN) by incorporating silver (Ag) through a surface modification approach. The modified Ag-containing nanoparticles (Ag-MBGN) maintained spherical shape, mesoporous structure, high dispersity, and apatite-forming ability after the surface functionalization. The antibacterial activity of Ag-MBGN was assessed firstly using a planktonic bacteria model. Moreover, a 3D tissue-engineered infected skin model was used for the first time to evaluate the antibacterial activity of Ag-MBGN at the usage dose of 1 mg/mL. In the planktonic bacteria model, Ag-MBGN exhibited a significant antibacterial effect against both Pseudomonas aeruginosa and Staphylococcus aureus in comparison to non-engineered (Ag-free) MBGN and the blank control. Moreover, Ag-MBGN did not show cytotoxicity towards fibroblasts at the usage dose. However, in the 3D infected skin model, Ag-MBGN only demonstrated antibacterial activity against S. aureus whereas their antibacterial action against P. aeruginosa was inhibited. In conclusion, surface modification by Ag incorporation is a feasible approach to enhance the antibacterial activity of MBGN without significantly impacting their morphology, polydispersity, and apatite-forming ability. The prepared Ag-MBGN are attractive building blocks for the development of 3D antibacterial scaffolds for tissue engineering.