Silicate Bioactive Glass Research Articles

Boron substitution in silicate bioactive glass scaffolds to enhance bone differentiation and regeneration

Commercially available bioactive glasses (BAGs) are exclusively used in powder form, due to their tendency to crystallize. Silicate BAG 1393 was developed to allow fiber drawing and scaffold sintering, but its slow degradation limits its potential. To enable scaffold manufacturing while maintaining glass dissolution rate close to that of commercially available BAGs, the borosilicate glass 1393B20 was developed. This study investigates the potential of 1393B20 scaffolds to support bone regeneration and mineralization in vitro and in vivo, in comparison to silicate 1393. Both scaffolds supported human adipose stem cells proliferation, either in direct contact for the 1393, or mainly around for the 1393B20. Similarly, both BAGs induced osteogenesis and angiogenesis in vitro, with a better pro-angiogenic influence of the 1393B20. In addition, these scaffolds supported bone regeneration and osteoclast/osteoblast activity in vivo in critical-sized rat calvarial defect. Nevertheless, mineralization and collagen formation were significantly enhanced for the 1393B20, at 3-months post-implantation, assigned to faster and more complete dissolution of the scaffolds. Thus, 1393B20 demonstrates greater promise for bone tissue engineering certainly due to its time-controlled release of boron and silicon. Statement of significanceBioactive glasses (BAGs) show great promise in bone tissue engineering as they effectively bond with bone tissue, fostering integration and regeneration. Silicate BAG 1393 was developed to allow fiber drawing and scaffold sintering, but its slow degradation limits its potential. To enable scaffold manufacturing while maintaining glass dissolution rate close to that of commercially available BAGs, the borosilicate glass 1393B20 was developed. Both BAGs induced osteogenesis and angiogenesis in vitro, with a better pro-angiogenic influence of the 1393B20. The presence of boron in the 1393B20 enhanced mineralization and collagen formation in vivo compared to 1393, probably due to its faster dissolution rate. Here, 1393B20 demonstrated greater promise for bone tissue engineering compared to the well-known 1393 BAG.

Multifunctional Biocomposites: Synthesis, Characterization, and Prospects for Regenerative Medicine and Controlled Drug Delivery.

This article presents a new method for preparing multifunctional composite biomaterials with applications in advanced biomedical fields. The biomaterials consist of dicalcium phosphate (DCPD) and bioactive silicate glasses (SiO2/Na2O and SiO2/K2O), containing the antibiotic streptomycin sulfate. Materials were deeply characterized by X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopy, and zeta potential analysis, UV-visible spectrophotometry, and ion-exchange measurement were applied in a simulating body fluid (SBF) solution. The main results include an in situ chemical transformation of dicalcium phosphate into an apatitic phase under the influence of silicate solutions and the incorporation of the antibiotic. The zeta potential showed a decrease in surface charge from ζ = -24.6 mV to ζ = -16.5 mV. In addition, a controlled and prolonged release of antibiotics was observed over a period of 37 days, with a released concentration of up to 755 ppm. Toxicity tests in mice demonstrated good tolerance of the biomaterials, with no significant adverse effects. Moreover, these biomaterials have shown potent antibacterial activity against various bacterial strains, including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, suggesting their potential use in tissue engineering, drug delivery, and orthopedic and dental implants. By integrating the antibiotic into the biomaterial composites, we achieved controlled release and prolonged antibacterial efficacy. This research contributes to advancing biomaterials by exploring innovative synthetic routes and showcasing their promise in regenerative medicine and controlled drug delivery.

Efficacy of Ga3+ ions on structural, biological and antimicrobial activity of mesoporous lithium silicate bioactive glasses for tissue engineering

Mesoporous bioactive glass nanoparticles (MBGNPs) containing therapeutic ions have shown significant promise in the realm of hard and soft tissue repair and regeneration, owing to their multifunctional biological properties. In this study, gallium-incorporated silica-based gallium incorporated MBGNPs (Ga-MBGNPs) with fixed amount of Li2O (8 mol %) were synthesized using an emulsion-assisted sol-gel method. The impact of Ga2O3 integration into the silicate glass network was evaluated by investigating the microtextural properties. The results confirmed the production of spherical-shaped, nano-sized, amorphous particles with an enhanced specific surface area and ordered hexagonal meso-porosity (10–20 nm) in the developed Ga-MBGNPs. The in vitro bioactivity, assessed through hydroxyapatite (HAp) layer formation in simulated body fluid (SBF), over varying time intervals (0, 1, 3, 7, 14 & 21 days), revealed pronounced formation of short rod-like carbonated HAp with increasing immersion time and Ga3+ content in all glasses. However, a delayed apatite formation was observed for composition-dependent Ga-4 and Ga-5 MBGs during the initial incubation periods (1, 3, and 7 days). Further, the presence of Li + ions along with Ga3+ enhanced the apatite deposition when compared with the only Ga3+ inclusion. Evaluation of degradation rate and pH values indicated enhanced apatite formation with lower Ga ion content, while a slight reduction was noted with higher Ga ion content, attributable to the presence of reactive Si–O–Si bonds. Furthermore, analysis using a Zeta potential analyzer confirmed the dispersibility and bioreactivity of all glass powders owing to their higher negative surface charge. Moreover, Ga-MBGNPs exhibited notable antimicrobial effects against both E. coli and S. aureus bacteria due to the release of Ga3+ ions. Overall, the findings suggest that the incorporation of Ga in MBGNPs renders them potential multifunctional candidates for expediting the healing of bone tissue injuries in biomedical applications.

Bioactive Glass and Silica Particles for Skeletal and Cardiac Muscle Tissue Regeneration.

When skeletal and cardiac tissues are damaged, surgical approaches are not always successful and tissue regeneration approaches are investigated. Reports in the literature indicate that silica nanoparticles and bioactive glasses (BGs), including silicate bioactive glasses (e.g., 45S5 BG), phosphate glass fibers, boron-doped mesoporous BGs, borosilicate glasses, and aluminoborates, are promising for repairing skeletal muscle tissue. Silica nanoparticles and BGs have been combined with polymers to obtain aligned nanofibers and to maintain controlled delivery of nanoparticles for skeletal muscle repair. The literature indicates that cardiac muscle regeneration can be also triggered by the ionic products of BGs. This was observed to be due to the release of vascular endothelial growth factor and other growth factors from cardiomyocytes, which regulate endothelial cells to form capillary structures (angiogenesis). Specific studies, including both in vitro and in vivo approaches, are reviewed in this article. The analysis of the literature indicates that although the research field is still very limited, BGs are showing great promise for muscle tissue engineering and further research in the field should be carried out to expand our basic knowledge on the application of BGs in muscle (skeletal and cardiac) tissue regeneration. Impact statement This review highlights the potential of silica particles and bioactive glasses (BGs) for skeletal and cardiac tissue regeneration. These biomaterials create scaffolds triggering muscle cell differentiation. Ionic products from BGs stimulate growth factors, supporting angiogenesis in cardiac tissue repair. Further research is required to expand our know-how on silica particles and BGs in muscle tissue engineering.

Very Large Pore Mesoporous Bioactive Silicate Glasses: Comparison of Behavior toward Classical Mesoporous Bioactive Glasses in Terms of Drug Loading/Release and Bioactivity.

Considering the increase in patients who suffer from osteoporosis and the bone defects that occur in these patients, bone tissue regeneration is a promising option to solve this problem. To achieve a synergistic effect between the synthesis of a proper structure and bioactive/pharmaceutical activity, ions with a physiological effect can be added to silica structures, such as Ca2+, thanks to its bioactive behavior, and Ga3+ for its antibacterial and anticancer action. In this work, the synthesis of large pore mesoporous silica (LPMS), potential bioactive glasses containing Ca2+ and Ga3+, has been studied. Corresponding structures, in terms of composition, have been synthesized following the Sol-Gel EISA (Evaporation Induced Self-Assembly) process (obtaining Classical Mesoporous Silica, MS). Pore structure characterization of LPMSs and MSs has been performed using N2 adsorption/desorption and Hg-porosimetry, showing the presence of pores for LPMSs in the range of 20-60 and 200-600 nm. Nisin, a polycyclic antibacterial peptide, has been used for load tests. The load and release tests performed highlight a higher loading and releasing, doubled for LPMSs if compared to MSs. To confirm the maintenance of the structure of LPMSs and their mechanical strength and resistance, scanning electron microscopy images were acquired before and after release tests. Ca and Ga release in SBF has been studied through inductively coupled plasma-optical emission spectroscopy (ICP-OES), showing a particularly high release of these ions performed with LPMSs. The bioactive behavior of Ca-containing structures has been confirmed using FT-IR (Fourier-transform infrared spectroscopy), SEM-EDS (Scanning Electron Microscope-Energy Dispersive Spectroscopy), and X-ray powder diffraction (XRDP). In conclusion, LPMSs showed better loading and releasing properties compared with classical MS and better release in terms of active ions. In addition, it has also been demonstrated that LPMSs have bioactive behavior (a well-known characteristic of MSs).

Enhancement of optical and radiation shielding properties in calcium–magnesium silicate bioactive glasses through Na2O and P2O5 additives

The present study investigates the influence of Na2O/MgO and P2O5/SiO2 substitutions on the structure and protective properties of bioactive glasses composed of 32CaO–19MgO–0.5P2O5–0.5CaF2–48SiO2 (mole %). The glass samples are prepared using the conventional melt-quenching method. Optical analyses, including refractive index (n), molar refraction (Rm), and cationic polarizability (αm), are calculated and discussed to examine structural modifications. Raman spectroscopy is employed for detailed structural analysis. The effects of compositional changes on the protective parameters are thoroughly investigated by theoretically determining mass attenuation using the newly developed Phy-X/PSD software and XCOM programs, which are then experimentally confirmed at three selected radioactive isotope energies. Experimental measurements of mass attenuation coefficient follow the sequence: MACG1 > MACG2 > MACG3 > MACG4. Raman spectroscopy results indicate that the glass network primarily consists of silicate and phosphate species as the main structural units. An increase in the molar ratio of Na2O and P2O5 improves the radiation shielding effectiveness of the samples. Among them, sample G5, with the lowest SiO2 and MgO content, exhibits the best shielding characteristics due to its high density and molar fraction of Na2O and P2O5. A correlation between microhardness and protective effectiveness is also established. The obtained results support the potential use of these glasses as dual agents for both radiation shielding and medical devices simultaneously.

In vitro bioactivity and biocompatibility assessment of PCL/PLA–scaffolded mesoporous silicate bioactive glass: Role of boron activation

Bioactive glasses with rapid biodegradation and efficient biomineralization for damaged bone tissue repair remain deficient. Based on this fact, some new types of boron-activated mesoporous Bioactive silicate glasses (BMSGs) were made to determine the feasibility of achieving their improved mechanical strength, structure, porosity, biodegradability and bone healing performance. Four samples of the form xB2O3 – (80–x) SiO2 – 15CaO – 5P2O5 with x is 0, 5, 10, and 15 mol% were prepared using a unified sol-gel/evaporation induced self-assembly (SG-EISA) process. Furthermore, the solvent casting/partial leaching method was used to Scaffold the proposed BMSGs by polycaprolactone/polylacticacid (named as BMSG-PPS). The role of boron concentration fine-tuning in modifying the glasses morphology, structure, Bioactivity and Biocompatibility was assessed in vitro by immersing them in simulated body fluid (SBF) at various durations. Intense XRD peak at 31.7° confirmed the existence of crystalline hydroxyl carbonate apatite (HCA) in the glasses. Glass made with 10 mol% of boron (BMSG-PPS10) showed the strongest crystalline peak of HCA amongst all the studied samples. FESEM image of the Scaffold surface also revealed the presence of HCA agglomeration after 168 h of immersion in the SBF. The boron-free sample (BMSG-PPS0) showed strong agglomeration of HCA and Ca to P ratio (1.78±0.01) close to bone. After 168 h of immersion in the SBF solution, the symmetric stretching of PO43–and CO32–bands in the glass became more prominent. After 168 h of immersion in the SBF, the samples’ weight loss and solution pH correspondingly varied in the range of 5.66–7.37 % and 6.80–7.02. In addition, ICP–OES analyses of the glasses verified an increase of Si release in the SBF from the silicate network, indicating their rapid biodegradation. Briefly, the proposed BMSG–PPS with improved Bioactivity and Biocompatibility may be beneficial for various bio-medical implant coating applications.

Enhanced antimicrobial properties and bioactivity of 3D-printed titanium scaffolds by multilayer bioceramic coating for large bone defects

The restoration of large bone defects caused by trauma, tumor resection, or infection is a major clinical problem in orthopedics and dentistry because postoperative infections, corrosion, and limited osteointegration of metal implants can lead to loosening of the implant. The aim of this study was to improve the surface properties of a 3D-printed (electron beam melting) Ti6Al4V-based macroporous scaffold by multilayer coating with bioactive silicate glasses (BAGs) and hydroxyapatite doped with a silver (AgHAP) or AgHAP additionally sonochemically modified with ZnO (ZnO-AgHAP). The coated scaffolds AgHAP_BAGs_Ti and ZnO-AgHAP_BAGs_Ti enhanced cytocompatibility in L929 and MRC5 cell lines and expressed bioactivity in simulated body fluid. A lower release of vanadium ions in coated samples compared to bare Ti scaffold indicates decreased dissolution of Ti alloy in coated samples. The coated samples reduced growth of Escherichia coli and Staphylococcus aureus for 4–6 orders of magnitude. Therefore, the 3D-printed Ti-based scaffolds coated with BAGs and (ZnO-)AgHAP have great potential for application as a multifunctional implant with antibacterial properties for the restoration of defects in load-bearing bones.

New Mg/Sr phosphate bioresorbable glass system with enhanced sintering properties

Phosphate glasses are ideal candidates to substitute traditional silicate bioactive glasses as they can exhibit controlled ion release. Furthermore, phosphate glasses possess congruent dissolution and also resistance to crystallization, two properties that are favorable for the processing of 3D porous scaffolds. However, most of the phosphate glasses also exhibit a fast dissolution rate, which is inappropriate for bone tissue regeneration. In this context, a new bioresorbable phosphate glass within the 45P2O5- 2.5B2O3- 2.5SiO2- 10Na2O- 20CaO- (20-x) SrO- (x)MgO (in %mol) composition was developed. Magnesium is substituted for strontium in order to promote bone formation but in the present study, its role is mainly to favor sintering at lower temperatures without crystallization. The in vitro dissolution in simulated body fluid was assessed for glass particles <38 μm (pH, ICP, SEM-EDS). All glasses were found bioresorbable, rather than bioactive. The newly developed phosphate glasses containing Sr and Mg were found to have a slower dissolution rate when compared to traditional metaphosphate glasses while maintaining their congruent dissolution and hot forming ability. All glasses were 3D printed into scaffolds with controlled pore size and without apparent crystallization. The substitution of SrO for MgO was shown to be highly effective in enhancing the sintering ability of the material by enabling sintering at lower temperatures while avoiding the risk of crystallization leading to the processing of scaffolds with mechanical properties, in compression, above that of the cancellous bone.

Effect of germanium oxide on the structural aspects and bioactivity of bioactive silicate glass

Ternary silicate glass (69SiO2–27CaO–4P2O5) was synthesized with the sol–gel route, and different percentages of germanium oxide GeO2 (6.25, 12.5, and 25%) and polyacrylic acid (PAA) were added. DFT calculations were performed at the B3LYP/LanL2DZ level of theory for molecular modelling. X-ray powder diffraction (XRPD) was used to study the effect of GeO2/PAA on the structural properties. The samples were further characterized using DSC, ART-FTIR, and mechanical tests. Bioactivity and antibacterial tests were assessed to trace the influence of GeO2 on biocompatibility with biological systems. Modelling results demonstrate that molecular electrostatic potential (MESP) indicated an enhancement of the electronegativity of the studied models. While both the total dipole moment and HOMO/LUMO energy reflect the increased reactivity of the P4O10 molecule. XRPD results confirmed the samples formation and revealed the correlation between the crystallinity and the properties, showing that crystalline hydroxyapatite (HA) is clearly formed in the highest percentages of GeO2, proposing 25% as a strong candidate for medical applications, consistent with the results of mechanical properties and the rest of the characterization results. Simulated body fluid (SBF) in vitro experiments showed promising biocompatibility. The samples showed remarkable antimicrobial and bioactivity, with the strongest effect at 25%. The experimental findings of this study revealed that the incorporation of GeO2 into the glass in terms of structural characteristics, bioactivity, antimicrobial properties, and mechanical properties is advantageous for biomedical fields and especially for dental applications.

Preparation and Characterization of Dental Pit and Fissure Sealant Based on Calcium Sodium Silicate Bioactive Glasses

This study aimed to prepare a resin based dental sealant loaded with novel bioactive glass formulated from (50 wt% calcium silicate and 50 wt% sodium silicate) with different percentages of fluorapatite. Four glass batches were formulated then characterized using Fourier Transform Infrared Spectroscopy analysis, X-ray powder diffraction analysis and Transmission electron microscopy. Density, microhardness and bioactivity testing after insertion in artificial saliva were done. Four bisphenol A-glycidyl methacrylate (Bis-GMA) based sealants loaded with the glass batch that showed the preeminent properties and silica fillers were prepared. The prepared sealants were compared to commercial sealants regarding flow, curing depth, compressive strength and microhardness. Sealant composition that showed comparable properties to that of the commercial sealant was selected for pH changes and ion release testing after immersion in artificial saliva for different time intervals. Results indicated amorphous nature, bioactive behavior and apatite forming ability of the tested glass batches. Experimental sealant revealed comparable tested properties with lower compressive strength compared to the commercial sealants at P < 0.001. The mean pH values of the tested sealants ranged from 6.75 to 6.35 with extended calcium and phosphorus ion release up to 90 days. It was concluded that the 85 wt% calcium silicate and sodium silicate with 15 wt% fluorapatite had the best trend regarding ion release and apatite forming ability. Sealant loaded with 65 wt% bioactive glass, 10 wt% sintered nanosilica and 10 wt% nanosilica had the best acceptable mechanical properties. The novel pit and fissure sealant is a promising bioactive and ion releasing material.

Mussel-Inspired Polydopamine Composite Mesoporous Bioactive Glass Nanoparticles: An Exploration of Potential Metal-Ion Loading Platform and In Vitro Bioactivity.

Exploring new approaches to realize the possibility of incorporating biologically active elements into mesoporous silicate bioactive glass nanoparticles (MBG NPs) and guaranteeing their meso- structural integrity and dimensional stability has become an attractive and interesting challenge in biomaterials science. We present a postgrafting strategy for introducing different metal elements into MBG NPs. This strategy is mediated by polydopamine (PDA) coating, achieving uniform loading of copper or copper-cobalt on the particles efficiently and ensuring the stability of MBG NPs in terms of particle size, mesoporous structure, and chemical structure. However, the PDA coating reduced the ion-binding free energy of the MBG NPs for calcium and phosphate ions, resulting in the deposition of minimal CaP clusters on the PDA@MBG NP surface when immersed for 7 days in simulated body fluid, indicating the absence of hydroxyapatite mineralization.

Process parameter optimisation for manufacturing porous bioactive silicate glass microspheres via flame spheroidisation: The goldilocks effect

This study investigated the influence of flame spheroidisation process parameters for successfully manufacturing solid (dense) and highly porous microspheres from Food and Drug Administration approved bioactive 45S5 glass and 45S5 with addition of viscosity modifiers (i.e. 2 and 5 mol% borax and V2O5), compared against successfully processed phosphate glass microspheres (termed P40). Characterisation studies performed included thermal analysis (SDT), glass viscosity measurements using high temperature rotational viscometry and hot stage microscopy, X-ray diffraction, scanning electron microscopy and energy dispersive X-ray analysis.This study revealed that aside from intrinsic material properties (i.e. melt temperature and viscosity profiles), process parameters including starting glass particle size, cooling rate and gas flow rates were important factors in achieving the desired porous glass microsphere morphology. Considering the above influential factors, a processing model has been proposed for the manufacture of highly porous microspheres from bioactive silicate glasses.

Comprehensive assessment of SrO and CuO co-incorporated 50S6P amorphous silicate bioactive glasses in vitro: Revealing bioactivity properties of bone graft biomaterial for bone tissue engineering applications

Bioactivity is critically important for a glass material to be used in bone tissue engineering, which is stated to be affected by the addition of therapeutic ions such as Sr and Cu. In this study, the findings of a comprehensive in vitro study on the bioactivity of previously produced and characterized in terms of structure, composition and thermal features novel SrO and CuO co-incorporated 50S6P (SiO2–CaO–Na2O–P2O5, SrO–CuO) glasses were discussed. Herein, chemical bond, morphology, composition, and crystallinity changes on the amorphous silicate glasses were investigated using FT-IR, SEM-EDX, and XRD analysis, respectively. Furthermore, quantitative assessment of glass ionic dissolution products concentrations were performed in contact with simulated body fluid by ICP-OES analysis. SrO and CuO co-incorporated 50S6P amorphous silicate glasses showed an appropriate release profile in terms of its ionic products (Si4+: 18.5–32.6, Ca2+: 132.1–234.3, Sr2+: 1.29–2.35, Cu2+: 2.28–3.34, ppm), which resulted in the formation of Ca–P layer and the proceeding of its accumulation, further conformed with FT-IR and SEM-EDX. Furthermore, apatite layer, which consists of crystal apatite ranging in size (6.5–9.8 nm) having different degree of crystallinity percentages (2.5–22.4%), was formed on the glasses surface within 28 days in SBF. The results revealed that Sr incorporation (4.22 wt %) has an enhancing effect on bioactivity, whereas increased Cu incorporation (0.10–0.26 wt %) had a relatively inhibitory effect on bioactivity of the glasses. These findings are indicators of desirable bioactive features of 50S6P glasses. Thus, these bioactive glasses are acceptable to be utilized in bone tissue engineering application as bone graft biomaterials.

Bioactive Glass-Ceramic Scaffolds Coated with Hyaluronic Acid-Fatty Acid Conjugates: A Feasibility Study.

Promoting bone healing is a key challenge in our society that can be tackled by developing new implantable biomaterials provided with regenerative properties. In this work, the coating of three-dimensional porous glass-derived scaffolds with hyaluronic acid (HA)-fatty acids was investigated for the first time. The starting scaffolds, based on bioactive silicate glass, were produced by foam replication followed by sintering; then, HA-palmitate and HA-oleate conjugate coatings were deposited on the scaffold struts through a dipping procedure. FT-IR analysis confirmed the successful deposition of the coatings on the surface and struts of the scaffolds, the foam-like architecture of which was maintained as assessed by SEM investigations. The in vitro bioactivity of the HA-fatty-acid-coated scaffolds was studied by immersion tests in simulated body fluid and the subsequent evaluation of hydroxyapatite formation. The deposition of the polymeric coating did not inhibit the apatite-forming ability of scaffolds, as revealed by the formation of nanostructured hydroxyapatite agglomerates 48 h from immersion. These promising results motivate further investigation of these novel bioactive systems, which are expected to combine the bone-bonding properties of the glass with the wound-healing promotion carried out by the polymeric conjugates.

Halide-containing bioactive glasses enhance osteogenesis in vitro and in vivo

The application of bone substitutes to reconstruct bone defects is a strategy for repairing alveolar bone loss caused by periodontal disease. Bioactive glasses (BGs) are attractive synthetic bone substitutes owing to their abilities to degrade, form bone-like mineral and stimulate bone regeneration. Our previous studies showed that the incorporation of fluoride into alkali-free bioactive silicate glass promoted osteogenesis to some extent in vitro, while the incorporation of chloride facilitated glass degradation and accelerated the formation of hydroxyapatite. However, whether there is a synergistic effect of incorporating fluoride and chloride on further enhancement of osteogenesis and angiogenesis in vitro and in vivo was not known. Therefore, we synthesized three halide-containing BGs with fluoride only, or chloride only, or mixed fluoride and chloride, investigated their physicochemical properties and osteogenic and angiogenic effects both in vitro and in vivo. The results showed that the addition of both fluoride and chloride in a bioactive silicate glass could combine the structural roles of both, leading to a faster apatite formation than the glass with the presence of fluoride only and a more stable fluorapatite formation than the glass with the presence of chloride only, which formed hydroxyapatite upon immersion. The studied BGs were cytocompatible, as suggested by the cytotoxicity evaluation of hPDLSCs cultivated in the extracted BGs-conditioned culture media. More importantly, these BGs stimulated osteogenic differentiation of hPDLSCs without adding growth factors as indicated by the fact that BGs-conditioned media up-regulated the expression of BMP-2, OPN and VEGF of hPDLSCs and promoted the formation of bone nodules and collagen in vitro. By comparison, the incorporation of fluoride facilitated the expression of osteogenic-related biomarkers and bone nodule formation preferentially, while the incorporation of chloride induced the expression of angiogenic-related biomarkers and collagen formation. The in vivo investigation results demonstrated that the developed halide-containing BGs accelerated the process of bone regeneration, while the glass with mixed fluoride and chloride showed the most significant promotion effect among the three BGs. Therefore, our findings revealed a synergistic effect of incorporating fluoride and chloride into a BG on osteogenesis and angiogenesis in vitro and in vivo and highlighted the potential of fluoride and chloride containing bioactive glasses being bone substitutes for clinical use.

Robocasting of multicomponent sol-gel–derived silicate bioactive glass scaffolds for bone tissue engineering

Robocasting is universally recognized as an affordable and reproducible manufacturing strategy to process glass and glass-ceramic materials in the form of highly ordered porous scaffolds for bone tissue engineering (BTE) applications. Nevertheless, while being widely applied to melt-derived bioactive glasses, this technique was seldom implemented with sol-gel materials due to the intrinsic difficulties in producing suitable inks for extrusion and thus, good printing outcomes. The present experimental work describes a new and relatively easy method to manufacture multicomponent sol-gel bioactive silicate scaffolds (oxide system: 47.5SiO2–20CaO–10MgO–10Na2O-10 K2O-2.5P2O5, mol.%) using dried gels as basic material within the ink composition, which allows by-passing intermediate heat treatments that are usually detrimental to the bioactive potential of the material in physiological environment. The scaffolds, exhibiting a total porosity of 81 vol%, were characterized in terms of morphological-compositional features and bioactivity in simulated body fluid (SBF), paying special attention to ion release and surface modifications occurring upon soaking (apatite-forming ability). The compressive strength of the scaffolds (around 5 MPa) was comparable to that of human cancellous bone. Collectively, the results supported the possibility of using robocast sol-gel–derived scaffolds in BTE approaches. Furthermore, a comparison with robocast scaffolds based on a melt-derived glass with the same composition was reported in order to investigate the effect of the synthesis route on the dissolution behavior and morphological features of the final biomaterials.

Highly bioactive bone cement microspheres based on α-tricalcium phosphate microparticles/mesoporous bioactive glass nanoparticles: Formulation, physico-chemical characterization and in vivo bone regeneration

Calcium phosphate cement (CPC) is a self-setting, biocompatible and osteoconductive bone cement, however its use as a bone substitute is still limited owing to its low bioactivity (i.e. its slow in vivo resorption and slow new bone formation rate) which is a challenging issue to be addressed. Herein, we report for the first time highly bioactive bone cement microspheres formulated from a cement paste containing α-tricalcium phosphate microparticles (α-TCP) and mesoporous calcium silicate bioactive glass nanoparticles (mesoporous BGn) using a water-in-oil emulsion method. Indeed, bioactive microspheres possess high potential as bone defect fillers for bone regeneration. The α-TCP microparticles were prepared by a solid state synthesis at 1400 ºC while mesoporous BGn were synthesized by template-assissted ultrasound-mediated sol-gel method. The particle size distribution of as-prepared cement microspheres was in the range of 200 – 450 µm with a sphericity index in the range of 0.92 – 0.94. The surface morphology of α-TCP microspheres revealed α-TCP micoparticles with smooth surfaces whereas α-TCP/BGn microspheres unveiled nano-roughened α-TCP microparticles. The as-prepared α-TCP/BGn cement microspheres exhibited larger specific surface area ca 18.6 m2/g, sustained release of soluble silicate (SiO44-) ions (118 ppm within a week) and high protein adsorption capacity (252 mg/g). Notably, the α-TCP/BGn cement microspheres showed excellent in vitro surface bioactivity via formation of massive amounts of bone-like hydroxyapatite spherules and aggregates on their surfaces after soaking in simulated body fluid. Importantly, the in vivo implantation of as-prepared α-TCP/BGn cement microspheres in rat calvarial critical size bone defects for 6 weeks unveiled high in vivo bioactivity in terms of substantial new bone ingrowth and significant new bone formation within the bone defect as evidenced by histological analyses, X-ray radiography and micro-computed tomography evaluations.

In Vivo Evaluation of 3D-Printed Silica-Based Bioactive Glass Scaffolds for Bone Regeneration.

Bioactive glasses are often designed as porous implantable templates in which newly-formed bone can grow in three dimensions (3D). This research work aims to investigate the bone regenerative capability of silicate bioactive glass scaffolds produced by robocasting in comparison with powder and granule-like materials (oxide system: 47.5SiO2-10Na2O-10K2O-10MgO-20CaO-2.5P2O5, mol.%). Morphological and compositional analyses performed by scanning electron microscopy (SEM), combined with energy dispersive spectroscopy (EDS) after the bioactivity studies in a simulated body fluid (SBF) confirmed the apatite-forming ability of the scaffolds, which is key to allowing bone-bonding in vivo. The scaffolds exhibited a clear osteogenic effect upon implantation in rabbit femur and underwent gradual resorption followed by ossification. Full resorption in favor of new bone growth was achieved within 6 months. Osseous defect healing was accompanied by the formation of mature bone with abundant osteocytes and bone marrow cells. These in vivo results support the scaffold’s suitability for application in bone tissue engineering and show promise for potential translation to clinical assessment.

In vitro and in ovo impact of the ionic dissolution products of boron-doped bioactive silicate glasses on cell viability, osteogenesis and angiogenesis

Due to the pivotal role of angiogenesis in bone regeneration, the angiogenic properties of biomaterials are of high importance since they directly correlate with the biomaterials’ osteogenic potential via ‘angiogenic-osteogenic coupling’ mechanisms. The impact of bioactive glasses (BGs) on vascularization can be tailored by incorporation of biologically active ions such as boron (B). Based on the ICIE16-BG composition (in mol%: 49.5 SiO2, 36.3 CaO, 6.6 Na2O, 1.1 P2O5, 6.6 K2O), three B-doped BGs have been developed (compositions in mol%: 46.5/45.5/41.5 SiO2, 36.3 CaO, 6.6 Na2O, 1.1 P2O5, 6.6 K2O, 3/4/8 B2O3). The influence of B-doping on the viability, cellular osteogenic differentiation and expression of osteogenic and angiogenic marker genes of bone marrow-derived mesenchymal stromal cells (BMSCs) was analyzed by cultivating BMSCs in presence of the BGs’ ionic dissolution products (IDPs). Furthermore, the influence of the IDPs on angiogenesis was evaluated in ovo using a chorioallantoic membrane (CAM) assay. The influence of B-doped BGs on BMSC viability was dose-dependent, with higher B concentrations showing limited negative effects. B-doping led to a slight stimulation of osteogenesis and angiogenesis in vitro. In contrast to that, B-doping significantly enhanced vascularization in ovo, especially in higher concentrations. Differences between the results of the in vitro and in ovo part of this study might be explained via the different importance of vascularization in both settings. The implementation of new experimental models that cover the ‘angiogenic-osteogenic coupling’ mechanisms is highly relevant, for instance via extending the application of the CAM assay from solely angiogenic to angiogenic and osteogenic purposes.