Fairly high concentrations of magnesium and lithium are conducive to improving the osteogenic and angiogenic capacities. In the current study, lithium-containing magnesium phosphate-based ceramics (AMP/LMPGs) were prepared from amorphous magnesium phosphate (AMP) at a low sintering temperature (650 °C), and the lithium/magnesium-containing phosphate glasses (LMPGs) were utilized as sintering additives. During the sintering procedure of AMP/LMPGs, the AMP reacted with LMPGs, producing new compounds. The AMP/LMPGs displayed nano-size grains and plentiful micropores. The addition of LMPGs noticeably increased the porosity as well as compressive strength of the AMP/LMPGs ceramics. The AMP/LMPGs sustainedly released Mg, P and Li ions, forming Mg-rich ionic microenvironment, which ameliorated cellular proliferation, osteogenic differentiation and proangiogenic capacities. The AMP/LMPGs ceramics with considerably high compressive strength, osteostimulation and proangiogenic effects were expected to efficiently regenerate the bone defects.

Phosphate-based glasses (PBGs) are promising materials for bone repair and regeneration as they can be formulated to be compositionally similar to the inorganic components of bone. Alterations to the PBG formulation can be used to tailor their degradation rates and subsequent release of biotherapeutic ions to induce cellular responses, such as osteogenesis. In this work, novel invert-PBGs in the series xP2O5·(56 - x)CaO·24MgO·20Na2O (mol%), where x is 40, 35, 32.5 and 30 were formulated to contain pyro (Q1) and orthophosphate (Q0) species. These PBGs were processed into highly porous microspheres (PMS) via flame spheroidisation, with ~68% to 75% porosity levels. Compositional and structural analysis using EDX and 31P-MAS NMR revealed that significant depolymerisation occurred with reducing phosphate content which increased further when PBGs were processed into PMS. A decrease from 50% to 0% in Q2 species and an increase from 6% to 35% in Q0 species was observed for the PMS when the phosphate content decreased from 40 to 30 mol%. Ion release studies also revealed up to a four-fold decrease in cations and an eight-fold decrease in phosphate anions released with decreasing phosphate content. In vitro bioactivity studies revealed that the orthophosphate-rich PMS had favourable bioactivity responses after 28 days of immersion in simulated body fluid (SBF). Indirect and direct cell culture studies confirmed that the PMS were cytocompatible and supported cell growth and proliferation over 7 days of culture. The P30 PMS with ~65% pyro and ~35% ortho phosphate content revealed the most favourable properties and is suggested to be highly suitable for bone repair and regeneration, especially for orthobiologic applications owing to their highly porous morphology.

Phosphate-based glasses such as pure germanophosphate can be achieved at moderately low temperature by means of affordable chemical substances. Nowadays, they become more stimulating because they can be easily doped with alkali, transition metal ions, and rare earth oxides to afford the anticipated physical and/or chemical features for nanoscience applications. Herein, we report an experimental study dealing with the structure of pure germanophosphate glass samples of GeO 2 prepared with different concentrations ranging from 20 up to 70 mole%. 31 P magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy has been employed to characterize the co-formed glasses by two different glass-forming oxides. The components of the phosphate species ( Q n ) in each sample were determined by analyzing the MAS NMR spectra. Interestingly, 31 P MAS NMR spectrum for each sample was found to be characteristic powder patterns of the middle units Q2 . Q2  unit found herein has one oxygen atom bonded towards one germanium atom (non-bridging) and the other two oxygens are bonding towards two phosphorus atoms (bridging) of phosphate group (PO4 ). The results show that Q2 split into two units, Q2 I and Q2 II, due to different shielding of the phosphorus nucleus provided by the next nearest neighbor atoms. The chemical shift is interpreted in terms of the structure of each building unit of the phosphate group. The results obtained herein shed light on the way how to explore the revealed structure of the prepared glasses for the development of supported catalysts. Indeed, owing to their high chemical/thermal stability, the co-formed germanophosphate glasses obtained may prove as useful substrates for potential nanocatalysts.

Wound healing is a highly dynamic process and innovative therapeutic approaches are currently developed to address challenges of providing optimal wound care. In this study, phosphate-based glasses in the (CuO)x ·(KPO3 )79.5-x ·(ZnO)20 ·(Ag2 O)0.5 system (CuKPO3 ZnAg), with different CuO/ KPO3 ratios were prepared by melt-quenching technique. Constant Cu concentrations were released from the samples during immersion in Simulated Body Fluid (SBF), while Zn concentrations were slightly decreased over time. Glass surface phosphatation leading to formation of Zn crystalline salts was revealed through spectroscopic techniques. This finding was supported by SEM images that illustrated new compound formation. Subsequent cytotoxicity evaluation on HaCaT Keratinocytes using the indirect MTT cell viability assay revealed a CuO concentration-dependent cytotoxicity profile and excellent biocompatibility at low CuO concentrations, in all CuKPO3 ZnAg glasses. Furthermore, the (CuO)5 ·(KPO3 )74.5 ·(ZnO)20 ·(Ag2 O)0.5 sample (5CuKPO3 ZnAg), demonstrated superior antibacterial potency against S. aureus (ATCC 25923) strain compared to amoxicillin and ciprofloxacin. In vivo full-thickness wound healing evaluation showed a significantly higher regenerative effect of the 5CuKPO3 ZnAg sample, in terms of angiogenesis, collagen synthesis and re-epithelialization compared to non-treated wounds. These findings advance our understanding of the therapeutic perspectives of phosphate-based glasses, showing promising potential for wound-healing applications.

Phosphate-based glasses (PBGs) offer significant therapeutic potential due to their bioactivity, controllable compositions, and degradation rates. Several PBGs have already demonstrated their ability to support direct cell growth and in vivo cytocompatibility for bone repair applications. This study investigated development of PBG formulations with pyro- and orthophosphate species within the glass system (40 - x)P2O5·(16 + x)CaO·20Na2O·24MgO (x = 0, 5, 10 mol%) and their effect on stem cell adhesion properties. Substitution of phosphate for calcium revealed a gradual transition within the glass structure from Q2 to Q0 phosphate species. Human mesenchymal stem cells were cultured directly onto discs made from three PBG compositions. Analysis of cells seeded onto the discs revealed that PBG with higher concentration of pyro- and orthophosphate content (61% Q1 and 39% Q0) supported a 4.3-fold increase in adhered cells compared to glasses with metaphosphate connectivity (49% Q2 and 51% Q1). This study highlights that tuning the composition of PBGs to possess pyro- and orthophosphate species only, enables the possibility to control cell adhesion performance. PBGs with superior cell adhesion profiles represent ideal candidates for biomedical applications, where cell recruitment and support for tissue ingrowth are of critical importance for orthopaedic interventions.

Mesoporous phosphate-based glasses have great potential as biomedical materials being able to simultaneously induce tissue regeneration and controlled release of therapeutic molecules. In the present study, a series of mesoporous phosphate-based glasses in the P2O5-CaO-Na2O system, doped with 1, 3, and 5 mol% of Sr2+, were prepared using the sol-gel method combined with supramolecular templating. A sample without strontium addition was prepared for comparison. The non-ionic triblock copolymer EO20PO70EO20 (P123) was used as a templating agent. Scanning electron microscopy (SEM) images revealed that all synthesized glasses have an extended porous structure. This was confirmed by N2 adsorption-desorption analysis at 77 K that shows a porosity typical of mesoporous materials. 31P magic angle spinning nuclear magnetic resonance (31P MAS-NMR) and Fourier transform infrared (FTIR) spectroscopies have shown that the glasses are mainly formed by Q1 and Q2 phosphate groups. Degradation of the glasses in deionized water assessed over a 7-day period shows that phosphate, Ca2+, Na+, and Sr2+ ions can be released in a controlled manner over time. In particular, a direct correlation between strontium content and degradation rate was observed. This study shows that Sr-doped mesoporous phosphate-based glasses have great potential in bone tissue regeneration as materials for controlled delivery of therapeutic ions.

Phosphate-based glasses (PBGs) are bioactive and fully degradable materials with tailorable degradation rates. PBGs can be produced as porous microspheres through a single-step process, using changes in their formulation and geometry to produce varying pore sizes and interconnectivity for use in a range of applications, including biomedical use. Calcium phosphate PBGs have recently been proposed as orthobiologics, based on their in vitro cytocompatibility and ion release profile. In this study, porous microspheres made of two PBG formulations either containing TiO2 (P40Ti) or without (P40) were implanted in vivo in a large animal model of bone defect. The biocompatibility and osteogenic potential of these porous materials were assessed 13 weeks postimplantation in sheep and compared to empty defects and autologous bone grafts used as negative and positive controls. Histological analysis showed marked differences between the two formulations, as lower trabeculae-like interconnection and higher fatty bone marrow content were observed in the faster degrading P40-implanted defects, while the slower degrading P40Ti material promoted dense interconnected tissue. Autologous bone marrow concentrate (BMC) was also incorporated within the P40 and P40Ti microspheres in some defects; however, no significant differences were observed in comparison to microspheres implanted alone. Both formulations induced the formation of a collagen-enriched matrix, from 20 to 40% for P40 and P40Ti2.5 groups, suggesting commitment toward the bone lineage. With the faster degrading P40 formulation, mineralization of the tissue matrix was observed both with and without BMC. Some lymphocyte-like cells and foreign body multinucleated giant cells were observed with P40Ti2.5, suggesting that this more durable formulation might be linked to an inflammatory response. In conclusion, these first in vivo results indicate that PBG microspheres could be useful candidates for bone repair and regenerative medicine strategies and highlight the role of material degradation in the process of tissue formation and maturation.

The unique property of phosphate-based glasses and fibres to be completely dissolved in aqueous media is largely dependent on the glass composition. This article focuses on investigating the effect of replacing Na2O with 3 and 5 mol% Fe2O3 on cytocompatibility, thermal and dissolution properties of P2O5-CaO-Na2O-MgO-B2O3 glass system, where P2O5 content was fixed at 45 mol%. The effect of increasing Fe2O3 from 3 to 5 mol% on P2O5-CaO-Na2O-MgO glasses was also evaluated. The glass transition temperature, onset of crystallisation temperature and liquidus temperature were found to decrease with increasing Fe2O3 content and the addition of B2O3, while the thermal expansion values were found to decrease. The density of the glasses decreased with increasing Fe2O3 content. However, an increase in the density was observed by the addition of 5 mol% B2O3. The dissolution properties and mode of bulk glass and fibres were also examined which were found to decrease with increasing B2O3 and Fe2O3. However, it was found that the dissolution properties of the glasses containing both B2O3 and Fe2O3 were lower than only Fe2O3 containing glasses. The in vitro cell culture studies using human osteoblast like (MG63) cell lines revealed that the glasses containing both B2O3 and Fe2O3 maintained and showed higher cell viability as compared to the only Fe2O3 containing glasses. Glasses containing both B2O3 and Fe2O3 showed a pronounced effect on the dissolution rate of the glasses, which eventually improved the cytocompatibility properties of the glasses investigated.

This study aimed at evaluating the potential effect of gallium-incorporated phosphate-based glasses towards periodontitis-associated bacteria, Porphyromonas gingivalis, and matrix metalloproteinase-13. Periodontitis describes a group of inflammatory diseases of the gingiva and supporting structures of the periodontium. They are initiated by the accumulation of plaque bacteria, such as the putative periodontal pathogen Porphyromonas gingivalis, but the host immune response such as elevated matrix metalloproteinases are the major contributing factor for destruction of periodontal tissues. Antibacterial assays of gallium-incorporated phosphate-based glasses were conducted on Porphyromonas gingivalis ATCC 33277 using disc diffusion assay on fastidious anaerobe agar and liquid broth assay in a modified tryptic soy broth. In vitro study investigated the effect of gallium on purified recombinant human matrix metalloproteinase-13 activity using matrix metalloproteinase assay kit. In vivo biocompatibility of gallium-incorporated phosphate-based glass was evaluated in rats as subcutaneous implants. Antibacterial assay of gallium displayed activity against Porphyromonas gingivalis (inhibition zone of 22 ± 0.5 mm compared with 0 mm for control glass, c-PBG). Gallium in the glass contributed to growth inhibitory effect on Porphyromonas gingivalis (up to 1.30 reductions in log 10 values of the viable counts compared with control) in a modified tryptic soy broth. In vitro study showed gallium-incorporated phosphate-based glasses inhibited matrix metalloproteinase activity significantly (p ≤ 0.01) compared with c-PBG. Evaluation of in vivo biocompatibility of gallium-incorporated phosphate-based glasses in rats showed a non-toxic and foreign body response after 2 weeks of implantation. The results indicate that gallium ions might act on multiple targets of biological mechanisms underlying periodontal disease. Moreover, gallium-incorporated phosphate-based glasses are biocompatible in a rat model. The findings warrant further investigation and will have important clinical implications in the future treatment and management of periodontitis.

Ultrasound imaging is a powerful tool in medicine because of the millisecond temporal resolution and submillimeter spatial resolution of acoustic imaging. However, the current generation of acoustic contrast agents is primarily limited to vascular targets due to their large size. Nanosize particles have the potential to be used as a contrast agent for ultrasound molecular imaging. Silica-based nanoparticles have shown promise here; however, their slow degradation rate may limit their applications as a contrast agent. Phosphate-based glasses are an attractive alternative with controllable degradation rate and easily metabolized degradation components in the body. In this study, biodegradable P2O5-CaO-Na2O phosphate-based glass nanospheres (PGNs) were synthesized and characterized as contrast agents for ultrasound imaging. The structure of the PGNs was characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), (31)P magic angle spinning nuclear magnetic resonance ((31)P MAS NMR), and Fourier transform infrared (FTIR) spectroscopy. The SEM images indicated a spherical shape with a diameter size range of 200-500 nm. The XRD, (31)P NMR, and FTIR results revealed the amorphous and glassy nature of PGNs that consisted of mainly Q(1) and Q(2) phosphate units. We used this contrast to label mesenchymal stem cells and determined in vitro and in vivo detection limits of 5 and 9 μg/mL, respectively. Cell counts down to 4000 could be measured with ultrasound imaging with no cytoxicity at doses needed for imaging. Importantly, ion-release studies confirmed these PGNs biodegrade into aqueous media with degradation products that can be easily metabolized in the body.