Development of Resorbable Phosphate-Based Glass Microspheres as MRI Contrast Media Agents.

In this research, resorbable phosphate-based glass (PBG) compositions were developed using varying modifier oxides including iron (Fe2O3), copper (CuO), and manganese (MnO2), and then processed via a rapid single-stage flame spheroidisation process to manufacture dense (i.e., solid) and highly porous microspheres. Solid (63-200 µm) and porous (100-200 µm) microspheres were produced and characterised via SEM, XRD, and EDX to investigate their surface topography, structural properties, and elemental distribution. Complementary NMR investigations revealed the formation of Q2, Q1, and Q0 phosphate species within the porous and solid microspheres, and degradation studies performed to evaluate mass loss, particle size, and pH changes over 28 days showed no significant differences among the microspheres (63-71 µm) investigated. The microspheres produced were then investigated using clinical (1.5 T) and preclinical (7 T) MRI systems to determine the R1 and R2 relaxation rates. Among the compositions investigated, manganese-based porous and solid microspheres revealed enhanced levels of R2 (9.7-10.5 s-1 for 1.5 T; 17.1-18.9 s-1 for 7 T) and R1 (3.4-3.9 s-1 for 1.5 T; 2.2-2.3 s-1 for 7 T) when compared to the copper and iron-based microsphere samples. This was suggested to be due to paramagnetic ions present in the Mn-based microspheres. It is also suggested that the porosity in the resorbable PBG porous microspheres could be further explored for loading with drugs or other biologics. This would further advance these materials as MRI theranostic agents and generate new opportunities for MRI contrast-enhancement oral-delivery applications.

Optimisation of the Flame Spheroidisation Process for the Rapid Manufacture of Fe3O4-Based Porous and Dense Microspheres.

The rapid, single-stage, flame-spheroidisation process, as applied to varying Fe3O4:CaCO3 powder combinations, provides for the rapid production of a mixture of dense and porous ferromagnetic microspheres with homogeneous composition, high levels of interconnected porosity and microsphere size control. This study describes the production of dense (35-80 µm) and highly porous (125-180 µm) Ca2Fe2O5 ferromagnetic microspheres. Correlated backscattered electron imaging and mineral liberation analysis investigations provide insight into the microsphere formation mechanisms, as a function of Fe3O4/porogen mass ratios and gas flow settings. Optimised conditions for the processing of highly homogeneous Ca2Fe2O5 porous and dense microspheres are identified. Induction heating studies of the materials produced delivered a controlled temperature increase to 43.7 °C, indicating that these flame-spheroidised Ca2Fe2O5 ferromagnetic microspheres could be highly promising candidates for magnetic induced hyperthermia and other biomedical applications.

Tailoring Pyro-and Orthophosphate Species to Enhance Stem Cell Adhesion to Phosphate Glasses.

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.

Micropatterning of nanocomposite polymer scaffolds using sacrificial phosphate glass fibers for tendon tissue engineering applications.

This study presents a simple and reproducible method of micropatterning the novel nanocomposite polymer (POSS-PCU) using a sacrificial phosphate glass fiber template for tendon tissue engineering applications. The diameters of the patterned scaffolds produced were dependent on the diameter of the glass fibers (15 µm) used. Scaffolds were tested for their physical properties and reproducibility using various microscopy techniques. For the first time, we show that POSS-PCU supports growth of human tenocytes cells. Furthermore, we show that cellular alignment, their biological function and expression of various tendon related proteins such as scleraxis, collagen I and III, tenascin-C are significantly elevated on the micropatterned polymer surfaces compared to flat samples. This study demonstrated a simple, reproducible method of micropatterning POSS-PCU nanocomposite polymer for novel tendon repair applications, which when provided with physical cues could help mimic the microenvironment of tenocytes cells.

Effect of cellulose nanowhiskers on surface morphology, mechanical properties, and cell adhesion of melt-drawn polylactic Acid fibers.

Polylactic acid (PLA) fibers were produced with an average diameter of 11.2 (± 0.9) µm via a melt-drawing process. The surface of the PLA fibers was coated with blends of cellulose nanowhiskers (CNWs) (65 to 95 wt %) and polyvinyl acetate (PVAc). The CNWs bound to the smooth PLA fiber surface imparted roughness, with the degree of roughness depending on the coating blend used. The fiber tensile modulus increased 45% to 7 GPa after coating with 75 wt % CNWs compared with the uncoated PLA fibers, and a significant increase in the fiber moisture absorption properties at different humidity levels was also determined. Cytocompatibility studies using NIH-3T3 mouse fibroblast cells cultured onto CNWs-coated PLA surface revealed improved cell adhesion compared with the PLA control, making this CNW surface treatment applicable for biomedical and tissue engineering applications. Initial studies also showed complete cell coverage within 2 days.

PDI-Functionalized Glass Beads: Efficient, Metal-Free Heterogeneous Photocatalysts Suitable for Flow Photochemistry.

Perylene diimides (PDI) have an extraordinary ability to activate both energy and electron transfer processes upon light excitation; however, their extremely low solubility has hindered their wide use as photocatalysts. Here, we show that the combination of solid-supported PDIs with continuous flow photochemistry offers a promising strategy for process intensification and a scalable platform for heterogeneous photocatalysis. The photocatalyst immobilized onto glass beads is highly efficient, easy to separate, and extremely reusable, with a broad synthetic application range. Using the photo-oxidation of n-butyl sulfide as a benchmark reaction, we demonstrate that immobilized PDI are highly active, outperforming reported homogeneous photosensitizers, and capable of extensive reuse (turnover number (TON) >57,000 over 2 months). Transferring the process from batch to flow results in a 10-fold reduction in irradiation time and an increase in the space-time yield by a factor of 33 (40 vs 1338 mmol-1 h-1 L-1 batch vs flow). What is more, the same catalyst sample can be used for the preparation of a range of sulfoxides, the aza-Henry reaction between nitromethane and N-Ar tetrahydroisoquinolines, and the photo-oxidation of furfural with high catalytic activity. Overall, our work combines the remarkable photocatalytic properties of PDI with inert, easy-to-handle glass beads, producing hybrid materials that are reusable and can be adapted for performing heterogeneous photocatalysis in a range of scalable photochemical reactors.

A phosphate glass reinforced composite acrylamide gradient scaffold for osteochondral interface regeneration.

The bone-cartilage interface is defined by a unique arrangement of cells and tissue matrix. Injury to the interface can contribute to the development of arthritic joint disease. Attempts to repair osteochondral damage through clinical trials have generated mixed outcomes. Tissue engineering offers the potential of integrated scaffold design with multiregional architecture to assist in tissue regeneration, such as the bone-cartilage interface. Challenges remain in joining distinct materials in a single scaffold mass while maintaining integrity and avoiding delamination. The aim of the current work is to examine the possibility of joining two closely related acrylamide derivatives such as, poly n-isopropyl acrylamide (pNIPAM) and poly n­tert­butyl acrylamide (pNTBAM). The target is to produce a single scaffold unit with distinct architectural regions in the favour of regenerating the osteochondral interface. Longitudinal phosphate glass fibres (PGFs) with the formula 50P2O5.30CaO.20Na2O were incorporated to provide additional bioactivity by degradation to release ions such as calcium and phosphate which are considered valuable to assist the mineralization process. Polymers were prepared via atom transfer radical polymerization (ATRP) and solutions cast to ensure the integration of polymers chains. Scaffold was characterized using scanning electron microscope (SEM) and Fourier transform infra-red (FTIR) techniques. The PGF mass degradation pattern was inspected using micro computed tomography (µCT). Biological assessment of primary human osteoblasts (hOBs) and primary human chondrocytes (hCHs) upon scaffolds was performed using alizarin red and colorimetric calcium assay for mineralization assessment; alcian blue staining and dimethyl-methylene blue (DMMB) assay for glycosaminoglycans (GAGs); immunostaining and enzyme-linked immunosorbent assay (ELISA) to detect functional proteins expression by cells such as collagen I, II, and annexin A2. FTIR analysis revealed an intact unit with gradual transformation from pNIPAM to pNTBAM. SEM images showed three distinct architectural regions with mean pore diameter of 54.5 µm (pNIPAM), 16.5 µm (pNTBAM) and 118 µm at the mixed interface. Osteogenic and mineralization potential by cells was observed upon the entire scaffold's regions. Chondrogenic activity was relevant on the pNTBAM side of the scaffold only with minimal evidence in the pNIPAM region. PGFs increased mineralization potential of both hOBs and hCHs, evidenced by elevated collagens I, X, and annexin A2 with reduction of collagen II in PGFs scaffolds. In conclusion, pNIPAM and pNTBAM integration created a multiregional scaffold with distinct architectural regions. Differential chondrogenic, osteogenic, and mineralized cell performance, in addition to the impact of PGF, suggests a potential role for phosphate glass-incorporated, acrylamide-derivative scaffolds in osteochondral interface regeneration.

The Use of Microspheres for Cancer Embolization Therapy: Recent Advancements and Prospective.

Embolization therapy involving biomaterials has improved the therapeutic strategy for most liver cancer treatments. Developing biomaterials as embolic agents has significantly improved patients' survival rates. Various embolic agents are present in liquid agents, foam, particulates, and particles. Some of the most applied embolic agents are microparticles, such as microspheres (3D micrometer-sized spherical particles). Microspheres with added functionalities are currently being developed for effective therapeutic embolization. Their excellent properties of high surface area and capacity for being loaded with radionuclides and alternate active or therapeutic agents provide an additional advantage to overcome limitations from traditional cancer treatments. Microspheres (non-radioactive and radioactive) have been widely used and explored for localized cancer treatment. Non-radioactive microspheres exhibit improved clinical performance as drug delivery vehicles in chemotherapy due to their controlled and sustained drug release to the target site. They offer better flow properties and are beneficial for the ease of delivery via injection procedures. In addition, radioactive microspheres have also been exploited for use as an embolic platform in internal radiotherapy as an alternative to cancer treatment. This short review summarizes the progressive development of non-radioactive and radioactive embolic microspheres, emphasizing material characteristics. The use of embolic microspheres for various modalities of therapeutic arterial embolization and their impact on therapeutic performance are also discussed.

Development of samarium-doped phosphate glass microspheres for internal radiotheranostic applications.

Internal radiotherapy delivers radioactive sources inside the body, near to or into malignant tumours, which may be particularly effective when malignancies are not responding to external beam radiotherapy. A pure beta emitter, 90Y, is currently used for internal radiotherapy. However, theranostic radionuclide-doped microspheres can be developed by incorporating 153Sm, which emits therapeutic beta and diagnostic gamma energies. This study investigated the production of high concentrations of samarium-content doped phosphate-based glass microspheres. The glass P60 (i.e. 60P2O5-25CaO-15Na2O) was mixed with Sm2O3 at ratios of 75:25 (G75:Sm25), 50:50 (G50:Sm50) and 25:75 (G25:Sm75) and processed via flame spheroidisation. Scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) confirmed the microsphere uniformity with significantly high samarium content up to 44 % in G25:Sm75. Via X-ray diffraction (XRD) analysis, samarium-doped microspheres appeared to be glass-ceramic in nature. Mass-loss, size and pH changes were performed over 28 days, revealing a significant increase in samarium microsphere stability. After 15 min of neutron activation (neutron flux 3.01 × 1013 n.cm-2.s-1), the specific activity of the microspheres (G75:Sm25, G50:Sm50 and G25:Sm75) was 0.28, 0.54 and 0.58 GBq.g-1, respectively. Therefore, the samarium microspheres produced in this study provide great potential for improving internal radiotherapy treatment for liver cancer by avoiding complex procedures and using less microspheres with shorter irradiation time.

In vitro immunomodulatory effect of solid versus porous phosphate-based glass microspheres using macrophages.

This study aimed to investigate the immunomodulatory effect of two different forms of phosphate-based glass microspheres (solid and porous), on human macrophages. Human THP-1 monocytes were converted to M0 macrophages after being treated with 100 ng/mL phorbol 12-myristate 13-acetate for 48 h. The differentiated cells were analysed for the CD14 marker using flow cytometry. The adhesion, spreading, and viability of M0 macrophages grown directly or indirectly (extracts) at varying concentrations of solid and porous glass microspheres (GMs) were analysed via phase contrast microscopy, confocal microscopy, and XTT assay. The expression of IL-8, IL-1ß, IL-6, IL-10, TNF-α, and IL-12p70 cytokines was investigated using flow cytometry. The conversion to M0 macrophages was confirmed by their adherent nature, increased granularity, and CD14 expression. The results showed that both solid and porous GMs or extracts favored the attachment, spreading, and proliferation of macrophages in a comparable manner to cells grown in a normal tissue culture medium. Only the higher concentration of porous GMs (10 mg/mL) changed the morphology of M0 macrophages and increased the expression of IL-1ß and IL-8 pro-inflammatory cytokines; this could be related to the fast degradation nature of porous GMs. Of the six cytokines analysed, M0 macrophages grown directly or indirectly with GMs only expressed IL-1ß, IL-10, and IL-8. Accordingly, solid microspheres may have advantages as regenerative agents due to their controlled degradation.

Production of Nano Hydroxyapatite and Mg-Whitlockite from Biowaste-Derived products via Continuous Flow Hydrothermal Synthesis: A Step towards Circular Economy.

Biowastes from agriculture, sewage, household wastes, and industries comprise promising resources to produce biomaterials while reducing adverse environmental effects. This study focused on utilising waste-derived materials (i.e., eggshells as a calcium source, struvite as a phosphate source, and CH3COOH as dissolution media) to produce value-added products (i.e., calcium phosphates (CaPs) derived from biomaterials) using a continuous flow hydrothermal synthesis route. The prepared materials were characterised via XRD, FEG-SEM, EDX, FTIR, and TEM analysis. Magnesium whitlockite (Mg-WH) and hydroxyapatite (HA) were produced by single-phase or biphasic CaPs by reacting struvite with either calcium nitrate tetrahydrate or an eggshell solution at 200 °C and 350 °C. Rhombohedral-shaped Mg-WH (23-720 nm) along with tube (50-290 nm diameter, 20-71 nm thickness) and/or ellipsoidal morphologies of HA (273-522 nm width) were observed at 350 °C using HNO3 or CH3COOH to prepare the eggshell and struvite solutions, and NH4OH was used as the pH buffer. The Ca/P (atomic%) ratios obtained ranged between 1.3 and 1.7, indicating the formation of Mg-WH and HA. This study showed that eggshells and struvite usage, along with CH3COOH, are promising resources as potential sustainable precursors and dissolution media, respectively, to produce CaPs with varying morphologies.

Upcycling Glass Waste into Porous Microspheres for Wastewater Treatment Applications: Efficacy of Dye Removal.

Each year about 7.6 million tons of waste glasses are landfilled without recycling, reclaiming or upcycling. Herein we have developed a solvent free upcycling method for recycled glass waste (RG) by remanufacturing it into porous recycled glass microspheres (PRGMs) with a view to explore removal of organic pollutants such as organic dyes. PRGMs were prepared via flame spheroidisation process and characterised using Scanning Electron Microscopy (SEM), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) and Mercury Intrusion Porosimetry (MIP) analysis. PRGMs exhibited 69% porosity with overall pore volume and pore area of 0.84 cm3/g and 8.6 cm2/g, respectively (from MIP) and a surface area of 8 m2/g. Acid red 88 (AR88) and Methylene blue (MB) were explored as a model source of pollutants. Results showed that removal of AR88 and MB by PRGMs was influenced by pH of the dye solution, PRGMs doses, and dye concentrations. From the batch process experiments, adsorption and coagulation processes were observed for AR88 dye whilst MB dye removal was attributed only to adsorption process. The maximum monolayer adsorption capacity (qe) recorded for AR88, and MB were 78 mg/g and 20 mg/g, respectively. XPS and FTIR studies further confirmed that the adsorption process was due to electrostatic interaction and hydrogen bond formation. Furthermore, dye removal capacity of the PRGMs was also investigated for column adsorption process experiments. Based on the Thomas model, the calculated adsorption capacities at flow rates of 2.2 mL/min and 0.5 mL/min were 250 mg/g and 231 mg/g, respectively which were much higher than the batch scale Langmuir monolayer adsorption capacity (qe) values. It is suggested that a synergistic effect of adsorption/coagulation followed by filtration processes was responsible for the higher adsorption capacities observed from the column adsorption studies. This study also demonstrated that PRGMs produced from recycled glass waste could directly be applied to the next cyclic experiment with similar dye removal capability. Thus, highlighting the circular economy scope of using waste inorganic materials for alternate applications such as pre-screening materials in wastewater treatment applications.

Rheological, Surface Tension and Conductivity Insights on the Electrospinnability of Poly(lactic-co-glycolic acid)-hyaluronic Acid Solutions and Their Correlations with the Nanofiber Morphological Characteristics.

In this study, solutions were prepared with fixed concentrations of hyaluronic acid (HA) but varied concentrations of poly (lactic-co-glycolic acid) (PLGA) to emphasize the effects of PLGA concentration and HA addition on solution properties and to further evaluate their electrospinning performance. The dependence of specific viscosity on PLGA concentration was studied to determine the concentration regimes and evaluate the critical concentration (Ce) for successful fiber generation. The Ce of PLGA solutions is 12.07% compared to 10.09% for PLGA-HA solutions. Blending with HA results in a lower concentration dependence and better consistency to the theoretical scaling mechanisms due to the additional topological constrains, which thus result in more chain entanglements. Solutions in semi-dilute entangled regimes show the crossover of complex moduli, verifying the stable and reliable entanglement network. Higher concentrations and HA addition both led to lower crossover frequencies and, thus, a longer relaxation time. The effects of a higher PLGA concentration and HA addition on the surface tension were not evident. However, the HA addition significantly improved the solution conductivity up to three times in the pure PLGA solutions due to its polyelectrolyte nature. Defect-free and uniform nanofibers were generated from 35% to 40% of the PLGA-HA solutions, yet fibers with bead-on-string structures were produced from all studied pure PLGA solutions. Such solution characteristics and parametric correlations can provide predictive insights on tailoring the morphological characteristics of nanofibers for specific applications.

L-DOPA coating improved phosphate glass fibre strength and fibre/matrix interface.

The levodopa (L-DOPA) has been reported as a promising adhesive for various materials. In this study, we utilized L-DOPA as an interfacial agent for phosphate glass fibre/polycaprolactone (PGF/PCL) composites, with the aim to enhance the interfacial properties between the fibres and polymer matrix. The PGFs were dip-coated in varying concentrations of L-DOPA solution ranging between 5 and 40 g L-1. The fibre strength and interfacial shear strength (IFSS) of the composites were measured via a single fibre tensile test and single fibre fragmentation test, respectively. It was found that the L-DOPA agent (at conc. 10 g L-1) significantly improved the IFSS of the composites up to 27%. Also, the L-DOPA coating (at conc. 40 g L-1) significantly increased the glass fibre strength up to 18%. As a result, an optimum coating level could be tailored depending on application and whether fibre strength or IFSS was of greater importance. In addition, SEM and TGA analyses were used to detect and quantify the coating agents. FTIR and XPS further confirmed presence of the coating and indicated the zwitterionic crystals of L-DOPA and the formation of a melanin-like polymer layer. The spectroscopy data also evidenced that both catechol and amine groups contributed to the interaction between the L-DOPA and the PGF surface.

Evolution of silicate bioglass particles as porous microspheres with a view towards orthobiologics.

Although FDA approved and clinically utilised, research on 45S5 Bioglass® and S53P4 including other bioactive glasses continues in order to advance their applicability for a range of alternate applications. For example, rendering these particles porous would enable incorporation of varying biological payloads (i.e. cells, drugs and growth factors) and making them spherical would enhance their flow properties enabling delivery to target sites via minimally invasive injection procedures. This paper reports on the manufacture of solid (non-porous; SGMS) and highly porous microspheres (PGMS) with large external pores and fully interconnected porosity from bioactive silicate glass formulations (45S5 and S53P4) via a single stage flame spheroidisation process and their physicochemical properties including in vitro biological response. Morphological and physical characterisation of the SGMS and PGMS revealed interconnected porosity up to 65 ± 5%. Mass loss studies comparing between SGMS and PGMS revealed 1.5 times higher mass loss for the PGMS over 28 days. Also, in vitro bioactivity studies using simulated body fluid (SBF) revealed hydroxyapatite (HA) formation at earlier time point for PGMS compared to their SGMS counterparts (i.e day 1 for PGMS and day 3 for SGMS of 45S5). In addition, HA layers were also formed in cell culture media, with the exception of SGMS of 45S5, which revealed CaP formation with a ratio of 1.52-1.78. Direct cell seeding and indirect cell culture studies (via incubation with microsphere degradation products) revealed mouse 3T3 cells were able to grow and undergo osteogenic differentiation in vitro, confirming cytocompatibility of both 45S5 and S53P4 SGMS and PGMS. More importantly and especially for orthobiologic applications, cells were observed to have migrated within the pores of the PGMS. As such, the PGMS developed from these bioactive silicate glasses are highly promising candidate materials for orthobiologics and alternate applications requiring delivery of biologic payloads.

Developing Echogenic Materials as Catheters for Use with Ultrasound.

Patients with peripherally inserted central catheters (PICCs) are routinely discharged with the catheters in place. These patients experience complications due to undetected thrombosis or accidental dislodgement, with tracking through limited X-ray imaging. Developing catheters with the capability to be tracked without the need for X-ray imaging would greatly benefit these patients by decreasing patient stress, reducing time to diagnosis, and increasing nursing home capabilities. This study reports on the incorporation of echogenic microspheres into catheters to produce bulk echogenic effects for developments in the field of real-time ultrasound tracking of polymeric medical devices. The impact on elastic modulus, ultrasound contrast, and cytocompatibility of the polymer was analyzed when incorporating up to 10 wt % glass microspheres. Up to this loading level, the elastic modulus was found to remain constant. However, at 10 wt %, extrusion defects due to agglomeration, air bubbles, and shearing were numerous and deemed detrimental to ultrasound imaging. Successful, defect-free samples were produced with 5 wt % microsphere loading and when embedded in a soft tissue phantom revealed a significant increase in the signal-to-noise ratio as compared to the polymer alone. Preliminary results have shown a successful increase in polymer's echogenic properties, without undermining its mechanical and cytocompatibility properties.

Developing Porous Ortho- and Pyrophosphate-Containing Glass Microspheres; Structural and Cytocompatibility Characterisation.

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.

Effect of phosphate-based glass fibre surface properties on thermally produced poly(lactic acid) matrix composites.

Incorporation of soluble bioactive glass fibres into biodegradable polymers is an interesting approach for bone repair and regeneration. However, the glass composition and its surface properties significantly affect the nature of the fibre-matrix interface and composite properties. Herein, the effect of Si and Fe on the surface properties of calcium containing phosphate based glasses (PGs) in the system (50P(2)O(5)-40CaO-(10-x)SiO(2)-xFe(2)O(3), where x = 0, 5 and 10 mol.%) were investigated. Contact angle measurements revealed a higher surface energy, and surface polarity as well as increased hydrophilicity for Si doped PG which may account for the presence of surface hydroxyl groups. Two PG formulations, 50P(2)O(5)-40CaO-10Fe(2)O(3) (Fe10) and 50P(2)O(5)-40CaO-5Fe(2)O(3)-5SiO(2) (Fe5Si5), were melt drawn into fibres and randomly incorporated into poly(lactic acid) (PLA) produced by melt processing. The ageing in deionised water (DW), mechanical property changes in phosphate buffered saline (PBS) and cytocompatibility properties of these composites were investigated. In contrast to Fe10 and as a consequence of the higher surface energy and polarity of Fe5Si5, its incorporation into PLA led to increased inorganic/organic interaction indicated by a reduction in the carbonyl group of the matrix. PLA chain scission was confirmed by a greater reduction in its molecular weight in PLA-Fe5Si5 composites. In DW, the dissolution rate of PLA-Fe5Si5 was significantly higher than that of PLA-Fe10. Dissolution of the glass fibres resulted in the formation of channels within the matrix. Initial flexural strength was significantly increased through PGF incorporation. After PBS ageing, the reduction in mechanical properties was greater for PLA-Fe5Si5 compared to PLA-Fe10. MC3T3-E1 preosteoblasts seeded onto PG discs, PLA and PLA-PGF composites were evaluated for up to 7 days indicating that the materials were generally cytocompatible. In addition, cell alignment along the PGF orientation was observed showing cell preference towards PGF.

Rapid conversion of highly porous borate glass microspheres into hydroxyapatite.

This paper reports on the rapid development of porous hydroxyapatite (HA) microspheres with large external pores and fully interconnected porosity. These porous microspheres were produced by converting borates glasses (namely 45B5, B53P4 and 13-93B) into HA by immersing them in potassium phosphate media and simulated body fluid (SBF). Solid (SGMS) non-porous and highly porous (PGMS) microspheres were prepared from borate glasses via a novel flame spheroidisation process and their physicochemical properties including in vitro biological response were investigated. Morphological and physical characterisation of the PGMS showed interconnected porosity (up to 75 ± 5%) with average external pore sizes of 50 ± 5 µm. Mass loss, ion release, X-ray diffraction (XRD) and Scanning electron microscopy (SEM) analysis confirmed complete conversion to HA in 0.02 M K2HPO4 solution for the PGMS (with exception of 13-93B glass) and at significantly faster rates compared to their SGMS counterparts. However, 13-93B microspheres only converted to HA in Na2HPO4 solution. The in vitro SBF bioactivity studies for all the borate compositions showed HA formation and much earlier for PGMS compared to SGMS. Direct cell culture studies using hMSCs revealed that the converted porous HA microspheres showed enhanced pro-osteogenic properties compared to their unconverted counterparts and such are considered as highly promising candidate materials for bone repair (and orthobiological) applications.

Effect of varying the Mg with Ca content in highly porous phosphate-based glass microspheres.

This paper reports on the role of phosphate-based glass (PBG) microspheres and their physicochemical properties including in vitro biological response to human mesenchymal stem cells (hMSCs). Solid and porous microspheres were prepared via a flame spheroidisation process. The Mg content in the PBG formulations explored was reduced from 24 to 2 mol% with a subsequent increase in Ca content. A small quantity of TiO2 (1 mol%) was added to the lower Mg-content glass (2 mol%) to avoid crystallisation. Morphological and physical characterisation of porous microspheres revealed interconnected porosity (up to 76 ± 5 %), average external pore sizes of 55 ± 5 µm with surface areas ranging from 0.38 to 0.43 m2 g-1. Degradation and ion release studies conducted compared the solid (non-porous) and porous microspheres and revealed 1.5 to 2.5 times higher degradation rate for porous microspheres. Also, in vitro bioactivity studies using simulated body fluid (SBF) revealed Ca/P ratios for porous microspheres of all three glass formulations were between 0.75 and 0.92 which were within the range suggested for precipitated amorphous calcium phosphate. Direct cell seeding and indirect cell culture studies (via incubation with microsphere degradation products) revealed hMSCs were able to grow and undergo osteogenic differentiation in vitro, confirming cytocompatibility of the formulations tested. However, the higher Mg content (24 mol%) porous microsphere showed the most potent osteogenic response and is therefore considered as a promising candidate for bone repair applications.