Imperial College London


Faculty of EngineeringDepartment of Materials

Professor of Biomaterials



+44 (0)20 7594 6749julian.r.jones




207GoldsmithSouth Kensington Campus





Publication Type

253 results found

Verdolotti L, Oliviero M, Lavorgna M, Santillo C, Tallia F, Iannace S, Chen S, Jones JRet al., 2021, “Aerogel-like” polysiloxane-polyurethane hybrid foams with enhanced mechanical and thermal-insulating properties, Composites Science and Technology, Vol: 213, Pages: 1-9, ISSN: 0266-3538

New organic-inorganic polyurethane-based hybrids with enhanced mechanical properties and thermal insulation properties are reported. Polyurethane-based hybrids are characterized by the intimate interactions of their inorganic and organic co-networks and prepared by sol-gel approach, have exhibited properties exceeding those of polyurethane foams, e.g. enhanced thermal stability, durability and thermal insulating effectiveness. However, mechanical properties have previously been poor. Here, new porous organic-inorganic materials consisting of a polyurethane network modified by in-situ formation of aerogel-like polysiloxane domains, were developed. They exhibit a multiscale-porosity which enhances the insulation, mechanical and thermal properties. The synthesis was performed through a novel stepwise process consisting of: preparation of a siloxane precursor based on methyl-triethoxysilane and tetraethoxysilane; functionalization of traditional polyol for polyurethane foams with 3-(triethoxysilanepropyl)isocyanate as coupling agent; use of suitable catalysts and silicone surfactants; and foaming with methylene-di-isocyanate compound. The siloxane precursors and coupling agent led to formation of “aerogel-like” polysiloxane domains within the walls and struts of the polyurethane foams. The synthesis method enabled increased incorporation of the “aerogel-like” polysiloxane structures into the foams, compared to literature, with 20 wt% SiO2, reducing thermal conductivity of the hybrid foams 30% compared with pristine polyurethane, in addition to significant improvement in thermal stability and mechanical properties.

Journal article

Riveiro A, Amorim S, Solanki A, Costa DS, Pires RA, Quintero F, del Val J, Comesaña R, Badaoui A, Lusquiños F, Maçon ALB, Tallia F, Jones JR, Reis RL, Pou Jet al., 2021, Hyaluronic acid hydrogels reinforced with laser spun bioactive glass micro- and nanofibres doped with lithium, Materials Science and Engineering: C, Vol: 126, Pages: 1-12, ISSN: 0928-4931

The repair of articular cartilage lesions in weight-bearing joints remains as a significant challenge due to the low regenerative capacity of this tissue. Hydrogels are candidates to repair lesions as they have similar properties to cartilage extracellular matrix but they are unable to meet the mechanical and biological requirements for a successful outcome. Here, we reinforce hyaluronic acid (HA) hydrogels with 13-93-lithium bioactive glass micro- and nanofibres produced by laser spinning. The glass fibres are a reinforcement filler and a platform for the delivery of therapeutic lithium-ions. The elastic modulus of the composites is more than three times higher than in HA hydrogels. Modelling of the reinforcement corroborates the experimental results. ATDC5 chondrogenic cells seeded on the composites are viable and more proliferation occurs on the hydrogels containing fibres than in HA hydrogels alone. Furthermore, the chondrogenic behavior on HA constructs with fibres containing lithium is more marked than in hydrogels with no-lithium fibres.

Journal article

Chung JJ, Yoo J, Sum BST, Li S, Lee S, Kim TH, Li Z, Stevens MM, Georgiou TK, Jung Y, Jones JRet al., 2021, 3D printed porous methacrylate/silica hybrid scaffold for bone substitution, Advanced Healthcare Materials, Vol: 10, Pages: 1-13, ISSN: 2192-2640

Inorganic–organic hybrid biomaterials made with star polymer poly(methyl methacrylate-co-3-(trimethoxysilyl)propyl methacrylate) and silica, which show promising mechanical properties, are 3D printed as bone substitutes for the first time, by direct ink writing of the sol. Three different inorganic:organic ratios of poly(methyl methacrylate-co-3-(trimethoxysilyl)propyl methacrylate)-star-SiO2 hybrid inks are printed with pore channels in the range of 100–200 µm. Mechanical properties of the 3D printed scaffolds fall within the range of trabecular bone, and MC3T3 pre-osteoblast cells are able to adhere to the scaffolds in vitro, regardless of their compositions. Osteogenic and angiogenic properties of the hybrid scaffolds are shown using a rat calvarial defect model. Hybrid scaffolds with 40:60 inorganic:organic composition are able to instigate new vascularized bone formation within its pore channels and polarize macrophages toward M2 phenotype. 3D printing inorganic–organic hybrids with sophisticated polymer structure opens up possibilities to produce novel bone graft materials.

Journal article

Barrioni BR, de Carvalho SM, Naruphontjirakul P, Norris E, Kelly NL, Hanna JV, Jones JR, Pereira MDMet al., 2021, Cobalt-containing spherical glass nanoparticles for therapeutic ion release, Journal of the American Ceramic Society, ISSN: 0002-7820

Bioactive glass nanoparticles (BGNPs) can be internalized by cells, allowing the intracellular release of dissolution products with therapeutic benefit. Different therapeutic ions can be incorporated into the glass network that can promote angiogenesis via simulation of hypoxia conditions and consequent activation of pro-angiogenic genes. Here, novel monodispersed spherical dense BGNPs were obtained by a modified Stöber method with the SiO2–CaO–CoO composition, with diameters of 92 ± 1 nm, with cobalt as the pro-angiogenic ion. The presence of Co2+ species and the role of Co and Ca as network modifiers in the silica glass were confirmed by X-ray photoelectron spectroscopy and 29Si solid-state magic-angle spinning nuclear magnetic resonance, respectively. Controlled Co2+ ion release was observed in culture media, and no cytotoxicity was observed by (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide cell viability assay on human osteosarcoma cells in direct contact with the nanoparticles. This study demonstrated that Co2+ ions can be incorporated into dense and spherical BGNPs, and these materials exhibit great potential as intracellular ion delivery systems with therapeutic properties.

Journal article

Pou-Alvarez P, Riveiro A, Ramon Novoa X, Jin X, del Val J, Comesana R, Boutinguiza M, Lusquinos F, Jones JR, Teresa Perez-Prado M, Pou Jet al., 2021, Laser-guided corrosion control: a new approach to tailor the degradation of Mg-alloys, Small, Vol: 17, Pages: 1-10, ISSN: 1613-6810

Despite corrosion being commonly seen as a problem to be avoided, applications such as batteries or biodegradable implants do benefit from corrosion‐like phenomena. However, current strategies address corrosion control from a global perspective for a whole component, without considering local adaptations to functionality specifications or inhomogeneous environments. Here, a novel concept is presented: the local control and guidance of corrosion through a laser surface treatment. Immersion tests in saline solution of AZ31 magnesium alloy samples show degradation rates reduced up to 15 times with the treatment, owing to a fast passivation after the induced microstructural modifications. By controlling the treatment conditions, the degradation can be restricted to delimited regions and driven towards specific directions. The applicability of the method for the design of tailored degradation biomedical implants is demonstrated and uses for cathodic protection systems and batteries can also be anticipated.

Journal article

Nelson M, Li S, Page SJ, Shi X, Lee PD, Stevens MM, Hanna JV, Jones JRet al., 2021, 3D printed silica-gelatin hybrid scaffolds of specific channel sizes promote collagen Type II, Sox9 and Aggrecan production from chondrocytes, Materials Science and Engineering: C, Vol: 123, Pages: 1-12, ISSN: 0928-4931

Inorganic/organic hybrids have co-networks of inorganic and organic components, with the aim of obtaining synergy of the properties of those components. Here, a silica-gelatin sol-gel hybrid “ink” was directly 3D printed to produce 3D grid-like scaffolds, using a coupling agent, 3-glycidyloxypropyl)trimethoxysilane (GPTMS), to form covalent bonds between the silicate and gelatin co-networks. Scaffolds were printed with 1 mm strut separation, but the drying method affected the final architecture and properties. Freeze drying produced <40 μm struts and large ~700 μm channels. Critical point drying enabled strut consolidation, with ~160 μm struts and ~200 μm channels, which improved mechanical properties. This architecture was critical to cellular response: when chondrocytes were seeded on the scaffolds with 200 μm wide pore channels in vitro, collagen Type II matrix was preferentially produced (negligible amount of Type I or X were observed), indicative of hyaline-like cartilaginous matrix formation, but when pore channels were 700 μm wide, Type I collagen was prevalent. This was supported by Sox9 and Aggrecan expression. The scaffolds have potential for regeneration of articular cartilage regeneration, particularly in sports medicine cases.

Journal article

Pinna A, Baghbaderani MT, Hernandez VV, Naruphontjirakul P, Li S, McFarlane T, Hachim D, Stevens MM, Porter AE, Jones JRet al., 2021, Nanoceria provides antioxidant and osteogenic properties to mesoporous silica nanoparticles for osteoporosis treatment, ACTA BIOMATERIALIA, Vol: 122, Pages: 365-376, ISSN: 1742-7061

Journal article

Parkes M, Tallia F, Young G, Cann P, Jones J, Jeffers Jet al., 2021, Tribological evaluation of a novel hybrid for repair of articular cartilage defects, Materials Science and Engineering C: Materials for Biological Applications, Vol: 119, Pages: 1-10, ISSN: 0928-4931

The friction and wear properties of silica/poly(tetrahydrofuran)/poly(ε-caprolactone) (SiO2/PTHF/PCL-diCOOH) hybrid materials that are proposed as cartilage tissue engineering materials were investigated against living articular cartilage. A testing rig was designed to allow testing against fresh bovine cartilage. The friction force and wear were compared for five compositions of the hybrid biomaterial articulating against freshly harvested bovine cartilage in diluted bovine calf serum. Under a non-migrating contact, the friction force increased and hence shear force applied to the opposing articular cartilage also increased, resulting in minor damage to the cartilage surface. This worse case testing scenario was used to discriminate between material formulations and revealed the increase in friction and damaged area was lowest for the hybrid containing the most silica. Further friction and wear tests on one hybrid formulation with an elastic modulus closest to that of cartilage were then conducted in a custom incubator system. This demonstrated that over a five day period the friction force, cell viability and glucosaminoglycan (GAG) release into the lubricant were similar between a cartilage-cartilage interface and the hybrid-cartilage interface, supporting the use of these materials for cartilage repair. These results demonstrate how tribology testing can play a part in the development of new materials for chondral tissue engineering.

Journal article

Solanki A, Lali F, Autefage H, Agarwal S, Nommeots-Nomm A, Metcalfe A, Stevens M, Jones Jet al., 2021, Bioactive glasses and electrospun composites that release cobalt to stimulate the HIF pathway for wound healing applications, Biomaterials Research, Vol: 25, ISSN: 2055-7124

BackgroundBioactive glasses are traditionally associated with bonding to bone through a hydroxycarbonate apatite (HCA) surface layer but the release of active ions is more important for bone regeneration. They are now being used to deliver ions for soft tissue applications, particularly wound healing. Cobalt is known to simulate hypoxia and provoke angiogenesis. The aim here was to develop new bioactive glass compositions designed to be scaffold materials to locally deliver pro-angiogenic cobalt ions, at a controlled rate, without forming an HCA layer, for wound healing applications.MethodsNew melt-derived bioactive glass compositions were designed that had the same network connectivity (mean number of bridging covalent bonds between silica tetrahedra), and therefore similar biodegradation rate, as the original 45S5 Bioglass. The amount of magnesium and cobalt in the glass was varied, with the aim of reducing or removing calcium and phosphate from the compositions. Electrospun poly(ε-caprolactone)/bioactive glass composites were also produced. Glasses were tested for ion release in dissolution studies and their influence on Hypoxia-Inducible Factor 1-alpha (HIF-1α) and expression of Vascular Endothelial Growth Factor (VEGF) from fibroblast cells was investigated.ResultsDissolution tests showed the silica rich layer differed depending on the amount of MgO in the glass, which influenced the delivery of cobalt. The electrospun composites delivered a more sustained ion release relative to glass particles alone. Exposing fibroblasts to conditioned media from these composites did not cause a detrimental effect on metabolic activity but glasses containing cobalt did stabilise HIF-1α and provoked a significantly higher expression of VEGF (not seen in Co-free controls).ConclusionsThe composite fibres containing new bioactive glass compositions delivered cobalt ions at a sustained rate, which could be mediated by the magnesium content of the glass. The dis

Journal article

Nelson M, Tallia F, Page SJ, Hanna JV, Fujita Y, Obata A, Kasuga T, Jones JRet al., 2021, Electrospun cotton–wool-like silica/gelatin hybrids with covalent coupling, Journal of Sol-Gel Science and Technology, Vol: 97, Pages: 11-26, ISSN: 0928-0707

Inorganic/organic sol–gel hybrids consist of co-networks of inorganic and organic components that can lead to unique properties, compared to conventional composites, especially when there is covalent bonding between the networks. The aim here was to develop new electrospun silica/gelatin sol–gel hybrids, with covalent coupling and unique 3D cotton–wool-like morphology for application as regenerative medicine scaffolds. Covalent coupling is critical for obtaining sustained dissolution of the fibres and we identified the sol–gel synthesis conditions needed for coupling within the electrospun fibres. Under carefully controlled conditions, such as constant humidity, we investigated the effect of the electrospinning process variables of sol viscosity (and aging time) and amount of coupling agent on the 3D morphology of the fibres, their structure (bonding) and dissolution, identifying a detailed optimised protocol for fibre scaffold production.

Journal article

Ferreira SA, Young G, Jones JR, Rankin Set al., 2021, Bioglass/carbonate apatite/collagen composite scaffold dissolution products promote human osteoblast differentiation, Materials Science and Engineering: C, Vol: 118, Pages: 1-13, ISSN: 0928-4931

OssiMend® Bioactive (Collagen Matrix Inc., NJ) is a three-component porous composite bone graft device of 45S5 Bioglass/carbonate apatite/collagen. Our in vitro studies showed that conditioned media of the dissolution products of OssiMend Bioactive stimulated primary human osteoblasts to form mineralized bone-like nodules in vitro in one week, in basal culture media (no osteogenic supplements). Osteoblast differentiation was followed by gene expression analysis and a mineralization assay. In contrast, the dissolution products from commercial OssiMend (Bioglass-free carbonate apatite/collagen scaffolds), or from 45S5 Bioglass particulate alone, did not induce the mineralization of the extracellular matrix, but did induce osteoblast differentiation to mature osteoblasts, evidenced by the strong upregulation of BGLAP and IBSP mRNA levels. The calcium ions and soluble silicon species released from 45S5 Bioglass particles and additional phosphorus release from OssiMend mediated the osteostimulatory effects. Medium conditioned with OssiMend Bioactive dissolution had a much higher concentration of phosphorus and silicon than media conditioned with OssiMend and 45S5 Bioglass alone. While OssiMend and OssiMend Bioactive led to calcium precipitation in cell culture media, OssiMend Bioactive produced a higher concentration of soluble silicon than 45S5 Bioglass and higher dissolution of phosphorus than OssiMend. These in vitro results suggest that adding 45S5 Bioglass to OssiMend produces a synergistic osteostimulation effect on primary human osteoblasts.

Journal article

Li Volsi A, Tallia F, Iqbal H, Georgiou TK, Jones JRet al., 2020, Enzyme degradable star polymethacrylate/silica hybrid inks for 3D printing of tissue scaffolds, Materials Advances, Vol: 1, ISSN: 2633-5409

There is unmet clinical need for scaffolds that can share load with the host tissue while biodegrading under the action of enzymes present at the site of implantation. The aim here was to create the first enzyme cleavable inorganic–organic hybrid “inks” that can be 3D printed as scaffolds for bone regeneration. Inorganic–organic hybrids are co-networks of inorganic and organic components. Although previous hybrids performed well under cyclic loads, there was little control over their degradation. Here we synthesised new hybrids able to degrade in response to endogenous tissue specific metallo proteinases (collagenases) that are involved in natural remodeling of bone. Three well-defined star polymers, of the monomer 3-(trimethoxysilyl)propyl methacrylate (TMSPMA) and of methyl methacrylate (MMA), of different architectures were prepared by RAFT polymerisation. The linear arms were connected together at an enzyme degradable core using a collagenase cleavable peptide sequence (GLY-PRO-LEU-GLY-PRO-LYS) modified with dimethacryloyl groups as a crosslinker for RAFT polymerisation. The effect of polymer architecture, i.e. the position of the TMSPMA groups on the polymers, on bonding between networks, mechanical properties, biodegradation rate and 3D printability, via direct ink writing, was investigated for the first time and was proven to be critical for all three properties. Specifically, hybrids made with star polymers with the TMSPMA close to the core exhibited the best mechanical properties, improved printability and a higher degradation rate.

Journal article

Barrak FN, Li S, Muntane AM, Jones JRet al., 2020, Particle release from implantoplasty of dental implants and impact on cells, International Journal of Implant Dentistry, Vol: 6, Pages: 1-9, ISSN: 2198-4034

BackgroundWith increasing numbers of dental implants placed annually, complications such as peri-implantitis and the subsequent periprosthetic osteolysis are becoming a major concern. Implantoplasty, a commonly used treatment of peri-implantitis, aims to remove plaque from exposed implants and reduce future microbial adhesion and colonisation by mechanically modifying the implant surface topography, delaying re-infection/colonisation of the site. This in vitro study aims to investigate the release of particles from dental implants and their effects on human gingival fibroblasts (HGFs), following an in vitro mock implantoplasty procedure with a diamond burr.Materials and methodsCommercially available implants made from grade 4 (commercially pure, CP) titanium (G4) and grade 5 Ti-6Al-4 V titanium (G5) alloy implants were investigated. Implant particle compositions were quantified by inductively coupled plasma optical emission spectrometer (ICP-OES) following acid digestion. HGFs were cultured in presence of implant particles, and viability was determined using a metabolic activity assay.ResultsMicroparticles and nanoparticles were released from both G4 and G5 implants following the mock implantoplasty procedure. A small amount of vanadium ions were released from G5 particles following immersion in both simulated body fluid and cell culture medium, resulting in significantly reduced viability of HGFs after 10 days of culture.ConclusionThere is a need for careful evaluation of the materials used in dental implants and the potential risks of the individual constituents of any alloy. The potential cytotoxicity of G5 titanium alloy particles should be considered when choosing a device for dental implants. Additionally, regardless of implant material, the implantoplasty procedure can release nanometre-sized particles, the full systemic effect of which is not fully understood. As such, authors do not recommend implantoplasty for the treatment of peri-implantiti

Journal article

Clark J, Heyraud A, Tavana S, Al-Jabri T, Tallia F, Clark B, Blunn G, Cobb J, Hansen U, Jones J, Jeffers Jet al., 2020, Exploratory full-field mechanical analysis across the osteochondral tissue– biomaterial interface in an ovine model, Materials, Vol: 13, ISSN: 1996-1944

Osteochondral injuries are increasingly prevalent, yet success in articular cartilage regeneration remains elusive, necessitating the development of new surgical interventions and novel medical devices. As part of device development, animal models are an important milestone in illustrating functionality of novel implants. Inspection of the tissue-biomaterial system is vital to understand and predict load-sharing capacity, fixation mechanics and micromotion, none of which are directly captured by traditional post-mortem techniques. This study aims to characterize the localised mechanics of an ex vivo ovine osteochondral tissue–biomaterial system extracted following six weeks in vivo testing, utilising laboratory micro-computed tomography, in situ loading and digital volume correlation. Herein, the full-field displacement and strain distributions were visualised across the interface of the system components, including newly formed tissue. The results from this exploratory study suggest that implant micromotion in respect to the surrounding tissue could be visualised in 3D across multiple loading steps. The methodology provides a non-destructive means to assess device performance holistically, informing device design to improve osteochondral regeneration strategies.

Journal article

Clark J, Tavana S, Heyraud A, Tallia F, Jones J, Hansen U, Jeffers Jet al., 2020, Quantifying 3D strain in scaffold implants for regenerative medicine, Materials, Vol: 13, ISSN: 1996-1944

Regenerative medicine solutions require thoughtful design to elicit the intended biological response. This includes the biomechanical stimulus to generate an appropriate strain in the scaffold and surrounding tissue to drive cell lineage to the desired tissue. To provide appropriate strain on a local level, new generations of scaffolds often involve anisotropic spatially graded mechanical properties that cannot be characterised with traditional materials testing equipment. Volumetric examination is possible with three-dimensional (3D) imaging, in situ loading and digital volume correlation (DVC). Micro-CT and DVC were utilised in this study on two sizes of 3D-printed inorganic/organic hybrid scaffolds (n = 2 and n = 4) with a repeating homogenous structure intended for cartilage regeneration. Deformation was observed with a spatial resolution of under 200 µm whilst maintaining displacement random errors of 0.97 µm, strain systematic errors of 0.17% and strain random errors of 0.031%. Digital image correlation (DIC) provided an analysis of the external surfaces whilst DVC enabled localised strain concentrations to be examined throughout the full 3D volume. Strain values derived using DVC correlated well against manually calculated ground-truth measurements (R2 = 0.98, n = 8). The technique ensures the full 3D micro-mechanical environment experienced by cells is intimately considered, enabling future studies to further examine scaffold designs for regenerative medicine.

Journal article

Shi X, Nommeots-Nomm A, Todd NM, Devlin-Mullin A, Geng H, Lee PD, Mitchell CA, Jones JRet al., 2020, Bioactive glass scaffold architectures regulate patterning of bone regeneration in vivo, Applied Materials Today, Vol: 20, Pages: 1-11, ISSN: 2352-9407

The architecture of bone scaffolds, such as pore dimensions, connectivity and orientation can regulate osteogenic defect repair, as can their rate of degradation. Synthetic bone grafts have historically been developed with foam structures to mimic trabecular bone. Now, Additive Manufacturing techniques enable production of open and regular pore architectures with improved compressive strengths. Here, we compare two types of bioactive glass scaffolds, made of the highly biodegradable ICIE16 composition, with distinctively different architectures but matched interconnect sizes (~150 µm), produced via two different techniques: gel-cast foaming and direct ink writing. A rabbit lateral femoral defect model was used to compare the effect of their architecture on in vivo bone regeneration, relative to a defect only control group, after 4 and 10 weeks of implantation. 3D X-ray microcomputed tomography (micro-CT), correlated to histology and back-scatter electron microscopy (BS-SEM) permitted quantitative evaluation of new bone ingrowth and degradation of the scaffolds. Both foam and printed scaffolds showed equal or higher bone ingrowth compared to the control group. After 4 weeks, the foam group showed the highest osteogenesis, with 51% more bone ingrowth than the defect only controls, but after 10 weeks the defect treated with the printed scaffold had the most bone ingrowth (40% more than the empty defect). Energy dispersive X-ray (EDS) mapping revealed degradation of the glass and calcium-phosphate deposition. The foam group showed more rapid degradation than the printed group, due to higher total porosity (even though interconnected pore size was equivalent). The foam scaffold appeared to allow rapid bone ingrowth and cancellous bone formation, whereas the printed scaffold seemed to provoke cortical-like bone formation, while remaining in place for longer than the 10 week study. While the foam's concave architectures promote initial bone ingrowth, the higher stren

Journal article

Li S, Tallia F, Mohammed AA, Stevens MM, Jones JRet al., 2020, Scaffold channel size influences stem cell differentiation pathway in 3-D printed silica hybrid scaffolds for cartilage regeneration, Biomaterials Science, Vol: 8, Pages: 4458-4466, ISSN: 2047-4830

We report that 3-D printed scaffold channel size can direct bone marrow derived stem cell differentiation. Treatment of articular cartilage trauma injuries, such as microfracture surgery, have limited success because durability is limited as fibrocartilage forms. A scaffold-assisted approach, combining microfracture with biomaterials has potential if the scaffold can promote articular cartilage production and share load with cartilage. Here, we investigated human bone marrow derived stromal cell (hBMSC) differentiation in vitro in 3-D printed silica/poly(tetrahydrofuran)/poly(ε-caprolactone) hybrid scaffolds with specific channel sizes. Channel widths of ∼230 μm (210 ± 22 μm mean strut size, 42.4 ± 3.9% porosity) provoked hBMSC differentiation down a chondrogenic path, with collagen Type II matrix prevalent, indicative of hyaline cartilage. When pores were larger (∼500 μm, 229 ± 29 μm mean strut size, 63.8 ± 1.6% porosity) collagen Type I was dominant, indicating fibrocartilage. There was less matrix and voids in smaller channels (∼100 μm, 218 ± 28 μm mean strut size, 31.2 ± 2.9% porosity). Our findings suggest that a 200–250 μm pore channel width, in combination with the surface chemistry and stiffness of the scaffold, is optimal for cell–cell interactions to promote chondrogenic differentiation and enable the chondrocytes to maintain their phenotype.

Journal article

Chen S, Greasley SL, Ong ZY, Naruphontjirakul P, Page SJ, Hanna J, Redpath AN, Tsigkou O, Rankin S, Ryan MP, Porter AE, Jones JRet al., 2020, Biodegradable zinc-containing mesoporous silica nanoparticles for cancer therapy, Materials Today, Vol: 6, Pages: 1-11, ISSN: 1369-7021

Triple-negative breast cancers are extremely aggressive with limited treatment options because of the reduced response of the cancerous cells to hormonal therapy. Here, monodispersed zinc-containing mesoporous silica nanoparticles (MSNPs-Zn) were produced as a tuneable biodegradable platform for delivery of therapeutic zinc ions into cells. We demonstrate that the nanoparticles were internalized by cells, and a therapeutic dose window was identified in which the MSNPs-Zn were toxic to breast cancer cells but not to healthy epithelial (MCF-10a) cells or to murine macrophages. A significant reduction in the viability of triple negative MDA-MB-231 and MCF-7 (ER+) breast cancer cells was seen following 24 h exposure to MSNPs-Zn. The more aggressive MDA-MB-231 cells, with higher metastatic potential, were more sensitive to MSNPs-Zn than the MCF-7 cells. MSNPs-Zn underwent biodegradation inside the cells, becoming hollow structures, as imaged by high-resolution transmission electron microscopy. The mesoporous silica nanoparticles provide a biodegradable vehicle for therapeutic ion release inside cells.

Journal article

Mohammed AA, Pinna A, Li S, Sang T, Jones JRet al., 2020, Auto-catalytic redox polymerisation using nanoceria and glucose oxidase for double network hydrogels, Journal of Materials Chemistry B, Vol: 8, Pages: 2834-2844, ISSN: 2050-750X

A novel auto-catalytic reaction, a combination of naturally occurring enzyme glucose oxidase (GOx) and amine-functionalised cerium oxide nanoparticles (nanoceria), was employed for open vessel free radical polymerisation of double network hydrogels (DNHGs). The nanoceria also incorporated into the gels to enhance mechanical strength. GOx reduces atmospheric O2 to H2O2, causing a cyclic change of cerium ion states, resulting in propagating free radicals in the carbon group in the amino functionalised nanoceria surface. We synthesised novel nanocomposite DNHGs by grafting polymers onto amine-functionalised nanoceria (ANC), with poly(2-acrylamido-2-methylpropanesulfonic acid), PAMPS, and polyacrylamide (PAAm) in the first and second networks respectively. The graft polymerisation was initiated using the alternating cerium states on the ANC. GOx held two major roles within the reaction: to provide an oxygen free system, without any other form of degassing, and to provide cyclical cerium ion states between Ce4+ and Ce3+, creating new free radicals for polymerisation. Polymer conversion using ANC as the sole initiator in the presence of GOx resulted in 83% conversion for PAMPS and 64% PAAm. Polymers degassed only with argon resulted in less than 55% conversion for both PAAm and PAMPS, proving that the addition of GOx enhanced the reaction. The new gels (1.76 MPa) showed an order of magnitude improvement in mechanical properties compared to DNHG made without ANC/GOx (0.10 MPa).

Journal article

Norris E, Ramos-Rivera C, Poologasundarampillai G, Clark JP, Ju Q, Obata A, Hanna JV, Kasuga T, Mitchell CA, Jell G, Jones JRet al., 2019, Electrospinning 3D bioactive glasses for wound healing., Biomedical Materials, Vol: 15, Pages: 1-14, ISSN: 1748-6041

An electrospinning technique was used to produce three-dimensional (3D) bioactive glass fibrous scaffolds, in the SiO2-CaO system, for wound healing applications. Previously, it was thought that 3D cotton wool-like structures could only be produced when the sol contained calcium nitrate, implying that the Ca2+ and its electronic charge had a significant effect on the structure produced. Here, fibres with a 3D appearance were also electrospun from compositions containing only silica. A polymer binding agent was added to inorganic sol-gel solutions, enabling electrospinning prior to bioactive glass network formation and the polymer was removed by calcination. While the addition of Ca2+ contributes to the 3D morphology, here we show that other factors, such as relative humidity, play an important role in producing the 3D cotton-wool-like macrostructure of the fibres. A human dermal fibroblast cell line (CD-18CO) was exposed to dissolution products of the samples. Cell proliferation and metabolic activity tests were carried out and a VEGF ELISA showed a significant increase in VEGF production in cells exposed to the bioactive glass samples compared to control in DMEM. A novel SiO2-CaO nanofibrous scaffold was created that showed tailorable physical and dissolution properties, the control and composition of these release products are important for directing desirable wound healing interactions.

Journal article

Barrioni BR, Norris E, Li S, Naruphontjirakul P, Jones JR, Pereira MDMet al., 2019, Osteogenic potential of sol-gel bioactive glasses containing manganese, Journal of Materials Science: Materials in Medicine, Vol: 30, ISSN: 0957-4530

Bioactive glasses (BGs) are widely used for bone regeneration, and allow the incorporation of different ions with therapeutic properties into the glass network. Amongst the different ions with therapeutic benefits, manganese (Mn) has been shown to influence bone metabolism and activate human osteoblasts integrins, improving cell adhesion, proliferation and spreading. Mn has also been incorporated into bioceramics as a therapeutic ion for improved osteogenesis. Here, up to 4.4 mol% MnO was substituted for CaO in the 58S composition (60 mol% SiO2, 36 mol% CaO, 4 mol% P2O5) and its effects on the glass properties and capability to influence the osteogenic differentiation were evaluated. Mn-containing BGs with amorphous structure, high specific surface area and nanoporosity were obtained. The presence of Mn2+ species was confirmed by X-ray photoelectron spectroscopy (XPS). Mn-containing BGs presented no cytotoxic effect on human mesenchymal stem cells (hMSCs) and enabled sustained ion release in culture medium. hMSCs osteogenic differentiation stimulation and influence on the mineralisation process was also confirmed through the alkaline phosphatase (ALP) activity, and expression of osteogenic differentiation markers, such as collagen type I, osteopontin and osteocalcin, which presented higher expression in the presence of Mn-containing samples compared to control. Results show that the release of manganese ions from bioactive glass provoked human mesenchymal stem cell (hMSC) differentiation down a bone pathway, whereas hMSCs exposed to the Mn-free glass did not differentiate. Mn incorporation offers great promise for obtaining glasses with superior properties for bone tissue regeneration.

Journal article

Barrioni BR, Naruphontjirakul P, Norris E, Li S, Kelly NL, Hanna J, Stevens MM, Jones JR, Pereira MDMet al., 2019, Effects of manganese incorporation on the morphology, structure and cytotoxicity of spherical bioactive glass nanoparticles, Journal of Colloid and Interface Science, Vol: 547, Pages: 382-392, ISSN: 0021-9797

Bioactive glass nanoparticles (BGNPs) are of great interest in tissue engineering as they possess high dissolution rate and capability of being internalized by cells, releasing their dissolution products with therapeutic benefits intracellularly. A modified Stöber process can be applied to obtain different BGNPs compositions containing therapeutic ions while maintaining controllable particle morphology, monodispersity and reduce agglomeration. Here, BGNPs containing Mn, an ion that has been shown to influence the osteoblast proliferation and bone mineralization, were evaluated. Particles with up to 142.3 ± 10.8 nm and spherical morphology were obtained after MnO incorporation in the SiO2 – CaO system. X-ray photoelectron spectroscopy (XPS) indicated the presence of Mn2+ species and also a reduction in the number of bridging oxygen bonds due to the Ca and Mn. The Ca and Mn network modifier role on the silica network was also confirmed by magic-angle spinning 29Si solid-state nuclear magnetic resonance (MAS NMR). MTT evaluation showed no reduction in the mitochondrial metabolic activity of human mesenchymal stem cells exposed to the glass ionic products. Thus, evaluation showed that Mn could be incorporated into BGNPs by the modified Stöber method while maintaining their spherical morphology and features as a promising strategy for tissue regeneration.

Journal article

Autefage H, Allen F, Tang HM, Kallepitis C, Gentleman E, Reznikov N, Nitiputri K, Nommeots-Nomm A, Young G, Lee PD, Pierce BF, Wagermaier W, Fratzl P, Goodship A, Jones JR, Blunn G, Stevens Met al., 2019, Multiscale analyses reveal native-like lamellar bone repair and near perfect bone-contact with porous strontium-loaded bioactive glass, Biomaterials, Vol: 209, Pages: 152-162, ISSN: 0142-9612

The efficient healing of critical-sized bone defects using synthetic biomaterial-based strategies is promising but remains challenging as it requires the development of biomaterials that combine a 3D porous architecture and a robust biological activity. Bioactive glasses (BGs) are attractive candidates as they stimulate a biological response that favors osteogenesis and vascularization, but amorphous 3D porous BGs are difficult to produce because conventional compositions crystallize during processing. Here, we rationally designed a porous, strontium-releasing, bioactive glass-based scaffold (pSrBG) whose composition was tailored to deliver strontium and whose properties were optimized to retain an amorphous phase, induce tissue infiltration and encourage bone formation. The hypothesis was that it would allow the repair of a critical-sized defect in an ovine model with newly-formed bone exhibiting physiological matrix composition and structural architecture. Histological and histomorphometric analyses combined with indentation testing showed pSrBG encouraged near perfect bone-to-material contact and the formation of well-organized lamellar bone. Analysis of bone quality by a combination of Raman spectral imaging, small-angle X-ray scattering, X-ray fluorescence and focused ion beam-scanning electron microscopy demonstrated that the repaired tissue was akin to that of normal, healthy bone, and incorporated small amounts of strontium in the newly formed bone mineral. These data show the potential of pSrBG to induce an efficient repair of critical-sized bone defects and establish the importance of thorough multi-scale characterization in assessing biomaterial outcomes in large animal models.

Journal article

Nommeots-Nomm A, Ligorio C, Bodey AJ, Cai B, Jones JR, Lee PD, Poologasundarampillai Get al., 2019, Four-dimensional imaging and quantification of viscous flow sintering within a 3D printed bioactive glass scaffold using synchrotron X-ray tomography, Materials Today Advances, Vol: 2, ISSN: 2590-0498

Bioglass® was the first material to form a stable chemical bond with human tissue. Since its discovery, a key goal was to produce three-dimensional (3D) porous scaffolds which can host and guide tissue repair, in particular, regeneration of long bone defects resulting from trauma or disease. Producing 3D scaffolds from bioactive glasses is challenging because of crystallization events that occur while the glass particles densify at high temperatures. Bioactive glasses such as the 13–93 composition can be sintered by viscous flow sintering at temperatures above the glass transition onset (Tg) and below the crystallization temperature (Tc). There is, however, very little literature on viscous flow sintering of bioactive glasses, and none of which focuses on the viscous flow sintering of glass scaffolds in four dimensions (4D) (3D + time). Here, high-resolution synchrotron-sourced X-ray computed tomography (sCT) was used to capture and quantify viscous flow sintering of an additively manufactured bioactive glass scaffold in 4D. In situ sCT allowed the simultaneous quantification of individual particle (local) structural changes and the scaffold's (global) dimensional changes during the sintering cycle. Densification, calculated as change in surface area, occurred in three distinct stages, confirming classical sintering theory. Importantly, our observations show for the first time that the local and global contributions to densification are significantly different at each of these stages: local sintering dominates stages 1 and 2, while global sintering is more prevalent in stage 3. During stage 1, small particles coalesced to larger particles because of their higher driving force for viscous flow at lower temperatures, while large angular particles became less faceted (angular regions had a local small radius of curvature). A transition in the rate of sintering was then observed in which significant viscous flow occurred, resulting in large reduction of surfac

Journal article

Mohammed AA, Aviles Milan J, Li S, Chung JJ, Stevens MM, Georgiou TK, Jones JRet al., 2019, Open vessel free radical photopolymerization of double network gels for biomaterial applications using glucose oxidase, Journal of Materials Chemistry B, Vol: 7, Pages: 4030-4039, ISSN: 2050-750X

Polymerization of certain gels in the presence of oxygen can lead to hindered reaction rates and low conversion rates, limiting the use of open vessel polymerization and material synthesis. Here, the oxido-reductase enzyme glucose oxidase (GOx) was used to enable open vessel free radical photopolymerization (FRP) of neutral polyacrylamide (PAAm), and polyelectrolyte poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS) under ambient conditions. GOx successfully blocks the inhibition pathways created by O2 in FRP, dramatically increasing the polymer conversion rate for both polymers. In the presence of GOx, PAAm and PAMPS achieved conversion of 78% and 100% respectively at a photoinitiator (PI) concentration of 0.05 wt% with GOx, compared to 0% without GOx at the same PI concentration. Cytotoxicity studies of these polymers show high cell viability after GOx is denatured. Double network hydrogels (DNHGs) were successfully produced using the polymers and use of GOx improved compressive fracture stress by a factor of ten. Vinyl functionalized silica nanoparticles (VSNPs) were used as cross linkers of the first network to further enhance the mechanical properties.

Journal article

Parichart N, Tsigkou O, Li S, Porter A, Jones Jet al., 2019, Human mesenchymal stem cells differentiate into an osteogenic lineage in presence of strontium containing bioactive glass nanoparticles, Acta Biomaterialia, Vol: 90, Pages: 373-392, ISSN: 1742-7061

While bioactive glass and ions released during its dissolution are known to stimulate osteoblast cells, the effect bioactive glass has on human stem cells is not clear. Here, we show that spherical monodispersed strontium containing bioactive nanoparticles (Sr-BGNPs) of composition 90.6 mol% SiO2, 5.0 mol% CaO, 4.4% mol% SrO (4.4%Sr-BGNPs) and 88.8 mol% SiO2, 1.8 mol% CaO, and 9.4 mol% SrO (9.4%Sr-BGNPs) stimulate bone marrow derived human stem cell (hMSC) differentiation down an osteogenic pathway without osteogenic supplements. The particles were synthesised using a modified Stӧber process and had diameters of 90 ± 10 nm. Previous work on similar particles that did not contain Sr (80 mol% SiO2, 20 mol% CaO) showed stem cells did not differentiate when exposed to the particles. Here, both compositions of the Sr-BGNPs (up to concentration of 250 μg/mL) stimulated the early-, mid-, and late-stage markers of osteogenic differentiation and accelerated mineralisation in the absence of osteogenic supplements. Sr ions play a key role in osteogenic stem cell differentiation. Sr-BGNP dissolution products did not adversely affect hMSC viability and no significant differences in viability were measured between each particle composition. Confocal and transmission electron microscopy (TEM) demonstrated that monodispersed Sr- BGNPs were internalised and localised within vesicles in the cytoplasm of hMSCs. Degradation of particles inside the cells was observed, whilst maintaining effective cations (Ca and Sr) in their silica network after 24 h in culture. The uptake of Sr-BGNPs by hMSCs was reduced by inhibitors of specific routes of endocytosis, indicating that the Sr-BGNPs uptake by hMSCs was probably via mixed endocytosis mechanisms. Sr-BGNPs have potential as injectable therapeutic devices for bone regeneration or treatment of conditions such as osteoporosis, because of their ability deliver a sustained release of osteogenic inorganic cations, e.g. calcium (Ca) or a

Journal article

Paxton NC, Ren J, Ainsworth MJ, Solanki AK, Jones JR, Allenby MC, Stevens M, Woodruff MAet al., 2019, Rheological characterization of biomaterials directs additive manufacturing of strontium-substituted bioactive Gglass/polycaprolactone microfibers, Macromolecular Rapid Communications, Vol: 40, Pages: 1-6, ISSN: 1022-1336

Additive manufacturing via melt electrowriting (MEW) can create ordered microfiber scaffolds relevant for bone tissue engineering; however, there remain limitations in the adoption of new printing materials, especially in MEW of biomaterials. For example, while promising composite formulations of polycaprolactone with strontium‐substituted bioactive glass have been processed into large or disordered fibres, from what is known, biologically‐relevant concentrations (>10 wt%) have never been printed into ordered microfibers using MEW. In this study, rheological characterization is used in combination with a predictive mathematical model to optimize biomaterial formulations and MEW conditions required to extrude various PCL and PCL/SrBG biomaterials to create ordered scaffolds. Previously, MEW printing of PCL/SrBG composites with 33 wt% glass required unachievable extrusion pressures. The composite formulation is modified using an evaporable solvent to reduce viscosity 100‐fold to fall within the predicted MEW pressure, temperature, and voltage tolerances, which enabled printing. This study reports the first fabrication of reproducible, ordered high‐content bioactive glass microfiber scaffolds by applying predictive modeling.

Journal article

Riveiro A, Quintero F, Del Val J, Pires RA, Comesaña R, Lusquiños F, Jones JR, Reis RL, Pou Jet al., 2019, Laser spinning of 13-93 bioactive glass nanofibers, Pages: 946-951

Over the past decades, bioactive glasses have been extensively studied for bone regeneration applications due to their ability to bond to living tissues and osteogenesis properties through the controlled release of biologically active ions. Bioactive glasses are mainly used in bone and dental repair products in form of granules or a putty, if mixed with a binder; however, their potential application could be increased if bioactive glasses were transformed into meshes of micro- and nanofibers. Meshes of nanosized fibers have potential application as a 3D macroporous scaffold, can be used for nanocomposites, or in wound care as a bioactive dressing. In this work, we report the production of 13-93 bioactive glass micro- and nanofibers using laser spinning technique. The degradation rates and release rate of active ions were determined. The excellent bioactivity of the nanofiber is confirmed in vitro after tested in simulated body fluid due to the rapid induction of bonelike minerals onto the surface of the fibers. Based on this study, these meshes of 13-93 bioactive glass are regarded as a promising next-generation biomaterial for bone regeneration applications.

Conference paper

El Ghamrawy A, de Comtes F, Koruk H, Mohammed A, Jones JR, Choi JJet al., 2019, Acoustic streaming in a soft tissue microenvironment, Ultrasound in Medicine and Biology, Vol: 45, Pages: 208-217, ISSN: 0301-5629

We demonstrated that sound can push fluid through a tissue-mimicking material. Although acoustic streaming in tissue has been proposed as a mechanism for biomedical ultrasound applications, such as neuromodulation and enhanced drug penetration, streaming in tissue or acoustic phantoms has not been directly observed. We developed a material that mimics the porous structure of tissue and used a dye and a video camera to track fluid movement. When applied above an acoustic intensity threshold, a continuous focused ultrasound beam (spatial peak time average intensity: 238 W/cm2, centre frequency: 5 MHz) was found to push the dye axially, that is, in the direction of wave propagation and in the radial direction. Dye clearance increased with ultrasound intensity and was modelled using an adapted version of Eckart's acoustic streaming velocity equation. No microstructural changes were observed in the sonicated region when assessed using scanning electron microscopy. Our study indicates that acoustic streaming can occur in soft porous materials and provides a mechanistic basis for future use of streaming for therapeutic or diagnostic purposes.

Journal article

Labbaf S, Houreh AB, Rahimi M, Ting HK, Jones JR, Nasr-Esfahani MHet al., 2018, Bioactive glass-polycaprolactone fiber membrane and response of dental pulp stem cells in vitro, Biomedical Glasses, Vol: 4, Pages: 123-130, ISSN: 2299-3932

The study reports the fabrication and in vitro biological evaluation of a sol-gel derived bioactive glass (BG) / polycaprolactone (PCL) composite fiber membrane, as a potential candidate for bone regeneration applications. The non woven composite mats were prepared by introducing the glass particles into the electrospinning process. Adding the glass improved the homogeneity of the fibers. The apatite forming ability of the membranes in simulated body fluid were evaluated and showed that hydroxyapatite had formed within 21 days in SBF and completely covered the surface of the membrane. In cell culture, dental pulp stem cells adhered proliferated and produced mineralized matrix on the PCL/BG fiber membrane.

Journal article

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