Imperial College London

ProfessorJulianJones

Faculty of EngineeringDepartment of Materials

Professor of Biomaterials
 
 
 
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Contact

 

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

 
 
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Location

 

207GoldsmithSouth Kensington Campus

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Summary

 

Publications

Publication Type
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267 results found

Barrak FN, Li S, Mohammed AA, Myant C, Jones JRet al., 2022, Anti-inflammatory properties of S53P4 bioactive glass implant material., Journal of Dentistry, Vol: 127, ISSN: 0300-5712

OBJECTIVES: To assess whether the dissolution products of S53P4 bioactive glass (BG) affect cellular response of macrophages and clinically relevant peri-implant cell populations to dental implant particles in vitro. Cells chosen were human gingival fibroblasts (HGFs), osteoblasts and bone marrow derived stromal cells (HBMSCs). METHODS: Melt-derived S53P4 bioactive glass were prepared. HGFs, Saos-2 human osteoblastic cell line, HBMSCs and macrophages, derived from THP-1 human monocytic cell line, were cultured in the presence of particles from commercially pure titanium (Ti-CP4), grade 5 titanium alloy (Ti-6Al-4V), titanium-zirconium alloy (Ti-15Zr) or zirconia (Zr) (with respective diameters of 34.1 ± 3.8, 33.3 ± 4.4, 97.8 ± 8.2 and 71.3 ± 6.1 µm) with or without S53P4 dissolution products (conditioned media contained 327.30 ± 2.01 ppm Ca, 51.34 ± 0.41 ppm P and 61.48 ± 1.17 ppm Si, pH 8.01 ± 0.21). Inflammatory and macrophage polarisation markers including TNF-ɑ, IL-1, IL-6 and CD206 were quantified using enzyme-linked immunosorbent assay (ELISA). RESULTS: The presence of Ti-6Al-4V implant particles significantly induced the expression of pro-inflammatory markers in all tested cell types. S53P4 BG dissolution products regressed the particle induced up-regulation of pro-inflammatory markers and, appeared to suppress M1 macrophage polarisation. CONCLUSIONS: Implant particles, Ti-6Al-4V in particular, resulted in significant inflammatory responses from cells. S53P4 BG may possess anti-inflammatory properties and potentially mediate macrophage polarisation behaviour. CLINICAL SIGNIFICANCE: The findings highlight that the use and benefits of BG is a promising field of study. Authors believe more collective efforts are required to fully understand the reliability, efficiency and exact mechanisms of action of BG in the search for new generation of treatme

Journal article

Ganeshaaraj G, Kaushalya S, Kondarage AI, Karunaratne A, Jones JR, Nanayakkara NDet al., 2022, Semantic segmentation of micro-CT images to analyze bone ingrowth into biodegradable scaffolds., 44th Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), Publisher: IEEE, Pages: 3830-3833, ISSN: 1557-170X

The healing of bone fractures is a complex and well-orchestrated physiological process, but normal healing is compromised when the fracture is large. These large non-union fractures often require a template with surgical intervention for healing. The standard treatment, autografting, has drawbacks such as donor site pain and limited availability. Biodegradable scaffolds developed using biomaterials such as bioactive glass are a potential solution. Investigation of bone ingrowth into biodegradable scaffolds is an important aspect of their development. Micro-CT (μ-CT) imaging is widely used to evaluate and quantify tissue ingrowth into scaffolds in 3D. Existing segmentation techniques have low accuracy in differentiating bone and scaffold, and need improvements to accurately quantify the bone in-growth into the scaffold using μ-CT scans. This study proposes a novel 3-stage pipeline for better outcome. The first stage of the pipeline is based on a convolutional neural network for the segmentation of the scaffold, bone, and pores from μ-CT images to investigate bone ingrowth. A 3D rigid image registration procedure was employed in the next stage to extract the volume of interest (VOI) for the analysis. In the final stage, algorithms were developed to quantitatively analyze bone ingrowth and scaffold degradation. The best model for segmentation produced a dice similarity coefficient score of 90.1, intersection over union score of 83.9, and pixel accuracy of 93.1 for unseen test data.

Conference paper

Ren Y, Autefage H, Jones JR, Stevens MM, Bagot PAJ, Moody MPet al., 2022, Developing atom probe tomography to characterize Sr-loaded bioactive glass for bone scaffolding, Microscopy and Microanalysis, Vol: 28, Pages: 1310-1320, ISSN: 1431-9276

In this study, atom probe tomography (APT) was used to investigate strontium-containing bioactive glass particles (BG-Sr10) and strontium-releasing bioactive glass-based scaffolds (pSrBG), both of which are attractive biomaterials with applications in critical bone damage repair. We outline the challenges and corresponding countermeasures of this nonconductive biomaterial for APT sample preparation and experiments, such as avoiding direct contact between focussed ion beam micromanipulators and the extracted cantilever to reduce damage during liftout. Using a low imaging voltage (≤3 kV) and current (≤500 pA) in the scanning electron microscope and a low acceleration voltage (≤2 kV) and current (≤200 pA) in the focussed ion beam prevents tip bending in the final stages of annular milling. To optimize the atom probe experiment, we considered five factors: total detected hits, multiple hits, the background level, the charge-state ratio, and the accuracy of the measured compositions, to explore the optimal laser pulse for BG-Sr10 bioactive glass. We show that a stage temperature of 30 K, 200–250 pJ laser pulse energy, 0.3% detection rate, and 200 kHz pulse rate are optimized experimental parameters for bioactive glass. The use of improved experimental preparation methods and optimized parameters resulted in a 90% successful yield of pSrBG samples by APT.

Journal article

Skandalis A, Selianitis D, Sory DR, Rankin SM, Jones JR, Pispas Set al., 2022, Poly(2-(dimethylamino) ethyl methacrylate)-b-poly(lauryl methacrylate)-b-poly(oligo ethylene glycol methacrylate) triblock terpolymer micelles as drug delivery carriers for curcumin, JOURNAL OF APPLIED POLYMER SCIENCE, Vol: 139, ISSN: 0021-8995

Journal article

Tallia F, Ting HK, Page S, Clark J, Li S, Sang T, Russo L, Stevens M, Hanna JV, Jones Jet al., 2022, Bioactive, degradable and tough hybrids through calcium and phosphate incorporation, Frontiers in Materials, Vol: 9, ISSN: 2296-8016

We report the first inorganic/organic hybrids that show outstanding mechanical properties (withstanding cyclic loading) and bone bioactivity. This new hybrid material may fulfil the unmet clinical need for bioactive synthetic bone grafts that can withstand cyclic loading. A SiO2/PTHF/PCL-diCOOH sol-gel hybrid system, that combined inorganic and organic co-networks at the molecular level, previously demonstrated unprecedented synergy of properties, with excellent flexibility and promoted formation of articular cartilage matrix in vitro. Here, for the first time, calcium and phosphate ions were incorporated into the inorganic component of the hybrid network, to impart osteogenic properties. Calcium methoxyethoxide and triethyl phosphate were the calcium and phosphate precursors because they allow for incorporation into the silicate network at low temperature. The hybrid network was characterised with ATR-FTIR, XRD and solid-state NMR,which proved calcium and phosphate incorporation and suggested the Ca2+ ions also interacted with PCL-diCOOH through ionic bonds. This resulted in an increased strength (17-64 MPa) and modulus of toughness (2.5-14 MPa) compared to the original SiO2/PTHF/PCL-diCOOH hybrid material (which showed strength of ̃3 MPa and modulus of toughness of ̃0.35 MPa), while also maintaining the ability to withstand cyclic loading. The presence of calcium and phosphates in the silicate network resulted in a more congruent dissolution of the inorganic and organic co-networks in TRIS buffer. This was shown by the presence of silicon, calcium and phosphate ions along with PCL in the TRIS buffer after 1 week, whereas Ca-free hybrids mainly released PCL with negligible Si dissolution. The presence of calcium and phosphates also enabled deposition of hydroxycarbonate apatite following immersion in simulated body fluid, which was not seen on Ca-free hybrid. All hybrids passed cell cytotoxicity tests and supported pre-osteoblast cell attachment. The phosphate-fr

Journal article

Barrak F, Li S, Muntane A, Bhatia M, Crossthwaite K, Jones Jet al., 2022, Particle release from dental implants immediately after placement - An ex vivo comparison of different implant systems, Dental Materials, Vol: 38, Pages: 1004-1014, ISSN: 0109-5641

ObjectivesMetallic element release during implant placement can lead to mucositis and peri-implantitis. Here, using ex vivo porcine mandibles, the release of metallic elements into the surrounding bone with different material and geometrical designs was quantified.MethodsImplants from BioHorizons® and Straumann® (Bone level, tapered/cylindrical, 3/4 mm body diameter, Ti-CP4/Ti-6Al-4V/Ti-15Zr) systems were used. Micro computed tomography and inductively coupled plasma optical emission spectroscopy was used to visualise and quantify metallic elements in bone, following acid digestion. Implant surfaces were examined with scanning electron microscopy and internalization of implant particles by human gingival fibroblasts (HGFs) and RAW 264.7 macrophages were demonstrated in vitro.ResultsImplants with wider body diameters resulted in higher metallic element release. Ti-6Al-4V implants released significantly more metallic elements in comparison to both Ti-CP4 and Ti-15Zr devices with similar design and dimensions. Tapered Ti-CP4 implants released less compared to those with cylindrical design. Al three types of particles were internalized by HGFs and RAW 264.7.SignificanceTi-CP4 and Ti-15Zr appear to be more suitable materials, however, further studies are required to elucidate the biological effects of the fine particles and/or metallic species from dental implants. Authors would like to raise the awareness in the dental profession community that careful evaluation of the materials used in dental implants and the potential risks of the individual constituents of any alloy are needed. The potential cytotoxicity of Ti-6Al-4V implant particles should be highlighted. Further investigations on the biological effect of the fine particles or metallic species released from dental implants are also needed.

Journal article

Thanasrisuebwong P, Jones JR, Eiamboonsert S, Ruangsawasdi N, Jirajariyavej B, Naruphontjirakul Pet al., 2022, Zinc-containing sol-gel glass nanoparticles to deliver therapeutic ions, Nanomaterials, Vol: 12, Pages: 1-25, ISSN: 2079-4991

Zn-containing dense monodispersed bioactive glass nanoparticles (Zn-BAGNPs) have been developed to deliver therapeutic inorganic trace elements, including Si, Ca, Sr, and Zn, to the cells through the degradation process, as delivery carriers for stimulating bone regeneration because of their capacity to induce osteogenic differentiation. The sol–gel-derived dense silica nanoparticles (SiO2-NPs) were first synthesized using the modified Stöber method, prior to incorporating therapeutic cations through the heat treatment process. The successfully synthesized monodispersed Zn-BAGNPs (diameter of 130 ± 20 nm) were homogeneous in size with spherical morphology. Ca, Sr and Zn were incorporated through the two-step post-functionalization process, with the nominal ZnO ratio between 0 and 2 (0, 0.5, 1.0, 1.5 and 2.0). Zn-BAGNPs have the capacity for continuous degradation and simultaneous ion release in SBF and PBS solutions due to their amorphous structure. Zn-BAGNPs have no in vitro cytotoxicity on the murine pre-osteoblast cell (MC3T3-E1) and periodontal ligament stem cells (PDLSCs), up to a concentration of 250 µg/mL. Zn-BAGNPs also stimulated osteogenic differentiation on PDLSCs treated with particles, after 2 and 3 weeks in culture. Zn-BAGNPs were not toxic to the cells and have the potential to stimulate osteogenic differentiation on PDLSCs. Therefore, Zn-BAGNPs are potential vehicles for therapeutic cation delivery for applications in bone and dental regenerations.

Journal article

Kondarage A, Poologasundarampillai G, Nommeots-Nomm A, Lee PD, Lalitharatne TD, Nanayakkara ND, Jones JR, Karunaratne Aet al., 2022, In situ 4D tomography image analysis framework to follow sintering within 3D-printed glass scaffolds, Journal of the American Ceramic Society, Vol: 105, Pages: 1671-1684, ISSN: 0002-7820

We propose a novel image analysis framework to automate analysis of X-ray microtomography images of sintering ceramics and glasses, using open-source toolkits and machine learning. Additive manufacturing (AM) of glasses and ceramics usually requires sintering of green bodies. Sintering causes shrinkage, which presents a challenge for controlling the metrology of the final architecture. Therefore, being able to monitor sintering in 3D over time (termed 4D) is important when developing new porous ceramics or glasses. Synchrotron X-ray tomographic imaging allows in situ, real-time capture of the sintering process at both micro and macro scales using a furnace rig, facilitating 4D quantitative analysis of the process. The proposed image analysis framework is capable of tracking and quantifying the densification of glass or ceramic particles within multiple volumes of interest (VOIs) along with structural changes over time using 4D image data. The framework is demonstrated by 4D quantitative analysis of bioactive glass ICIE16 within a 3D-printed scaffold. Here, densification of glass particles within 3 VOIs were tracked and quantified along with diameter change of struts and interstrut pore size over the 3D image series, delivering new insights on the sintering mechanism of ICIE16 bioactive glass particles in both micro and macro scales.

Journal article

Barrioni BR, de Carvalho SM, Naruphontjirakul P, Norris E, Kelly NL, Hanna JV, Jones JR, Pereira MDMet al., 2022, Cobalt-containing spherical glass nanoparticles for therapeutic ion release, Journal of the American Ceramic Society, Vol: 105, Pages: 1765-1777, 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

Naruphontjirakul P, Li S, Pinna A, Barrak F, Chen S, Redpath AN, Rankin SM, Porter AE, Jones JRet al., 2022, Interaction of monodispersed strontium containing bioactive glass nanoparticles with macrophages, Biomaterials Advances, Vol: 133, Pages: 1-12, ISSN: 2772-9508

The cellular response of murine primary macrophages to monodisperse strontium containing bioactive glass nanoparticles (SrBGNPs), with diameters of 90 ± 10 nm and a composition (mol%) of 88.8 SiO2–1.8CaO-9.4SrO (9.4% Sr-BGNPs) was investigated for the first time. Macrophage response is critical as applications of bioactive nanoparticles will involve the nanoparticles circulating in the blood stream and macrophages will be the first cells to encounter the particles, as part of inflammatory response mechanisms. Macrophage viability and total DNA measurements were not decreased by particle concentrations of up to 250 μg/mL. The Sr-BGNPs were actively internalised by the macrophages via formation of endosome/lysosome-like vesicles bordered by a membrane inside the cells. The Sr-BGNPs degraded inside the cells, with the Ca and Sr maintained inside the silica network. When RAW264.7 cells were incubated with Sr-BGNPs, the cells were polarised towards the pro-regenerative M2 population rather than the pro-inflammatory M1 population. Sr-BGNPs are potential biocompatible vehicles for therapeutic cation delivery for applications in bone regeneration.

Journal article

Mohammed AA, Merrild NG, Li S, Pinna A, Jones JRet al., 2022, Double-Network Hydrogels Reinforced with Covalently Bonded Silica Nanoparticles via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemistry, ACS Omega

Hydrogels have progressed from single-network materials with low mechanical integrity to double-network hydrogels (DNHGs) with tough, tunable properties. In this work, we introduce a nanocomposite structure into the first network of a DNHG. Amine-functionalized silica nanoparticles (ASNPs) were covalently cross-linked by forming amide bonds through the carboxylic groups of polyacrylic acid (PAAc) in the first network. DNHGs with varying sizes of ASNPs (50, 100, and 150 nm) and varying concentrations (2.5, 10, 20, and 40 wt %) were explored and compared to a control without a nanocomposite structure. Compressive strengths improved from 0.10 MPa for the control to a maximum of 1.28 MPa for the PAAc/PAAm DNHGs. All hydrogels experienced increased resistance to strain with a maximum of 74% compared to 45% for the control. SEM images of freeze-dried gels showed that ASNPs were integrated into the gel mesh. Nanoparticle retention was calculated using thermal gravimetric analysis (TGA) with improved retention values for larger ASNPs. New DNHG composites have been formed with improved mechanical properties and a potential use in tissue engineering and biomaterial applications.

Journal article

Lee Y, Lester D, Jones J, Georgiou Tet al., 2021, Effect of polymer molecular mass and structure on the mechanical properties of polymer-glass hybrids, ACS Omega, Vol: 7, Pages: 786-792, ISSN: 2470-1343

Organic–inorganic hybrid materials are a promising class of materials for tissue engineering and other biomedical applications. In this systematic study, the effect of the polymer molecular mass (MM) with a linear architecture on hybrid mechanical properties is reported. Well-defined linear poly(methyl methacrylate-co-(3-(trimethoxysilyl)propyl methacrylate)) polymers with a range of MMs of 9 to 90 kDa and one 90 kDa star-shaped polymer were synthesized and then used to form glass–polymer hybrids. It was demonstrated that increasing linear polymer MM decreases the resultant hybrid mechanical strength. Furthermore, a star-polymer hybrid was synthesized as a comparison and demonstrated significantly different mechanical properties relative to its linear-polymer counterpart.

Journal article

Narayan R, Basu B, Goel A, Jones J, Jung Set al., 2021, Next generation bioceramics, JOURNAL OF THE AMERICAN CERAMIC SOCIETY, ISSN: 0002-7820

Journal article

Ju Q, Zenji T, Maçon ALB, Norris E, Poologasundarampillai G, Obata A, Jones JR, Kasuga Tet al., 2021, Silver-doped calcium silicate sol-gel glasses with a cotton-wool-like structure for wound healing, Materials Science and Engineering: C, Vol: 134, Pages: 112561-112561, ISSN: 0928-4931

Skin has excellent capacity to regenerate, however, in the event of a large injury or burn skin grafts are required to aid wound healing. The regenerative capacity further declines with increasing age and can be further exacerbated with bacterial infection leading to a chronic wound. Engineered skin substitutes can be used to provide a temporary template for the damaged tissue, to prevent/combat bacterial infection and promote healing. In this study, the sol-gel process and electrospinning were combined to fabricate 3D cotton-wool-like sol-gel bioactive glass fibers that mimic the fibrous architecture of skin extracellular matrix (ECM) and deliver metal ions for antibacterial (silver) and therapeutic (calcium and silica species) actions for successful healing of wounds. This study investigated the effects of synthesis and process parameters, in particular sintering temperature on the fiber morphology, the incorporation and distribution of silver and the degradation rate of fibers. Silver nitrate was found to decompose into silver nanoparticles within the glass fibers upon calcination. Furthermore, with increasing calcination temperature the nanoparticles increased in size from 3 nm at 600 °C to ~25 nm at 800 °C. The antibacterial ability of the Ag-doped glass fibers decreased as a function of the glass calcination temperature. The degradation products from the Ag-doped 3D non-woven sol-gel glass fibers were also found to promote fibroblast proliferation thus demonstrating their potential for use in skin regeneration.

Journal article

Kondarage AI, Gayani B, Poologasundarampillai G, Nommeots-Nomm A, Lee PD, Lalitharatne TD, Nanayakkara ND, Jones JR, Karunaratne Aet al., 2021, Detection and tracking volumes of interest in 3D printed tissue engineering scaffolds using 4D imaging modalities., 43rd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), Pages: 1230-1233, ISSN: 1557-170X

Additive manufacturing (AM) platforms allow the production of patient tissue engineering scaffolds with desirable architectures. Although AM platforms offer exceptional control on architecture, post-processing methods such as sintering and freeze-drying often deform the printed scaffold structure. In-situ 4D imaging can be used to analyze changes that occur during post-processing. Visualization and analysis of changes in selected volumes of interests (VOIs) over time are essential to understand the underlining mechanisms of scaffold deformations. Yet, automated detection and tracking of VOIs in the 3D printed scaffold over time using 4D image data is currently an unsolved image processing task. This paper proposes a new image processing technique to segment, detect and track volumes of interest in 3D printed tissue engineering scaffolds. The method is validated using a 4D synchrotron sourced microCT image data captured during the sintering of bioactive glass scaffolds in-situ. The proposed method will contribute to the development of scaffolds with controllable designs and optimum properties for the development of patient-specific scaffolds.

Conference paper

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

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

Osteoporosis, a chronic metabolic bone disease, is the most common cause of fractures. Drugs for treating osteoporosis generally inhibit osteoclast (OC) activity, but are rarely aimed at encouraging new bone growth and often cause severe systemic side effects. Reactive oxygen species (ROS) are one of the key triggers of osteoporosis, by inducing osteoblast (OB) and osteocyte apoptosis and promoting osteoclastogenesis. Here we tested the capability of the ROS-scavenger nanoceria encapsulated within mesoporous silica nanoparticles (Ce@MSNs) to treat osteoporosis using a pre-osteoblast MC3T3-E1 cell monoculture in stressed and normal conditions. Ce@MSNs (diameter of 80 ± 10 nm) were synthesised following a scalable two-step process involving sol-gel and wet impregnation methods. The Ce@MSNs at concentration of 100 μg mL−1 induced a significant reduction in oxidative stress produced by t-butyl hydroperoxide and did not alter cell viability significantly. Confocal microscopy showed that MSNs and Ce@MsNs were internalised into the cytoplasm of the pre-osteoblasts after 24 h but were not in the nucleus, avoiding any DNA and RNA modifications. Ce@MSNs provoked mineralisation of the pre-osteoablasts without osteogenic supplements, which did not occur when the cells were exposed to MSN without nanoceria. In a co-culture system of MC3T3-E1 and RAW264.7 macrophages, the Ce@MSNs exhibited antioxidant capability and stimulated cell proliferation and osteogenic responses without adding osteogenic supplements to the culture. The work brings forward an effective platform based for facile synthesis of Ce@MSNs to interact with both OBs and OCs for treatment of osteoporosis.

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

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