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  1. Alhalawani AM, Towler MR
    J Biomater Appl, 2013 Nov;28(4):483-97.
    PMID: 23812580 DOI: 10.1177/0885328213495426
    Sternotomy and sternal closure occur prior to and post cardiac surgery, respectively. Although post-operative complications associated with poor sternal fixation can result in morbidity, mortality, and considerable resource utilization, sternotomy is preferred over other methods such as lateral thoracotomy. Rigid sternal fixation is associated with stability and reduced incidence of post-operative complications. This is a comprehensive review of the literature evaluating in vivo, in vitro, and clinical responses to applying commercial and experimental surgical tools for sternal fixation after median sternotomy. Wiring, interlocking, plate-screw, and cementation techniques have been examined for closure, but none have experienced widespread adoption. Although all techniques have their advantages, serious post-operative complications were associated with the use of wiring and/or plating techniques in high-risk patients. A fraction of studies have analyzed the use of sternal interlocking systems and only a single study analyzed the effect of using kryptonite cement with wires. Plating and interlocking techniques are superior to wiring in terms of stability and reduced rate of post-operative complications; however, further clinical studies and long-term follow-up are required. The ideal sternal closure should ensure stability, reduced rate of post-operative complications, and a short hospitalization period, alongside cost-effectiveness.
  2. Curran DJ, Rubin L, Towler MR
    PMID: 26327784 DOI: 10.4137/CMAMD.S29061
    An off-the-shelf Raman Spectrometer (RS) was used to noninvasively determine the presence of monosodium urate (MSU) crystals on the metatarsophalangeal joint (MTPJ) of a single gout sufferer. The spectrum sourced from the clinically diagnosed gout sufferer was compared to that sourced from an age-matched healthy subject scanned using the same protocol. Minimal signal processing was conducted on both spectra. Peaks characteristic of MSU crystals were evident on the spectrum sourced from the gout sufferer and not on the spectrum from the healthy control.

    Study done in Canada
  3. Pourshahrestani S, Zeimaran E, Djordjevic I, Kadri NA, Towler MR
    Mater Sci Eng C Mater Biol Appl, 2016 Jan 1;58:1255-68.
    PMID: 26478429 DOI: 10.1016/j.msec.2015.09.008
    Hemorrhage is the most common cause of death both in hospitals and on the battlefield. The need for an effective hemostatic agent remains, since all injuries are not amenable to tourniquet use. There are many topical hemostatic agents and dressings available to control severe bleeding. This article reviews the most commonly used inorganic hemostats, subcategorized as zeolite and clay-based hemostats. Their hemostatic functions as well as their structural properties that are believed to induce hemostasis are discussed. The most important findings from in vitro and in vivo experiments are also covered.
  4. Rahimnejad Yazdi A, Torkan L, Stone W, Towler MR
    PMID: 28152268 DOI: 10.1002/jbm.b.33856
    Zinc borate glasses with increasing gallium content (0, 2.5, 5, 10, and 15 Wt % Ga) were synthesized and their degradation, bioactivity in simulated body fluid (SBF), and antibacterial properties were investigated. ICP measurements showed that increased gallium content in the glass resulted in increased gallium ion release and decreased release of other ions. Degradability declined with the addition of gallium, indicating the formation of more symmetric BO3 units with three bridging oxygens and asymmetric BO3 units with two bridging oxygens in the glass network as the gallium content in the series increased. The formation of amorphous CaP on the glass surface after 24 h of incubation in SBF was confirmed by SEM, XRD, and FTIR analyses. Finally, antibacterial evaluation of the glasses using the agar disc-diffusion method demonstrated that the addition of gallium increased the antibacterial potency of the glasses against P. aeruginosa (Gram-negative) while decreasing it against S. epidermidis (Gram-positive); considering the ion release trends, this indicates that the gallium ion is responsible for the glasses' antibacterial behavior against P. aeruginosa while the zinc ion controls the antibacterial activity against S. epidermidis. The statistical significance of the observed trends in the measurements were confirmed by applying the Kruskal-Wallis H Test. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 367-376, 2018.
  5. Matinmanesh A, Li Y, Clarkin O, Zalzal P, Schemitsch EH, Towler MR, et al.
    J Mech Behav Biomed Mater, 2017 11;75:212-221.
    PMID: 28756281 DOI: 10.1016/j.jmbbm.2017.07.030
    Bioactive glasses have been used as coatings for biomedical implants because they can be formulated to promote osseointegration, antibacterial behavior, bone formation, and tissue healing through the incorporation and subsequent release of certain ions. However, shear loading on coated implants has been reported to cause the delamination and loosening of such coatings. This work uses a recently developed fracture mechanics testing methodology to quantify the critical strain energy release rate under nearly pure mode II conditions, GIIC, of a series of borate-based glass coating/Ti6Al4V alloy substrate systems. Incorporating increasing amounts of SrCO3in the glass composition was found to increase the GIICalmost twofold, from 25.3 to 46.9J/m2. The magnitude and distribution of residual stresses in the coating were quantified, and it was found that the residual stresses in all cases distributed uniformly over the cross section of the coating. The crack was driven towards, but not into, the glass/Ti6Al4V substrate interface due to the shear loading. This implied that the interface had a higher fracture toughness than the coating itself.
  6. Pourshahrestani S, Kadri NA, Zeimaran E, Towler MR
    Biomater Sci, 2018 Dec 18;7(1):31-50.
    PMID: 30374499 DOI: 10.1039/c8bm01041b
    Immediate control of uncontrolled bleeding and infection are essential for saving lives in both combat and civilian arenas. Inorganic well-ordered mesoporous silica and bioactive glasses have recently shown great promise for accelerating hemostasis and infection control. However, to date, there has been no comprehensive report assessing their specific mechanism of action in accelerating the hemostasis process and exerting an antibacterial effect. After providing a brief overview of the hemostasis process, this review presents a critical overview of the recently developed inorganic mesoporous silica and bioactive glass-based materials proposed for hemostatic clinical applications and specifically investigates their unique characteristics that render them applicable for hemostatic applications and preventing infections. This article also identifies promising new research directions that should be undertaken to ascertain the effectiveness of these materials for hemostatic applications.
  7. Matinmanesh A, Li Y, Nouhi A, Zalzal P, Schemitsch EH, Towler MR, et al.
    J Mech Behav Biomed Mater, 2018 02;78:273-281.
    PMID: 29190533 DOI: 10.1016/j.jmbbm.2017.11.015
    It has been reported that the adhesion of bioactive glass coatings to Ti6Al4V reduces after degradation, however, this effect has not been quantified. This paper uses bilayer double cantilever (DCB) specimens to determine GIC and GIIC, the critical mode I and mode II strain energy release rates, respectively, of bioactive coating/Ti6Al4V substrate systems degraded to different extents. Three borate-based bioactive glass coatings with increasing amounts of incorporated SrO (0, 15 and 25mol%) were enamelled onto Ti6Al4V substrates and then immersed in de-ionized water for 2, 6 and 24h. The weight loss of each glass composition was measured and it was found that the dissolution rate significantly decreased with increasing SrO content. The extent of dissolution was consistent with the hypothesis that the compressive residual stress tends to reduce the dissolution rate of bioactive glasses. After drying, the bilayer DCB specimens were created and subjected to nearly mode I and mode II fracture tests. The toughest coating/substrate system (one composed of the glass containing 25mol% SrO) lost 80% and 85% of its GIC and GIIC, respectively, in less than 24h of degradation. The drop in GIC and GIIC occurred even more rapidly for other coating/substrate systems. Therefore, degradation of borate bioactive glass coatings is inversely related to their fracture toughness when coated onto Ti6A4V substrates. Finally, roughening the substrate was found to be inconsequential in increasing the toughness of the system as the fracture toughness was limited by the cohesive toughness of the glass itself.
  8. Wren AW, Hassanzadeh P, Placek LM, Keenan TJ, Coughlan A, Boutelle LR, et al.
    Macromol Biosci, 2015 Aug;15(8):1146-58.
    PMID: 25923463 DOI: 10.1002/mabi.201500109
    Silver (Ag) coated bioactive glass particles (Ag-BG) were formulated and compared to uncoated controls (BG) in relation to glass characterization, solubility and microbiology. X-ray diffraction (XRD) confirmed a crystalline AgNP surface coating while ion release studies determined low Ag release (<2 mg/L). Cell culture studies presented increased cell viability (127 and 102%) with lower liquid extract (50 and 100 ml/ml) concentrations. Antibacterial testing of Ag-BG in E. coli, S. epidermidis and S. aureus significantly reduced bacterial cell viability by 60-90%. Composites of Ag-BG/CMC-Dex Hydrogels were formulated and characterized. Agar diffusion testing was conducted where Ag-BG/hydrogel composites produced the largest inhibition zones of 7 mm (E. coli), 5 mm (S. aureus) and 4 mm (S. epidermidis).
  9. Zeimaran E, Pourshahrestani S, Djordjevic I, Pingguan-Murphy B, Kadri NA, Towler MR
    Mater Sci Eng C Mater Biol Appl, 2015 Aug;53:175-88.
    PMID: 26042705 DOI: 10.1016/j.msec.2015.04.035
    Biodegradable elastomers have clinical applicability due to their biocompatibility, tunable degradation and elasticity. The addition of bioactive glasses to these elastomers can impart mechanical properties sufficient for hard tissue replacement. Hence, a composite with a biodegradable polymer matrix and a bioglass filler can offer a method of augmenting existing tissue. This article reviews the applications of such composites for skeletal augmentation.
  10. Zeimaran E, Pourshahrestani S, Djordjevic I, Pingguan-Murphy B, Kadri NA, Wren AW, et al.
    J Mater Sci Mater Med, 2016 Jan;27(1):18.
    PMID: 26676864 DOI: 10.1007/s10856-015-5620-2
    Bioactive glasses may function as antimicrobial delivery systems through the incorporation and subsequent release of therapeutic ions. The aim of this study was to evaluate the antimicrobial properties of a series of composite scaffolds composed of poly(octanediol citrate) with increased loads of a bioactive glass that releases zinc (Zn(2+)) and gallium (Ga(3+)) ions in a controlled manner. The antibacterial activity of these scaffolds was investigated against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The ability of the scaffolds to release ions and the subsequent ingress of these ions into hard tissue was evaluated using a bovine bone model. Scaffolds containing bioactive glass exhibited antibacterial activity and this increased in vitro with higher bioactive glass loads; viable cells decreased to about 20 % for the composite scaffold containing 30 % bioactive glass. The Ga(3+) release rate increased as a function of time and Zn(2+) was shown to incorporate into the surrounding bone.
  11. Abhishek A, Curran DJ, Bilwani F, Jones AC, Towler MR, Doherty M
    Rheumatology (Oxford), 2016 Feb;55(2):379-80.
    PMID: 26342227 DOI: 10.1093/rheumatology/kev339
    Study done in England
  12. Yatongchai C, Placek LM, Curran DJ, Towler MR, Wren AW
    J Biomater Appl, 2015 Nov;30(5):495-511.
    PMID: 26116020 DOI: 10.1177/0885328215592866
    Hydroxyapatite (Ca10(PO4)6(OH)2) is widely investigated as an implantable material for hard tissue restoration due to its osteoconductive properties. However, hydroxyapatite in bulk form is limited as its mechanical properties are insufficient for load-bearing orthopedic applications. Attempts have been made to improve the mechanical properties of hydroxyapatite, by incorporating ceramic fillers, but the resultant composite materials require high sintering temperatures to facilitate densification, leading to the decomposition of hydroxyapatite into tricalcium phosphate, tetra-calcium phosphate and CaO phases. One method of improving the properties of hydroxyapatite is to incorporate bioactive glass particles as a second phase. These typically have lower softening points which could possibly facilitate sintering at lower temperatures. In this work, a bioactive glass (SiO2-CaO-ZnO-Na2O-TiO2) is incorporated (10, 20 and 30 wt%) into hydroxyapatite as a reinforcing phase. X-ray diffraction confirmed that no additional phases (other than hydroxyapatite) were formed at a sintering temperature of 560 ℃ with up to 30 wt% glass addition. The addition of the glass phase increased the % crystallinity and the relative density of the composites. The biaxial flexural strength increased to 36 MPa with glass addition, and there was no significant change in hardness as a function of maturation. The pH of the incubation media increased to pH 10 or 11 through glass addition, and ion release profiles determined that Si, Na and P were released from the composites. Calcium phosphate precipitation was encouraged in simulated body fluid with the incorporation of the bioactive glass phase, and cell culture testing in MC-3T3 osteoblasts determined that the composite materials did not significantly reduce cell viability.
  13. Alhalawani AM, Curran DJ, Pingguan-Murphy B, Boyd D, Towler MR
    J Funct Biomater, 2013;4(4):329-57.
    PMID: 24956193 DOI: 10.3390/jfb4040329
    This study investigates the use of gallium (Ga) based glass polyalkenoate cements (GPCs) as a possible alternative adhesive in sternal fixation, post sternotomy surgery. The glass series consists of a Control (CaO-ZnO-SiO2), and LGa-1 and LGa-2 which contain Ga at the expense of zinc (Zn) in 0.08 mol% increments. The additions of Ga resulted in increased working time (75 s to 137 s) and setting time (113 to 254 s). Fourier Transform Infrared (FTIR) analysis indicated that this was a direct result of increased unreacted poly(acrylic acid) (PAA) and the reduction of crosslink formation during cement maturation. LGa samples (0.16 wt % Ga) resulted in an altered ion release profile, particularly for 30 days analysis, with maximum Ca2+, Zn2+, Si4+ and Ga3+ ions released into the distilled water. The additions of Ga resulted in increased roughness and decreased contact angles during cement maturation. The presence of Ga has a positive effect on the compressive strength of the samples with strengths increasing over 10 MPa at 7 days analysis compared to the 1 day results. The additions of Ga had relatively no effect on the flexural strength. Tensile testing of bovine sterna proved that the LGa samples (0.16 wt % Ga) are comparable to the Control samples.
  14. Rodriguez O, Stone W, Schemitsch EH, Zalzal P, Waldman S, Papini M, et al.
    Heliyon, 2017 Oct;3(10):e00420.
    PMID: 29034340 DOI: 10.1016/j.heliyon.2017.e00420
    In an attempt to combat the possibility of bacterial infection and insufficient bone growth around metallic, surgical implants, bioactive glasses may be employed as coatings. In this work, silica-based and borate-based glass series were synthesized for this purpose and subsequently characterized in terms of antibacterial behavior, solubility and cytotoxicity. Borate-based glasses were found to exhibit significantly superior antibacterial properties and increased solubility compared to their silica-based counterparts, with BRT0 and BRT3 (borate-based glasses with 0 and 15 mol% of titanium dioxide incorporated, respectively) outperforming the remainder of the glasses, both borate and silicate based, in these respects. Atomic Absorption Spectroscopy confirmed the release of zinc ions (Zn(2+)), which has been linked to the antibacterial abilities of glasses SRT0, BRT0 and BRT3, with inhibition effectively achieved at concentrations lower than 0.7 ppm. In vitro cytotoxicity studies using MC3T3-E1 osteoblasts confirmed that cell proliferation was affected by all glasses in this study, with decreased proliferation attributed to a faster release of sodium ions over calcium ions in both glass series, factor known to slow cell proliferation in vitro.
  15. Pourshahrestani S, Zeimaran E, Adib Kadri N, Gargiulo N, Samuel S, Naveen SV, et al.
    J Mater Chem B, 2016 Jan 07;4(1):71-86.
    PMID: 32262810 DOI: 10.1039/c5tb02062j
    Haemorrhage remains the leading cause of potentially survivable death in both military and civilian populations. Although a large variety of hemostatic agents have been developed, many of them have an inadequate capacity to induce hemostasis and are not effective in killing bacteria. In recent years, mesoporous bioactive glasses (MBGs) were found to be effective in inducing hemostasis. However, the materials may not be considered as ideal hemostats since they do not offer antimicrobial activity. The gallium ion (Ga+3) not only exhibits antibacterial properties but also accelerates the blood coagulation cascade. The aim of this study was to develop MBGs containing various concentrations of Ga2O3 (1, 2 & 3 mol%) via the evaporation-induced self-assembly (EISA) process and investigate whether the addition of Ga3+ would induce both hemostatic and antibacterial effects. The results indicated that the incorporation of lower Ga2O3 content (1 mol%) into the MBG system improved structural properties including the specific surface area, mesopore size and pore volume as well as the release of silicon and calcium ions. The bioactive glass was found to stimulate blood coagulation, platelet adhesion and thrombus generation and exerted an antibacterial effect against both Escherichia coli and Staphylococcus aureus. Likewise, Ga-doped MBGs showed excellent cytocompatibility even after 3 days, with the 1% Ga2O3-containing MBG attaining the best biocompatibility that render them safe hemostatic agents for stopping bleeding. This study demonstrated that the lowest Ga2O3-substituted MBG can be a potent candidate for controlling haemorrhage and wound infection.
  16. Pourshahrestani S, Zeimaran E, Kadri NA, Gargiulo N, Jindal HM, Naveen SV, et al.
    ACS Appl Mater Interfaces, 2017 Sep 20;9(37):31381-31392.
    PMID: 28836753 DOI: 10.1021/acsami.7b07769
    Chitosan-based hemostats are promising candidates for immediate hemorrhage control. However, they have some disadvantages and require further improvement to achieve the desired hemostatic efficiency. Here, a series of 1% Ga2O3-containing mesoporous bioactive glass-chitosan composite scaffolds (Ga-MBG/CHT) were constructed by the lyophilization process and the effect of various concentrations of Ga-MBG (10, 30, and 50 wt %) on the hemostatic function of the CHT scaffold was assessed as compared to that of Celox Rapid gauze (CXR), a current commercially available chitosan-coated hemostatic gauze. The prepared scaffolds exhibited >79% porosity and showed increased water uptake compared to that in CXR. The results of coagulation studies showed that pure CHT and composite scaffolds exhibited increased hemostatic performance with respect to CXR. Furthermore, the composite scaffold with the highest Ga-MBG content (50 wt %) had increased capability to enhancing thrombus generation, blood clotting, and platelet adhesion and aggregation than that of the scaffold made of pure CHT. The antibacterial efficacy and biocompatibility of the prepared scaffolds were also assessed by a time-killing assay and an Alamar Blue assay, respectively. Our results show that the antibacterial effect of 50% Ga-MBG/CHT was more pronounced than that of CHT and CXR. The cell viability results also demonstrated that Ga-MBG/CHT composite scaffolds had good biocompatibility, which facilitates the spreading and proliferation of human dermal fibroblast cells even with 50 wt % Ga-MBG loading. These results suggest that Ga-MBG/CHT scaffolds could be a promising hemostatic candidate for improving hemostasis in critical situations.
  17. Pourshahrestani S, Kadri NA, Zeimaran E, Gargiulo N, Samuel S, Naveen SV, et al.
    Biomed Mater, 2018 02 08;13(2):025020.
    PMID: 29148431 DOI: 10.1088/1748-605X/aa9b3e
    Mesoporous bioactive glass containing 1% Ga2O3 (1%Ga-MBG) is attractive for hemorrhage control because of its surface chemistry which can promote blood-clotting. The present study compares this proprietary inorganic coagulation accelerator with two commercial hemostats, CeloxTM (CX) and QuikClot Advanced Clotting Sponge PlusTM (ACS+). The results indicate that the number of adherent platelets were higher on the 1%Ga-MBG and CX surfaces than ACS+ whereas a greater contact activation was seen on 1%Ga-MBG and ACS+ surfaces than CX. 1%Ga-MBG not only resulted in larger platelet aggregates and more extensive platelet pseudopodia compared to CX and ACS+ but also significantly accelerated the intrinsic pathways of the clotting cascade. In vitro thrombin generation assays also showed that CX and ACS+ induced low levels of thrombin formation while 1%Ga-MBG had significantly higher values. 1%Ga-MBG formed a larger red blood cell aggregate than both CX and ACS+. Direct exposure of 1%Ga-MBG to fibroblast cells increased cell viability after 3 days relative to CX and ACS+, inferring excellent cytocompatibility. The results of this study promote 1%Ga-MBG as a promising hemostat compared to the commercially available products as it possesses essential factors required for coagulation activation.
  18. Beattie JR, Cummins NM, Caraher C, O'Driscoll OM, Bansal AT, Eastell R, et al.
    PMID: 27429561 DOI: 10.4137/CMAMD.S38493
    Raman spectroscopy was applied to nail clippings from 633 postmenopausal British and Irish women, from six clinical sites, of whom 42% had experienced a fragility fracture. The objective was to build a prediction algorithm for fracture using data from four sites (known as the calibration set) and test its performance using data from the other two sites (known as the validation set). Results from the validation set showed that a novel algorithm, combining spectroscopy data with clinical data, provided area under the curve (AUC) of 74% compared to an AUC of 60% from a reduced QFracture score (a clinically accepted risk calculator) and 61% from the dual-energy X-ray absorptiometry T-score, which is in current use for the diagnosis of osteoporosis. Raman spectroscopy should be investigated further as a noninvasive tool for the early detection of enhanced risk of fragility fracture.

    Study site: England
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