[show abstract][hide abstract] ABSTRACT: 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.
Journal of Functional Biomaterials. 11/2013; 4:329-357.
[show abstract][hide abstract] ABSTRACT: Due to the deficiencies of current commercially available biological bone grafts, alternative bone graft substitutes have come to the forefront of tissue engineering in recent times. The main challenge for scientists in manufacturing bone graft substitutes is to obtain a scaffold that has sufficient mechanical strength and bioactive properties to promote formation of new tissue. The ability to synthesise hydrogel based composite scaffolds using photopolymerisation has been demonstrated in this study. The prepared hydrogel based composites were characterised using techniques including Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy-dispersive X-ray spectrometry (EDX), rheological studies and compression testing. In addition, gel fraction, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), porosity and swelling studies of the composites were carried out. It was found that these novel hydrogel bioglass composite formulations did not display the inherent brittleness that is typically associated with bioactive glass based bone graft materials and exhibited enhanced biomechanical properties compared to the polyethylene glycol hydrogel scaffolds along. Together, the combination of enhanced mechanical properties and the deposition of apatite on the surface of these hydrogel based composites make them an ideal candidate as bone graft substitutes in cancellous bone defects or low load bearing applications.
[show abstract][hide abstract] ABSTRACT: Embolization with micron-sized particulates is widely applied to treat uterine fibroids. The objective of this work was to develop mixture designs to predict materials composition–structure–property relationships for the SiO2–CaO–ZnO–La2O3–TiO2–MgO–SrO–Na2O glass system and compare its fundamental materials properties (density and cytocompatibility), against a state-of-the-art embolic agent (contour polyvinyl alcohol) to assess the potential of these materials for embolization therapies. The glass structures were evaluated using 29Si MAS NMR to identify chemical shift and line width; the particulate densities were determined using helium pycnometry and the cell viabilities were assessed via MTT assay. 29Si MAS NMR results indicated peak maxima for each glass in the range of −82.3 ppm to −89.9 ppm; associated with Q2 to Q3 units in silicate glasses. All experimental embolic compositions showed enhanced in vitro compatibility in comparison to Contour PVA with the exceptions of ORP9 and ORP11 (containing no TiO2). In this study, optimal compositions for cell viability were obtained for the following compositional ranges: 0.095–0.188 mole fraction ZnO; 0.068–0.159 mole fraction La2O3; 0.545–0.562 mole fraction SiO2 and 0.042–0.050 mole fraction TiO2. To ensure ease of producibility in obtaining good melts, a maximum loading of 0.068 mole fraction La2O3 is required. This is confirmed by the desirability approach, for which the only experimental composition (ORP5) of the materials evaluated was presented as an optimum composition; combining high cell viability with ease of production (0.188 mole fraction ZnO; 0.068 mole fraction La2O3; 0.562 mole fraction SiO2 and 0.042 mole fraction TiO2).
Journal of Biomaterials Applications 09/2013; 28(3):416-433. · 2.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aluminum-free glass polyalkenoate cements (GPC) have been hindered for use as injectable bone cements by their inability to balance handling characteristics with mechanical integrity. Currently, zinc-based, aluminum-free GPCs demonstrate compression strengths in excess of 60MPa, but set in c. 1-2min. Previous efforts to extend the setting reaction have remained clinically insufficient and are typically accompanied by a significant drop in strength. This work synthesized novel glasses based on a zinc silicate composition with the inclusion of GeO2, ZrO2, and Na2O, and evaluated the setting reaction and mechanical properties of the resultant GPCs. Germanium based GPCs were found to have working times between 5 and 10min, setting times between 14 and 36min, and compression strengths in excess of 30MPa for the first 30 days. The results of this investigation have shown that the inclusion of GeO2, ZrO2, and Na2O into the glass network have produced, for the first time, an aluminum-free GPC that is clinically viable as injectable bone cements with regards to handling characteristics and mechanical properties.
Journal of the mechanical behavior of biomedical materials. 04/2013; 23C:8-21.
[show abstract][hide abstract] ABSTRACT: Novel bioactive glasses that can release ions such as strontium and zinc provide bone growth enhancement and antibacterial properties that earlier-generation bioglasses did not possess. These glasses find applications in bone cementation, restoration and in tissue engineering. In this paper, we present combined experimental and simulation studies to explain the structure and diffusion of ZnO–SrO–CaO–Na2O–SiO2 bioactive glasses with the aim of understanding the short and medium range structure of these glasses, the structural correlation to their dissolution behaviors, and their bioactivity. High energy X-ray diffraction experiments have been performed to obtain structural information and to validate the structure models from simulations. Three glass compositions with ZnO/Na2O substitutions have been studied using molecular dynamics simulations to characterize the glass structure and calculate the ionic diffusion in these glasses. The results provide insight to local environments and structural role of zinc ions, the medium range structural features such as Qn distribution, and ionic diffusion characteristics of these bioactive glasses. The structure and ionic diffusion results are discussed in correlation to the dissolution behaviors and the bioactivity of these glasses.
[show abstract][hide abstract] ABSTRACT: Poly (lactide-co-glycolide) (PLGA) - Pluronic F127 - glass composites have demonstrated excellent potential, from the perspective of controlled mechanical properties and cytocompatibility, for peripheral nerve regeneration. In addition to controlling the mechanical properties and cytotoxicity for such composite devices, the glass component may mediate specific responses upon implantation via degradation in the physiological environment and release of constituent elements. However, research focused on quantifying the release levels of such therapeutic ions from these experimental medical devices has been limited. To redress the balance, this paper explores the ion release profiles for Si(4+), Ca(2+), Na(+), Zn(2+), and Ce(4+) from experimental composite nerve guidance conduits (CNGC) comprising PLGA (at 12.5, and 20wt.%), F127 (at 0, 2.5 and 5wt.%) and various loadings of Si-Ca-Na-Zn-Ce glass (at 20 and 40wt.%) for incubation periods of up to 28days. The concentration of each ion, at various time points, was determined using Inductively Coupled Plasma-Atomic Emission Spectrometry (Perkin Elmer Optima 3000). It was observed that the Si(4+), Na(+), Ca(2+), Zn(2+) release from CNGCs in this study ranged from 0.22 to 6.477ppm, 2.307 to 3.277ppm, 40 to 119ppm, and 45 to 51ppm, respectively. The Ce(4+) concentrations were under the minimum detection limits for the ICP instrument utilized. The results indicate that the ion release levels may be appropriate to mediate therapeutic effects with respect to peripheral nerve regeneration. The data generated in this paper provides requisite evidence to optimize composition for pre-clinical evaluation of the experimental composite.
[show abstract][hide abstract] ABSTRACT: PLGA/pluronic F127 based nerve guidance conduits (NGCs) for peripheral nerve regeneration offer excellent potential for clinical use. To date, little emphasis has been directed towards the effect of pluronic F127 on their subsequent mechanical properties as a function of degradation time or the physiological environment. This report was designed to redress the balance. This study synthesised 5 groups of 20wt% PLGA NGCs with varied additions of pluronic F127 (range 0-5wt%) to obtain Young's Moduli (E) in the range of 7-107MPa, depending on degradation conditions and pluronic F127 content.
Journal of the mechanical behavior of biomedical materials. 06/2012; 14C:180-185.
[show abstract][hide abstract] ABSTRACT: A radiopaque particulate material one or more of SiO2, TiO2, La2O3, Na2O and MgO and useful for embolization which optionally includes therapeutic components that are released in vivo.
[show abstract][hide abstract] ABSTRACT: Regression surface modeling has been applied to examine and predict the network connectivity (NC), ther-mal properties and radiopacity of a series of La 2 O 3 –TiO 2 doped zinc–silicate (Zn–Si) bioglasses. The objective of this work is to provide new regression models based on a design of mixture (DOM) approach for predicting the NC, thermal responses and radiopacity for phosphate free, Zn–Si bioglasses that include variable ratios of SiO 2 , ZnO, La 2 O 3 and TiO 2 . To ensure a comprehensive examination of the composition–property relation-ships, the experimental design varied the ratios of SiO 2 , ZnO, La 2 O 3 and TiO 2 within the glass network. Regression models were deployed to analyze data derived from NC calculations, differential scanning calorimetry and axial CT scans. It was observed that, for the glasses examined, the NC ranged from 2.41 to 2.83. The observed values of glass transition temperature (T g) ranged from 597 to 690 °C and for the first point of crystallization temperature (T p 1) it was observed that the values ranged from 620 to 700 °C. Both T g and T p 1 regression models predominantly showed that an increase in La 2 O 3 (at the expense of ZnO) results in an increase of both thermal properties. In addition, increasing the La 2 O 3 /ZnO ratio is also observed to result in a shift towards achieving higher levels of radiopacity. In general, regression modeling of the radiopacity data indicated that increased loadings of La 2 O 3 , TiO 2 and ZnO are required at the expense of SiO 2 in order to increase the radiopaque nature of the glasses. The application of this methodology provides a more statistically robust approach over existing models that exist in the literature for predicting the properties of multi-component zinc–silicates doped with La 2 O 3 and TiO 2 .
Journal of Non-Crystalline Solids 01/2012; 358:3388-3395. · 1.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: There exists clinical evidence of fractures in adjacent vertebrae subsequent to vertebral augmentation procedures, such as vertebroplasty (VP) and kyphoplasty (KP). A potential contributory factor to such fractures may be the excessive mismatch of mechanical properties between contemporary bone cements (i.e. polymethyl methacrylate (PMMA) and bisphenol-a-glycidyl dimethacrylate (BIS-GMA)) and bone. Aluminum-free glass polyalkenoate cements (GPCs) present an interesting alternative to conventional bone cements. GPCs adhere to the philosophy that implant materials should have mechanical characteristics similar to those of the bone, and also offer chemical adhesion and intrinsic bioactivity. However, their influence on the loading patterns of augmented vertebrae (as compared with conventional bone cements) is not available in the literature. The present work investigates how the moduli of PMMA, BIS-GMA and GPC implants affect the stress distribution within a single, augmented vertebra, in both healthy and osteoporotic states. Using a finite element model of the L4 vertebra derived from computed tomography data, with simulated augmentation, it was found that, as cement stiffness increased, stress was redistributed from the cortical and trabecular bone to the cement implant. The GPC implant exhibited the least effect on stress redistribution in both the healthy and osteoporotic models compared to its acrylic counterparts. The significance of this work is that, under simulated physiological loading conditions, aluminum-free GPCs exhibit stress distribution throughout the vertebral body similar to that of the healthy bone. In comparison to conventional augmentation materials, the use of aluminum-free GPCs in VP and KP may help to ameliorate the clinical complication of adjacent vertebral body compression fractures.
Journal of the mechanical behavior of biomedical materials. 01/2012; 5(1):283-90.
[show abstract][hide abstract] ABSTRACT: Novel composite microspheres were synthesized by thermally induced phase separation and success-fully optimized via response surface methodology (RSM) based on a 5-level, 2-factor D-Optimal experimental design. The parameters were based on two compositional factors: PLGA (10–20 wt%) and ORP5 glass (0–20 wt%) in 12 experimental runs. Using the RSM approach, key composition-property relationships were identified; where the optimum composites derived for these microspheres was a PLGA/ORP5 content of 10.59 wt%:2.01 wt%. A maximum loading of 4.30 wt% ORP5 glass is required to establish target cell viabilities of $ 100% from 12 to 120 h incubation periods. This study highlights the value of RSM in optimizing properties for these composite microspheres and shows their potential for use in peripheral vascular embolization procedures. & 2012 Elsevier B.V. All rights reserved.
[show abstract][hide abstract] ABSTRACT: The use of artificial bone grafts has increased in order to satisfy a growing demand for bone replacement materials. Initial mechanical stability of synthetic bone grafts is very advantageous for certain clinical applications. Coupled with the advantage of mechanical strength, a material with inherent antibacterial properties would be very beneficial. A series of strontium-doped zinc silicate (Ca-Sr-Na-Zn-Si) glass ceramics have been characterized in terms of their crystalline structure, biaxial flexural strength and antibacterial efficacy based on the identification of optimum sintering conditions. All three glass ceramics, namely, BT110, BT111, and BT112 were found to be fully crystalline, with BT111 and BT112 comprising of biocompatible crystalline phases. The biaxial flexural strengths of the three glass ceramics ranged from 70 to 149 MPa and were shown to be superior to those of clinically established ceramics in dry conditions and following incubation in simulated physiological conditions. The bacteriostatic effect for each glass ceramic was also established, where BT112 showed an inhibitory effect against three of the most common bacteria found at implantation sites, namely, Enterococcus faecalis, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa. The results of the evaluation suggest that the materials studied offer advantages over current clinical materials and indicate the potential suitability of the glass ceramics as therapeutic bone grafts.
Journal of Biomaterials Applications 12/2011; · 2.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: The use of nerve guidance conduits to repair peripheral nerve discontinuities has attracted much attention from the biomaterials community, with many resorbable and non-resorbable materials in clinical use. However, a material with ideal biocompatibility, sufficient mechanical properties (to match that of the regenerating nerve) coupled with a suitable degradation rate, has yet to be realized. Recently, potential solutions (composite nerve guidance conduits) which support the emerging philosophy of allowing synthetic materials to establish key interactions with cells in ways that encourage self-repair (i.e. ionic mediators of repair such as those observed in hard tissue regeneration) have been proposed in the literature; such composites comprise specially designed bioactive phosphate-free glasses embedded in degradable polymeric matrices. Whilst much research has focussed on the optimization of such composites, there is no published literature on the performance of these experimental compositions under simulated physiological conditions. To address this key limitation, this paper explores the time-dependent variations in wet-state mechanical properties (tensile modulus and ultimate tensile strength) for NGC composites containing various compositions of PLGA (at 12.5, and 20 wt%), F127 (at 0, 2.5 and 5 wt%) and various loadings of Si-Na-Ca-Zn-Ce glass (at 0 and 20 wt%). It was observed that Young's modulus and ultimate tensile strength of these composites were in the range 5-203 MPa and 1-7 MPa respectively, indicating comparable mechanical performance to clinical materials. Furthermore, an analysis of the cytocompatibility of experimental compositions showed comparable (in some instances superior), compatibility when compared with the commercial product Neurolac(®). Based on current synthetic devices and the demands of the indication, the CNGCs examined in this work offer appropriate mechanical properties and compatibility to warrant enhanced development.
Journal of the mechanical behavior of biomedical materials. 10/2011; 4(7):1266-74.
[show abstract][hide abstract] ABSTRACT: Bioactive and degradable porous bioceramics play an important role in many clinical situations. Porosity is essential to the performance of a material that is proposed to be used as an implantable osseous scaffold. Scaffolds provide a three dimensional support and template to osseous integration and vascularization. Combining the porosity of a scaffold with the ability of the scaffold material to deliver therapeutic ions to the site of implantation goes some way towards developing an ideal bone graft. A series of strontium-doped zinc silicate (Ca-Sr-Na-Zn-Si) glass ceramics scaffolds were developed, whose porosity was measured to be between 93% and 96%, which is advantageous in terms of osseous integration and vascularization. The levels of Zn(2+) and Sr(2+) detected as a result of degradation of the crystalline phases were found to be 1.4-600 parts per million (ppm) and 0-583 ppm, respectively. The levels detected correlate well with the levels of Sr(2+) and Zn(2+)ions typically associated with clinical benefits, including antibacterial efficacy, osteoblastic differentiation and impaired osteoclastic resorption.
Journal of Biomaterials Applications 09/2011; · 2.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: Bone grafts are required in many clinical situations. Autografts are the traditional gold standard for treating conditions requiring bone grafts. However autografts have inherent drawbacks such as donor site morbidity, pain and increased operative time. An alternative for autografts are synthetic grafts. A series of strontium doped zinc silicate glasses were developed which were investigated using high temperature X-ray diffraction (HT-XRD) in order to establish phase transformations, which occur up to the first crystallization temperature, (Tp1), thus identifying the composition–structure relationships which arise during this thermal processing. In analysing BT110 it was observed that all glass material crystallised into 4 phases including strontium zinc silicate, sodium calcium silicate, calcium silicate and strontium silicate, leaving no residual glass phase. BT111 and BT112 were shown to contain a residual glassy phase alongside for BT111, sodium zinc silicate, larnite and silicon oxide and for BT112 strontium silicate, calcium silicate, sodium silicate and silicon oxide. In the case of BT111 the residual glass phase appears to be rich in strontium. The residual glass phase being Sr enriched with respect to the glass-ceramic may offer increased release of Sr2+ from the material; important for the regulation of osteoblastic and osteoclastic activity. BT113 crystallized to form strontium silicate, sodium silicate, and strontium zinc silicate. BT114 crystallized to form strontium silicate and sodium silicate. The biocompatibility of phases formed in BT113 and BT114 is as yet unknown. Further knowledge will be generated by later work examining the biocompatibility of these phases identified in this research. However, on the basis of these results, the materials (BT110–BT112) exhibit potential as a bone graft substitutes, whilst BT113–BT114 give rise to phases with unknown biocompatibility and so warrant further investigation.Research highlights► Sr-doped zinc silicate materials comprise of biocompatible crystalline materials. ► Appear to demonstrate a residual glassy phase at Tp1. ► Potential for exerting a marked influence on chemical stability.
Journal of Non-Crystalline Solids 05/2011; 357(10):2097-2102. · 1.60 Impact Factor
[show abstract][hide abstract] ABSTRACT: Bioactive glasses have demonstrated tailored therapeutic ion release, primarily with respect to the augmentation of hard tissues. However, controlled degradation and release of therapeutic ions from biomaterials may also play an important role in soft tissue regeneration such as repair of peripheral nerve discontinuities. In this study, three silica based glasses (0.5SiO2–0.2CaO–0.13ZnO–XNa2O–(0.17–X) CeO2) where, (0.04 < X < 0.14) were synthesised and characterised. The local environment of the 29Si isotope was probed for each glass using 29Si MAS–NMR, whilst the thermal characteristics of each glass were examined using DTA. Following these analyses, ion release profiles for Ca2+ and Zn2+ were evaluated; an equivalent specific surface area of 1 m2 of each glass powder was incubated (37 °C) in 10 ml of citric acid buffer and TRIS–HCI buffer solution (pH 3.0 and pH 7.4 respectively) for incubation periods of up to 30 days. The Zn2+ concentration of each filtrate was analysed using flame Atomic Absorption Spectroscopy (Varian AA240FS Fast Sequential AAS) and the Ca2+ concentration of each filtrate was determined using Inductively Coupled Plasma–Mass Spectrometer (Varian 820 ICP–MS). Results obtained from the 29Si MAS–NMR spectra indicated Q2 structures pervading the network. An analytical model was proposed to analyse the ion release profiles for each glass, and indicated heterogeneous dissolution of glass networks. The ion release data demonstrates that ion release in the range (19.26–3130 ppm) for Ca2+ and in the range (5.97–4904 ppm) for Zn2+ occurred. Release of such elements, at appropriate levels, from peripheral nerve guidance conduits may be advantageous with respect to the repair of peripheral nerve discontinuities.
Materials Science and Engineering: C. 04/2011; 31(3):669–676.
[show abstract][hide abstract] ABSTRACT: Several nerve guidance conduits (NGCs) and nerve protectant wraps are approved by the US Food and Drug Administration (FDA) for clinical use in peripheral nerve repair. These devices cover a wide range of natural and synthetic materials, which may or may not be resorbable. This review consolidates the data pertaining to all FDA approved materials into a single reference, which emphasizes material composition alongside pre-clinical and clinical safety and efficacy (where possible). This article also summarizes the key advantages and limitations for each material as noted in the literature (with respect to the indication considered). In this context, this review provides a comprehensive reference for clinicians which may facilitate optimal material/device selection for peripheral nerve repair. For materials scientists, this review highlights predicate devices and evaluation methodologies, offering an insight into current deficiencies associated with state-of-the-art materials and may help direct new technology developments and evaluation methodologies thereof.
[show abstract][hide abstract] ABSTRACT: The objective of this work was to examine the main (individual), combined (interaction) and second-order (quadratic) effects
of: (i) poly(d,l-lactide-co-glycolide) (PLGA), (ii) F127, and (iii) a zinc-silicate based bioactive glass, on the cytotoxicity and ultimate tensile strength
of an experimental nerve guidance conduit (NGC). The experimental plan was carried out according to a Box–Behnken design matrix.
The effects of each compositional factor were quantified using response surface methodology (RSM) techniques. Linear and quadratic
polynomial equations were developed to examine cytotoxicity (after incubation at 3, 7 and 28days) and initial ultimate tensile
strength (UTS0). Multiple regression analyses showed that the developed models yielded a good prediction for each response examined. It
was observed that the beneficial effects of PLGA and bioactive glass on controlling cytotoxicity appeared greater than that
of F127. Furthermore, the experimental conduits (with the exception of CNGC-I and CNGC-K) generally showed superior cytocompatibility
when compared with the comparable literature for the clinically used nerve guidance conduit Neurolac®. In this investigation, optimal compositions for cell viability were obtained for the following composition: PLGA=18.89wt%/F127=0.52wt%/glass=12.71wt%.
The optimization of composition with respect to ultimate tensile strength was also established (desired UTS0 being based on the properties of the control device Neurolac® whose UTS is c.20MPa). The desired UTS0 of≤20MPa was found for the composition: PLGA=18.63wt%/F127=0.77wt%/glass=5.54wt%. A UTS0≤30MPa was recorded for the composition: PLGA=18.34wt%/F127=0.62wt%/glass=9.83wt%, such tensile strengths are comparable
to, reported values for Neurolac®. Examination of the composition–property relationships with respect to combining cell viability and UTS0 indicated preferred compositions in the range 17.97–19.90wt% PLGA, 0.16–1.13wt% F127 and between 5.54 and≤20wt% glass.
This research demonstrates the value of a design of experiments approach for the design of novel nerve guidance conduits,
and shows that the materials examined may have potential for the repair of peripheral nerve discontinuities.
Journal of Materials Science Materials in Medicine 01/2011; 22(4):945-959. · 2.14 Impact Factor