[Show abstract][Hide abstract] ABSTRACT: Polylactic acid (PLA) fibers were produced with an average diameter of 11.2 (±0.9) μm via a melt-drawing process. The surface of the PLA fibers was coated with blends of cellulose nanowhiskers (CNWs) (65 to 95 wt %) and polyvinyl acetate (PVAc). The CNWs bound to the smooth PLA fiber surface imparted roughness, with the degree of roughness depending on the coating blend used. The fiber tensile modulus increased 45% to 7 GPa after coating with 75 wt % CNWs compared with the uncoated PLA fibers, and a significant increase in the fiber moisture absorption properties at different humidity levels was also determined. Cytocompatibility studies using NIH-3T3 mouse fibroblast cells cultured onto CNWs-coated PLA surface revealed improved cell adhesion compared with the PLA control, making this CNW surface treatment applicable for biomedical and tissue engineering applications. Initial studies also showed complete cell coverage within 2 days.
[Show abstract][Hide abstract] ABSTRACT: Si–Ca–Zn–La–Ti–Mg–Sr–Na glasses have demonstrated excellent biocompatibility both in vitro using the MTT/LDH assays (with L929 mouse fibroblast cells and human blood platelets), and in vivo using New Zealand White rabbits. However, the biological evaluation of the materials was performed on as-manufactured glass granules that were autoclaved, rather than aged or γ-irradiated glass microspheres; the sterilization procedure required prior to implantation of these materials in its final form inside the human body. Given the fact that when a glass is subjected to aging either accelerated or natural changes in its physical properties can take place, it is imperative to determine whether the structure of such glasses will be altered over time in order to substantiate shelf-life claims. The structure of such glasses may also be altered as a result of exposure to the typical amounts of γ-irradiation required to sterilize such materials prior to implantation. This paper therefore examines the structure of Si–Ca–Zn–La–Ti–Mg–Sr–Na glasses using XRD, DSC, pycnometry, 29Si MAS-NMR and ICP–OES to evaluate both the effect of accelerated aging and multiple cycles of 30 kGy γ-irradiation on their structure and subsequent radiopacity. The 29Si MAS-NMR results indicate that the peak maxima for each glass remain between − 83 ppm and − 86 ppm; a chemical shift for 29Si associated with Q2 to Q3 units in silicate glasses, and that the local environment around the 29Si isotope remains unaltered as a result of aging or exposure. Additional analysis (XRD, DSC, pycnometry, ICP–OES and radiopacity) showed that the glass transition temperature, Tg (676 ± 4 °C) typically remains unchanged, as a result of exposure to both accelerated aging and ionizing radiation, as do the density (3.63 ± 0.02 g/cm3) radiopacity (7049 ± 847HU), chemical composition and XRD diffractograms for each glass. Therefore it can be concluded that the accelerated aging conditions tested herein or use of 30 kGy γ-irradiation dose or subsequent effects does not affect the local environment of the 29Si isotope in the glasses, nor does it significantly alter the XRD diffraction patterns, chemical composition, Tg, density or the radiopacity values for the glass composition (0.562Si–0.035Ca–0.188Zn–0.068La–0.042Ti–0.035 Mg–0.035Sr–0.035Na) described in this work.
Journal of Non-Crystalline Solids 01/2014; 402:84–90. · 1.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Embolization of vascular tumors is an important tool in minimally invasive surgical intervention. Radiopaque, non-degradable, and non-deformable spherical zinc–silicate glass particles were produced in a range of 45–500 μm. Three size ranges (45–150, 150–300, and 300–500 μm) were used in the current study. The glass microspheres were eluted in polar (saline solution) and non-polar (dimethyl sulfoxide) medium, and ion release profiles were recorded using inductively coupled plasma atomic emission spectroscopy. Approximately 80% of Gaussian distribution was achieved by simple sieving. The ions released from the microspheres were dependent upon surface area to volume ratio as well as the nature of elution media. Greater ions were released from smaller particles (45–150 μm) having largest surface area in polar medium. For the genotoxicity bacterial mutation Ames assay, the concentrations of all the ions were well below their therapeutic concentration reported in the literature. No mutagenic effect was observed in the bacterial mutation Ames test. Hence, it can be concluded that the glass microspheres produced herein are non-mutagenic further supporting the materials potential as a suitable embolic agent.
Journal of Biomaterials Applications 01/2014; · 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: 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: 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: 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. · 1.72 Impact Factor
[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 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: 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. · 1.72 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
[Show abstract][Hide abstract] ABSTRACT: Many commercial bone grafts cannot regenerate healthy bone in place of diseased bone. Bioactive glasses have received much attention in this regard due to the ability of their ionic dissolution products to promote cell proliferation, cell differentiation and activate gene expression. Through the incorporation of certain ions, bioactive glasses can become therapeutic for specific pathological situations. Calcium-strontium-sodium-zinc-silicate glass bone grafts have been shown to release therapeutic levels of zinc and strontium, however the in vitro compatibility of these materials is yet to be reported. In this study, the in vitro cytocompatibility of three different calcium-strontium-sodium-zinc-silicate glasses was examined as a function of their ion release profiles, using Novabone® bioglass as a commercial comparison. Experimental compositions were shown to release Si(4+) ranging from 1 to 81 ppm over 30 days; comparable or enhanced release in comparison to Novabone. The maximum Ca(2+) release detected for experimental compositions was 9.1 ppm, below that reported to stimulate osteoblasts. Sr(2+) release was within known therapeutic ranges, and Zn(2+) release ranged from 0.5 to 1.4 ppm, below reported cytotoxic levels. All examined glass compositions show equivalent or enhanced in vitro compatibility in comparison to Novabone. Cells exposed to BT112 ionic products showed enhanced cell viabilities indicating cell proliferation was induced. The ion release profiles suggest this effect was due to a synergistic interaction between certain combinations and concentrations of ions. Overall, results indicate that the calcium-strontium-sodium-zinc-silicate glass compositions show equivalent or even enhanced in vitro compatibility compared to Novabone®.
Journal of Materials Science Materials in Medicine 10/2010; 21(10):2827-34. · 2.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Polymethlylmethacrylate (PMMA) is the most frequently used cement for percutaneous vertebroplasty and kyphoplasty. To aid visualisation during surgery cements are doped with radiopacifying agents such as Barium sulphate (Ba(2)SO(4)) or Zirconium Dioxide (ZiO(2)). Mounting research suggests that these agents may impair the biocompatibility of the cements. However, incorporating an alternative radiopacifier agent with excellent biocompatibility would be a significant step forward. Bioactive radiopaque glasses incorporating elements such as strontium (Sr) and zinc (Zn), known to have beneficial and therapeutic effects on bone, are of great interest in this respect. In this study, the Ba(2)SO(4) of the commercially available Spineplex was incrementally replaced with a radiopaque therapeutic glass composition. The resulting effects on cement setting time, peak isotherm, ultimate compressive strength, Young's modulus (up to 30 days cement maturation) and radiopacity were evaluated. The substitution lead to an increase in cement setting time from 13.1 mins for Spineplex to 16.6-18.3 mins for the glass substituted cements. The peak exotherm during curing was reduced from 74 degrees C for Spineplex to a minimum of 51 degrees C for the fully substituted cement, indicating that reduced thermal necrosis in the in vivo setting is likely with these materials. Ultimate compressive strength and Young's modulus of each formulation showed no significant deterioration due to the substitution. Finally, the radiopacity of the substituted cements were reduced by up to a maximum of 18% in comparison to the control. However, the experimental formulations still maintained radiopacity equivalent to several millimetres of aluminium. As such the substituted cements had substantial equivalence to the Spineplex control. In order to assess the clinical relevance of these findings further investigation is warranted.
Journal of Materials Science Materials in Medicine 09/2009; 21(1):53-8. · 2.14 Impact Factor