Nijmegen, Netherlands
Nijmegen, Netherlands
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Gabbai-Armelin P.R.,Federal University of São Carlos | Gabbai-Armelin P.R.,Radboud University Nijmegen | Cardoso D.A.,Radboud University Nijmegen | Cardoso D.A.,EMCM B.V. | And 6 more authors.
RSC Advances | Year: 2014

The objective of the study was to prepare an injectable composite for bone regeneration based on the combination of a highly bioactive glass-ceramic (Biosilicate®) and alginate by optimizing the ratio of Biosilicate®/alginate. These formulations were evaluated in terms of injectability, visco-elastic properties, degradation (i.e. mass loss, pH, calcium deposition) and cytotoxycity. The results showed that by mixing Biosilicate® and alginate, it is possible to obtain an injectable biocomposite material that exhibits interesting elastic properties. Furthermore, the formulations with higher alginate (up to 20 wt%) content showed higher mechanical stability compared to pure Biosilicate®. All formulations mineralized in Simulated Body Fluid (SBF) during the initial 4 days of testing. The cytotoxicity of conditioned media obtained via incubation of the formulations showed negative effects on cell viability but this effect was nullified with increasing the number of washing post-treatments (especially in the case of the formulation containing Biosilicate®/alginate of 42.5/7.5 wt%). Based on the results of the present study, it can be concluded that the material properties of injectable Biosilicate®/alginate formulations seem suitable for bone regenerative applications, for which future studies should aim at biological evaluation in animal experimental models. This journal is © the Partner Organisations 2014.

Cardoso D.A.,Radboud University Nijmegen | Cardoso D.A.,EMCM B.V. | Ulset A.-S.,Norwegian University of Science and Technology | Bender J.,Bender Analytical Holding B.V. | And 3 more authors.
Macromolecular Bioscience | Year: 2014

Degradation of alginate remains a critical issue to allow predictable biological performance upon implantation of alginate-based materials. Therefore, the objective of the current study is to compare the effects of γ-irradiation (dry state, 20-80 kGy), partial (1 and 4%) periodate oxidation (aqueous solution), and autoclaving (dry state) on the molecular weight of alginate, as well as the degradation behavior of alginate-based composites. The results show that γ-irradiation is by far the most destructive technique characterized by strongly reduced molecular weights and rapid loss of composite integrity upon soaking in simulated body fluid. Partial periodate oxidation is less destructive as characterized by more moderate decreases in molecular weight, but the production of hydrolytically labile bonds compromises the integrity of the resulting composites. Autoclaving is shown to be a powerful tool to reduce the molecular weight of alginate in a controllable and mild manner without compromising the integrity of the resulting alginate-hydroxyapatite composites, simply by increasing the number of repetitive autoclaving cycles. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Faraj K.A.,Radboud University Nijmegen | Faraj K.A.,EMCM BV | Faraj K.A.,Salahaddin University Erbil | Brouwer K.M.,Radboud University Nijmegen | And 10 more authors.
Tissue Engineering and Regenerative Medicine | Year: 2011

Ethylene oxide (EtO) gassing and β- and γ-irradiation are currently used for sterilising collagen scaffolds. During the process, scaffolds may undergo chemical and physical alterations that may compromise their structural integrity and functional characteristics. In this study, we compared the effects of EtO gassing, and β- and γ-irradiation at 15 and 25 kGy on type I collagen fibril-based scaffolds with and without crosslinking, and with and without heparin. Evaluation was performed using a wide range of biophysical, biochemical, morphological and biological parameters. EtO treatment, β-irradiation and γ-irradiation did not induce morphological changes, nor did they have an effect on the amount of primary amine groups, or the amount of heparin covalently attached to the scaffolds. Cytocompatibility was also not affected. Irradiation, however, did result in collagen degradation products, a decrease in collagen denaturation temperature, and an increase in proteolytic degradation, all in a dose dependent fashion. These parameters were hardly influenced by EtO treatment. Sterilisation methods had hardly any effect on tensile strength of crosslinked scaffolds, but -surprisingly- they increased the tensile strength of non-crosslinked scaffolds. In conclusion, a number of the collagen scaffold parameters were influenced by sterilisation, whereas others were not. Irradiation had a much larger effect than EtO. However, tensile strength and cytocompatibility, important in tissue engineering, were not negatively influenced by any of the methods. Therefore, aspects like costs, safety and practicality of use may be taken into account in the choice of sterilisation method.

Alves Cardoso D.,EMCM B.V. | Alves Cardoso D.,Radboud University Nijmegen | Van Den Beucken J.J.J.P.,Radboud University Nijmegen | Both L.L.H.,EMCM B.V. | And 3 more authors.
Journal of Biomedical Materials Research - Part A | Year: 2014

An emerging approach toward development of injectable, self-setting, and fully biodegradable bone substitutes involves the combination of injectable hydrogel matrices with a dispersed phase consisting of nanosized calcium phosphate particles. Here, novel injectable composites for bone regeneration have been developed based on the combination of ultrapure alginate as the matrix phase, crystalline CaP [monetite and poorly crystalline hydroxyapatite (HA)] powders as both a dispersed mineral phase and a source of calcium for cross-linking alginate, glucono-delta-lactone (GDL) as acidifier and glycerol as both plasticizer and temporary sequestrant. The composites were maximized with respect to CaP content to obtain the highest amount of osteoconductive filler. The viscoelastic and physicochemical properties of the precursor compounds and composites were analyzed using rheometry, elemental analysis (for calcium release and uptake), acidity [by measuring pH in simulated body fluid (SBF)], general biocompatibility (subcutaneous implantation in rabbits), and osteocompatibility (implantation in femoral condyle bone defect of rabbits). The gelation of the resulting composites could be controlled from seconds to tens of minutes by varying the solubility of the CaP phase (HA vs. monetite) or amount of GDL. All composites mineralized extensively in SBF for up to 11 days. In vivo, the composites also disintegrated upon implantation in subcutaneous or bone tissue, leaving behind less degradable but osteoconductive CaP particles. Although the composites need to be optimized with respect to the available amount of calcium for cross-linking of alginate, the beneficial bone response as observed in the in vivo studies render these gels promising for minimally invasive applications as bone-filling material. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 808-817, 2014. Copyright © 2013 Wiley Periodicals, Inc.

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