Polymer/bioactive glass nanocomposites for biomedical applications: A review
Introduction
Bioactive glasses of silicate composition, which were first developed by Hench and co-workers in 1969 [1], represent a group of surface reactive materials which are able to bond to bone in physiological environment [2]. Bioactive glasses most widely used in biomedical applications consist of a silicate network incorporating sodium, calcium and phosphorus in different relative proportions. The classical 45S5 bioactive glass composition universally known as Bioglass® (composition in wt.%: 45% SiO2, 24.5% Na2O, 24.5% CaO and 6% P2O5), for example, has approval of the US Food and Drug Administration (FDA) and is used in clinical treatments of periodontal diseases as bone filler as well as in middle ear surgery [2]. Other bioactive glass compositions contain no sodium or have additional elements incorporated in the silicate network such as fluorine, magnesium, strontium, iron, silver, boron, potassium or zinc [3], [4], [5], [6], [7], [8], [9].
Fabrication techniques for bioactive glasses include both traditional melting methods and sol–gel techniques [2], [3], [4], [10]. The typical feature common to all bioactive glasses, being melt or sol–gel derived, is the ability to interact with living tissue forming strong bonds to bone (and in some cases soft) tissue, a property commonly termed bioreactivity or bioactivity [2]. The bonding to bone is established by the precipitation of a calcium–deficient, carbonated apatite surface layer on the bioactive glass surface when in contact with relevant physiological fluid or during in vivo applications. It is now widely accepted that for establishing bond with bone, such biologically active apatite surface layer must form at the material/bone interface [2], [11]. The development of these bioactive apatite layers is the common characteristic of all known inorganic materials used for orthopedic implants, bone replacement and bone tissue engineering scaffolds [2], [12].
Early applications of bioactive glasses were in the form of solid pieces for small bone replacement, i.e. in middle ear surgery [2]. Later, other clinical applications of bioactive glasses were proposed, for example in periodontology [13], [14], endodontology [15], [16] or as coating on metallic orthopedic implants [17], [18]. More recently, great potential has been attributed to the application of bioactive glasses in tissue engineering and regenerative medicine [12], [19], [20], [21], [22]. Bone tissue engineering is one of the possible most exciting future clinical applications of bioactive glasses, e.g. to fabricate optimal scaffolds with osteogenic and angiogenic potential [22]. Both micron-sized and nanoscale particles are considered in this application field, which includes also the fabrication of composite materials, e.g. combination of biodegradable polymers and bioactive glass [12], [20], [23], as discussed in detail further below. Moreover the surface modification of such biodegradable composites with smart polymers allows to produce substrates in which bio-mineralization could be triggered by the action of external stimuli, such as temperature or pH [24], [25]. In this context, bioactive silicate glasses exhibit several advantages in comparison to other bioactive ceramics, e.g. sintered hydroxyapatite. For example, it has been demonstrated that dissolution products from bioactive glasses upregulate the expression of genes that control osteogenesis [19], which explains the higher rate of bone formation in comparison to other inorganic ceramics such as hydroxyapatite [26]. Further studies using 45S5 Bioglass® particles have shown encouraging results regarding potential angiogenic effects of Bioglass®, i.e. increased secretion of vascular endothelial growth factor (VEGF) in vitro and enhancement of vascularisation in vivo [27], [28], [29]. In addition, the incorporation of specific ions in the silicate network, such as Ag and Zn, has been investigated in order to develop antibacterial materials [30], [31], [32]. Bioactive glasses can also serve as vehicle for the local delivery of selected ions which can act to control specific cell functions, for example Co addition to suppress cell hypoxia [33]. Bioactive glasses are also being considered as haemostatic agents. For example, Bioglass® has been shown to reduce the clotting time of blood by 25% in laboratory tests (Lee–White Coagulation), with ionic release of calcium (Clotting factor IV) being considered a reason for its haemostatic properties. [34]. Moreover ferromagnetic bioactive glasses and glass–ceramics containing magnetite are being developed for hyperthermia treatment of cancer [35].
The range of bioactive glasses exhibiting these attractive properties has been extended over the years, in terms of both chemical composition and morphology, as new preparation methods have become available. In addition, all the specific effects and advantages of bioactive glasses mentioned above, including surface bioreactivity, can be enhanced or modified and controlled to a greater extent, if nanoparticles (or nanofibres) are available, as opposed to conventional micron-sized powders. This is relevant both for bioactive glasses used in particulate form as coatings in biomedical devices or as filler in composite materials, e.g. as biodegradable implants, dental fillers, tissue engineering scaffolds, tissue guidance membranes or drug delivery systems.
Bioactive glass/biodegradable polymer composite materials have emerged recently as new family of bioactive materials with applications ranging from structural implants to tissue engineering scaffolds [12]. These composites exploit the flexibility of polymers with the stiffness, strength and bioactive character of the bioactive glass fillers. So far, most work on this class of composites has been carried out using conventional (micron-size) bioactive glass particles as fillers (or coatings) [12]. However, recent research to be reviewed in this paper demonstrates the application of nano-sized bioactive glass particles and nanofibres (which have become available only in the last few years), in a range of novel composites with improved performance for biomedical applications, in particular tissue engineering and regenerative medicine.
Thus the topic of biodegradable/bioactive glass nanocomposites will be the subject of this review, which covers the available literature on production and characterization of nano-structured bioactive silicate glasses and their application in nanocomposites for biomedical applications. Section 2 discusses the key characteristics of nanoscale bioactive glasses. Different synthesis methods for bioactive glass nanoparticles and nanofibres are reviewed in Section 3. In Section 4, a comprehensive review of composite systems incorporating bioactive glass nanoparticles or nanofibres is presented while in Section 5 the state of the art is summarized and the scope for further research developments in the field is highlighted.
Section snippets
Characteristics of nanoscale bioactive glasses
A reduction in size to the nanometer scale of bioactive glass particles (or fibres) leads to a new family of nanostructured biomaterials which, combined with polymer matrices to form composites, are expected to exhibit enhanced performance in existing biomedical applications, leading also to new application opportunities. The higher specific surface area of nanoscale bioactive glasses allows not only for a faster release of ions but also a higher protein adsorption and thus enhanced bioactivity
Fabrication techniques for bioactive glass nanoparticles and nanofibres
In the last few years silicate bioactive glass nanoparticles and nanofibres have become available and they are starting to be used in a range of biomedical applications in combination with polymers, forming nanocomposites. The success of the work carried out so far and the potential applications of these novel materials have prompted the preparation of the present review. In this Section the processing methods to fabricate nanoscale bioactive glasses are discussed.
General characteristics of bioactive nanocomposites
The combination of biodegradable polymers and bioactive ceramics (and glasses) results in a new group of composite materials for applications as temporary orthopedic implants, bone filler materials or as 3D biocompatible scaffolds in the field of tissue engineering [12], [38]. The goal of these composite materials is to impart strength and bioactivity by an inorganic bioactive filler while keeping the positive properties of the polymer such as flexibility and capacity to deform under loads. The
Conclusions
The preparation of bioactive glasses in nanoparticle and nanofibre form has recently become feasible by advances in wet and dry synthesis methods. Nanoscale particulate and nanofibre bioactive glasses have shown advantages over conventional (micron-sized) bioactive glasses due to their large surface area and enhanced solubility as well as reactivity coupled with the possibility to induce nanotopographic surface features in composite materials. These nanomaterials have also inspired researchers
Acknowledgement
ME gratefully acknowledges the financial support by The Scientific and Technological Research Council of Turkey (TUBITAK), Turkey.
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