Elsevier

Acta Biomaterialia

Volume 8, Issue 1, January 2012, Pages 361-372
Acta Biomaterialia

Alkali-free bioactive glasses for bone tissue engineering: A preliminary investigation

https://doi.org/10.1016/j.actbio.2011.08.026Get rights and content

Abstract

An alkali-free series of bioactive glasses has been designed and developed in the glass system CaO–MgO–SiO2–P2O5–CaF2 along the diopside (CaMgSi2O6)–fluorapatite (Ca5(PO4)3F)–tricalcium phosphate (3CaO·P2O5) join. The silicate network in all the investigated glasses is predominantly coordinated in Q2 (Si) units, while phosphorus tends to remain in an orthophosphate (Q0) environment. The in vitro bioactivity analysis of glasses has been made by immersion of glass powders in simulated body fluid (SBF) while chemical degradation has been studied in Tris–HCl in accordance with ISO-10993-14. Some of the investigated glasses exhibit hydroxyapatite formation on their surface within 1–12 h of their immersion in SBF solution. The sintering and crystallization kinetics of glasses has been investigated by differential thermal analysis and hot-stage microscopy, respectively while the crystalline phase evolution in resultant glass–ceramics has been studied in the temperature range of 800–900 °C using powder X-ray diffraction and scanning electron microscopy. The alkaline phosphatase activity and osteogenic differentiation for glasses have been studied in vitro on sintered glass powder compacts using rat bone marrow mesenchymal stem cells. The as-designed glasses are ideal candidates for their potential applications in bone tissue engineering in the form of bioactive glasses as well as glass/glass–ceramic scaffolds.

Introduction

Bioactive glasses and glass–ceramics (GCs) are a class of biomaterials which elicit a special response on their surface when in contact with biological fluids, leading to strong bonding to living tissues. In the field of bone tissue engineering (TE), bioactivity is defined as the ability of the material to bond to bone tissue via the formation of a bone-like hydroxyapatite (HA) layer on its surface. Due to their salient features, for example enhanced angiogenesis and up-regulation of specific genes that control the osteoblast cell cycle, bioactive glasses and GCs are being considered as potential materials for bone regeneration and TE [1].

Since the discovery of 45S5 Bioglass® [2], many artificial biomaterials based on, or inspired by, Hench’s glasses have been developed and successfully employed in clinical applications for repairing and replacing parts of the human body. This field is continuously expanding: new processing routes have extended the range of applications towards new exciting directions in biomedicine [3], many of which still rely on the original Hench’s base formulation, which has now become the paradigm of bioactive materials.

Although the use of 45S5 glass in numerous clinical programs has exhibited favorable healing capability, one of the main problems associated with this glass is its high dissolution rate [4], mainly owing to its high alkali content. This causes fast resorption that may negatively affect the balance of natural bone remodelation and in particular the physiologically vital process of angiogenesis, thus leading to gap formation between the tissue and the implant material [5]. Similarly, most of the bioactive glass compositions investigated so far [6], [7], [8], [9], [10], [11] contain significant amounts of alkali oxides (Na2O, K2O). Although the incorporation of alkali oxides in bioactive glass is advantageous for their production, as they reduce the melting temperature of the glass, their presence in bioactive glass can reduce the usefulness of the glass in vivo. In particular, the bioactive glasses having high alkali metal content are susceptible to water uptake by osmosis, resulting in swelling and cracking of the polymer matrix embedding them in composites, and may, in the case of degradable polymer composites, exhibit increased levels of degradation. Such bioactive glasses may also be unsuitable for use as coatings for metal prosthetics due to increased coefficient of thermal expansion due to the presence of alkali metals. Furthermore, high levels of alkali cations degrade the sintering ability of bioactive glasses by increasing the crystallization tendency of glass, thus rendering them unfit for use as bioactive porous scaffolds or porous coatings. For example, in the case of 45S5 Bioglass®, owing to its poor sintering ability, there have been problems with the manufacture of highly porous scaffolds possessing good mechanical strength from its glass powders as it needs extensive densification to strengthen the solid phase, i.e. the struts in the foam-like structure, which would otherwise be made of loosely bonded particles and thus be too fragile to handle [12]. Also, it has been noticed that crystallization of 45S5 Bioglass® turns this glass into an inert material [13].

The present investigation is an attempt to find a feasible solution for the above discussed long-standing problem of designing alkali-free bioactive glasses with high bioactivity, lower dissolution and good sintering behavior in comparison to 45S5 glass. The investigated glass compositions have been designed in the system diopside (hereafter referred to as Di)–fluorapatite (hereafter referred to as FA)–tricalcium phosphate (hereafter referred to as TCP) with a general formula (Di)(90−x)–(FA)10–(TCP)x (x = 10–40 wt.%). The compositions were designed considering the fact that the structure of amorphous Di glass (CaO·MgO·2SiO2) is dominated by Q2 (Si) species [14], which is an important and positive attribute as it is well known that the highest bioactivity from a phospho-silicate glass can be expected if Qn (Si) units (n: number of bridging oxygens) are dominated by chains of Q2 metasilicates, which are occasionally cross-linked through Q3 units, whereas Q1 units terminate the chains [15]. Further, Di is known to exhibit good sintering behavior, thus resulting in mechanically strong bioactive materials [16]. However, the major drawback of Di-based glasses and GCs is their low dissolution rate [17], which could be controlled by addition/substitution of some bioresorbable material (for example: TCP) in the final product. Therefore, the addition of TCP at the expense of Di in the glass compositions is expected to enhance their solubility as well as their bioactivity in physiological fluids. Also, the addition of TCP to Di is expected to improve its sintering ability as it has been reported that the flexural strength of eutectic GC composition 38 TCP–62 Di (wt.%) is higher than 200 MPa [18], [19]. Furthermore, the addition of FA in the glass system was made with an aim of introducing fluoride ions in the amorphous glass structure, which is of high interest in both orthopaedics as well as dentistry [7], [11] and in order to obtain FA as one of the crystalline phases in the resultant GCs due to its higher chemical stability in comparison to hydroxyapatite [Ca5(PO4)3OH] [11]. However, the amount of FA was maintained low (10 wt.%) and constant in the investigated glass compositions because of the fact that fluoride ions tend to control the dissolution of glasses by acting as corrosion inhibitor [7] while the amount of P2O5 in the glass should be maintained lower than 10 mol.% so that the resulting phosphate species in bioactive glass can coordinate themselves in orthophosphate environment (Q0) species, thus enhancing the bioactivity of glass [15].

Section snippets

Synthesis of glasses

A series of glass compositions in the system (Di)(90−x)–(FA)10–(TCP)x (x = 10, 20, 30, 40 wt.%) was prepared by the melt-quenching technique. The glasses have been labeled in accordance with their respective TCP content, i.e. TCP-10, TCP-20, TCP-30 and TCP-40, respectively. Table 1 presents the compositions of the investigated glasses. In the present study, high-purity powders of SiO2 (purity > 99.5%), CaCO3 (>99.5%), MgCO3 (BDH Chemicals Ltd, UK, purity > 99.0%), NH4H2PO4 (Sigma–Aldrich, Germany,

Glass-forming ability

For all the investigated glass compositions (x = 10–40 wt.%), melting at 1570 °C for 1 h was sufficient to obtain bubble-free, transparent and amorphous glasses (Fig. 1). The glass-forming ability diminished with further increase in TCP content in glasses (x > 40 wt.%) as resultant glass frits were prone to spontaneous crystallization even after supercooling in cold water, thus resulting in white, opaque material with FA as the only crystalline phase, as revealed by XRD analysis (not shown).

Conclusions

An insight into the influence of varying Di/TCP ratio on the structure, biodegradation and sintering-crystallization behavior of glasses in the Di–FA–TCP system has been presented. The as-obtained results depict the potential of investigated glass compositions for their application in human biomedicine. The following conclusions can be drawn from the above discussed results:

  • (i)

    Amorphous glasses could be obtained only for compositions with TCP ⩽40 wt.% where FA content has been kept constant i.e., 10

Acknowledgments

The financial support from FCT-Portugal is highly acknowledged. Also, Saurabh Kapoor is thankful to CICECO and University of Aveiro for the research scholarship. Partial supports from the National Research Foundation, Republic of Korea (Research Centers Program, Grant# 2009-0093829 and WCU Program, Grant# R31-10069) are also acknowledged.

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