The central idea of ELYNS is to make the scholarly
literature and scientific wisdom free and open to the
scientific as well as the common world.

Bioactive Glasses for Orthopedic and Orthodontic Implant Applications

Published Date: July 24, 2017

Bioactive Glasses for Orthopedic and Orthodontic Implant Applications

Anusha Thampi VV and Subramanian B*

Electrochemical Materials Science Division, CSIR-Central Electrochemical Research Institute, Karaikudi, India

*Corresponding author: Subramanian B, Electrochemical Materials Science Division, CSIR-Central Electrochemical Research Institute, 630003, Karaikudi, India, E-mail:

Citation: Anusha Thampi VV, Subramanian B (2017) Bioactive Glasses for Orthopedic and Orthodontic Implant Applications. Ely J Mat Sci Tech 1(1): 101




Bioactive glasses are successfully used in orthopedics and orthodontics due to their ability to remineralise the apatite layer through a cascade of reactions when in contact with the physiological fluids. They are classified as second generation biomaterial for its bioactivity. Their ability to trigger gene activation through ionic dissolution paved way for design of third generation biomaterial that can be used for tissue regeneration. Their ability to prevent chronic bone infections and oral diseases laid example for fourth generation biomaterials for prevention of organ damage. Here, the preparation and coating methods of bioactive glass and their applications as implants are discussed. The review also covers the mechanism of bioactivity induced by these glasses. Ion substituted bioactive glass and the application of bioactive glass in orthopedics and orthodontics are also included in this review.

Keywords: Bioactive glasses; Orthopaedics; Biomaterials



Advances in technology and discovery of new medicines have increased the life expectancy of the population worldwide in past several decades. The rise in average life calls for the need of new prosthesis because as the body ages it is more prone to ailments. Bioactive glass has emerged as an ideal material for bone cement and coatings, since its discovery, because of its bioactive nature. It was first discovered by Hench et al. in 1969 and since then many researchers across the globe have made attempts to understand the mechanisms of bone bonding by these glasses. According to Hench et al. [1], the primary clinical applications involving bioactive glass is to turn on body’s own bone repair process called osteostimulation. The in vivo data of revealed osteostimulation ability of these glasses was presented by Oonishi et al. [2].

Bioactive glasses are amorphous and biologically active silicate based synthetic materials that are able to form tenacious bonds with bone by forming apatite on reacting with physiological fluids. The original bioactive glass discovered by Hench et al. 45S5 has a composition 46 mol% SiO2, 24.4 mol% Na2O, 26.9 mol% CaO and 2.6 mol% P2O5. This bioactive glass is manufactured commercially under the name bioglass®. This opened the field of bioceramics which includes bioactive glasses of various compositions, glass-ceramics, synthetic hydroxyapatite and other calcium phosphates. This review gives an overview of methods of synthesis of bioactive glasses, techniques for coating bioactive glass on substrates, mechanism of their bioactivity and their applications in orthopedics and orthodontics.

Top ↑

Synthesis of Bioactive Glasses


The attractiveness of bioactive glass is due to their ability to dissolve gradually when implanted and release ions that would promote bone bonding. Since bioactivity is directly proportional to the rate of glass dissolution, a number of synthesis methods have been adopted to increase the porosity which in turn increases the surface to volume ratio of the synthesized material [3].

Melt Quench Synthesis

The original bioactive glass, 45S5, developed by Hench et al. was through melt quench method where the precursors (related oxide materials) were melted at a relatively high temperature above 1300°C [4]. The mixture thus obtained is ground to break agglomerates and to enhance the homogeneity, the mixture can be ground in a ball mill in wet medium like acetone. The resultant is air dried to remove the medium and to obtain fine bioactive glass powders [5]. Flame spraying on metal organic precursors leads to the synthesis of nanoparticles of size 20–80 nm that were collected on a filter above the flame. The resultant nanoparticles were amorphous in nature [6].

Sol Gel Synthesis

Sol gel technique (Figure 1) is an alternative method used for the synthesis of bioactive glasses. A sol is a dispersion of colloidal particles in a liquid whereas a gel is a rigid network comprised of interconnected pores and polymeric chains. The advantage of sol-gel synthesis over melt quench method is because of its low-temperature processing of glasses. Li et al. [7] in 1991 showed the synthesis of silicate based bioactive glasses by sol-gel technique. The typical precursors used in the synthesis include tetraethyl orthosilicate calcium nitrate and triethyl phosphate. Interconnected 3D-network forms as a result of hydrolysis and polycondensation of organometallic precursors which subsequently leads to the formation of gel [8–11]. The gel thus formed is calcined at a temperature range of 600–700°C to form the glass. This method has some limitations like calcination step is required to remove the organic contents and also it is not a continuous process, compositional variation can occur batch to batch [12].

Figure 1: A schematic representation of bioactive glass synthesis by (a) acid catalyzed sol-gel (b) acid – base catalyzed sol gel [92].


A modified stober process is used in a typical sol-gel process to introduce Ca2+ and PO43- ions into the silica networks. The process can happen in two trends as follows:

In the first trend, the synthesis of silica nanoparticles occurs followed by Ca2+ and PO43- adsorption on its surface.

In the second trend, Ca2+ and PO43- ions are introduced along with silica precursor prior to raise in pH to form particles. In this process, either TEOS/Ca2+/PO43- acidic mixture is added to an ammonia solution or concentrated NH4OH is drop wise added into TEOS/Ca2+/PO43- acidic mixture [13–22].

Microwave Synthesis

Recently microwave assisted synthesis technique is gaining more attention as it is a rapid and low-cost method. The precursors in water are irradiated with microwave and the obtained powder is washed, filter separated and dried in a hot air oven at 80°C and then calcined at 700°C to obtain bioactive glass [23].

It should be noted that sol-gel method for synthesis of bioactive glass is gaining attention around the globe. The lower stabilization temperature of about 700°C in the case of sol-gel technique as compared to the melt-quench method has raised its preference among researchers worldwide. In addition to this, gel derived bioactive glass showed compared dissolution and higher rate of HA formation compared to its melt-cast counterpart. Also gel-derived bioactive glass shows finer platelets of HA unlike melt-cast bioactive glass [24]. Thus we can say that the sol-gel derived bioactive glasses are preferred because of its higher compositional range of bioactivity and higher surface area that results in better binding to the living tissues [25]. In brief, using sol-gel chemistry, bioactivity can thus be controlled not only by the composition but also by the process in itself.

Top ↑

Fabrication of Bioactive Glass Coatings


Bioactive glasses can be used to impart bioactivity to metallic implants which are otherwise bioinert. The bone bonding ability of these glasses will avoid aseptic loosening of implants inside human body [26]. Cracking and poor reliability at the glass-metal interface has limited the success of bioactive glass coating on metallic implants. Selection of suitable deposition method and optimizing the glass composition should be given more attention to obtain a homogeneous and compact coating. Various techniques are available to fabricate bioactive glass coatings on implant surfaces which are discussed below:


To fabricate bioactive glass coatings by enameling, glass powder of size less than 50 µm obtained by milling in a ball mill are made into suspension in ethanol/isopropanol and the metal (Ti or Ti-alloy) is dipped into it while continuously stirring the suspension. The firing cycle can be done in air or nitrogen. The advantages of this method include its simplicity, low cost, and easy operation. The method has some disadvantages, if the firing temperature is less than 750°C, results in a porous coating with poor adhesion whereas temperature > 850°C results in dewetting and/or formation of bubbles. A temperature range 800 ≤ T < 850°C for a period less than 1 min results in coatings with excellent adhesion. Typical 45S5 bioactive glass cannot be used in this process as the difference in thermal expansion coefficient lead to complete crystallization of these glasses even at low firing temperature (700°C). Coatings belonging to the family of glasses in SiO2-Na2O-K2O-CaO-MgO-P2O5 system which has its coefficient of thermal expansion close to Ti alloys can be fabricated using this method [26–27].

Plasma Spray

The plasma spray process happens by injecting a gas flow into a chamber with gas temperature raised up to 10000K – 30000K by means of an electric arc and following accelerated flow through a nozzle, are forced to deposit on the metal surface as coating. The particles of grain size below 80 µm deposit one on another, thereby raising the coating thickness up to 100 µm. The advantages of the method include high deposition speed, reduced metal surface modifications and minimum size tolerance [28]. The structure of bioactive glass remains amorphous and hence the original properties are conserved during the process. The disadvantage of the process includes the development of residual tensile stress at the interface between coating and substrate due to coupled effect of coefficient of thermal expansion mismatch and fast cooling rate of coating material, the development of residual tensile stress can lead to cracking and delamination of the coating. The superior properties like bioactivity and preservation of amorphous nature even at high temperature are considered as great advantages that result in better performance and long term stability.

Pulsed Laser Deposition

The method comprises of irradiating the target (made of bulk bioactive glass) with a laser, expansion of the ablated products and interaction, nucleation and growth of the material on the substrate surface as a coating/thin film. The advantages of pulsed laser deposition technique are the (i) growth of materials with high melting point (ii) stoichiometry transfer of the target composition and (iii) absence of contamination.

Another variant of the process is Reactive Pulsed Laser Deposition (RPLD) where a gas phase chemistry process can be induced to form a new compound by a reaction between the reacting atmosphere and the energetic species in the plasma plume. The parameters influencing the thin films include: substrate temperature, laser wavelength, energy density, target properties, deposition rate and reactive atmosphere. The differences in morphological features obtained from laser ablated bioactive glass thin films may be attributed to the difference in thermal conductivity between the glass and the metallic substrates [29].


The ease to control chemical composition and possibility of low-temperature synthesis has made sol-gel technique an ideal method to prepare various materials. Coatings of bioactive glass can be obtained by simply dipping the substrates in sols and then withdrawing at suitable rates. The coatings are aged and dried at low temperatures and heated to 900°C to attain stability and adherence. The coatings developed, exhibited, tailored chemical composition, microstructure, crystallinity and adhesive strength [26–28].

Electrophoretic Deposition

The process of electrophoretic deposition consists of two steps: electrophoresis and deposition. The success of the method is due its simplicity, low cost and ability to deposit material on complex shaped substrates. The method also promises high purity and microstructural homogeneity of the deposits. The basic principle (shown in Figure 2) behind electrophoretic deposition is the movement of ionized particles under an electric field and its deposition onto one of the electrodes. The EPS process can be controlled by optimizing parameters like deposition voltage, current, concentration and time. After the deposition process, the coated substrates are dried and sintered at 800-1000°C. EPD can produce coatings with thickness from less than 1 µm to more than 500 µm [27,28], as shown in figure 3.

Figure 2: Electrophoretic Deposition (EPD) cell set up for bioactive glass deposition [93].

Top ↑

Ion Beam Assisted Deposition

One of the latest techniques in the field of thin film deposition is ion beam assisted deposition, where, energetic ion beam bombardment leads to film growth by a combination of ion implantation and vacuum deposition (PVD or CVD) [29]. Strong adhering films can be obtained by this method as the interface between substrate and film is mixed by high energy ions. The major disadvantage of this technique is its low deposition rate. Argon, oxygen and nitrogen are the common gases used in this process. The use of these gases adds to another disadvantage i.e. these gases can occupy the interstitial spaces between the thin film/coating formed leading to their contamination [29].

Ion Substituted Bioactive Glasses


The quest to enhance the physical and biomedical properties has led to the incorporation of various elements into the glass matrix which in turn influences the structure and bioactivity of these glasses [25].

Silver Based Bioactive Glasses

One of the major causes for implant failure is implant infections caused by the colonization of bacteria on the implant surfaces. This can lead to implant failure causing a revision surgery. Employing silver into bioactive glass as an antimicrobial agent has been investigated by various researchers. The ability of Ag2O to reduce into Ag in the presence of UV light is an important property that is exploited in Ag incorporated bioactive glass systems. Ag ions in a gel-glass system enables controlled and sustained release of antibacterial agent, which is useful for the preservation of antibacterial efficiency of bioactive glasses in the body fluids [25]. The antibacterial effect of these glasses can be due to either of the following reasons:

  • Interference with electron transport

  • Binding with DNA

  • Interaction with cell components [30,31]

Although silver release can hinder bone implant infections, higher concentrations of Ag are cytotoxic to the surrounding tissues. A concentration of 0.75–1 wt% is considered non toxic while a concentration equal or above 2 wt% is highly toxic to the surrounding cells/tissues. The structure of bioactive glass is influenced by the introduction of Ag into the matrix. The replacement of calcium with silver reduces the glass dissolution as it minimizes the number of non-bridging oxygen. Calcium is a divalent ion and hence produces two non-bridging oxygen groups whereas Ag is a monovalent ion, thereby producing only one non-bridging oxygen in the silica network [32].

Magnesium Based Bioactive Glasses

Magnesium is one of the most important elements present in human body parts like enamel, dentine and bone. It also forms part of many enzyme cofactors. The addition of MgO in bioactive glass matrix is found to decrease the glass transition temperature and dilatometeric softening point while it increases the thermal expansion coefficient. This effect can be attributed to the poorer bond strength of MgO in comparison to Si-O, which in turn weakens the overall glass structure. The presence of Mg in the glass matrix improves the glass dissolution and increases the silica layer thickness. However it is also reported that the rate of glass degradation decreases with increase in MgO content (above 7 mole %) thereby retarding the formation of apatite layer on the glass surface [33–35].

Zinc Based Bioactive Glasses

Zinc is known to have an important role in bone formation, both in vivo and in vitro. It helps in bone cell growth, development and differentiation. It also acts as a cofactor for many enzymes. It is reported that the incorporation of about 5 mol% of Zn into glass matrix does not alter the bioactivity [36] whereas a concentration of above 20 wt% can lead to drop in dissolution activity and incapability of glass to form HA [37]. A concentration less than 0.4 mol % shows rapid in vivo bioactive responses.

The replacement of CaO by ZnO, decreases the glass transition considerably. This happens because the tetrahedral ZnO42- ions formed requires Ca2+ for charge balance. This removes cations from the silica network and increases the number of bridging oxygen. The newly formed Si-O-Zn has much lower bond strength compared to Si-O-Si thereby reducing glass transition [38].

Aluminium Based Bioactive Glasses

Al2O3 in glass matrix enhances the long term stability by reducing the solubility as much as possible without affecting the bioactivity. It eliminates some of the non–bridging oxygen thereby bringing more network compactness. A strengthen glass structure with higher hardness is obtained by enhanced bond strength as a result of ionic link in alumina doped bioactive glass. It is reported that the dissolved Al ions from the glass-ceramic has an inhibiting effect on normal mineralisation of the surrounding bony tissues [39] up to 1.5 wt% of Al2O3 can be included in the glass matrix without causing any effect on bioactivity. If the concentration increases to 1.7 wt % no apatite is formed on the glass surface. The concentration of alumina required to suppress the bioactivity depends on the composition and chemical durability of the glass. Some borate glasses react rapidly in an aqueous solution, thus the amount of alumina required to suppress their bioactivity is expected to be higher [25]. Also it is reported that the thermal expansion coefficient of bioactive glass decreases with increased concentration of alumina. The change in aluminium coordination as a result of Al3+ ions between phosphate chain, creates stronger ionic cross linking that eventually decreases the thermal expansion coefficient [40].

Potassium Based Bioactive Glass

Substitution of sodium oxide with potassium oxide reduces crystallization tendency of bioactive glasses when treated at relatively higher temperature to enhance their properties. The coefficient of thermal expansion of K2O substituted glass is 13.8 × 10-6/K which is almost similar to that of 45S5 bioglass [12.7 x 10-6/K] [41]. The density and microhardness is also varied in the case of substituted glass as potassium oxide is heavier than Na2O. Potassium cations act as network modifiers and initiate the disruption of the continuity of the glass network by breaking Si-O-Si bonds which in turn creates new non-bridging oxygen groups. A higher concentration of K2O weakens the molecular network. Generally, formation of apatite layer in K-bioactive glass systems is inferior to K-free variety [42–45].

Fluoride Based bioactive Glass

The inclusion of fluoride ions improves the bone binding ability of bioactive glasses. These are known to have a stimulating influence on osteoblast cells when applied at concentrations in the range of 25-500 ng/ml, while concentrations more than 500 ng/ml can suppress osteoblast activity [46]. A higher fluoride can be toxic and lead to dental and skeletal fluorosis and promotes oxidative cell damage as designated by increased lactate dehydrogenase formation and accumulated extracellular Malondialdehyde when examined in contact with osteoblasts [47]. Fluoride doped glasses are able to form flourapatite [FAp] which is chemically more stable than HCA. These are commercially attractive for use in dental biomaterials as fluoride is known to inhibit the formation of alveolar cavities. A higher phosphate content is essential to obtain FAp glass ceramics with intact bioactive silicate phase. Also, apatite formation can occur within six hours on glasses with higher phosphate content. Thus glasses used in toothpastes should execute their function by making FAp before diluted by salivary actions [48]. It is reported that an increased content of CaF2 enhances the network connectivity of glasses [49] while it is also argued that the addition of fluorine has no influence on the network connectivity or concentration of non-bridging oxygen, but it is coordinated with Ca2+ [50]. It was observed that the substitution of Na2O by CaF2 reinforces the molecular network of the glass due to the formation of Si-O-Ca-O-Si groups whereas a replacement of CaO by CaF2 weakens the glass framework due to the formation of nano aggregates of Na+F- besides Ca2+F- [51].

Strontium Based Bioactive Glasses

Due to its similarity with calcium, a high concentration of Strontium (Sr) can accumulate in bone and replace calcium in metabolic processes [52]. Sr can be used to prevent and treat osteoporosis as it stimulates new bone formation and it inhibits osteoclast mediated resorption. Addition of strontium into glass matrix induces the adhesion of osteoblast like cells, Saos-2, thereby significantly improving the cytocompatibility of these glasses. An increased proliferation and alkaline phosphates activity was reported in cells cultured in contact with Sr-substituted bioactive glass [53]. It is to be noted that if calcium is replaced by strontium on a weight basis, HA can form faster whereas if strontium is substituted on a molar basis, the network structure of glass remains unaltered and the bioactivity is retained [54–56]. Presently, Sr-doped bioactive glass of composition 44.08 SiO2-24Na2O-21.60CaO-4.43SrO-5.88P2O5 systems is commercially available under the trade name stone bone TM [57].

Top ↑

Mechanism of Bioactivity


The structural difference between conventional glasses and bioactive glasses leads to the pronounced differences in their properties. The ability of bioactive glass to form more open silicate networks when in contact with body fluids imparts bioactivity to these materials [58]. As a result of ionic dissolution into the surrounding fluid, an apatite layer is formed which in turn leads to bone regeneration. The mechanism of apatite layer formation on bioactive glasses has been widely studied both in vivo and in vitro (Figure 3).

Figure 3: SEM micrograph of (a) Bioactive glass powder prepared by sol-gel Technique (b) Bioactive glass coating on Ti substrate deposited by EPD technique.


Apatite Layer Formation

When immersed in physiological fluids, bioactive glasses forms an apatite surface layer, which is the key to their bioactivity [59,60]. The term apatite comprises of a group of calcium orthophosphates, which allows for a wide variety of substitutions like CO3-, OH-, F- etc. the apatite layer formed on bioactive glass surface is mostly carbonate substituted (Hydroxy carbonate apatite, HCA). The stages of HCA formation in body fluid (both in vivo and in vitro) can be divided into five stages as below [61,62]:

  • Rapid cation exchange of Na+ and/Ca2+ with H+ from solution, creating silanol bonds (Si-OH) on the glass surface. The pH of the solution increases and a silica rich region forms near the glass surface. Phosphate if present in the composition is also lost from the glass.

  • High local pH leads to attack of the silica glass network by OH-, breaking Si-O-Si bonds. Soluble silica is lost in the form of Si (OH)4 to the solution, leaving more Si-OH (silanols) at the glass-solution interface.

  • Condensation of silanol groups at the glass surface and their further repolymersation leading to silica rich layer.

  • Migration of Ca2+ and PO43- groups to the surface through the silica rich layer, from the solution and forming amorphous CaO-P2O5 rich film.

  • Incorporation of carbonate and hydroxyl groups from solution to CaO-P2O5 film and crystallization thereof to form HCA (Figure 4).

 Figure 4: Sequence of interfacial reactions between bone and bioactive glass [91].

 Top ↑

The rate limiting step in the formation of HCA is the glass composition. Lower silica content indicates a lesser connected silica network that is prone to dissolution leading to a quicker completion of the above mentioned steps. The silica content is the key ingredient for network formation leading to bioactivity and as a thump rule, it can be stated that melt driven glasses with compositions containing more than 60% SiO2 are bioinert and non-bioactive and sol-gel glasses can be bioactive up to 90% SiO2 content.

Ionic Dissolution and Osteogenesis

The stages after HCA layer formation are less understood. The only explored fact is the types of protein that gets adsorbed onto HCA layer and induces cell attachment, differentiation and bone regeneration. Researchers have observed that human osteoblast cells when cultured on bioactive glass are able to produce extracellular matrix (ECM) without the need for usual supplements of hormones that are used to induce the same when other bioceramics are used [63–66]. It was observed that the ionic dissolution products from the bioactive glass (45S5) are able to trigger seven families of genes in primary human osteoblasts and also raise the intracellular calcium levels. The ability of bioactive glass to recruit osteoprogenitor cells in vivo and direct them to bone differentiation pathways are also studied [67,68]. In conclusion, the rate of dissolution and HCA layer formation promotes bioactivity and provides ability to bioactive glasses to stimulate bone regeneration at cellular levels.

Application of Bioactive Glasses in Orthodontics


One of the major disadvantages of any tooth surgery is the risk of contamination by microbes (both resident and transient oral bacteria). Calcium hydroxide suspension can be used as an efficient disinfectant but it has two drawbacks (i) it is relatively inefficient towards alkali resistant microbe (ii) it may reduce the flexural strength of dentine making it more prone to fracture. Bioactive glasses of type SiO2-Na2O-CaO-P2O5 is a possible alternative to calcium hydroxide [69–75]. These glasses not only help in dentine mineralisation but also exert an antimicrobial effect by releasing Na+ and Ca2+ or by raising pH by incorporating H3O+ protons into the medium. The release of silica, Ca2+ and P ions also kills the oral microbiota [76–79].

Application against Dentine Hypersensitivity

Dentine Hypersensitivity (DH) is a major oral health problem faced by people around the globe. The condition is characterised by severe pain arising in response stimuli, typically thermal, chemical or tactile [80]. The problem arises due to the exposure of dentinal tubules as the tooth’s natural enamel is worn off. However, it is now established that daily brushing with toothpaste containing bioactive glass can reduce dentine hypersensitivity.

Sensodyne toothpaste–commercially called NovaMin, is calcium sodium phosphosilcate bioactive glass with ionic forms of calcium and phosphorous that builds strong teeth. The composition of NovaMin includes 46 mol% SiO2, 26.9 mol% CaO, 24.4 mol% Na2O and 2.6 mol% P2O5 (Figure 5). The formulation of bioactive glass in NovaMin reacts with saliva, releases cations and opens silica rich layer that precipitates calcium phosphate on the glass leading to mineralisation of apatite resembles the natural enamel. Although this apatite layer is not permanent, continuous brushing with the toothpaste can maintain this layer thereby protecting the teeth from dentine hypersensitivity [81].

Figure 5: (a) ATR/FTIR Spectrum of original Novamin paste (b) SEM micrograph of Novamin particles at 35000X magnification [90].


BioMin is another example of toothpaste containing bioactive glass. BioMin not only addresses tooth sensitivity but also fights against tooth decay and acid erosion. BioMin contains fluorine as one of the ingredients and also has a higher phosphate content that silica as compared to the original NovaMin. BioMinF (fluoride containing BioMin) dissolves slowly by releasing calcium, phosphorous, and fluorine ions, stretching the release over 8-12 hours for long lasting protection. The fluroapatite formed by BioMinF is more resistant against acids produced by bacteria and also triggers remineralisation. The long lasting protection of BioMin is due to the presence of polymer that binds calcium on to the enamel [82].

Bioactive Glass for Tooth Fillings

Dental caries is one of the serious health issues faced by people worldwide. A number of dental restorative materials are available to seal the cavity formed by tooth decay. It would be a great step in the field of dentistry if the life of tooth filling composites can be prolonged. Recent researches have shown promising ability of bioactive glass to extend the life span of tooth filling composites when added to them as an ingredient. Studies have shown that the depth of bacterial penetration into the interface of the tooth filling containing bioactive glass is way smaller compared to composites that lack bioactive glasses. Tooth fillings will bioactive glass are expected to slow down secondary decay and also remineralize the lost filling material thereby prolonging the life of tooth fillers [83].

Top ↑

Application of Bioactive Glasses in Orthopaedics


Bioactive Glasses for Bone and Joint Infections

Chronic osteomyelitis is a disease characterised by the infection of bone marrow and cortex leading to severe bone loss. The problem is traditionally solved with intensive use of antibiotics. Recently it was discovered that antibacterial bioactive glass (S53P4) can be effectively used for fighting this disease. S53P4 bioactive glass is a synthetic and resorbable biomaterial comprising 53 mol% SiO2, 23 mol% Na2O, 20 mol% CaO and 4 mol% P2O5. Commercially it is manufactured and marketed as BonAlive® granules by BonAlive biomaterials Ltd in turku, Finland. The antimicrobial ability of S53P4 glass depends on two processes that occurs as the material reacts with the physiological fluids via

  • Release of sodium that elevates pH, which is unliked by the bacteria

  • Ionic dissolution from the surface that enhances osmotic pressure, thereby halting the bacterial growth.

The positive clinical effect of using S53P4 bioactive glass for treating chronic bone infection is exhibited as a combined effect of bacterial growth inhibition, bioactivity and bone growth promotion [84].

Bioactive Glass Coating for Metallic Implants

The common metals used for orthopaedic implants are cobalt alloys, SS 316L, Ti and Ti alloys. These metals are biocompatible inside body but there is always a risk about their corrosion products and a concern on their bioactivity. Bioactive glass can be used as an ideal material for the surface modification of metallic implants because

  • They enhance osseointegration of implants

  • Protects the metallic implants from the surrounding corrosive environment [85]

Coating the metallic implants with bioactive glass can be considered as a good approach to combine the mechanical properties, corrosion resistance and bioactivity in one material [86]. These glasses prevent the formation of fibrous tissue at the implant-bone interface and leads to a strong bond between the implant and tissue [87]. Imparting bioactivity to transition metal nitride thin films is yet another application of bioactive glasses. Fabricating a thin scaffold of bioactive glass (Figure 6) with polymer on to transition metal nitride thin films can enhance its osseointegration properties also improve the blood compatibility [88,89]. Recent researches have shown that a few families of bioactive glasses are able to bind with both hard and soft tissues without an intercede of fibrous tissue layer. Also these glasses are found to be non-allergic, non-cytotoxic and causes no immunogenic responses inside the body [90,91].

Figure 6: SEM micrograph of bioactive glass–PCL scaffold on titanium carbon nitride coated Ti-alloys [89].




Bioactive glass, since its discovery, has emerged as an important biomaterial, available in multiple forms for its users. The bioactivity of these glasses is related to the formation of a biologically active apatite layer on the surface of the glasses. Studies show that BGs are non-toxic and enhance cementoblast viability, metabolic and mitochondrial activity. They can be synthesized by a number of methods and can be applied on to different substrates in the form of coatings. Controlling the initial composition and processing parameters of BGs enhances their abilities of revascularization, differentiation of cells, enzyme activity and osteoblast adhesion. Considering the existing applications, there is a strong rationale for additional use in medicine and dentistry, and further research is needed to explore further applications. To successfully develop new compositions, it is necessary for researchers to take more structural approach when designing bioactive glasses.
Top ↑



  1. Larry L. Hench, Julian R. Jones. Bioactive Glasses: Frontiers and Challenges. Front Bioeng Biotechnol. 2015;3:194.
  2. Oonishi H, Hench LL, Wilson J, Sugihara F, Tsuji E, Matsuura M, et al. Quantitative comparison of bone growth behavior in granules of Bioglass (R), A-W glass-ceramic, and hydroxyapatite. J Biomed Mater Res. 2000;51(1):37–46.
  3. Charlotte V, Jean-Marie N. Bioactive Glass Nanoparticles: From Synthesis to Materials Design for Biomedical Applications. Materials. 2016;9(4):288–305.
  4. Andersson OH, Liu G, Karlsson KH, Niemi L, Miettinen J, Juhanoja J. In vivo behaviour of glasses in the SiO2­-Na2O­-CaO­-P2O5­-Al2O3­-B2O3 system. Journal of Materials Science: Materials in Medicine. 1990;1(4):219­–227.
  5. Kaur G, Pickrell G, Sriranganathan N, Kumar V, Homa D. Review and the state of the art: Sol–gel and melt quenched bioactive glasses for tissue engineering. J Biomed Mater Res Part B. 2015;104(6):1248–1275. doi: 10.1002/jbm.b.33443
  6. Brink M, Turunen T, Happonen R­P, Yli­ Urpo A. Compositional dependence of bioactivity of glasses in the system Na2O­-K2O­-MgO­-CaO­-B2O-P2O-SiO2. J Biomed Mater Res. 1997;37(1):114–21.
  7. Yamamuro T, Hench LL, Wilson J. Calcium phosphate and hydroxylapatite ceramics. Handbook of Bioactive Ceramics, Vol. 2.Boca Raton: CRC Press; 1990.
  8. Flory PJ. Chapter IX. Principles of Polymer Chemistry. Ithaca, NY: Cornel University Press; 1953.
  9. Hench LL, West JK. The sol-gel process. Chem Rev. 1990;90(1):33–72.
  10. West JK, Nikles R, LaTorre G. In Better Ceramics through Chemistry III, Vol. 121. In: Brinker CJ, Clark DE, Ulrich DR, editors. Pittsburgh, PA: Materials Research Society; 1988. p 219.
  11. V Aina, G Lusvardi, G Malavasi, L Menabue, C Morterra. Fluoride­ containing bioactive glasses: surface reactivity in simulated body fluids solutions. Acta Biomater. 2009;5(9):3548–62. doi: 10.1016/j.actbio.2009.06.009.
  12. Tsigkou O, Labbaf S, Stevens MM, Porter AE, Jones JR. Monodispersed bioactive glass submicron particles and their effect on bone marrow and adipose tissue-derived stem cells. Adv Healthc Mater. 2014;3(1):115–25. doi: 10.1002/adhm.201300126.
  13. Lukowiak A, Lao J, Lacroix J, Nedelec JM. Bioactive glass nanoparticles obtained through sol-gel chemistry. Chem Commun (Camb). 2013;49(59):6620–2. doi: 10.1039/c3cc00003f.
  14. Hong Z, Luz GM, Hampel PJ, Jin M, Liu A, Chen X, Mano JF. Mono-dispersed bioactive glass nanospheres: Preparation and effects on biomechanics of mammalian cells. J Biomed Mater Res A. 2010;95(3):747–54. doi: 10.1002/jbm.a.32898.
  15. Ajita J, Saravanan S, Selvamurugan N. Effect of size of bioactive glass nanoparticles on mesenchymal stem cell proliferation for dental and orthopedic applications. Mater Sci Eng C Mater Biol Appl. 2015;53:142–9. doi: 10.1016/j.msec.2015.04.041.
  16. Fan JP, Kalia P, Di Silvio L, Huang J. In vitro response of human osteoblasts to multi-step sol-gel derived bioactive glass nanoparticles for bone tissue engineering. Mater. Sci. Eng. C 2014;36:206–214.
  17. Luz GM, Mano JF. Nanoengineering of bioactive glasses: Hollow and dense nanospheres. J. Nanopart. Res. 2013;15:1–11.
  18. El-Kady AM, Ali AF, Farag MM. Development, characterization, and in vitro bioactivity studies of sol-gel bioactive glass/poly(L-lactide) nanocomposite scaffolds. Mater. Sci. Eng: C. 2010;30(1):120–131.
  19. El-Kady AM, Ali AF, Rizk RA, Ahmed MM. Synthesis, characterization and microbiological response of silver doped bioactive glass nanoparticles. Ceram Int. 2012;38:177–188.
  20. Delben JRJ, Pimentel OM, Coelho MB, Candelorio PD, Furini LN, dos Santos FA, et al. Synthesis and thermal properties of nanoparticles of bioactive glasses containing silver. J. Therm. Anal. Calorim. 2009;97:433–436.
  21. Xia W, Chang J. Preparation and characterization of nano-bioactive-glasses (NBG) by a quick alkali-mediated sol-gel method. Mater. Lett. 2007;61;3251–3253.
  22. Zhang J, Wang M, Cha JM, Mantalaris A.  The incorporation of 70s bioactive glass to the osteogenic differentiation of murine embryonic stems cells in 3D bioreactors. J Tissue Eng Regen Med. 2009(1):63-71. doi: 10.1002/term.135
  23. Sayed MR, Neda N, Misaq A, Daryoosh V, Lobat T. Effect of ion substitution on Properties of bioactive glasses: A review. Ceramics International. 2015;41(6): 7241–7251.
  24. Jie Ma, Chuanzhong Chen, Liang Yao, Quanhe Bao. Characterization of Some Methods of Preparation for Bioactive Glass Coating on Implants. Surface Review and Letters. 2006;13(1):93–102.
  25. Chuan ZC, Xian GM, Hui JY, Han Y, Ting H, Dian GW, et al. A Review of Coating Preparing Techniques of Bioactive Glass. Advanced Materials Research. 2014;833:202–207.
  26. Gabbi C, Cacchioli A, B Locardi, Guadagninol . Bioactive glass coating: physicochemical aspects and biological findings. Biomaterials. 1995;16(7):515–20.
  27. Yafan Z, Chuanzhong C, Diangang W. The Current Techniques for Preparing Bioglass Coatings. Surface Review and Letters. 2005;12(4):505–513.
  28. Efrima S, Brank BV. Silver colloids impregnating or coating bacteria. The journal of physical chemistry B. 1998;102(31):5947–5950.
  29. Liau SY, Read DC, Pugh WJ, Furr JR, Russell AD. Interaction of silver nitrate with readily identifiable groups: relationship to the antibacterial action of silver ions. Lett Appl Microbiol. 1997;25(4):279–83.
  30. Solioz M, Odermatt A. Copper and silver transport by copB-ATPase in membrane
    vesicles of enterococcus hirae. The journal of biological chemistry. 1995;270(16) :9217–9221.
  31. Dietrich E, Oudadesse H, Lucas-Girot A, Mami M. In vitro bioactivity of melt-derived glass 46S6 doped with magnesium. Journal of biomedical materials research. 2009;88A(4):1087–1096.
  32. Watts SJ, Hill RG, O'Donnell MD, Law RV. Influence of magnesia on the
    structure and properties of bioactive glasses. Journal of non-crystalline solids. 2010;356 (9-10):517–524.
  33. Oliveira JM, Correia RN, Fernandes MH. Effects of Si speciation on the in vitro
    bioactivity of glasses. Biomaterials. 2002;23(2):371–379.
  1. Balamurugan A, Balossier G, Kannan S, Michel J, Rebelo AH, Ferreira JM.
    Development and in vitro characterization of sol–gel derived CaO–P2O5–SiO2–ZnO
    bioglass. Acta Biomater. 2007 Mar;3(2):255–62.
  2. Aina V, Malavasi G, Fiorio Pla A, Munaron L, Morterra C. Zinc-containing bioactive glasses: Surface reactivity and behaviour towards endothelial cells. Acta Biomater. 2009;5(4):1211–22. doi: 10.1016/j.actbio.2008.10.020
  3.  Shahrabi S, Hesaraki S, Moemeni S, Khorami M. Structural discrepancies and in vitro nanoapatite formation ability of sol-gel derived glasses doped with different bone stimulator ions. Ceramics international. 2011;37(7):2737–2746.
  4.  Ohtsuki C, Kokubo T. Compositional dependence of bioactivity of glasses in the system CaO-SiO2-Al2O3: it’s in vitro evaluation. Journal of materials science: materials in medicine. 1992;3(2):119–125.
  5.  El-Kheshen AA, Khaliafa FA, Saad EA, Elwan RL. Effect of Al2O3 addition on bioactivity, thermal and mechanical properties of some bioactive glasses. Ceramics
    international. 2008;34(7):1667–1673.
  6.  Cannillo V, Sola A. Potassium-based composition for a bioactive glass. Ceramics
    international. 2009;35(8):3389–3393.
  7. Marikani, Maheswaran A, Premanathan M, Amalraj L. Synthesis and
    characterization of calcium phosphate based bioactive quaternary P2O5–CaO–Na2O–K2O glasses. Journal of non-crystalline solids. 2008;354(33): 3929–3934.
  8.  Serra J, Gonzalez P, Liste S, chiussi S, Leon B, Perez-amor M, et al. Influence of non-bridging oxygen groups on the bioactivity of silicate glasses. Journal of materials science: materials in medicine. 2002;13(12):1221–1225.
  9.  Salman SM, Salama SN, Abo-Mosallam HA. The role of strontium and potassium
    on crystallization and bioactivity of Na2O–CaO–P2O5–SiO2 glasses. Ceramics international. 2012;38(1):55–63.
  10. Vitale BC, Verne E, Appendino P. Macroporous bioactive glass-ceramic
    scaffolds for tissue engineering. Journal of materials science: materials in medicine. 2006;17(11):1069–1078.
  11.  Pak CYC, Zerwekh J E, Antich P. Anabolic effects of fluoride on bone. Trends in endocrinology and metabolism. 1995;6(7):229–234.
  12.  Li L. The biochemistry and physiology of metallic fluoride: action, mechanism, and
    implications, Critical reviews in oral biology and medicine. 2003;14(2):100–114.
  13. Furqan A Shah. Fluoride-containing bioactive glasses: Glass design, chemistry, in vitro bioactivity, cellular interactions, and recent developments. Mater Sci Eng C Mater Biol Appl. 2016;58:1279-89. doi: 10.1016/j.msec.2015.08.064
  14. Lusvardi G, Malavasi G, Cortada M, Menabue L, Menziani MC, Pedone A, et al. Elucidation of the structural role of fluorine in potentially bioactive glasses by
    experimental and computational investigation. J Phys Chem B. 2008;112(40):12730-9. doi: 10.1021/jp803031z
  15.  Hayashi M, Nabeshima N, Fukuyama H, Nagata K. Effect of fluorine on silicate
    network for CaO–CaF2–SiO2 and CaO–CaF2–SiO2–FeOx glasses. ISIJ International. 2002;42(4):352–358.
  16.  Lusvardi G, Malavasi G, Tarsitano F, Menabue L, Menziani M C, Pedone A.
    Quantitative Structure-Property Relationships of Potentially Bioactive Fluoro Phosphosilicate Glasses. The journal of physical chemistry B. J Phys Chem B. 2009;113(30):10331-8. doi: 10.1021/jp809805z
  17.  Usuda K, Kono K, Dote T, Watanabe M, Shimizu H, Tanimoto Y, Yamadori E, An overview of boron, lithium, and strontium in human health and profiles of these elements in urine of Japanese. Environ Health Prev Med. 2007;12(6):231–237. doi:  10.1007/BF02898029.
  18. Gentleman E, Fredholm YC, Jell G, Lotfibakhshaiesh N, O'Donnell MD, Hill RG. The effects of strontium-substituted bioactive glasses on osteoblasts and osteoclasts in vitro. Biomaterials. 2010 May;31(14):3949–56. doi: 10.1016/j.biomaterials.2010.01.121.
  19.  Lao J, Jallot E, Nedelec JM. Strontium-Delivering Glasses with Enhanced Bioactivity: A New Biomaterial for Antiosteoporotic Applications. Chemistry materials.  2008;20(15):4969–4973.
  20.  Lao J, Nedelec JM, Jallot E. New strontium-based bioactive glasses: physicochemical reactivity and delivering capability of biologically active dissolution products. Journal of materials chemistry. 2009;19:2940–2949.
  21.  O’Donnell MD, Hill RG. Influence of strontium and the importance of glass
    chemistry and structure when designing bioactive glasses for bone regeneration. Acta biomaterialia. 2010;6(7):2382–2385.
  22.   Hill RG, Stevens MM. Bioactive glass. US Patent, US 2009/0208428 A1. 2009.
  23. Delia S Brauer. Bioactive Glasses—Structure and Properties. Angew Chem Int Ed. 2015;54(14):2–24.
  24. Julian R Jones. Review of bioactive glass: From Hench to hybrids. Acta Biomater. 2013;9(1):4457–6. doi: 10.1016/j.actbio.2012.08.023
  25. Waltimo T, Mohn D, Paque F, Brunner TJ, Stark WJ, Imfeld T, et al. Fine-tuning of bioactive glass for root canal disinfection. J Dent Res. 2009;88(3):235–38.
  26. Clark AE, Pantano CG, Hench LL. Auger spectroscopic analysis of Bioglass corrosion films. J Am Ceram Soc. 1976;59(1-2):37–9.
  27. Hench LL. Bioceramics – from concept to clinic. J Am Ceram Soc. 1991;74(7):1487–510.
  28. Gough JE, Jones JR, Hench LL. Nodule formation and mineralisation of human primary osteoblasts cultured on a porous bioactive glass scaffold. Biomaterials. 2004;25(11):2039–46.
  29. Kaufmann E, Ducheyne P, Shapiro IM. Evaluation of osteoblast response to porous bioactive glass (45S5) substrates by RT-PCR analysis. Tissue Eng. 2000;6(1):19–28.
  30. Bosetti M, Cannas M. The effect of bioactive glasses on bone marrow stromal cells differentiation. Biomaterials. 2005;26(18):3873–9.
  31. Jones JR, Tsigkou O, Coates EE, Stevens MM, Polak JM, Hench LL. Extracellular matrix formation and mineralization of on a phosphate-free porous bioactive glass scaffold using primary human osteoblast (HOB) cells. Biomaterials. 2007;28(9):1653–63.
  32. Jell G, Notingher I, Tsigkou O, Notingher P, Polak JM, Hench LL, et al. Bioactive glass-induced osteoblast differentiation: a noninvasive spectroscopic study. J Biomed Mater Res A. 2008;86(1):31–40.
  33. Tsigkou O, Jones JR, Polak JM, Stevens MM. Differentiation of fetal osteoblasts and formation of mineralized bone nodules by 45S5 Bioglass conditioned medium in the absence of osteogenic supplements. Biomaterials. 2009;30(21):3542–50. doi: 10.1016/j.biomaterials.2009.03.019
  34. Prabhakar AR, Kumar SCH. Antibacterial effect of bioactive glass in combination with powdered enamel and dentin. Indian J Dent Res. 2010;21(1):30-4. doi: 10.4103/0970-9290.62807
  35. Beach CW, Calhoun JC, Bramwell JD, Hutter JW, Miller GA. Clinical evaluation of bacterial leakage of endodontic temporary filling materials. J Endod. 1996;22(9):459–62.
  36. Siren EK, Haapasalo MP, Ranta K, Salmi P, Kerosuo EN. Microbiological findings and clinical treatment procedures in endodontic cases selected for microbiological investigation. Int Endod J. 1997;30(2):91–5.
  37. Engstrom B. The significance of Enterococci in root canal treatment. Odontol Revy 1964;15:87–106.
  38. Bystrom A, Claesson R, Sundqvist G. The antibacterial effect of camphorated paramonochlorophenol, camphorated phenol and calcium hydroxide in the treatment of infected root canals. Endod Dent Traumatol. 1985;1(5):170–5.
  39. Evans M, Davies JK, Sundqvist G, Figdor D. Mechanisms involved in the resistance of Enterococcus faecalisto calcium hydroxide. Int Endod J. 2002;35(3):221–8.
  40. Grigoratos D, Knowles J, Ng YL, Gulabivala K. Effect of exposing dentine to sodium hypochlorite and calcium hydroxide on its flexural strength and elastic modulus. Int Endod J. 2001;34(2):113–9.
  41. Zehnder M, Soderling E, Salonen J, Waltimo T. Preliminary evaluation of bioactive glass S53P4 as an endodontic medication in vitro. J Endod. 2004;30(4):220–4.
  42. Allan I, Newman H, Wilson M. Antibacterial activity of particulate bioglass against supra- and subgingival bacteria. Biomaterials. 2001;22(12):1683–7.
  43. Zehnder M, Waltimo T, Sener B, Soderling E. Dentin enhances the effectiveness of bioactive glass S53P4 against a strain of Enterococcus faecalis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101(4):530–5.
  44. Anusha Thampi VV. Hydroxyapatite, alumina/zirconia, and nanobioactive glass cement for tooth-restoring applications. Ceramics International. 2014;40(9):14355–14365.
  45. Anthony LB Macon, Esther M Valliant, Jonathan S Earl, Julian R. Jones. Bioactivity of toothpaste containing bioactive glass in remineralizing media: effect of fluoride release from the enzymatic cleavage of monofluorophosphate. Biomed. Glasses 2015;1(1):41–50.
  46. Corvallis. Full article available at:  2015.
  47. Gocha A. BioMinbioglass toothpaste may better protect sensitive teeth and find its way into US market. The American Ceramic Society. 2016. Available from:
  48. Breakthrough toothpaste ingredient hardens your teeth while you sleep. EurekAlert! Science News. Public Release. 2016.
  49. Drago L, Romanò D, De Vecchi E, Vassena C, Logoluso N, Mattina R, et al. Bioactive glass BAG­-S53P4 for the adjunctive treatment of chronic osteomyelitis of the long bones: an in vitro and prospective clinical study. BMC Infect Dis. 2013;13:584. doi: 10.1186/1471-2334-13-584.
  50. Drnovšek N, Novak S, Dragin U, Ceh M, Gorenšek M, Gradišar M. Bioactive glass enhances bone ingrowth into the porous titanium coating on orthopaedic implants. Int Orthop. 2012;36(8):1739–45. doi: 10.1007/s00264-012-1520-y.
  51.  Fathi MH, Doostmohammadi A. Bioactive glass nanopowder and bioglass coating for biocompatibility improvement of metallic implant. journal of materials processing technology. 2009;209:1385–139.
  52. Sehrooten J, Helsen JA. Adhesion of bioactive glass coating to Ti6Al4V oral implant. Biomaterial. 2000;21(14):1461–1469.
  53. Oliva A, Salerno A, Locardi B, Riccio V, Della Ragione F, Iardino P, et al. Behaviour of human osteoblasts cultured on bioactive glass coatings. Biomaterial. 1998;19(11-12):1019–1025.
  54.  Anusha TVV, Subramanian B. Enhancement of bioactivity of pulsed magnetron sputtered TiCxNy with bioactive glass (BAG) incorporated polycaprolactone (PCL) composite scaffold. Journal of Alloys and Compounds. 2015;649:1210–1219.
  55. Sepulveda P, Jones JR, Hench LL. Bioactive sol–gel foams for tissue repair. J Biomed Mater Res. 2002;59(2):340–8.
  56. Hench LL, Polak.  Third-generation biomedical materials. Science. 2002;295(5557):1014–7.
  57.  Wang Z, Jiang T, Sauro S, Pashley DH,  Toledano M, Osorio R, et al. The dentine remineralization activity of a desensitizing bioactive glass-containing toothpaste: an in vitro study. Aust Dent J. 2011;56(4):372–81. doi: 10.1111/j.1834-7819.2011.01361.x.
  58. Larry LH. Chronology of Bioactive Glass Development and Clinical  applications. New Journal of Glass and Ceramics. 2013;3(2):67–73.
  59. Sohrabi M, Hesaraki S, Kazemzadeh A, Alizadeh M. Development of injectable biocomposites from hyaluronic acid and bioactive glass nano-particles obtained from different sol–gel routes.  Mater. Sci. Eng: C. 2013;33(7):3730–3744.
  60.  Boccaccini AR, Keim S, Ma R, Li Y, Zhitomirsky I. Electrophoretic deposition of biomaterials. J R Soc Interface. 20106;7 Suppl 5:S581-613. doi: 10.1098/rsif.2010.0156.focus.

Top ↑

Copyright: © 2017 Anusha T VV, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.