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https://doi.org/10.4155/tde.11.84

1

Mesoporous bioactive glasses as drug delivery and bone tissue

regeneration platforms

Chengtie Wu1,2, Jiang Chang1, Yin Xiao2

1. State Key Laboratory of High Performance Ceramics and Superfine Microstructure,

Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, People’s

Republic of China.

2. Institute of Health & Biomedical Innovation, Queensland University of Technology,

Brisbane, Queensland 4059, Australia.

Corresponding-Author E-mail: chengtie.wu@qut.edu.au (C. Wu).

Tel: 61-7-31386099; Fax: 61-7-31386030.

2

The use of mesoporous bioactive glasses (MBG) for drug delivery and bone tissue

regeneration has grown significantly over the past 5 years. In this review, we highlight the

recent advances made in the preparation of MBG particles, spheres, fibers and scaffolds. The

advantages of MBG for drug delivery and bone scaffold applications are related to this

material’s well-ordered mesopore channel structure, superior bioactivity, and the application

for the delivery of both hydrophilic and hydrophobic drugs. A brief forward-looking

perspective on the potential clinical applications of MBG in regenerative medicine is also

discussed.

Key Terms: mesoporous bioactive glass; drug delivery; bone tissue engineering;

bioactivity

Mesoporous bioactive glass: A new class of bioglass can be used for bone repair. It has

ordered mesopore channel structure and the pore size is in the range of 2-50 nm.

Drug delivery: is the method of administering a pharmaceutical compound to achieve a

therapeutic effect in humans or animals.

Bone tissue engineering: is a multidisciplinary field that applies the principles of biology and

engineering to develop tissue substitutes to restore, maintain, or improve the function of

diseased or damaged human tissues.

Bioactivity: Specific effect on, or a reaction in, living animal or human tissue upon exposure

to a substance.

3

1. The development of bioactive glasses

Over the past three decades bioactive glasses have played an increasingly important role in

bone tissue regeneration application by virtue of their excellent osteoconductivity, mechanical

strength, and generally good degradation rate. Several different types of bioactive glasses

have been investigated for their potential use for bone tissue regeneration. The development

of bioactive glasses has undergone three major stages according to their method of

preparation. The first generation bioactive glass, the melt-derived bioactive glass, was

pioneered by Hench [1,2]; the 45S5® bioactive glass was first developed using traditional melt

method at high temperature (1300-1500oC). Subsequently, Hench et al. conducted a large

number of in vivo experiments and confirmed that 45S5® was bioactive and able to bond

closely with the host bone tissue [1], and offered proof of its potential use as a bone substitute

material. The mechanism behind new bone formation on bioactive glass is closely associated

with the release of Na+ and Ca2+ ions and the deposition of a carbonated hydroxyapatite

(CHAp) layer. The apatite layer forms a strong chemical bond between 45S5 bioactive glass

and host bone [1]. Further studies have also shown that the Ca and Si released from the 45S5®

contribute to its bioactivity, as both Ca and Si are found to stimulate osteoblast proliferation

and differentiation [3-7]. Xynos et al. found that the expression of a potent osteoblast

mitogenic growth factor, insulin-like growth factor II (IGF-II) was increased up to 32% on the

exposure of osteoblasts to 45S5® [6], indicating that Ca and Si ions from 45S5® may increase

IGF-II expression in osteoblasts and possibly regulate the dissociation of this protein from the

IGF-II binding protein. Unbound IGF-II is thus likely to precipitate the increase in cell

proliferation observed in cell culture experiments, a feature which opened an entirely new

4

perspective of 45S5® glasses for bone tissue regeneration. Brennan et al. reported that 45S5®

glasses are able to absorb collagen in body environment [8]. Recently, melt-derived bioactive

glass scaffolds have been prepared for bone tissue engineering [9,10]. The 45S5® bioactive

glass is still considered to be the gold standard for bioactive glasses, although melt-derived

bioactive glass has a number of limitations. One of these limitations is the fact that it needs to

be melted at a very high temperature (>1300 oC) and another is its lack of a microporous

structure inside the materials; therefore, its bioactivity mainly depends on the contents of SiO2.

In melt-derived bioactive glass with SiO2 content lower than 53 mol.%, CHAp formation

occurs in one day under in vitro conditions and also bond rapidly to both bone and soft tissue

under in vivo conditions [11,12]. Bioactive glasses with SiO2 contents ranging from 53 to 58

mol.% develop an CHAp layer within 2 to 3 days under in vitro conditions. When implanted,

these materials only exhibit bone bonding and osteoconduction behavior. When the SiO2

content exceeds 60%, the bioactive glass does not develop an CHAp layer even after several

weeks in simulated body fluid (SBF) and fails to bond to either bone or to soft tissues [13].

The main reason is that high SiO2-containing glasses have stable net structure and are not

easy to release Na+ and Ca2+, leading to inadequate OH- groups on the surface of glasses to

induce apatite formation.

In the early 1990s, in an effort to overcome the limitation of melt-derived bioactive glass, Li

and colleagues synthesized a new class of bioactive glasses using sol-gel method, which

became known as the second generation bioactive glasses [14]. They were able to

demonstrate that this class of materials was bioactive in a wider compositional range when

compared with traditional melt-derived bioactive glasses. The glasses in the SiO2-CaO-P2O5

5

system had a silica content of up to 90% and were still capable of inducing the formation of

apatite layers, compared to the 60% SiO2 boundary of the melt-derived bioactive glasses [15].

Due to its greater surface area and porosity–properties derived from the sol–gel process, the

range of bioactive compositions for sol-gel-derived biolgasses is wider, and compared to

melt-derived bioactive glasses, these bioactive glasses exhibit higher bone bonding rates

coupled with excellent degradation and resorption properties [13,16,17]. Although traditional

sol-gel derived bioactive glass has better composition range and bioactivity than melt-derived

bioactive glass, the micropore distribution is not uniform and inadequate for efficient drug

delivery [18].

Porous materials can be divided into three categories according to their pore size. The pore

size for micropores, mesopores and macropores are defined as lower than 2nm, 2-50nm and

higher than 50nm, respectively. Mesoporous bioactive glasses (MBG) are considered the

third-generation of bioactive glasses and were developed in 2004 by the combination of

sol-gel method and supramolecular chemistry of surfactants [19,20]. These materials are

based on a CaO-SiO2-P2O5 composition and have a highly ordered mesopore channel

structure with a pore size ranging from 5–20 nm (See Figure 1). Compared to non-mesopore

bioactive glass (NBG), MBG possesses a more optimal surface area, pore volume, improved

in vitro apatite mineralization in simulated body fluids and excellent cytocompatibility

[20-23]. These are significant advantages and MBG is the best candidate material to be used

as a platform for efficient drug delivery [22] and bone tissue engineering. The study of MBG

for drug delivery and bone tissue engineering has been a hot area of research during the past

five years. Pure mesoporous SiO2 materials, such as Mobil Composition of Matters

6

(MCM)-41 and hexagonal mesoporous silica (SBA-15), have been shown to have too slow in

vitro apatite mineralization to be considered as bioactive bone grafts [24,25]; therefore, the

current MBG materials are mainly based on CaO-SiO2-P2O5 composition. Our group has

systematically studied the in vitro and in vivo behavior of MBG based on the latter

composition. Therefore, in this article, we mainly review the current research progress of

MBG based on CaO-SiO2-P2O5 composition for drug delivery and bone tissue engineering

application.

2. Preparation and characterization of MBG particles, spheres and fibers with

well-ordered mesopore channel structure and excellent bioactivity

The current method for preparing MBG is mainly acheived by incorporating non-ionic

surfatants (triblock copolymers, P123, F127, e.g.) into the reaction system [19,20]. The

incorporation of structure-directing agents is essential for successfully obtaining structures

with ordered mesopores; under appropriate synthesis conditions, these molecules

self-organize into micelles. The micelles link the hydrolyzed silica precursors through the

hydrophilic component and self-assembly to form an ordered mesophase. The ordering of the

material depends on factors such as, surfactant chemistry (ionic, non-ionic, polymeric, etc.)

and concentration, organic:inorganic phase volume ratio, temperature, and pH. Once the

product is dried and the surfactant removed (calcined or extracted with solvents), a

mesoporous structure is obtained, which exhibits a large surface area and porosity [13]. Using

this system it is currently possible to manufacture MBG powders, microspheres and fibers.

The textural characteristics of current MBG materials are mainly listed in Table 1.

7

2.1 MBG particles

The first ever MBG powders were prepared with the following compositions: 100Si,

80Si15Ca5P, 70Si25Ca5P and 60Si35Ca5P), and using P123 or F127, tetraethyl orthosilicate,

Ca(NO3)2·4H2O, triethyl phosphate, HCl and ethanol solvents. The P123 was removed by

calcining at 700 oC and highly-ordered MBG powders were obtained. The MBG particles had

high BET surface area (350 m2/g), pore volume (0.5 cm3/g) and well-ordered mesopore

channels (5 nm) [19]. In vitro assays revealed that this new class of MBG had significantly

improved apatite mineralization ability compared to non-mesoporous bioactive glasses (or

normal bioactive glasses, hereinafter referred as NBG) [20]. Besides the mesopore structure

of MBG, the chemical composition of MBG is the other important factor to influence in vitro

apatite mineralization in simulated body fluids. Apatite formation ability of MBG in SBF can

be modulated by changing their composition in the following sequence: 80Si15Ca5P >

70Si25Ca5P > 60Si35Ca5P > 100Si. Furthermore, MBG with different mesopore morphology

can be prepared by controlling preparation conditions [26]. Using acetic acid as a

structure-assisted agent and hydrolysis catalyst, Lei et al. synthesized MBG powders with

high specific surface area [27], and Xia et al. used P123 and hydrothermal treatment at 100oC

to prepare MBG powders (58Si23Ca9P and 77Si14Ca9P), both of which were shown to have

excellent in vitro bioactivity [28,29]. By incorporating Mg, Zn and Cu to replace parts of Ca

to prepare a multi-component MBG particles, Li et al. found that the apatite-formation ability

of MBG could be fine tuned [30].

2.2 MBG microspheres

8

MBG microspheres have also been prepared; these are defined as mesoporous hollow

bioactive glass microspheres with a uniform diameter range of 2–5 µm and a mesoporous

shell (500 nm) and can be prepared by a sol-gel method using polyethylene glycol (PEG) as a

template [31]. Zhao, et al. prepared MBG microsphere with high P2O5 contents (up to 15%),

and an approximate size of 4-5µm, by using co-surfactants of P123 and

cetyltrimethyl-ammonium bromide (CTAB) [32]. They found that the increase of P2O5

content in the MBG system enhances the surface area and pore volume and that this

significantly improved the in vitro bioactivity [32]. Applying CTAB as a template to prepare

MBG, Yun et al. produced nanospheres with both a large specific surface area (1040 m2/g) and

pore volume (1.54 cm3/g) [33]; the size of MBG nanospheres can furthermore be controlled

over a diameter range of 20 to 200 nm by the addition of various amounts of CaO.

2.3 MBG fibers

Interestingly, MBG can be prepared as ultrathin fibers by electron spin techniques pioneered

by Hong et al [34]. In their study, ultrathin MBG fibers, with hierachal nanoporosities and

high matrix homogeneities, were synthesized using electrospinning technique and P123-PEO

co-templates [34]. At the same time, by controlling the electrospinning conditions, they were

able to prepare MBG fibers with hollow cores and mesoprous walls; these fibers were found

to be highly bioactive [35].

3. MBG for efficient drug delivery

MBG materials have significantly improved surface area, nanopore volume and special

nano-channel structure, and for this reason they have been widely used for drug delivery in

9

the forms of powders, fibers, disks, microspheres, MBG/polymer composites and 3D

scaffolds.

3.1 MBG powders and fibers

Gentamicin was loaded into MBG particles by adsorption method by Xia et al. [29]; they

found that the amount of drugs capable of being loaded into MBG was three times more than

that of NBG and that MBG effectively decreased the initial burst release and released

gentamicin from the MBG at a much lower release rate, compared to NBG when soaked in

distilled water or SBF. Furthermore, the drug release was sensitive to the pH and ionic

concentration of the release medium, indicating that MBG is a promising drug delivery

system. The potential mechanism of MBG with a slow drug release rate is due to the

existence of great amounts of Si–OH groups in MBG, which play an important role in

interacting with gentamicin [29]. The surfactant plays an important role to influence the

loading and release of drug from MBG powders; P123-MBG has significantly higher loading

efficiency for drug (47.3%) than F127-MBG (16.6), which is attributed to the higher pore

volume and surface area for P123-MBG [36]. In another study, a photo-responsive coumarin

derivative was grafted onto MBG particles to develop photo-controlled molecular gates. Such

rapidly photo-responsive and biocompatible MBGs can be used as a novel function

nanocarrier with potential for drug delivery and disease therapy [37]. Magnetic MBG

particles can be made by incorporating parts of Fe3+ ions. Parts of Fe3O4 phase are formed in

MBG, contributing to the magnetic properties. Ibuprofen storage and release from magnetic

MBG powders show adjustable loading amounts from 199 to 420 mg/g with a sustained drug

release property [38]. Magnetic MBG could be applicable for selectively targeted drug

10

delivery and hyperthermia treatment of bone tumors [38]. Furthermore, hydrophobic model

drug, ipriflavone (an anti-osteoporotic drug) can also be loaded in silanol-functionalized

MBG powders. By tailoring the hydrophobicity of the surface with functional groups, the

drug-material link can be tuned, thereby ensuring the long-term delivery of ipriflavone [39].

MBG fibers could also be used for the drug carriers for an efficient drug delivery. The drug

loading capacity and drug release behavior of the MBG fibers strongly depends on the fiber

length; MBG fibers with fiber length >50µm are excellent carriers for drug delivery. The

shortening of the fiber length reduces drug loading amounts and accelerates its release [35].

The nanopore size in MBG fibers plays an important role to influence the loading and release

of drugs. When the pore size decreases, both surface area and pore volume increase. The drug

loading capacity increases and larger amounts of drug can be released in a controlled manner

from the fibers [34]. MBG disks of various compositions were successfully loaded with

tetracycline (TC); the TC was found to be loaded into the mesopores and by increasing the

CaO content in the MBG the loading ratio of TC/MBG could be increased as well. The drug

release behaviors of MBGs can be controlled by tailoring their composition and high

CaO-containing MBGs have a slow release profile and burst release [40]. The possible reason

is that TC will be chelated with calcium on the pore wall, which makes TC difficult to release

[40].

3.2 MBG microspheres

Recently we developed MBG microspheres for efficient protein delivery by a biomimetic

method [41]. Large sizes MBG microspheres with uniform morphology and a loose

microstructure (See Figure 2) can readily be prepared by the method of combining alginate

11

cross-linking CaCl2 with heat treatment. The protein-loading efficiency of MBG microspheres

is significantly enhanced by co-precipitating with apatite, and it appears that both the loading

efficiency and release kinetics of protein can be controlled by controlling the density of the

apatite formed on MBG microspheres by altering the soaking time in SBF [41]. In Figure 2-7,

our aim is to show that mesopore bioactive glass can be prepared to be different forms of

materials, such as microspheres, composite film and porous scaffolds. They contain

well-ordered mesopore channels in their inner of matrix. As we have shown that the

well-ordered mesopore channel structure of mesopore bioactive glass in Figure 1, we did not

show this structure in every form of MBG materials.

3.3 MBG composites

MBG can be used for the preparation of inorganic-organic composites with a controllable

drug function. In our own study, we have incorporated MBG, NBG and HAp powders into

alginate microspheres. MBG has significantly different dissolution compared to NBG and

HAp, and the drug loading and release kinetics of alginate microspheres can effectively be

controlled by their dissolution of the inorganic ions [42]. By incorporating MBG into PLGA

microspheres Li et al. produced a composite system with a slower release kinetic than pure

MBG and a more sustained drug delivery [43]. A novel dual-drug delivery system based on

MBG/polypeptide graft copolymer nanomicelle composites was loaded with water-soluble

gentamicin and fat-soluble naproxen. The release of the individual drugs from the polypeptide

nanomicelles was achieved by controlling the pH: gentamicin was release from the MBG in a

predominantly acidic environment whereas fast release of naproxen occurred in an alkaline

environment. Poly(γ-benzyl-L-glutamate)-poly(ethylene glycol) graft copolymer

12

(PBLG-g-PEG)/MBG nanomicelle composites can therefore be used as a dual-drug delivery

system and the individual drug release can be controlled by the pH of the surrounding

environment [44]. Mesoporous bioactive glasses (MBG) coated on macroporous poly(L-lactic

acid) (PLLA) scaffolds were prepared by Zhu and colleagues and loaded with gentamicin

sulfate; this system also showed a two-stage sustained release profile, which demonstrated

satisfactory antibacterial properties [45].

3.4 MBG scaffolds

MBG can also be prepared as 3D scaffolds as an efficient drug delivery system. We have

successfully loaded the glucocorticoid drug, dexamethasone (DEX), into MBG scaffolds

which maintained a sustained release for three weeks in PBS solution [46]. A modification of

the MBG scaffolds with silk protein further decreased the burst release of DEX [46]. MBG

scaffolds can load over twofold higher amount of gentamicin than NBG scaffolds and the

release rate of gentamicin from MBG scaffolds is much lower compared with that of NBG

scaffolds, consistent with a Fickian diffusion mechanism [47]. We have demonstrated that Zr

or Fe-containing MBG scaffolds also have a sustained release of drugs due to the existence of

a well ordered mesopore structure [48]. More recently we loaded DEX into MBG powders

and then used these drug-loaded MBG powders to prepare high-strength scaffolds by

3D-printing technique, thus confirming it as a useful method to load drugs into scaffolds and

achieving efficient drug delivery [49]. We have also shown that incorporating DEX into MBG

scaffolds significantly enhanced alkaline phosphatase and osteogenic gene expression

(collagen I, runt-related transcription factor 2, alkaline phosphatase and bone silaloprotein) in

human osteoblasts [50]. The results above indicate that MBG is a bioactive drug-delivery

13

system in a variety of forms: powders, fibers, disks, spheres and scaffolds, and that it can be

used for delivering hydrophilic and hydrophobic drugs for disease therapy and tissue

regeneration with a sustained release.

4. MBG for the application of bone regeneration

4.1 MBG/polymer composites

MBG possesses significantly improved surface area and nanopore volume compared to NBG

and these characteristics give this new class of bioactive glass superior bioactivity compared

to the more traditional bioactive glasses. In the past five years, MBG has therefore been

widely studied for applications in bone regeneration. One application is to incorporate MBG

powders into polymers to form a composite with significantly improved bioactivity. This was

done by Li et al., who prepared MBG/polycaprolactone (PCL) composite scaffolds and found

that the incorporation of MBG powders into PCL scaffolds stimulated the apatite

mineralization in SBF [51]. We have successfully prepared MBG/PLGA composite film by a

solvent casting method. The incorporation of MBG powders into PLGA film improves the

tensile strength and modulus, surface hydrophilicity and bioactivity. MBG also enhances the

mechanical strength, in vitro degradation, apatite-formation ability of PLGA films and pH

stability in SBF when compared to NBG (see Figure 3). The tensile strength of MBG/PLGA

(7MPa) is significantly higher than that of NBG/PLGA film (3MPa). Also, MBG/PLGA films

support the attachment and proliferation of human osteoblasts, and enhance ALP activity

compared to NBG/PLGA films [52]. We have also shown that MBG significantly enhance

apatite formation and the proliferation of bone marrow stromal cells (BMSCs) on alginate

14

spheres [42]. In an in vivo study we incorporated MBG powders into silk scaffolds and

implanted them into calvarial defects in SCID mice. We found that MBG/silk scaffolds

significantly improved de novo bone formation (see Figure 4) and increased type I collagen

expression, compared to NBG/silk and pure silk scaffolds [53]. These findings all point to

MBGs being excellent bioactive agents to enhance the bioactivity of polymer-based

biomaterials for potential bone regeneration application.

4.2 MBG scaffolds for bone tissue engineering

The other application of MBG is to prepare 3D scaffolds for bone tissue engineering [54]. We

have prepared MBG scaffolds with high porosity (90%) by using co-templates of P123 (for

mesopore structure) and polyurethane sponges (for large pores) (see Figure 5). The chemical

composition of the scaffolds were optimized and MBG scaffolds with the composition of

80Si15Ca5P were found to have the best apatite-mineraliazation ability [55]. MBG scaffolds

prepared by this method support the attachment (see Figure 6), proliferation and

differentiation of BMSCs [55]. Other studies performed in our laboratory have shown that

silk-modified MBG scaffolds significantly improved the proliferation, differentiation and

osteogenic gene expression [46]; we have also incorporated Fe into MBG scaffolds and found

that such scaffolds have magnetic properties and that trace Fe ions enhanced cell proliferation

and osteogenic differentiation [56].

Methyl cellulose was applied as a large-pore porogen by Yun et al. to prepare porous MBG

scaffolds, which showed superior apatite formation in SBF and supported the proliferation of

MG-63 cells [57]. Recently, 3D printing techniques have been used for the preparation of

MBG scaffolds; Yun and Garcia, et al. prepared hierarchical 3D porous MBG scaffolds using

15

a combination of sol-gel, double polymer template and rapid prototyping techniques [58,59].

In their study, they mixed an MBG gel with methylcellulose which was then printed and

sintered at 500–700ºC to remove the polymer templates and obtain MBG scaffolds. This

method for preparing MBG scaffolds is inconvenient, however, because of the need for

methylcellulose and the additional sintering procedure. Although the MBG scaffolds produced

this way have a uniform pore structure, they are exceedingly brittle and difficult to handle. In

addition to this, the mechanical strength of the obtained MBG scaffolds is unknown, but it is

thought that the strength is low since the scaffolds were sintered at only 550ºC. Furthermore,

the incorporation of methylcellulose created some micropores with diameters of several

micrometers, which will further decrease the mechanical strength of those MBG scaffolds

[49]. To solve this problem, we have recently prepared MBG scaffolds with hierarchical pore

architecture and well-ordered mesopores using the method of 3D-printing combined with

utilization of PVA as binder (see Figure 7). These scaffolds possess a high compressive

strength (16MPa) which is about 200 times greater than that of scaffolds prepared by

polyurethane foam templating (0.08MPa). The use of PVA as a binder in the MBG scaffolds

decreases their brittleness and significantly improves their toughness. The method described

in this study provides a new way to address issues common for inorganic biodegradable

scaffold materials, such as, uncontrollable pore architecture, low strength, high brittleness and

the requirement for second sintering. 3D-printed MBG scaffolds have excellent

apatite-mineralization capability and sustained drug-delivery properties, and are therefore a

promising candidate for bone regeneration [49].

16

5. Future perspective

The discovery of bioactive glasses have brought forward the promise of developing novel

bone substitutes for bone defect repair and regeneration, due to their excellent

osteoconductivity resulting from their special chemical composition. The combination of the

sol-gel method and supermolecular chemistry has led to a new class of bioactive glasses

(named as MBG) which are characterized by having a well-ordered mesopore channel

structure, high surface area and nanopore volume, and bioactivity. MBGs offer a suite of

features which are important for efficient drug delivery and bone regeneration. MBGs, as a

new class of bioactive material, were discovered only as recent as 2004, and although MBG

particles, fibers, spheres, disks and scaffolds have been developed for the potential application

of drug delivery and bone regeneration, there is, to our knowledge, no MBG product ready yet

for clinical applications. Important issues such as the mechanism of in vivo bone formation,

degradation and metabolism have to be investigated before this type of material is ready for

clinical trials. Nevertheless, one can expect that within the next 5 years MBGs will be tested

widely in large animal models, and arising from such tests is the high possibility for clinical

trials in the near future. There are two potential directions in which the continued

development of MBG can progress. The first is to apply MBG microspheres as an injectable

drug carrier for treating bone disease and regenerating bone defects with irregular shapes. The

second is to develop scaffolds for bone tissue engineering application in the following two

ways: (i) incorporating MBG particles into polymer scaffolds to improve the

osteoconductivity, and (ii) using novel 3D-printing techniques to prepare MBG scaffolds with

greater mechanical strength. The combination of efficient drug delivery with an MBG

17

scaffold is an attractive prospect for regenerative medicine of bone. Bone morphogenetic

proteins (BMP) are currently used to stimulate new bone growth; it is, however, exceedingly

expensive, has a short half-life and there are great difficulties with controlling its release in a

scaffold system. Our studies have shown that drugs can efficiently be delivered using an

MBG system and is capable of significantly enhancing the proliferation, differentiation and

osteogenic gene-expression of human osteoblasts. These findings provide the new paradigm

that osteoinductive drugs may be preloaded into an MBG scaffold system to stimulate in vitro

and in vivo osteogenesis for the purposes of bone tissue engineering. This notion has sound

scientific merit given that our preliminary in vivo testing of MBG scaffold in a small animal

model has confirmed the osteogenic properties of MBGs [53]. Follow-up studies will focus on

the in vivo testing for MBG scaffolds with or without loading drugs by using large animal

models.

Acknowledgements

This work has been supported by the Natural Science Foundation of China (Grant 30730034),

Vice-Chancellor Fellowship from Queensland University of Technology, the Alexander von

Stiffing Humboldt Foundation of Germany and One Hundred Talent Project, SIC-CAS. The

authors wish to thank Mr Thor Friis for assisting in the preparation of this manuscript.

18

Executive Summary

The development of bioactive glasses

• The development of bioactive glasses has undergone three important stages: melt-derived

bioactive glass, sol-gel bioactive glass and mesoporous bioactive glass (MBG).

• MBG has demonstrated improved bioactivity due to its special nanochannel structure and

high specific surface area.

Preparation of MBG with well-ordered mesopore channel structure and excellent bioactivity

• MBG can be prepared as powders, fibers, spheres, bulk and scaffolds by combining

supermolecular chemistry with special material technique.

MBG for efficient drug delivery

• MBG powders, fibers, spheres, bulk, scaffolds and their composites with polymers can be

used for loading hydrophilic and hydrophobic drugs with efficient delivery in body fluid-like

environment.

MBG for bone regeneration application

• MBG particles can be incorporated into polymer based materials to improve the osteogenesis.

MBG scaffolds can be used for bone tissue engineering.

Future perspective

• Osteogenic drug-loaded MBG scaffolds have great potential for improved bone regeneration.

• Large animal models should be used to test MBG scaffolds in vivo and it is expected that

MBG will be used clinically within the next five years.

19

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Table 1. The textural characteristics of for the typical MBG materials

MBG Textural Characteristics References Template Surface

area (m2/g)

Pore volume (cm3/g)

Pore size (nm)

Particles

P123

F127

300-350

228-300

0.4-0.49

0.36-0.42

4.3-4.6

5.0-7.1

[19]

F127 520 0.51 5.4 [26]

Acetic acid 189 0.37 5.1 [27]

P123 278-400 0.54-0.73 6.5-6.9 [29]

Spheres Polyethylene glycol 152 0.32 2-10 [31]

P123+CTAB 552-618 0.69-1.08 4.1-6.2 [32]

CTAB 1040 1.54 1.82-2.2 [33]

Fibers P123+PEO 97-276 0.17-0.41 1.5-65 [34,35]

Scaffolds P123+PU 250-350 0.4-0.5 5 [46,50,54,55]P123/F127+3D-Printing 152-310 0.235-0.356 4.2-5.0 [49,59]

P123: EO20PO70EO20; F127: EO106PO70EO106; CTAB: Cetyltrimethyl-ammonium bromide; PEO: Poly(ethylene oxide); PU: Polyurethane

23

Figure 1. Mesoporous bioactive glasses have a well-ordered mesopore channel structure (pore

size is about 5nm).

24

Figure 2. Large sized mesoporous bioactive glass spheres for efficient delivery of proteins.

25

Figure 3. Apatite mineralization is evident on 10%-MBG/PLAG films (a), but not on

10%-NBG/PLGA films (b).

(a)

(b)

50µm

50µm

26

Figure 4. In vivo bone formation of MBG/silk scaffolds transplanted into calvarial defects in

SCID mice for 8 weeks, as assessed by micro-CT scanning.

27

Figure 5. SEM image for MBG scaffolds by polyurethane sponge template.

28

Figure 6. BMSC attachment on the pore walls of MBG scaffolds after 7 days of culture.

29

Figure 7. MBG scaffolds prepared by 3D-printing technique.

300µm