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Abbreviation (ISO4): Prog Chem      Editor in chief: Jincai ZHAO

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Progress in Chemistry >

2024 , Vol. 36 >Issue 2: 271 - 284

DOI: https://doi.org/10.7536/PC230610

16

Synthesis and Application of Ion-Doped Mesoporous Bioactive Glasses

  • Qiwei Li ,
  • Jianguo Liao , *
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  • School of Materials Science and Engineering, Henan Polytechnic University, Jiaozuo 454000, China
* Corresponding author e-mail:

Received date: 2023-06-10

  Revised date: 2023-10-25

  Online published: 2024-01-08

Supported by

Science and Technology Research Project of Henan Province(222102310112)

Science and Technology Research Project of Henan Province(222102320028)

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Abstract

The research and development of bone filling and bone substitute biomaterials is one of the important research directions in the field of bone repair. Mesoporous bioactive glass (MBG) will play an important role in bone repair and regeneration because of its good bioactivity, adjustable pore size and ordered mesoporous structure. MBG with fiber, scaffold, hollow structure or nano-particle structure can be obtained by different preparation and processing methods. Many studies have shown that the incorporation of a small amount of therapeutic inorganic ions into MBG can endow them with more biological properties, including osteogenic, antibacterial, anti-inflammatory, hemostatic or anti-cancer properties. Moreover, MBG doped with inorganic ions still has excellent bioactivity after being processed as scaffolds or nanoparticles. In addition, the performance of MBG can be further improved by loading bioactive molecules, therapeutic drugs and stem cells into the mesoporous structure. In this paper, the synthesis of MBG, the antibacterial properties of metal ion-doped MBG and the application of MBG in other fields are reviewed.

Contents

1 Introduction

2 MBG synthesis

2.1 Preparation of MBG nanoparticles

2.2 Preparation of MBG fiber (MBGF)

2.3 Preparation of MBG microspheres

2.4 Preparation of MBG scaffold

3 MBG used as antimicrobial carrier

3.1 MBG as an antibiotic carrier

3.2 MBG used as antibacterial ion carrier

3.3 MBG doped with other antiseptic

4 MBG in other applications

4.1 MBG used in hemostasis

4.2 MBG used in anti-inflammation

4.3 MBG used in anti-cancer

4.4 MBG as coating material

5 Conclusion and prospect

Key words： mesoporous bioactive glass; bone regeneration; therapeutic inorganic ions; biological properties

Cite this article

Qiwei Li , Jianguo Liao . Synthesis and Application of Ion-Doped Mesoporous Bioactive Glasses[J]. Progress in Chemistry, 2024 , 36(2) : 271 -284 . DOI: 10.7536/PC230610

1 Introduction

Bones play an important role in maintaining movement and protecting organs. Bone defect is a common disease in orthopaedics, which has a long treatment cycle, especially the complications related to infection, trauma, tumor and inflammation[1,2]. Bone tissue can repair and regenerate itself, and small defects can usually heal spontaneously[3]; However, when the bone defect exceeds the critical size threshold (about > 2.0 cm) or more than 50.0% of the bone circumference is lost, it will lead to nonunion, malunion, or pathological fracture, so bone graft or bone replacement surgery is needed[4][4][5]. According to statistics, bone transplantation is the second most common tissue transplantation in the world, second only to blood transfusion. If the bone implant material can be loaded with drugs or growth factors and released continuously during the repair process, it can effectively promote bone healing and eradicate diseases[6]. It has been found that mesoporous nanomaterials can be used as bone implant materials loaded with drugs or growth factors due to their large specific surface area, high pore volume, adjustable pore size and unique mesoporous structure[7].
Bioglass (BGs), invented by Hench in 1969, is the first synthetic material found to form a tight bond with bone through the formation of hydroxyapatite carbonate (HCA)[8]; In the early 1990s, they prepared BGs powder at low temperature by Sol-Gel method, and proved that the structure of BGs was as important as its composition for its bioactivity through in vitro bioactivity experiments[9,10]. On this basis, Vallet-Reg Regí et al. Found that increasing the specific surface area and pore volume of BGs can greatly accelerate the deposition kinetics of HCA, thereby improving the osteogenic bioactivity of BGs[11]; More importantly, precise control of the porosity, pore size, and internal pore structure of BGs at different length sizes is essential for understanding structure-bioactivity relationships and rational design of better bone-forming biomaterials; At the beginning of the 20th century, Zhao et al. (2004) and Vallet-Reg Regí et al. (2006) respectively synthesized bioactive glasses (MBGs) with highly ordered mesoporous structures using the block copolymer template method[12][13]. Compared with traditional BGs, MBG has a high pore volume (about 1.0 cm3/g）) and a high specific surface area (up to 1134.0 m2/g）), which can accelerate the formation of hydroxyapatite (HA) and enhance the interface binding with bone tissue while showing good bioactivity and osteogenic activity[14][15][16]; Moreover, the ordered mesoporous structure of MBG (the size of narrow pores is 2.0 ~ 30.0 nm) can be adjusted by changing the type of surfactant during synthesis[9]; Based on this, MBG is considered to be a good inorganic carrier, and MBG has been studied as a carrier to control the release of drugs or bioactive molecules[17,18]. Compared with the drug delivery system established by traditional physical adsorption, MBG has better drug loading capacity and can inhibit the "burst effect" of drugs to a certain extent[19,20]. In addition, MBG has effective ion release ability in the body fluid microenvironment, so many researchers have incorporated ions of some therapeutic elements (such as lithium (Li), strontium (Sr), copper (Cu) and boron (B)) into MBG, showing high loading efficiency and effective release, and can endow MBG with new properties, such as copper （Cu2+ and Cu+）, silver （Ag+）, gallium （Ga3+） and zinc （Zn2+） and other functional ions can endow MBG with antibacterial properties[21⇓~23][24⇓~26]. In this paper, the synthesis of MBG, the antibacterial properties of metal ion doped MBG and the new progress of MBG in other applications are mainly introduced.

2 Synthesis of MBG

Vallet-Regi et al. Combined the S3ol-Gel method with supramolecular chemistry, and used surfactant as the structure-directing agent of supramolecular chemistry to synthesize MBG with ordered mesoporous structure, which improved the structure and performance of traditional BGs[13]. Because surfactant/precursor micelles usually self-assemble into spherical structures due to the tendency to minimum energy, or self-assemble into nanoblocks based on the specific morphology of the mesostructure (cubic structure,Two-dimensional hexagonal structure self-assembled into nanorods), so the ordered mesoporous structure of MBG is mainly affected by the nature and concentration of surfactant, pH, temperature and other factors[7][27][28][29]. MBG has been prepared into particles, fibers, spheres, three-dimensional scaffolds and composites with ordered mesoporous channel structure and excellent bioactivity, which can be applied to drug delivery and bone regeneration[30].

2.1 Preparation of MBG nanoparticles

Nanoparticles are the key component of MBG composites. At present, the main preparation method of MBG nanoparticles is Sol-Gel method. The main advantages of this method are low reaction temperature, good control of the chemical composition of the product, high product purity, narrow particle size distribution, and uniform nanostructure[31,32][33]. The main process comprises the following steps of: hydrolyzing an alkoxy metal compound in a precursor into a hydroxyl compound under an acidic condition; condensing the hydroxyl compound into nanoparticles under an alkaline condition; and finally, performing freeze drying and calcination treatment on a sample to obtain the product. Simila et al. Prepared MBG with a size range of 123.0 ~ 194.0 nm by Sol-Gel method, and showed good bioactivity and biocompatibility through in vitro experiments[34]. In addition, Zhang et al. Successfully synthesized erbium-doped (Er) mesoporous bioactive glass (Er-MBG) with an average particle size of 500.0 nm by Sol-Gel method, and it also showed excellent bioactivity while having higher specific surface area （418.8 m2/g） and mesopore volume （0.4 cm3/g）[35].

2.2 Preparation of MBG fiber (MBGF)

MBGF is mainly prepared by electrospinning technology[36,37]. The electrospinning method has the advantages of simplicity, easy operation, low manufacturing cost and the like, and the electrospinning equipment consists of a liquid propulsion device, a high-voltage electric field and a fiber collection device; The process comprises the following steps of: extruding an electrospinning solution to a needle by using a liquid propulsion device (such as an injector), wherein the solution is charged under the action of a high-voltage electric field between the needle and a receiving device, and then atomizing the charged solution into a micro jet (namely a fiber), and finally collecting the micro jet by the receiving device to obtain the electrospinning material. Qin et al. Prepared Ag2O doped MBGFs (Ag-MBGFs) by electrospinning, and found that the Ag-MBGFs had a special mesoporous and fibrous structure with a uniform diameter of 0.1 – 0.2 μm and a specific surface area of 40.2 m2/g. In vitro experimental results showed that the Ag-MB GFs had excellent bioactivity, antibacterial properties, drug loading and release properties[38]. Lu et al. Prepared Ce-MBGFs by combining Sol-Gel method and electrospinning technology, which had a uniform diameter of 0.7 – 0.9 μm, high hydrophilicity, no cytotoxicity to human cells, no inhibition of wound healing process, and showed good biological activity[39].

2.3 Preparation of MBG microspheres

MBG microspheres can be prepared by a combination of surfactant and other special techniques, such as crosslinking with alginate, co-templating, and hydrothermal methods, among which crosslinking with surfactant and alginate is the most commonly used method[40]. The process flow comprises the following steps of: (1) preparing MBG powder by combining a surfactant and a Sol-Gel method, adding the MBG powder into an aqueous solution, and stirring to form a slurry[41]; (2) dissolving alginate powder in water to form alginate solution, adding the alginate solution into MBG slurry, and stirring under the action of ultrasonic wave to form a uniform mixture; (3) drop that mixture into CaCl2 crosslinking solution to form spherical particle, and incubating and hardening the spherical particles in the crosslink solution; ④ The wet microspheres were filtered, dried at 50 ℃, and calcined at 680 ℃ for 3 H (the heating rate was 1 ℃/min) to obtain MBG microspheres.
Wu et al. Used alginate to crosslink with Ca2+ to prepare micron-sized MBG microspheres that could not only support the adhesion of bone marrow stromal stem cells (BMSC), but also control protein delivery[41]. Yun et al. Prepared MBG microspheres with a size of several hundred micrometers in hydrophobic solvent chloroform by combining the triblock copolymer template method and the Sol-Gel method, which had a specific surface area and pore volume of 1040.0 m2/g and 1.5 cm3/g, respectively, and showed good bioactivity and biodegradability in vitro[42]. Duan et al. Used cetyltrimethylammonium bromide (CTAB) as a mesoporous template to prepare hollow MBG microspheres by hydrothermal assisted self-transformation method, whose specific surface area and pore volume were 444.1 m2/g and 0.9 cm3/g, respectively[43]; At the same time, the in vitro drug release study showed that the MBG microspheres had certain sustained-release properties, and had potential applications in drug delivery and bone tissue regeneration.

2.4 Preparation of MBG scaffold

2.4.1 Foaming process

Foaming method can be used to prepare porous scaffolds, which can be divided into physical foaming, chemical foaming and mechanical foaming according to the formation of foam nuclei[44]. Mechanical foaming is to form bubble nuclei by mechanical stirring. Although it is easy to operate, the pore size is small; Although the formation process of chemical foaming nucleus is fast and efficient, chemical foaming agent is easy to cause pollution of raw materials[45]. Supercritical foaming technology is a promising preparation technology in physical foaming method. The foaming agent used in supercritical foaming technology is supercritical fluid (SCFs), which is a substance with pressure and temperature above the critical value, high density and low viscosity, such as supercritical carbon dioxide （ScCO2） and supercritical nitrogen （ScN2）.Its principle is to inject ScCO2 or ScN2 into the molten raw material system, after the gas and raw materials are fully mixed, the above mixed system is poured into the mold, with the decrease of air pressure, supercritical gas forms a large number of pores in the material system, thus realizing the preparation of porous materials[46].
Tainio et al. Successfully prepared poly (L-lactic acid-co-caprolactone) (PLCL) porous scaffolds (MBG/PLCL) containing 10.0, 30.0, and 50.0 wt% borosilicate MBG using the ScCO2 foaming technique, with the highest average pore size and porosity of 523.0 µm and 64.0% (30.0 wt% MBG/PLCL), respectively, and the highest Young's modulus of 90.0 MPa (50.0 wt% MBG/PLCL)[47]. Song et al. Prepared MBG/PLGA composite scaffolds with porosity of 73.0% – 85.0%, pore size of 120.0 – 320.0 μm, and interconnection rate of more than 95.0% by increasing the foaming pressure and prolonging the foaming time using the ScCO2 foaming method, and the strength and Young's modulus of MBG/PLGA composite scaffolds could be increased by up to 1.5 times and 3.0 times, respectively, compared with pure PLGA scaffolds[48]. Li et al. Prepared MBG/PLGA composite scaffolds with appropriate mechanical properties and degradability by ScCO2 foaming technology, and then doped with synthetic small molecule sphingoid phosphate FTY720 to obtain FTY/MBG-PLGA scaffolds. The average pore size of the scaffolds was (252.0 ± 45.0) μm, the porosity was 82.0%, the interconnection rate was as high as 96.0%, and the compressive strength was (1.9 ± 0.2) MPa[49]; After 4 weeks of immersion in PBS, the degradation rate of the scaffold was only 16.5%, and the FTY720, Ca2+, and silicon ion (Si4+) in the scaffold could be released continuously; The results of animal experiments showed that the FTY/MBG-PLGA scaffold achieved ideal coupling of angiogenesis and bone formation, which may be a promising strategy in bone regenerative medicine. Supercritical foaming technology is a promising method for the preparation of MBG scaffold materials because of its pollution-free, rapid and effective foaming.

2.4.2 Freeze drying method

The freeze-drying method is to process the raw material containing water into a specific shape, then change the water into ice by pre-cooling, then dry the raw material under high vacuum, and change the original position occupied by ice into pores after sublimation, thus obtaining porous materials[50]; Its main advantage is that the dried material maintains the original chemical composition and physical properties (such as porous structure, colloidal properties, etc.), and the heat consumption is less than other drying methods, but its cost is higher[51].
Santos et al. Compounded 58S-MBG and polycaprolactone (PCL) microspheres prepared by Sol-Gel method, and successfully prepared a composite scaffold with a total porosity of about 72.0% by freeze-drying technology. Its mechanical properties are similar to those of elastic porous solids, and its Young's modulus is (46.7 ± 9.4) MPa[52]; In vitro experiments showed that the composite scaffold could promote the formation of HA and the growth of osteoblasts. Guo et al. Synthesized Mg and Sr co-doped MBG/chitosan (CS) three-dimensional (3D) porous composite scaffolds by freeze-drying method, with an average pore size of (138.0 ± 7.0) μm, a porosity of 81.3%, and a maximum compressive modulus of (1.1 ± 0.02) MPa, which is 4.67 times that of pure CS scaffolds[50].

2.4.3 Polymer template method

The basic principle of polymer template method is to use the template agent to provide the precursor reaction space of the material, and remove the template agent after the reaction is completed to obtain the porous scaffold[53]. According to the composition of the template, the template method can be divided into soft template method and hard template method; Among them, the soft template method is composed of surfactant molecule aggregation (micelle, microemulsion, liquid crystal, etc.); The hard template method is a rigid template maintained by covalent bonds (polymer, porous silicon, metal template and natural polymer template)[54]. The polymer template method has the advantages of simple operation, high repetition rate, good predictability, and easy control of the structure of the prepared material.
Wu et al. Added europium (Eu) into MBG by in situ co-template method to obtain Eu-doped MBG (Eu-MBG) scaffolds with highly interconnected macropores (300.0 – 500.0 µm) and high specific surface area （140.0~290.0 m2/g） and ordered mesopores (5.0 nm), which have obvious luminescence characteristics and can be used for in vitro labeling of scaffolds and tissue cells, and can also label new bone tissue by releasing Eu3+ at bone tissue defects[55]; Eu-MBG scaffolds can also activate osteogenic differentiation and improve osteogenic capacity, especially for osteoporotic bone defects, which can significantly stimulate the formation of new bone. Luo et al. Used natural three-dimensional bacterial cellulose as a template to synthesize BG nanofiber scaffolds by template-assisted Sol-Gel method, then coated BG nanofibers with gelatin, and finally crosslinked with proanthocyanidins to obtain three-dimensional interconnected porous BG/gelatin nanocomposite scaffolds (see Figure 1).The scaffolds exhibited three pore structures (20.0 – 60.0 μm, 1.0 – 2.0 μm, 3.0 – 32.0 nm) and exhibited higher mechanical strength than pure BG scaffolds, which was more conducive to cell growth[56].
图1 BG/Gel-1（a 和 b）、 BG/Gel-2（c 和 d）和 BG/Gel-3（e 和 f）的 SEM 图和纳米纤维直径分布[56]

Fig. 1 SEM micrographs and nanofiber diameter distributions of BG/Gel-1 (a and b), BG/Gel-2 (c and d) and BG/Gel-3 (e and f) [56]

2.4.4 3D printing method

3D printing technology can not only quickly and efficiently print customized three-dimensional scaffolds with complex shapes, but also precisely control the porous structure of scaffolds on the micron scale[57]; Ink direct writing 3D printing (automatic slip casting) is widely used in the preparation of three-dimensional porous scaffolds of bioceramics and bioactive glass because of its fast printing speed, simple operation, low cost and high bioactivity[58].
Du et al. extracted 30.0 wt% silk fibroin (SF) solution from silkworm cocoons and compounded it with MBG to prepare MBG/SF scaffolds with porosity of more than 70.0% by 3D printing technology. Compared with MBG/PCL scaffolds, MBG/SF scaffolds have higher compressive strength (about 20.0 MPa) and good biocompatibility, and have the ability to promote bone formation[59]; The results of animal ectopic osteogenesis experiments in vivo showed that the gene expression levels of common osteogenic biomarkers of MBG/SF scaffolds were significantly better than those of MBG/PCL scaffolds. Chen et al. Prepared lithium-containing mesoporous bioactive glass/poly (lactic-co-glycolic acid) (Li-MBG/PLGA) composite scaffolds by 3D printing, and found that Li-MBG up-regulated ItGa3 and activated β-catenin/Tcf7/Ccn4 signaling pathway.The inhibition of high glucose on BMSC proliferation, migration and osteogenic differentiation was reversed, and the Li-MBG/PLGA composite scaffold could effectively repair severe skull defects in diabetic mice by recruiting stem cells, with good osteogenic effect[60]. Liao et al. Prepared porous Cu/Mg-BGs scaffolds with different Cu/Mg composition ratios by 3D printing technology. After sintering at 700 ℃, the high porosity of the scaffolds was 51.0% ± 1.2%, and the compressive strength was as high as (109.3 ± 8.2) MPa, which matched the strength of cortical bone (90.0 ~ 150.0 MPa)[61]; In vitro experiments showed that the scaffold supported the adhesion and growth of BMSC and showed good biological activity. In vivo experiments were consistent with in vitro osteogenesis experiments.

3 MBG as carrier of antibacterial agent

Prevention and treatment of infection is particularly important in the field of bone repair[62]. Because of its mesoporous structure, MBG can be used as a carrier for antibacterial agent storage and local sustained and controlled release to intrinsically inhibit the growth or survival of bacterial cells by releasing antibacterial metal ions or antibiotics bound in its glass network[63][64⇓~66]. The drug loading efficiency and release kinetics of MBG first depend on the environmental conditions (for example, the pH value and the type of fluid in which MBG is soaked) and the mesoporous characteristics, which can be finely regulated according to the glass synthesis process (for example, larger or smaller mesopores can be tailored to host drug molecules of different sizes), making MBG an effective carrier for drug delivery[30]; Secondly, the interaction between the scaffold and the precursor and the type of precursor selected are also very important. Surface modification is one of the effective strategies to regulate the interaction between the mesoporous carrier and the molecular precursor, which makes the precursor and the mesoporous carrier have a strong interaction, and can improve the loading of antibacterial agents or drugs[67].
The drug release of MBG is regulated by two different ways, including the Fick diffusion mechanism and the dissolution of MBG itself in the biological environment[41]. It has been shown that the release rate of various drugs in MBGs is slower than that of traditional BGs, thus ensuring a more lasting antibacterial effect[68]. Therefore, the loading of various antibacterial agents in the pores of MBG can improve and control its antibacterial activity for a long time, while the release of therapeutic molecules over time ensures its good biological activity.

3.1 MBG as antibiotic carrier

Bacterial infections caused by Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa are very common during or after bone-related surgery[62]. Traditional treatments include systemic antibiotics, wound drainage, surgical debridement, and sometimes implant removal, which leads to other complications such as loss of function and sepsis[69]; These traditional treatments can lead to additional pain and surgery for patients, and it is difficult to achieve sufficient drug concentration at the target site by oral or intravenous antibiotics, and because the drug concentration in the blood rises significantly, it becomes toxic at the peak, resulting in the deterioration of blood circulation[70]. A large number of Si-OH groups in the mesoporous structure of MBG interact with drugs and proteins through hydrogen bonds and van der Waals forces, which enables MBG to act as a transport carrier[71]. The use of MBG as an antibiotic delivery carrier not only improves the efficiency of antibiotic delivery at the site of infection, but also continuously eliminates infection and stimulates the bone healing process; It has little toxicity to human body and is easy to be accepted by patients[65].
Sanchez-Salcedo et al. Synthesized SiO2-P2O5-CaO-ZnO（ZnO=0, 2.5 and 4.0 mol%) glasses by Sol-Gel method. The diameter of the glasses is about 100.0 nm, the narrowest pore diameter is 2.5 nm, the maximum pore diameter is 6.0 ~ 8.0 nm, and the specific surface area is between 600.0~800.0 m2/g[72]; After loading (10.0 ~ 16.0) wt% curcumin, more than 90.0% of curcumin was released within 28 H in vitro, indicating that the doping of Zn increased the loading of curcumin, but delayed the release of Curcumin; On the other hand, in vitro studies on preosteoblasts and mesenchymal stem cells showed that nanoparticles containing Zn and curcumin could promote osteoblast differentiation, and had bactericidal effect on Staphylococcus aureus, which led to the degradation of preformed bacterial biofilm. Khanmohammadi et al. Coated vancomycin-loaded mesoporous bioglass/hydroxyapatite whisker/chitosan (CS) composite coating on titanium-based materials by electrophoretic deposition[73]; Compared with bare titanium, the coated sample showed 99.0% inhibition of Staphylococcus aureus, indicating its good antibacterial properties, and the released antibiotics did not have any toxic side effects on the activity of osteoblasts cultured on the composite coating.
The above studies show that the application of MBG loaded with antibiotics can avoid the shortcomings of traditional treatment methods, and as a carrier of antibiotics, MBG not only releases antibiotics for a long time to treat infections, but also has good biological activity and osteogenic activity, which can effectively repair bone defects and is one of the ideal choices for bone-related diseases and infections.

3.2 MBG as antibacterial ionophore

Due to the abuse of antibiotics, the resistance of bacteria to antibiotics has increased[74]. It has been found that metal and metal oxide nanoparticles can be used as antibacterial agents, and the antibacterial ions released by them are more effective against resistant strains of microbial pathogens, and also have the advantages of low toxicity and heat resistance[75]. Therefore, doping antibacterial metal or metal oxide nanoparticles into the MBG structure with controlled release is one of the most attractive strategies to inhibit bacterial growth and reproduction and prevent the increase of drug resistance[76]. In addition, the doped metal nanoparticles are usually encapsulated on the mesoporous wall, which can prevent the aggregation and degradation of metal nanoparticles, endowing MBG with excellent activity and stability[67]. Commonly used antibacterial ions generally include Ag+, Zn2+,Cu2+, Ga3+, Ce3+ and Ce4+, etc.Each ion acts through specific cellular and molecular mechanisms, and the main studies on the antibacterial effect of ion-doped MBG are shown in Table I[77⇓⇓~80].

3.2.1 Ag doped MBG

Antibacterial properties of Ag+ have been discovered in ancient times, and Ag+ has been widely used as a bactericide in medical treatment. Carta et al. Used neutron diffraction to study the structure and properties of silver-containing calcium-silicon Sol-Gel MBG with different Ag2O loadings (0, 2.0, 4.0, 6.0 mol%)[81]; The results show that the structure of MBG doped with Ag2O is not destroyed, and MBG still has bioactivity, and the presence of Ag+ endows MBG with effective antibacterial properties. Zheng et al. Found that Ag-MBG obtained by the surface modification method exhibited significant antibacterial effects against both Pseudomonas aeruginosa and Staphylococcus aureus, and showed no cytotoxicity against fibroblasts at low use doses[82]. Shuai et al. Used oxidative self-polymerization of dopamine to modify MBG to obtain pMBG, and then captured the Ag+ into the mesoporous channel through coordination reaction, and then reduced the Ag+ to Ag in situ by redox reaction of catechol group to obtain Ag-supported pMBG (Ag @ pMBG).Finally, the PLLA-PGA/Ag @ pMBG composite scaffold was prepared by selective laser sintering of Ag @ pMBG and PLLA-PGA (see Figure 2). The PLLA-PGA/Ag @ pMB composite scaffold had a bacteriostatic rate of more than 99.0% against Escherichia coli, and had long-term antibacterial activity, which could continuously release Ag/Ag+ within 28 days[83]; In addition, the composite scaffold also showed good cytocompatibility, which could promote the adhesion and proliferation of osteoblasts.
图2 （a）Ag@pMBG 制备的示意图，即通过邻苯二酚基团的氧化还原活性在 MBG 介孔通道的内表面和外表面原位还原 Ag+ 至 Ag 纳米颗粒。（b）用选择性激光烧结制备多孔复合支架的示意图。典型多孔支架（PLLA-PGA/ Ag@pMBG 和 PLLA-PGA/MBG）的宏观形貌（光学图像）表现出均匀的孔和支架结构[83]

Fig. 2 (a) Schematic of Ag@pMBG preparation, in situ reduction of Ag+ to Ag nanoparticles on the inner and outer surfaces of mesoporous channel of MBG by redox activity of catechol groups. (b) Schematic for preparation of porous composite scaffolds by selective laser sintering. The macroscopic morphology (optical images) of the typical porous scaffolds (PLLA-PGA/Ag@pMBG and PLLA-PGA/MBG) demonstrated a uniform pore and strut structure[83]

The above studies showed that Ag+/Ag had good antibacterial properties, and there was no cytotoxicity after doping in MBG, which improved the antibacterial properties of MBG while having no significant effect on its morphology, dispersion and bioactivity[84]. Therefore, the use of MBG as a Ag/Ag+ delivery vehicle to obtain its antibacterial properties is one of the important research directions.

3.2.2 Zinc (Zn) doped MBG

Zn is one of the most important trace elements in human body, which plays a vital role in the formation, mineralization, development and maintenance of healthy bones[85]; In addition, Zn2+ showed antibacterial activity against various bacterial strains[86]. It was found that the antibacterial activity of ZnO/Zn2+ depends on its particle size, concentration, morphology, and surface modification of the particles, etc[87][88][89][90].
Wajda et al. studied the antibacterial properties of Zn-MBG, and the results showed that 2.0 mol% and 4.0 mol% of Zn-MBG had significant antibacterial effects on Gram-positive and Gram-negative bacteria[92]. Nescakova et al. synthesized spherical and well-dispersed Zn-MBG nanoparticles with a size of (130.0 ± 10.0) nm (see Figure 3) and a higher specific surface area than MBG by microemulsion-assisted Sol-Gel method[91]; The incorporation of Zn2+ had no significant effect on the morphology of MBG particles, but Zn2+ inhibited the formation of HA in the early stage, and the powder with relatively high Zn content released low concentrations of Zn2+（0.6~1.2 mg/L） continuously, which enabled Zn-MBG to avoid potential toxic levels of Zn2+; In addition, the protein adsorption capacity of Zn-MBG is higher than that of MBG, which may be more favorable for the late attachment of cells.
图3 合成MBG（a，c）和Zn-MBG（b，d）的SEM图[91]

Fig. 3 Morphology of synthesized MBG (a, c) and Zn-MBG (b, d) particles obtained by SEM [91]

The above study shows that MBG doped with Zn2+ has excellent antibacterial effect on Gram-positive and Gram-negative bacteria, and the low concentration of Zn2+ released by Zn-MBG for a long time can avoid potential cytotoxicity, so Zn-MBG has great application potential in the field of bioactive fillers or drug delivery systems.

3.2.3 Copper (Cu) doped MBG

Cu is an essential trace element in most biological organs. At present, there are more than 30 known Cu-containing proteins, such as lysyl oxidase, respiratory terminal oxidase and superoxide dismutase[93]. CuO nanoparticles have significant antibacterial properties and have been used in a variety of biomedical materials, such as wound dressings, bandages, topical antibacterial ointments, and antibacterial coatings for medical devices[94]. Compared with Ag2O nanoparticles, CuO nanoparticles are not only cheap, widely available, easy to mix with a variety of polymers, but also relatively stable in physical and chemical properties[95].
Wu et al. Prepared Cu-MBG scaffolds with interconnected macropores (several hundred micrometers) and ordered mesoporous channels (about 5.0 nm), which showed higher inhibitory ability against Escherichia coli (DH5α) than (Cu-free) MBG[96]. Chitra et al. Synthesized Cu-MBG materials by Sol-Gel method. Through cell experiments, it was found that the inhibition rates of Cu-MBG against Enterococcus faecalis, Candida albicans and Staphylococcus aureus were 98.5%, 99.0% and 98.5%, respectively[97]; The incorporation of Cu promoted the production of reactive oxygen species (ROS), resulting in bacteriostatic effect. Yang et al. Used a modified one-pot two-phase layering method to prepare Cu-MBG, and then incorporated it into Mg-based scaffolds fabricated by laser powder bed fusion (LPBF). Through the sustained release of Cu2+ from Cu-MBG, Cu-MBG endowed Mg-based scaffolds with good antibacterial activity, with an antibacterial rate of 81.0% against DH5α[98]; In addition, Cu-MBG has excellent bioactivity, which effectively induces the in situ deposition of HA products and reduces the degradation rate of magnesium matrix.
The antibacterial activity of Cu-MBG is affected not only by the release of Cu2+ in the solution, but also by physical factors (size, morphology and temperature of the nanoparticles), chemical factors (pH value, dry and wet, and the composition of the surrounding medium), doping modification of other elements, and oxidation state of Cu[99,100][101][102][102][103][104][105][106].
The above studies showed that Cu2+ doped with MBG has antibacterial properties by generating ROS through redox reaction between Cu+/Cu2+, and this non-specific mode of action has a low possibility of inducing bacterial resistance[107]. Therefore, Cu-MBG has its unique advantages as an antimicrobial agent against drug-resistant infections.

3.2.4 Ce-doped MBG

Ce and its derivatives have been used as drugs for the treatment of wounds since the beginning of the 20th century[108,109]. In recent years, cerium oxide nanoparticles （CeO2NPs） have attracted great interest as antibacterial agents, and CeO2NPs has relatively low or even no toxicity to mammalian cells compared with Ag and Cu[110⇓~112].
Goh et al. Prepared MBG doped with CeO2（ mole fractions of 1.0, 5.0 and 10.0%) by a rapid alkali-mediated Sol-Gel method. It was found that due to the different initial content of Ce, the Ce in MBG would exist in Ce3+ or Ce4+ oxidation state, and the incorporation of Ce above 5.0% mole fraction could make MBG have antibacterial properties[113]; In addition, incorporation of CeO2 into MBG also showed good in vitro bioactivity. Kurtuldu et al. Synthesized Ce-MBG particles with an average size of 0.1 ~ 0.2 μm by microemulsion-assisted Sol-Gel method (see Fig. 4), and found that Ce-MBG had significant antibacterial properties against Gram-negative bacteria, and also had certain anti-inflammatory properties, which could be used to treat inflammatory bone diseases and bone infections[114].
图4 MBG的SEM图和粒度分布[114]

Fig. 4 SEM images and particle size distribution of MBG[114]

The toxicity of CeO2 particles to different colonies is not uniform and depends on various factors, including the method of synthesis and the environment of action[115]. Ce-MBG is non-toxic to normal human cells, and can also promote osteoblast differentiation, primary osteoblast mineralization, and collagen production[116]. Therefore, Ce-MBG has potential for biomedical applications in many aspects.

3.2.5 Gallium (Ga) doped MBG

Fe is essential for the growth and survival of most bacterial pathogens and is used in many physiological processes, including DNA synthesis, transcription, and cellular respiration[117]. Taking advantage of the nutritional vulnerability of bacteria, the purpose of antibacterial can be achieved by destroying the metabolic process of bacteria, and destroying the Fe metabolic process of bacteria is one of the main ways[117]. Since Ga and Fe have the same oxidation state (+ 3) and similar ionic radii （Ga3+ = 0.6262 Å, Fe3+ = 0.6565 Å), but also the tetrahedral ionic radii of both ions are very close （Ga3+ = 0.4747 Å, Fe3+ = 0.4949 Å), Ga can be taken up by bacteria and replace Fe, thus disrupting the Fe metabolism of bacteria[118].
Pourshahrestani et al. Prepared MBG containing Ga by evaporation-induced self-assembly process, and found that the incorporation of lower concentration of Ga2O3 could improve the structure of MBG, resulting in higher specific surface area, pore volume and narrower mesopore size distribution, as well as improving its cytocompatibility and antibacterial properties[119]; After 12 H, the release concentration of Ga3+ was the highest, and MBG containing 3.0 mol% Ga showed a high inhibition rate of 99.0% against Gram-positive bacteria (Staphylococcus aureus). Ga-MBG prepared by Kurtuldu et al. Using microemulsion-assisted Sol-Gel technology has a high specific surface area (about 480.0 m2/g） and pore volume （0.6 cm3/g）（, see Fig. 5)[120]; The results of in vitro experiments showed that the release of Ga3+ was relatively slow, and it had excellent antibacterial activity against Staphylococcus aureus and DH5α; In addition, Ga-MBG did not show any cytotoxicity to osteoblasts, significantly improved cell viability, and had good biological activity.
图5 Ga-MBG的SEM图[120]：（a）Ga1，（b）Ga3，（c）Ga5

Fig. 5 SEM of Ga-MBG [120]: (a) Ga1, (b) Ga3 and(c)Ga5

The above studies have shown that incorporation of Ga3+ can improve the structure of MBG and increase the antibacterial activity, but its use is not as common as that of Ag+; The major advantage of Ga3+ over Ag+ is a significant reduction in cytotoxicity to human cells at higher concentrations. Ga3+ by displacing the Fe3+（“ Trojan horse strategy in bacterial proteins "), thereby causing impairment of bacterial cell function."[121]. This specific effect makes Ga3+ doped with MBG as one of the effective strategies against drug-resistant strains.

3.3 Other antimicrobials doped with MBG

In addition to the above metal ions, other dopants added to the MBG structure can also improve its antibacterial activity. Such as Mn2+, Sr2+, and graphene oxide (GO), etc[122⇓⇓~125]. Tseng et al. Prepared Mn-doped BGs by spray pyrolysis, and found that the antibacterial activity of the undoped BG sample against Escherichia coli was 5.5%, and its antibacterial effect was negligible[126]; In contrast, the highest antibacterial activity of Mn-BGs against DH5α was 93.3%. Liu et al. Prepared Sr-doped 42SiO2-4P2O5-（39-x）CaO-15Na2O-xSrO glass by melt-quenching method, and Sr-MBG had significant inhibitory effect on the growth of Pseudomonas gingivalis and Actinomycetes comitans compared with the group without Sr[127]. Shih et al. Prepared GO-doped MBG by spray pyrolysis, and found that GO improved the antibacterial effect of MBG, with the highest antibacterial rate of 98.0%, but reduced the biological activity of MBG[126]. Akhavan et al. Found that the antibacterial activity of GO was due to the mechanical disruption of bacterial cell membrane caused by the direct contact between bacteria and GO nanosheets[128]. Therefore, MBG doped with antimicrobials is an effective means to combat drug-resistant bacteria in the current severe form of drug-resistant infections[129].
表1 离子掺杂MBG抗菌的主要研究汇总

Table 1 Summary of major studies on ion-doped MBG antibacterial agents

Ion(s) doped Composition Synthesis method Biocompatibility Bacterial
species		 Antibacterial properties Refs
Ag+/
Ag		 PLLA-PGA/xAg@pMBG
(x=0/2.0/4.0/6.0/ 8.0mol%)		 Sol-Gel The cells cultured on the scaffold with MBG exhibited a flatter morphology, indicating better cytocompatibility.
the degradation of MBG releases active elements (silicon and calcium) that could induce osteoblast differentiation.		 E. coli PLLA-PGA/MBG scaffolds had no antibacterial activity；
The bacteriostasis rates of composite scaffolds loaded with 2AG@PMBG and AG@PMBG were 80.0% and 83.0% ，respectively；
The bacteriostasis rate of composite scaffolds loaded with 6AG@PMBG and 8Ag@pMBG was more than 99.00%；		 83
Zn2+ 70SiO2-(30-x)CaO-xZnO
(x=0/2.0/4.0mol%)		 Sol-Gel All samples show very high levels of cell mitochondrial activity (> 80.0% of the reference control).
The results indicate that all glasses are not cytotoxic (viability is always above 80.0%, indicates that the material should be considered as not cytotoxic) and favorable for cell proliferation.		 E. coli
S.aureus		 When the ratio of the extract to the bacterial mixture was 1ml: 0.5 ml, the bacteriostasis rates of 2Zn-MBG to both bacteria were 100.0%, and the bacteriostasis rates of 4Zn-MBG to E. coli and S. aureus were 65.0% and 70.0%, respectively；
When the ratio was 1ml: 0.2 ml, the inhibition rates of 2Zn-MBG to both bacteria were 100%, while those of 4Zn-MBG to E. coli and S. aureus were 80.0% and 85.0%，respectively；		 92
Cu2+ 45SiO2-6P2O5-24.5CaO-(24.5-x)Na2O (x=0/0.5/1.5/2.5
mol%)		 Sol-Gel Ionic radii variations can influence the dissolution of calcium and phosphate, so apatite growth was gradually increased by addition of copper in BG system.
BG and copper incorporated BG showed almost similar bioactivity as well as exhibiting same apatite growth with the additional benefit of copper release.		 P.aeruginosa
E. coli
B.subtilis
S. aureus
E.faecalis
C.albicans		 Under the treatment of 1.5 cu-mbg and 2.5 cu-mbg, the viable cells of Pseudomonas aeruginosa and E. coli were completely inhibited, and the inhibitory effects on B. subtilis and S. aureus were obviously superior to those of Gram-negative；
CuBGs (20.0 μg/ml) had a rapid inhibitory effect on Gram-positive bacteria such as Enterobacter faecalis, Candida albicans and Staphylococcus aureus, with inhibition rates of 98.5%, 99.0% and 98.5%, respectively；		 97
Ce3+ 88.5SiO2-10.1
CaO-1.4Ce2O3		 Sol-Gel some apatite particles existed as hollow hemispheres on day 3 and day 7. as the immersion time increased to 14 days, when most of the apatite particles had grown into full spheres.
All samples induced the formation of apatite particles with Ca/P ratio close to 1.67 upon immersion in simulated body fluid (SBF), confirming their good bioactivity.		 E. coli
S. aureus
 Ce-MBG has antibacterial activity against Gram-positive bacteria and Gram-negative bacteria by producing reactive oxygen species；
When the concentration was 0.01 mg/ml, it had no effect on E. coli, but the survival rate decreased with the increase of MBG concentration；
When the concentration was 10.0 mg/ml, the growth of Staphylococcus aureus was inhibited completely；		 113
Ce3+/
Ga3+		 60.0SiO2-(40.0-
x)CaO-xGa2O3
(x=0/1.0/3.0/5.0mol%)		 Sol-Gel The Ca/P ratio on the MBGNPs surface was close to 1.64, which is similar to the Ca/P ratio in HA.
All Ga-doped MBGNPs showed the formation of a similar type of HA crystals on the surface. Increasing the amount of gallium doping resulted in significant refinement of precipitated HA crystals.		 E. coli
S. aureus
 Ga-MBG had a lower survival rate than Gram-positive bacteria and Gram-negative；
The inhibition rate of 5Ga-MBG was the highest at 6h；
Ga1 was the strongest at 6h and 24h after Gram-positive bacteria Gram-negative；
The inhibition rates of Ga1, Ga3 and Ga5 MBG on Gram-negative were significantly different at 24 h incubation.		 120

4 Other applications of MBG

4.1 Application of MBG in hemostasis

Excessive bleeding is common in adult patients, and causes include structural problems, drug effects, and systemic disease, as well as unintentional bleeding due to undiagnosed or newly acquired bleeding disorders[130]. MBG can induce hemostasis by activating coagulation factor XII and other coagulation proteins due to its high surface area and anionicity (glass effect), which is expected to solve the shortcomings of traditional hemostatic materials[131]. The results show that the addition of some trace element ions, such as Ce3+, Zn2+, and Ga3+, to the glass network of MBG can affect its hemostatic efficacy as well as antibacterial properties[132].
Roy et al. Prepared MBG with a composition of 70 SiO2:（30-x-y）CaO:xAl2O3:yZnO（ mole fraction X = 10.0% ~ 18.0%, y = 0% ~ 8.0%). Through in vivo acute skin toxicity test and in vivo hemostatic effect test, it was found that MBG accelerated the intrinsic and extrinsic coagulation cascade and thrombosis, and also had certain antibacterial activity. The MBG could be used as a hemostatic agent to control massive bleeding and infection[133]. In addition, Liu et al. Prepared Ce-MBG by freeze-drying method, and compounded with CS to prepare hemostatic sponge (Ce-MBG/CS) with excellent pore structure, porosity and water absorption. Its hemostatic performance is better than that of traditional gelatin sponge (GS). The addition of Ce- MBG can activate coagulation factor XII, induce endogenous coagulation pathway, and ensure thrombosis in vitro, platelet adhesion and blood compatibility[134]; In addition, the results of antibacterial experiments showed that Ce-MBG/CS was more effective than GS in killing Escherichia coli and Staphylococcus aureus.
Compared with the defects of traditional hemostatic materials, such as difficult shaping, poor adhesion to bone wound surface and easy to be washed away by blood flow, the unique mesoporous structure of MBG can be doped with hemostasis-related element ions to enhance its hemostatic performance.At the same time, it can improve the adhesion with the bone wound, and MBG hemostatic stent can be prepared according to the need, which is one of the effective ways to solve the defects of traditional hemostatic materials.

4.2 Application of MBG in anti-inflammation

During the healing and repair of bone defects, the uncontrolled inflammatory response may affect bone regeneration, in which acute and chronic inflammatory processes play an important role[135]. Dysregulation of inflammation not only leads to the transformation of acute inflammation triggered by endogenous or exogenous adverse stimuli into chronic inflammation, but also leads to increased bone resorption and inhibition of new bone formation[136,137]. Synergism between inflammatory cells (neutrophils and monocyte-macrophage-osteoclast cell lines) and cells associated with bone healing (mesenchymal stem cell-osteoblast cell lines and vascular lineage cells) is essential for bone formation, repair, and remodeling[138⇓~140]. It has been shown that moderate polarization of inflammatory M2 by macrophages can promote osteogenesis, so the addition of anti-inflammatory agents to MBG can promote efficient bone regeneration by regulating macrophage polarization[137].
Mo et al. Prepared β-cyclodextrin modified MBG nanoparticles (CD-MBG) by Sol-Gel composite template method, and then loaded the anti-inflammatory drug naringin (NG) in CD-MBG to obtain NG @ CD-MBG. The loading of NG made NG @ CDMBG have immunomodulatory function and the ability to inhibit the inflammatory response of macrophages, and NG @ CDMBG could promote the transformation of macrophages to M2 phenotype, synergistically promote the osteogenic differentiation of stem cells, and inhibit the generation of osteoclasts[141]; The results of in vivo experiments showed that NG @ CD-MBG had better ability to promote bone regeneration than MBG. In addition, Zn-MBG prepared by Sun et al. Has good in vitro osteogenic and anti-inflammatory activities under inflammatory conditions[142].
The above studies show that MBG can play a role in the bone healing process of early inflammation and bone remodeling by loading anti-inflammatory agents or doping metal ions after modification, which provides a new idea for the development of bone repair materials with good bone immunomodulatory properties.

4.3 Application of MBG in anticancer

The standard clinical treatment strategy for bone cancer involves surgical resection and repair of the reconstructed bone defect, followed by adjuvant radiation therapy or chemotherapy[143]. However, surgical resection of bone malignant tumors can lead to bone defects or delayed bone healing, so bone defect repair and reconstruction and local tumor recurrence inhibition are two common problems in orthopaedic surgery[144]. If bone repair materials can release anticancer substances and growth factors when they are used, they can not only effectively promote bone healing, but also inhibit tumor recurrence. Studies have found that MBG, as a carrier of immunomodulators, can also solve the problems of delivery and non-target side effects, amplify immunomodulatory effects, integrate the synergistic effects of different molecules, and most importantly, achieve the manipulation of living immune cells[145].
Ta Taşar et al. Prepared high porosity magnetic MBG by Sol-Gel method, and combined it with calcium sulfate cement (CSC) to form a composite scaffold (CSC-MBG). Under the condition of magnetic field in vitro, the temperature of CSC-MBG can reach about 43 ℃, and at this time, CSC- MBG will release Ca2+, resulting in cell death due to Ca overload[146]; At the same time, the appropriate pH value and osteogenic activity of CSC-MBG can promote postoperative bone repair and inhibit the growth of bone tumors. In addition, Kermani et al. Successfully synthesized a series of Fe-MBG by Sol-Gel method, and confirmed that Fe-MBG had a high activation potential for Fenton reaction through electrochemical tests (including cyclic voltammetry and AC impedance spectroscopy), which could activate Fenton reaction and subsequently produce ROS, such as -OH radicals, and then kill residual tumor cells[147].
MBG can be loaded with specific metal ions to make it magnetic for magnetic thermal synergistic tumor treatment, which can effectively prevent local tumor recurrence, and at the same time, MBG can promote the repair of bone defects caused by surgical resection, which provides a new idea for magnetic MBG treatment of tumor bone defects.

4.4 MBG as coating material

Bone defect is one of the most common problems in orthopaedics. Bone grafting is generally used to repair the defect site in clinic, especially for large bone defects caused by congenital malformation, tumor resection and traumatic fracture[148]. Traditional metallic biomaterials have sufficient mechanical properties (strength, elastic modulus, and ductility) for long-term support and maintenance of in vivo stability, so many metallic materials such as stainless steel, cobalt-chromium alloy, and titanium and its alloys are used as implant biomaterials, but they do not have good bioactivity and other biological functions[149][150]. Surface coating is one of the most commonly used methods to improve the biocompatibility and bioactivity of biomaterials. MBG can promote the better combination of metal implants and host tissues by forming HA at the interface, so as to improve their integration with host tissues and overall biological performance[151,152]; In addition, they can also regulate or inhibit the corrosion of implanted metals in biological environment, and prevent the damage of metal corrosion to human body, so MBG as a coating material is a new idea[153].
Haftbaradaran-Esfahani et al. prepared a porous alloy scaffold using cobalt-based alloy, and then prepared 58 S bioglass by Sol-Gel method and coated it to improve its mechanical properties and bioactivity. After the coating was dried and stabilized at 600 ℃ for 1 H, the porosity of the porous sample was about 36.0%.The pore size distribution is in the range of 25.0 ~ 400.0 μm, which is single-phase cobalt with face-centered cubic structure. However, the porosity of the coated cobalt-based alloy scaffolds is reduced by about 2.0%, and the pore size distribution is in the range of 100.0 ~ 400.0 μm. The compressive strength of the scaffolds is about 80.0 MPa, and the modulus is about 0.4 GPa[154]; After immersion in simulated body fluid for 28 d, the bioactivity of the coated sample increased significantly compared with that of the uncoated sample (see Fig. 6). Huo et al. Coated CS/Cu-MBG composite coating on the surface of titanium implant by electrophoretic deposition technology. Experiments showed that the coated titanium implant had good bioactivity and bone immunomodulation[155]; And due to the release of Cu2+, the implant has antibacterial effect and instantaneous bactericidal activity. In addition, Heise et al. Also coated CS/MBG composite coating on the surface of magnesium alloy substrate by electrophoretic deposition technology. The experimental results show that the coating can effectively protect the corrosion of the substrate, while endowing the magnesium alloy substrate with good bioactivity and enhancing bone integration[156]. A large number of studies have shown that it is feasible to promote bone repair and prevent bacterial infection by coating MBG on the surface of bone graft materials.
图6 多孔支架在体液中浸泡28  d后的SEM图：（a）未使用和（b）使用58S生物玻璃涂层[154]

Fig. 6 SEM images of porous Vitallium after 28 days soaking in SBF: (a) without and (b) with 58S Bioglass coating[154]

5 Conclusion and outlook

Due to the unique ordered mesoporous structure, MBG has a large number of nano-scale pores, which has obvious unique properties of nanomaterials, as well as excellent biocompatibility and bioactivity; It can not only promote bone regeneration and osseointegration, but also achieve antibacterial and other beneficial effects by loading therapeutic agents (including therapeutic inorganic ions, antibacterial agents and antibiotics) into its mesopores, so that the drugs can be released locally and controlled. MBG doped with inorganic ions can not only prevent the development of drug-resistant bacteria, but also fight against infection at bone defects with minimal human side effects. In addition, by loading anti-inflammatory and anticancer drugs, MBG can slowly release drugs for a long time to achieve the purpose of inhibiting or preventing inflammation and cancer recurrence; And MBG can be prepared into different forms such as scaffolds, fibers, coatings or nanoparticles. A large number of studies have found that MBG doped with inorganic ions or processed into different forms still shows excellent bioactivity.
However, there are still difficulties to be overcome in the clinical application of MBG. First of all, when MBG is made into scaffolds, it has high brittleness and low mechanical strength due to its mesoporous structure, which limits its application as a human implant. Second, although the released metal ions are effective against resistant strains, the ions released by MBG alone are often not effective in treating infections. In addition, MBG has high bioactivity, and when in contact with biological fluids, its surface rapidly forms a HA-like layer, which may hinder or slow down the release of biomolecules, drugs, or therapeutic ions from MBG. More importantly, when the MBG system becomes more complex with the addition of therapeutic ions, drugs, biological signals, and living cells, it is important to consider not only the interaction of each element with the matrix, but also the interaction between elements, ensuring that there is no harm to the human body. Although there are still some difficulties in the application of MBG, it has broad application prospects in the field of medical biomaterials through its excellent performance.

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