Boron-containing bioactive glasses in bone and soft tissue engineering

Boron is considered to influence the performance of several metabolic enzymes and boron deficiency is associated with impaired growth and abnormal bone development. As such, boron is a beneficial bioactive element for animals and humans. It is also well known that boron stimulates wound healing and improves bone health. The addition of boron in different proportions to bioactive glasses has significant effects on glass structure, glass processing parameters, biodegradability, biocompatibility, bioactivity and cytotoxicity. Different compositions of bioactive glasses (BGs) containing boron, including boron-doped, borosilicate and borate glasses, are being investigated for bone and soft tissue engineering under the premise that these BGs are suitable carriers of boron, indicating controlled release of B species in the biological environment. This paper reviews up to date research and applications of borate, borosilicate, and boron doped silicate and phosphate BGs focussing on their physical, structural, degradation and biological properties for hard and soft tissue regeneration.     

骨修复用生物玻璃研究进展

生物活性玻璃和生物微晶玻璃因其优异的生物活性及组分与性能可设计性而引起广泛关注,人们力图在其基础上研制出性能优良的骨修复材料.近来有报道发现特定组分的玻璃能激活基因从而促进骨组织再生,为生物玻璃的应用开拓了新的领域.本文综述了目前的生物玻璃及生物微晶玻璃体系、组分与制备工艺对其理化性能和生物活性的影响、生物活性的评价方式及其活性机理.     

Bioactive Glasses: From Macro to Nano

Bioactive glasses play an important role for the bone defects treatment. Forty years ago, it was discovered the first bioactive glass, Bioglass^®, obtained by melting and used in Orthopedics and Dentistry. Twenty years ago, another family of bioactive glasses obtained by solgel processing was reported. Solgel glasses exhibit high textural properties and quicker bioactive response than melt glasses. However, their presence in the market is scarce which could be explained considering that the improvements they bring do not justify the costs of their translation to product. In the last decade, so-called template glasses exhibiting greater bioactivity than solgel glasses were described. These glasses display high pore volume and ordered mesopore structure, which makes them optimal candidates for hosting biologically active substances. For these characteristics, template glasses are being considered ideal candidates for the scaffolds manufacture used in bone engineering. This article shows the main features of three families of bioactive glasses and the importance of their nanostructure in the bioactivity. We demonstrate here that glasses with identical composition may exhibit very different properties, specifically bioactivity, as a function of their nanostructure. This fact demonstrates the importance of controlling this nanostructure in the design of new bioactive materials for bone regeneration.     

Dissolution,bioactivity behavior,and cytotoxicity of rare earth-containing bioactive glasses (RE = Gd,Yb)

Rare earth-containing bioactive glasses (RE-BGs) have been poorly explored in the biomaterials field, although RE has optical, nuclear, and magnetic properties that could be used in different biomedical applications. In order to verify whether these glasses can be promising as biomaterials, we studied the dissolution, bioactivity, and cytotoxicity of RE-BGs based on the SiO₂–Na₂O–CaO–P₂O₅–RE₂O₃ (RE = Gd, Yb) system. The glasses were obtained by melting-quenching and their particle size was determined by laser diffraction. Their dissolution behavior was studied in Tris-HCl, while bioactivity was performed in simulated body fluid solution under physiological conditions during several periods. The cytotoxicity test was performed using glass-derived conditioned medium and mesenchymal stem cell derived from deciduous teeth. The dissolution results showed that the glasses dissolved under two different kinetics, which are lower for rare earth-containing glasses, due to the more covalent character of Si–O–RE bonds. The bioactivity results evidenced that all glasses showed bioactivity after 24 hours. However, gadolinium and ytterbium promoted a more calcium phosphate deposition, which contrasts with the slower dissolution kinetics of rare earth-containing glasses. All the glasses were considered biocompatible, showing cell viability higher than 80%. The overall results showed that RE-BGs are promising materials for applications that require bioactivity and/or biocompatibility.     

骨修复用生物玻璃的研究现状及其发展趋势

生物活性玻璃和生物微晶玻璃因其优异的生物活性及组分与性能的可设计性而引起广泛关注，人们力图在此基础上研制出性能优良的骨修复材料。笔者综述了目前生物玻璃及生物微晶玻璃体系、组分及其活性机理，探讨了其在医学领域的应用及其发展趋势。     

Effect of ion substitution on properties of bioactive glasses: A review

Bioactive glasses and glass-ceramics have recently found key applications in biomedicine, mainly for bone repair and replacement. Recent developments in the field of tissue engineering have re-invigorated the quest to enhance the physical and biomedical effectiveness of bioactive glasses and glass-ceramics by incorporation of different elements into the composition of these materials. Although most elements are included in the bioactive glass for the therapeutic benefits (e.g., Ag and Sr), they influence the structure and bioactivity of the glass. This review systematically discusses the influence of the addition of silver (Ag), magnesium (Mg), strontium (Sr), zinc (Zn), aluminum (Al), potassium (P), fluoride (F) and zirconia (ZrO₂) elements on the chemical, physical and therapeutic properties of bioactive glasses and glass-ceramics, which are expected to play an important role in the future of bone regenerative medicine. This article describes where these dopant ions fit into the glass structure and how these affect the delivery and properties of the glass as a whole.     

Development of microfibers for bone regeneration based on alkali-free bioactive glasses doped with boron oxide

In this paper, we present a new series of alkali-free bioactive glasses (BG) based on FastOs^® composition (38.49 SiO₂ – 36.07 CaO – 19.24 MgO – 5.61 P₂O₅ – 0.59 CaF₂, expressed in mol %), which was modified by partially replacing silicon dioxide network-former with boron trioxide network-former, utilizing calcium oxide as a charge compensator. The main objective of this study was to obtain a new family of bioactive glasses suitable for the fabrication of glass fibers. The BGs were prepared by melt quenching technique and their structural and thermal properties were determined. Glass rods were used to obtain fibers by the classic drawing technique. The bioactivity of the fibers was subsequently assessed through immersion tests in simulated body fluid (SBF) to establish their ability to form hydroxyl carbonated (HCA) apatite onto their surfaces. Glasses with moderate substitution of SiO₂ with B₂O₃ exhibited enhanced thermal properties, allowing to significantly suppress the crystallization trend, and favoring to draw the fibers. The structure of the studied glasses was obtained by NMR spectroscopy. The structure-property correlations were established by their relationship to the configurational entropy. Smaller amounts of substitution resulted in larger entropy of the glasses. Moreover the SBF tests revealed an extensive formation of HCA, comparable to the parent FastOs^®BG composition, which assures fast bonding to the bone. Thus, presented glass fibers may be considered as promising materials for wool-like bone implants or as reinforcing constituent of biopolymer matrix composites.     

Ceramic biomaterials: Properties,state of the art and future prospectives

This article gives an overview of ceramics-based biomaterials with particular emphasis on their various properties and health care applications. Furthermore, bio ceramics are grouped as oxide and nitride-based bioinert ceramics, bioresorbable calcium phosphate-based materials and bioactive glasses/glass ceramics. Ceramics and bioglasses are good biomaterials, here mainly focused on bone replacement applications. Mesoporous glasses, nanocrystalline ceramics and composites, having a high surface area, corrosion resistive and better mechanical properties, could be future biomaterials. Controlled porosity with uniform pores distributed biomaterials could be achieved using fine synthesis routes like sol-gel and additive manufacturing. Bioceramics and bioglasses could also be synthesized by agro-food wastes and optimize their properties according to need and applications easily. Moreover, these sustainable resources exhibit inherent porosity due to presence of organic substance attached with inorganic materials. As crystallinity increased, the bioactivity decreases of ceramics. Both properties can be optimised using nano-crystalline and composite biomaterials.     

生物活性玻璃多孔材料的制备及性能研究

采用溶胶-凝胶法制备生物活性玻璃58S及77S;通过熔融法制备生物活性玻璃45S5,分别向上述3种生物活性玻璃粉体以及它们的混合物中添加一定比例的造孔剂,通过一定的烧结工艺制成具有不同组成的生物活性多孔材料,利用体外实验方法结合DTA,SEM及FTIR等材料显微结构及性能研究手段分析比较了各种多孔材料的显微结构、表面形貌、抗折强度及生物活性.研究表明:58S和45S5混合制备的多孔材料是一种具有良好生物活性和生物矿化特性的生物材料,可用于制备骨缺损填充材料和骨组织工程支架.     

Two-step sinter-crystallization of K2O–CaO–P2O5–SiO2 (45S5-K) bioactive glass

Bioactive glasses and glass-ceramics (GCs) effectively regenerate bone tissue, however most GCs show improved mechanical properties. In this work, we developed and tested a rarely studied bioactive glass composition (24.4K₂O-26.9CaO-46.1SiO₂-2.6P₂O₅ mol%, identified as 45S5-K) with different particle sizes and heating rates to obtain a sintered GC that combines good fracture strength, low elastic modulus, and bioactivity. We analyzed the influence of the sintering processing conditions in the elastic modulus, Vickers microhardness, density, and crystal phase formation in the GC. The best GC shows improved properties compared with its parent glass. This glass achieves a good densification degree with a two-step viscous flow sintering approach and the resulting GC shows as high bioactivity as that of the standard 45S5 Bioglass®. Furthermore, the GC elastic modulus (56 GPa) is relatively low, minimizing stress shielding. Therefore, we unveiled the glass sintering behavior with concurrent crystallization of this complex bioactive glass composition and developed a potential GC for bone regeneration.     

Synthesis and characterization of sol-gel bioactive glass nanoparticles doped with boron and copper

In this work the sol-gel synthesis of bioactive glass nanoparticles containing both boron and copper oxides is reported for the first time in the literature. Two acid/base co-catalysed methods were compared. The obtained glasses have been characterized in terms of morphology, composition, particle surface area, phase analysis and bioactivity in acellular simulated body fluids. The almost spherical nanoparticles (<100 nm diameter) obtained are characterized by a certain degree of aggregation and have compositions, which are coherent with the theoretical ones. Each glass revealed the ability to promote the growth of hydroxyapatite on its surface during soaking in simulated body fluid, thus we can assume that the addition of boron and copper did not negatively affect the bioactivity of the sol-gel derived glasses. Future investigations will be devoted to biological characterizations for cytotoxicity, antibacterial properties and pro-angiogenetic abilities.     

Bioactive glass and glass-ceramic orbital implants

This review focuses on the applications of bioactive glasses and glass-ceramics in the field of orbital implants for ocular surgery. This use is relatively novel and less popular compared to the applications in orthopedics and dentistry for the repair of bone and teeth. Recent studies have shown the suitability of bioactive glasses and glass-ceramics in contact with soft tissues for promoting additional effects associated to the release of therapeutic inorganic ions. Specifically, the angiogenic and antibacterial actions that may be elicited by selected glass compositions are highly appealing for the development of new-generation orbital implants, since improved vascularization and antiseptic properties are the key for a higher success rate of anophthalmic socket procedures. An overall picture of existing orbital implants based on bioactive glasses is here provided, and the further potential and open challenges for future research in this field are highlighted and discussed.     

Magnesium-Containing Bioactive Glasses for Biomedical Applications

The importance of Mg in the human body, its key role in bone tissue development, in addition to its application to improve and modify physical, thermal, and mechanical properties of bioactive silicate glasses, make Mg a very interesting element as a component of bioactive glasses for medical applications. Although Mg is a typical element in the composition of numerous developed bioactive glasses, the analysis of the literature reveals that further research is required to gain comprehensive understanding about the effects of MgO on bioactive glass structure and properties. This article presents a comprehensive overview of the field of Mg-containing bioactive glasses discussing available compositions and summarizing existing knowledge on effects of MgO on glass properties. The biomedical applications of several developed glasses are discussed highlighting the distinct effects of Mg in relevant areas, such as bioactivity and cell response, and focusing on the most common applications for these glasses, such as bone cements, bioactive coatings, and scaffolds for bone tissue engineering. The effect of Mg on bone development is discussed and avenues for future research in the field are proposed, emphasizing the need to investigate unstudied properties of (already developed) Mg-containing glass compositions, such as angiogenesis-stimulating action and the effect on osteoclast functions, to develop new Mg-containing bioactive glasses as well as to make products of different shape designs such as nanoparticles, fibers, and complex porous structures.     

Synthesis,Characterization and Biological Evaluation of a New Sol-Gel Derived B and Zn-Containing Bioactive Glass: <Emphasis Type="Italic">In Vitro</Emphasis> Study

In this study we employed the sol-gel method to synthesize new CaO–P₂O₅–SiO₂–ZnO–B₂O₃ bioactive glasses. Three samples with various B₂O₃ content (5, 10 and 15 mol %) was prepared and their bioactivity were evaluated by immersion in simulated body fluid (SBF) and the glasses were characterized using X-ray diffraction (XRD), Fourier transform infrared (FTIR) and scanning electron microscopy (SEM). The experimental results revealed that with increasing the amount of boron content, a more crystalline domain can be observed in their XRD patterns and consequently the formation of hydroxyapatite (HA) increased. FTIR spectra showed that the sample containing 10 mol% of boron had the sharpest peaks attributed to the formation of hydroxyapatite. Biocompatibility of the samples was examined by MTT assay and alkaline phosphatase activity. The result ascertained that the synthesized bioactive glass had good biocompatibility and can serve as a bone substitute in bone defects.     

溶胶-凝胶生物活性玻璃多孔支架的制备与性能的研究

通过溶胶—凝胶法合成制备了CaO-P2O5-SiO2系统溶胶—凝胶生物活性玻璃,并通过一定的造孔工艺将其制备成用作骨组织工程支架的多孔材料。采用体外模拟实验方法及DTA、SEM及FTIR等材料显微结构及性能研究手段分析研究了造孔剂种类、添加量对多孔材料的显微结构、表面形貌、抗折强度以及生物活性的影响。     

Sodium is not essential for high bioactivity of glasses

This study aims to demonstrate that excellent bioactivity of glass can be achieved without the presence of an alkali metal component in glass composition. In vitro bioactivity of two sodium-free glasses based on the quaternary system SiO₂-P₂O₅-CaO-CaF₂ with 0 and 4.5 mol% CaF₂ content was investigated and compared with the sodium-containing glasses with equivalent amount of CaF₂. The formation of apatite after immersion in Tris buffer was followed by Fourier-transform infrared spectroscopy, X-ray diffraction, ³¹P and ¹⁹F solid-state MAS-NMR. The dissolution study was completed by ion release measurements in Tris buffer. The results show that sodium-free bioactive glasses formed apatite at 3 h of immersion in Tris buffer, which is as fast as the corresponding sodium-containing composition. This signifies that sodium is not an essential component in bioactive glasses and it is possible to make equally degradable bioactive glasses with or without sodium. The results presented here also emphasize the central role of the glass compositions design which is based on understanding of structural role of components and/or predicting the network connectivity of glasses.     

New trends in bioactive scaffolds: The importance of nanostructure

There are many criteria for an ideal scaffold that will stimulate the body's repair mechanisms to regenerate diseased or damaged bone to its original healthy state. These include having a pore network large and open enough for cells and blood vessels to penetrate and the ability to bond to bone. Sol–gel derived bioactive glasses have a nanoporosity that can control degradation rate. They can be foamed to produce scaffolds that mimic cancellous bone macrostructure. Bioactive glass foams with optimised nanoporosity are strong in compression; however, they have low toughness and pore strength when loaded in tension. Therefore an ideal scaffold would have all the properties of the glasses with enhanced toughness. This can only be achieved by creating new nanoscale composites. Resorbable polymers must interact with the silica based inorganic network at the nanoscale to maintain bioactivity and controlled resorption. This is a complex problem but may be the future of scaffold development.     

Er3+/Yb3+ co-doped bioactive glasses with up-conversion luminescence prepared by containerless processing

Er³⁺/Yb³⁺ co-doped bioactive glasses were prepared via containerless processing in an aerodynamic levitation furnace. The as-prepared glasses were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) equipped with energy dispersive X-Ray spectroscopy (EDX). The up-conversion luminescence of as-prepared glasses was measured using an Omni- 3007 spectrometer. Furthermore, the in vitro bioactivity was evaluated by soaking the materials in simulated body fluid, and the biocompatibility was evaluated in MC3T3-E1 cell culture.The results show that containerless processing is a unique method to prepare homogeneous rare earth doped bioactive glasses. The obtained Er³⁺/Yb³⁺ co-doped glasses show green and red up-conversion luminescence at the excitation of 980 nm laser. The XRD analysis confirmed that calcium silicate powders, as starting materials, were completely transformed from the original multi-crystalline phase (CS-P) into the amorphous-glassy phase (CS-G, EYS, LCS) via containerless processing. The SEM observation combined with EDX and FTIR analyses showed that the as-prepared glasses were bioactive. The cell proliferation assay also revealed that the as-prepared glasses were biocompatible and nontoxic to MC3T3-E1 cells. This study suggests that the luminescent bioactive glasses prepared by containerless processing could be used for studying biodegradation of bone implantation materials.     

Surface structures of sodium borosilicate glasses from molecular dynamics simulations

Surface plays an important role in the physical and chemical properties of oxide glasses and controls the interactions of these glasses with the environment, thus dominating properties such as the chemical durability and bioactivity. The surface atomic structures of a series of sodium borosilicate glasses were studied using classical molecular dynamics simulations with recently developed compositional dependent partial charge potentials. The surface structural features and defect speciation were characterized and compared with the bulk glasses with the same composition. Our simulation results show that the borosilicate glass surfaces have significantly different chemical compositions and structures as compared to the bulk. The glass surfaces are found to be sodium enriched and behave like borosilicate glasses with higher R (Na₂O/B₂O₃) values. As a result of this composition and associated structure changes, the amount of fourfold boron decreases at the surface and the network connectivity on the surface decreases. In addition to composition variation and local structure environment change, defects such as two‐membered rings and three‐coordinated silicon were also observed on the surface. These unusual surface composition and structure features are expected to significantly impact the chemical and physical properties and the interactions with the environments of sodium borosilicate glasses.     

New calcium‐free Na2O–Al2O3–P2O5 bioactive glasses with potential applications in bone tissue engineering

Sodium aluminophosphate glasses were evaluated for their bone repair ability. The glasses belonging to the system 45Na₂O–xAl₂O₃‐(55‐x)P₂O₅, with x = (3, 5, 7, 10 mol%) were prepared by a melt‐quenching method. We assessed the effect of Al₂O₃ content on the properties of Na₂O–Al₂O₃–P₂O₅ (NAP) glasses, which were characterized by density measurements, DSC analyses, solubility, bioactivity in simulated body fluid and cytocompatibility with MG‐63 cells. To the best of our knowledge, this is the first investigation of calcium‐free Na₂O–Al₂O₃–P₂O₅ system glasses as bioactive materials for bone tissue engineering.