Update on the use of 45S5 bioactive glass in the treatment of bone defects in regenerative medicine

Bone regeneration is a critical area in regenerative medicine,particularly in orthopedics,demanding effective biomedical materials for treating bone defects.45S5 bioactive glass(45S5 BG)is a promising material because of its osteoconductive and bioactive properties.As research in this field continues to advance,keeping up-to-date on the latest and most successful applications of this material is imperative.To achieve this,we conducted a comprehensive search on Pub-Med/MEDLINE,focusing on English articles published in the last decade.Our search used the keywords“bioglass 45S5 AND bone defect”in combination.We found 27 articles,and after applying the inclusion criteria,we selected 15 studies for detailed examination.Most of these studies compared 45S5 BG with other cement or scaffold materials.These comparisons demonstrate that the addition of various composites enhances cellular biocompatibility,as evidenced by the cells and their osteogenic potential.Moreover,the use of 45S5 BG is enhanced by its antimicrobial properties,opening avenues for additional investigations and applications of this biomaterial.

In Vitro Comparative Effect of Three Novel Borate Bioglasses on the Behaviors of Osteoblastic MC3T3-E1 Cells

Most related investigations focused on the effects of borate glass on cell proliferation/biocompatibility in vitro or bone repair in vivo; however, very few researches were carried out on other cell behaviors. Three novel borate bioglasses were designed as scaffolds for bone regeneration in this wok. Comparative effects of three bioglasses on the behaviors of osteoblastic MC3T3-E1 cells were evaluated. Excellent cytocompatibility of these novel borate bioglasses were approved in this work. Meanwhile, the promotion on cell proliferation, protein secretion and migration with minor cell apoptosis were also discussed in details, which contributed to the potential clinical application as a new biomaterial for orthopedics.

In-situ deposition of apatite layer to protect Mg-based composite fabricated via laser additive manufacturing

Biodegradable magnesium(Mg) and its alloy show huge potential as temporary bone substitute due to the favorable biocompatibility and mechanical compatibility. However, one issue deserves attention is the too fast degradation. In this work, mesoporous bioglass(MBG)with high pore volume(0.59 cc/g) and huge specific surface area(110.78 m^(2)/g) was synthesized using improved sol-gel method, and introduced into Mg-based composite via laser additive manufacturing. Immersion tests showed that the incorporated MBG served as powerful adsorption sites, which promoted the in-situ deposition of apatite by successively adsorbing Ca2+and HPO42-. Such dense apatite film acted as an efficient protection layer and enhanced the corrosion resistance of Mg matrix, which was proved by the electrochemical impedance spectroscopy measurements. Thereby, Mg based composite showed a significantly decreased degradation rate of 0.31 mm/year. Furthermore,MBG also improved the mechanical properties as well as cell behavior. This work highlighted the advantages of MBG in the fabrication of Mg-based implant with enhanced overall performance for orthopedic application.

e-PTFE与Bioglass结合修复重建下颌骨缺损的实验研究

目的 :通过动物实验 ,观察膜引导组织再生术 (MGTR)与生物活性材料结合修复重建下颌骨骨缺损的效果。方法 :手术制备下颌骨标准骨缺损不愈合模型 ,将膨体聚四氟乙烯膜 (e PTFE)与Bioglass结合修复下颌骨缺损。结果 :实验组 (e PTFE Bioglass)与对照组 (e PTFE)在术后各时点 2、4、8、12w新生骨形成量有显著差异 (P <0 0 5 )。结论 :MGTR与Bioglass结合修复重建下颌骨骨缺损 ,术后成骨早 ,术后 12w似正常骨质 ,为进一步临床应用提供实验依据。

Chemical Durability and Structural Properties of Al₂O₃-CaO-Na₂O-P₂O₅Glasses Studied by IR Spectroscopy, XRD and SEM

Various characterization techniques were used to study the composition of the glass series xAl2O3-(40 - x)CaO-10Na2O-50P2O5 (with 0 ≤ x ≤ 10) in terms of chemical durability, X-ray diffraction, IR spectroscopy and scanning electron microscopy (SEM). The improved chemical durability was attributed to the replacement of easily hydrated P-O-P bonds by covalent and resistant Ca-O-P and Al-O-P bonds. However, the change in the dissolution rate (DR) versus time showed a marked decrease in chemical durability with increasing the Al2O3 content to the detriment of the CaO content. The X-ray diffraction analysis of glasses annealed at 550°C and 660°C for 48 hours indicated the presence of pyrophosphate phases and predominant metaphosphates or cyclic metaphosphate phases when the Al2O3 content was ≤7.5 mol%. Nevertheless, both, X-ray diffraction and IR spectroscopy confirmed the structural tendency change from metaphosphate (Q2) and pyrophosphate structural units (Q1). Toward short isolated orthophosphate units (Q0) when the Al2O3 content above 7.5 mol%. SEM micrographs illustrated that the number of crystallites increased in the glass network when the Al2O3 content increased at the expense of the CaO content. An increase in the Al2O3 content to 10 mol% led to the formation of a larger number of crystallites of different sizes, dominated by small crystallite sizes assigned to short isolated orthophosphate groups. This phenomenon led to a decrease in chemical durability and seems to be a favorable factor for the formation of the apatite layers which enclose the glass, in a SBF solution test, able of regenerating bone tissue in biomedical application.

Effects of 45S5 bioglass on surface properties of dental enamel subjected to 35% hydrogen peroxide

Tooth bleaching agents may weaken the tooth structure. Therefore, it is important to minimize any risks of tooth hard tissue damage caused by bleaching agents. The aim of this study was to evaluate the effects of applying 45S5 bioglass （BG） before, after, and during 35% hydrogen peroxide （HP） bleaching on whitening efficacy, physicochemical properties and microstructures of bovine enamel. Seventy-two bovine enamel blocks were prepared and randomly divided into six groups： distilled deionized water （DDW）, BG, HP, BG before HP, BG after HP and BG during HP. Colorimetric and microhardness tests were performed before and after the treatment procedure. Representative specimens from each group were selected for morphology investigation after the final tests. A significant color change was observed in group HP, BG before HP, BG after HP and BG during HP. The microhardness loss was in the following order： group HP〉 BG before HP, BG after HP〉 BG during HP〉DDW, BG. The most obvious morphological alteration of was observed on enamel surfaces in group HP, and a slight morphological alteration was also detected in group BG before HP and BG after HP. Our findings suggest that the combination use of BG and HP could not impede the tooth whitening efficacy. Using BG during HP brought better protective effect than pre/post-bleaching use of BG, as it could more effectively reduce the mineral loss as well as retain the surface integrity of enamel. BG may serve as a promising biomimetic adjunct for bleaching therapy to prevent/restore the enamel damage induced by bleaching agents.

Preparation of Ti6Al4V/BG/HA graded coating by electrophoresis deposition in absolute alcohol medium

A codeposition of bioglass (BG) and hydroxyapatite (HA) on the substrate Ti6Al4V is realized in a nonaqueous solution system by inducing crystallization of HA on surface of the BG grain and electrophoresis deposition (EPD), and then a bioactive graded ceramic coating was obtained after sintering of the coating. This technique is a new method for making bioactive graded coating. The adhesive strength between the coating and the substrate reaches 18?MPa, and the better electrophoresis depositing parameters and optimal sintering procedure are obtained.

Chronology of Bioactive Glass Development and Clinical Applications

The key research and development steps for bioactive glass (45S5 Bioglass) are documented from the date of discovery in 1969 through FDA approvals of the first dental, ENT, maxillo-facial and orthopedic clinical products. Understanding the mechanisms and quantifying the rapid surface reactions to form a bone-bonding hydroxyl-carbonate apatite (HCA) layer on the bioactive glass in contact with living bone was a vital part of the early development of this class of biomaterials. A key later discovery was enhanced osteogenesis and in situ bone regeneration by controlled release of ionic dissolution products from the bioactive glass particulates that leads to up-regulation and activation of seven families of genes, a process called osteostimulation.

Regulating effect of borosilicate bioglass extract on the osteoblast proliferation activity and osteogenesis signaling pathway function

Objective: To study the regulating effect of borosilicate bioglass extract on the osteoblast proliferation activity and osteogenesis signaling pathway function. Methods: Osteoblasts MG-63 were cultured and divided into borosilicate group and control group that were treated with the culture medium containing borosilicate bioglass extract and the culture medium without extract respectively. After 24 h of treatment, the cell proliferation activity as well as the expression of proliferation activity markers, Wnt signaling pathway molecules and PI3K/AKT signaling pathway molecules was measured. Results: After 24 h of treatment, MTT cell viability of borosilicate group was significantly higher than that of control group, and ALP, OC, OPN, COL-I, Runx2, Wnt1, Wnt3a, β-catenin, LRP5, LRP6, p-PI3K, p-AKT, Bcl-2 and BMP protein expression in cells were significantly higher than those of control group. Conclusion: Borosilicate bioglass extract can enhance the proliferation activity of osteoblasts by activating Wnt pathway and PI3K/AKT pathway.

Modulating degradation of sodium alginate/bioglass hydrogel for improving tissue infiltration and promoting wound healing

More and more studies have recognized that the nanosized pores of hydrogels are too small for cells to normally grow and newly formed tissue to infiltrate,which impedes tissue regeneration.Recently,hydrogels with macropores and/or controlled degradation attract more and more attention for solving this problem.Sodium alginate/Bioglass(SA/BG)hydrogel,which has been reported to be an injectable and bioactive hydrogel,is also limited to be used as tissue engineering scaffolds due to its nanosized pores.Therefore,in this study,degradation of SA/BG hydrogel was modulated by grafting deferoxamine(DFO)to SA.The functionalized grafted DFO-SA(G-DFO-SA)was used to form G-DFO-SA/BG injectable hydrogel.In vitro degradation experiments proved that,compared to SA/BG hydrogel,G-DFO-SA/BG hydrogel had a faster mass loss and structural disintegration.When the hydrogels were implanted subcutaneously,G-DFO-SA/BG hydrogel possessed a faster degradation and better tissue infiltration as compared to SA/BG hydrogel.In addition,in a rat full-thickness skin defect model,wound healing studies showed that,G-DFO-SA/BG hydrogel significantly accelerated wound healing process by inducing more blood vessels formation.Therefore,G-DFO-SA/BG hydrogel can promote tissue infiltration and stimulate angiogenesis formation,which suggesting a promising application potential in tissue regeneration.

Characterization of porous Ti-bioglass composite produced by mechanical milling and space holder sintering

In this study, porous titanium-10 wt% bioglass(BG) composites were fabricated by the process of combining mechanical alloying with space holder sintering. The pore morphology and phase constituents of the milled powders and porous compacts were characterized by scanning electron microscopy(SEM), X-ray diffractometry(XRD), and Fourier transform infrared spectroscopy(FT-IR). The mechanical properties were determined by running compression test. The porosity of the sintered samples shows a downward trend with the increase of milling time. As the porosity increases, both the compressive strength and elastic modulus decrease. The results illustrate that the fabricated porous compacts with high porosity and suitable mechanical properties have the potential application in bone tissue engineering.

Hypoxia-mimicking 3D bioglass-nanoclay scaffolds promote endogenous bone regeneration

Large bone defect repair requires biomaterials that promote angiogenesis and osteogenesis.In present work,a nanoclay(Laponite,XLS)-functionalized 3D bioglass(BG)scaffold with hypoxia mimicking property was prepared by foam replication coupled with UV photopolymerization methods.Our data revealed that the incorporation of XLS can significantly promote the mechanical property of the scaffold and the osteogenic differentiation of human adipose mesenchymal stem cells(ADSCs)compared to the properties of the neat BG scaffold.Desferoxamine,a hypoxia mimicking agent,encourages bone regeneration via activating hypoxia-inducible factor-1 alpha(HIF-1α)-mediated angiogenesis.GelMA-DFO immobilization onto BG-XLS scaffold achieved sustained DFO release and inhibited DFO degradation.Furthermore,in vitro data demonstrated increased HIF-1αand vascular endothelial growth factor(VEGF)expressions on human adipose mesenchymal stem cells(ADSCs).Moreover,BG-XLS/GelMA-DFO scaffolds also significantly promoted the osteogenic differentiation of ADSCs.Most importantly,our in vivo data indicated BG-XLS/GelMA-DFO scaffolds strongly increased bone healing in a critical-sized mouse cranial bone defect model.Therefore,we developed a novel BG-XLS/GelMA-DFO scaffold which can not only induce the expression of VEGF,but also promote osteogenic differentiation of ADSCs to promote endogenous bone regeneration.

Bioglass enhances the production of exosomes and improves their capability of promoting vascularization

Recently,exosomes have been extensively applied in tissue regeneration.However,their practical applications are severely restricted by the limited exosome secretion capability of cells.Therefore,developing strategies to enhance the production of exosomes and improve their biological function attracts great interest.Studies have shown that biomaterials can significantly enhance the paracrine effects of cells and exosomes are the main signal carriers of intercellular paracrine communication,thus biomaterials are considered to affect the exosome secretion of cells and their biological function.In this study,a widely recognized biomaterial,45S5 Bioglass®(BG),is used to create a mild and cell-friendly microenvironment for mesenchymal stem cells(MSCs)with its ion products.Results showed that BG ion products can significantly improve exosome production of MSCs by upregulating the expression of neutral sphingomyelinase-2(nSMase2)and Rab27a which enhanced the nSMases and Rab GTPases pathways,respectively.Besides,microRNA analysis indicates that BG ion products can modulate the cargoes of MSCs-derived exosomes by decreasing microRNA-342-5p level while increasing microRNA-1290 level.Subsequently,the function of exosomes is modified as their capabilities of promoting the vascularization of endothelial cells and facilitating the intradermal angiogenesis are enhanced.Taken together,BG ion products are confirmed to enhance exosome production and simultaneously improve exosome function,suggesting a feasible approach to improve the practical application of exosomes in regenerative medicine.

Nanotherapeutics for regeneration of degenerated tissue infected by bacteria through the multiple delivery of bioactive ions and growth factor with antibacterial/angiogenic and osteogenic/odontogenic capacity

Therapeutic options are quite limited in clinics for the successful repair of infected/degenerated tissues.Although the prevalent treatment is the complete removal of the whole infected tissue,this leads to a loss of tissue function and serious complications.Herein the dental pulp infection,as one of the most common dental problems,was selected as a clinically relevant case to regenerate using a multifunctional nanotherapeutic approach.For this,a mesoporous bioactive glass nano-delivery system incorporating silicate,calcium,and copper as well as loading epidermal growth factor(EGF)was designed to provide antibacterial/pro-angiogenic and osteo/odontogenic multiple therapeutic effects.Amine-functionalized Cu-doped bioactive glass nanospheres(Cu-BGn)were prepared to be 50–60 nm in size,mesoporous,positive-charged and bone-bioactive.The Cu-BGn could release bioactive ions(copper,calcium and silicate ions)with therapeutically-effective doses.The Cu-BGn treatment to human umbilical vein endothelial cells(HUVEC)led to significant enhancement of the migration,tubule formation and expression of angiogenic gene(e.g.vascular endothelial growth factor,VEGF).Furthermore,the EGF-loaded Cu-BGn(EGF@Cu-BGn)showed pro-angiogenic effects with antibacterial activity against E.faecalis,a pathogen commonly involved in the pulp infection.Of note,under the co-culture condition of HUVEC with E.faecalis,the secretion of VEGF was up-regulated.In addition,the osteo/odontogenic stimulation of the EGF@Cu-BGn was evidenced with human dental pulp stem cells.The local administration of the EGF@Cu-BGn in a rat molar tooth defect infected with E.faecalis revealed significant in vivo regenerative capacity,highlighting the nanotherapeutic uses of the multifunctional nanoparticles for regenerating infected/damaged hard tissues.

Osteostimulation of bioglass

Bioglass, with the code name 45S5, contains 45% silica, 24.5% CaO, 24.5% Na2O and 6% P2O5 in weight percent. All of these oxides are mixed together and melted at around 1350℃ to form a homogeneous silica network glass.1 Bioglass possesses fast biological response and fast bioactivity, when implanted in living tissue. Since Hench et alI reported over 35 years ago that the bioglass composition could chemically bind to bone,

Synthesis and Properties of Ag-doped Titanium-10 wt% 45S5 Bioglass Nanostructured Scaffolds

A new kind of biomedical Ti-45S5 Bioglass-Ag nanocomposites and their scaffolds with antibacterial function was developed by the introduction of 1.5 wt% Ag into the Ti-10 wt% 45S5 Bioglass matrix. The microstructure, hardness and corrosion resistance in Ringer solution of the Ag-doped Ti-45S5 glass were investigated. The Vickers hardness of the bulk Ti-10 wt% 45S5 Bioglass-1.5 wt% Ag nanocomposites reached 480 HVo.3. Contact angles of water on the micro- crystalline Ti and nanostructured Ti-10 wt% 45S5 Bioglass-1.5 wt% Ag sample were determined and show visible decrease from 55.2° to 49.6°. In vitro tests culture of normal human osteoblast cells showed very good cells proliferation, colonization and multilayering. In vitro bacterial adhesion study indicated a significantly reduced number of bacteria （Staphylococcus aureus） on the bulk nanostructured Ti-10 wt% 45S5 Bioglass-1.5 wt% Ag plate surface in comparison with that on microcrystalline Ti plate surface. Development of porous Ti-10 wt% 45S5 Bioglass-1.5 wt% Ag scaffolds aims in enhancing bone ingrowth and prosthesis fixation.

Superior biocompatibility and comparable osteoinductive properties: Sodium-reduced fluoride-containing bioactive glass belonging to the CaO–MgO–SiO2 system as a promising alternative to 45S5 bioactive glass

Bioactive glasses(BGs)are promising bone substitute materials.However,under certain circumstances BGs such as the well-known 45S5 Bioglass®(composition in wt%:45.0 SiO2,24.5 Na2O,24.5 CaO,6.0 P2O5)act cytotoxic due to a strong increase in pH caused by a burst release of sodium ions.A potential alternative is a sodiumreduced fluoride-containing BG belonging to the CaO–MgO–SiO2 system,namely BG1d-BG(composition in wt%:46.1 SiO2,28.7 CaO,8.8 MgO,6.2 P2O5,5.7 CaF2,4.5 Na2O),that has already been evaluated in-vitro,in-vivo and in preliminary clinical trials.Before further application,however,BG1d-BG should be compared to the benchmark amongst BGs,the 45S5 Bioglass®composition,to classify its effect on cell viability,proliferation and osteogenic differentiation of human mesenchymal stem cells(MSCs).Therefore,in this study,the biocompatibility and osteogenic potential of both BGs were investigated in an indirect and direct culture setting to assess the effect of the ionic dissolution products and the BGs’physical presence on the cells.The results indicated an advantage of BG1d-BG over 45S5 Bioglass®regarding cell viability and proliferation.Both BGs induced an earlier onset of osteogenic differentiation and accelerated the expression of late osteoblast marker genes compared to the control group.In conclusion,BG1d-BG is an attractive candidate for further experimental investigation.The basic mechanisms behind the different impact on cell behavior should be assessed in further detail,e.g.by further alteration of the BG compositions.

Preparation and Characterization of Porous Calcium Phosphate Bioceramics

β-tricalcium phosphate （β-TCP） powder and Na20-CaO-MgO-P205 glass binder were synthesized and mixed, and then the biodegradable porous calcium phosphate ceramics were successfully prepared by foaming and sintering at 850℃. The as-prepared ceramics possess a high porosity with partial three-dimension interconnected macro- and micro-pores. As in vitro experiment testified, the calcium phosphate ceramics （CPCs） has good degradability.

Strengthening mechanisms in carbon nanotube reinforced bioglass composites

Carbon nanotube reinforced bioglass composites have been successfully synthesized by two comparative sintering techniques, i.e., spark plasma sintering （SPS） and conventional compaction and sinteirng. The composites show improved mechanical properties, with SPS technique substantially better than conventional compact and sintering approach. Using SPS, compared with the 45S5Bioglass matrix, the maximum flexural strength and fracture toughness increased by 159% and 105%, respectively. Enhanced strength and toughness are attributed to the interfacial bonding and bridging effects between the carbon nanotubes and bioglass powders during crack propagations.

Poly（L-lactide）-grafted Bioglass/Poly（lactide-co-glycolide） Scaffolds with Supercritical CO2 Foaming Reprocessing for Bone Tissue Engineering

The bioglass particles/poly（lactide-co-glycolide）（BG/PLGA） scaffold has been extensively explored for biomedical applications due to its excellent advantages of mechanical property and controllable degradation rate. In ottr previous studies, the BG nanoparticle sttrface-grafted with poly（L-lactide）（PLLA） could substantially improve the phase compatibility between the polymer matrix and the inorganic phase and the biocompatibility of the scaffolds. However, using the traditional preparation methods to prepare the composite scaffold can barely achieve a high po- rosity and porous connectivity. In this work, the PLLA-grafted bioglass/PLGA（g-BG/PLGA） scaffolds were prepared by supercritical carbon dioxide foaming（Sc-CO2） with before or after particulate leaching（PL） method（Sc-CO2-PL or PL-Sc-CO2 method, PL/Sc-CO2 methods） and their applications in bone replacement and tissue engineering were investigated. The porosities of the g-BG/PLGA scaffolds prepared by the PL/Sc-CO2 methods were higher than 90%, and their mechanical properties had similar values with human cancellous bone. The proliferations of osteoblasts on the scaffolds were dependent on different preparation methods. The PL/Sc-CO2 methods significantly increased the proliferations of the cells. Computed tomography（CT） three-dimensional（3D） reconstruction tomographies of the implantation study for repairing calvarium defects of rabbits demonstrated that the calvarium defects were almost completely filled by the osteotylus in PL/Sc-CO2 method group at 12 week post-surgery, while there was little callus formation in PL method group and untreated control group. These results indicate that the g-BG/PLGA scaffolds prepared by the PL/Sc-CO2 methods exhibit rapid mineralization and osteoconductivity and are the optimal composites for bone repair.