Characterization and Performance of Magnesium Doped Bioactive Glass Nanoparticles

The bioactive glass and related biomaterials have become increasingly popular, and have also attracted the research interest of many researchers in recent years due its special performance and tissue engineering application. In this study, to create a material with a variety of properties Mg doped hollow bioactive glass (Mg-HBG) of 80SiO2-5P2O5-10CaO-5MgO system had been produced by using a sol-gel method. The porous structure nanoparticles were specifically made by employing the cetyltrimethylammonium bromide (CTAB) as a surfactant. Magnesium was selected as a doped material with HBG, because it is the most existing cations in the human body which helps for bone metabolism as well as it has antibacterial property. Based on different investigations resulted nanoparticle with the inclusion of the lower molar fractions magnesium has good tested result. For a drug model vancomycin hydrochloride (VAN) was used in this study and it has also good antibacterial activity effect. These findings help the possibility of using Mg-HBG nanoparticles to treat infectious bone abnormalities by demonstrating their compatibility with antibiotics, drug loading and release behavior.

Coating of bioactive glass on magnesium alloys to improve its degradation behavior: Interfacial aspects

The preferable mechanical properties of Mg alloys along with excellent compatibility with human bone have established their applicability as implant biomaterials.However,a higher corrosion/degradation rate of Mg alloys in body fluids limits its biomedical applications.In this direction,surface modification and coating are explored as appropriate strategies to mode the degradation rate of Mg alloys.The constituents of bioactive glass(BG)provide strength,bio-inertness and bone bonding capability.Hence,researchers have explored the coating of BG on Mg alloys and investigated chemical,mechanical and biological properties of the coated alloys.In this review,we have made an attempt to compile the literature works done on the coating of BG on Mg alloys and its features.Underlying interfacial aspects of the coated substrates towards the degradation behavior are highlighted.The way forward to further improve the coating characteristics of BG coated Mg alloys are remarked.

Biodegradation behavior of polymethyl methacrylate−bioactive glass 45S5 composite coated magnesium in simulated body fluid

The biodegradation behavior of Mg,coated by polymethyl methacrylate as well as polymethyl methacrylate(PMMA)−bioactive glass(BG)composite was investigated.Electrophoretic deposition and dip coating techniques were adopted to prepare composite coating using a suspension of different percentages of the above two chemical materials.The deposited coatings were characterized using SEM,EDS,FTIR,and water contact angle measurements.Biodegradation behavior study of the coated Mg was performed using linear polarization,impedance spectroscopy,and immersion tests in simulated body fluid.The compact and homogeneous composite coating was developed as evidenced by electron microscopy results.The water contact angle measurement showed a 44°increase in the contact angle of the composite coated Mg compared to the uncoated one.The composite coating was covered by a bone-like hydroxyapatite layer after 336 h,indicating that the coating has an excellent in vitro bioactivity.The electrochemical testing results confirmed a significant reduction,96.9%,in the biodegradation rate of Mg coated with the composite prepared from 45 g/L PMMA+3.5 g/L 45S5 GB suspension compared to that of the uncoated one.Therefore,the composite coated Mg can be proposed as a promising material for biodegradable implant application.

Preparation and Characterization of the System SiO_2-CaO-P_2O_5 Bioactive Glasses by Microemulsion Approach

The system of SiO2-CaO-P2O5 bioactive glasses （BG） were successfully synthesized by microemulsion approach. X-ray diffraction （XRD）,scanning electron micro scopy（SEM） and energy dispersive X-ray （EDX） analyses, transmission electron microscopy（TEM）,Fourier transform infrared spectroscopy （FTIR）, BET N2 gas adsorption analysis techniques were utilized in order to evaluate the phase composition, dimension, morphology, interconnectivity of pores and particle size of the synthesized BG respectiveely. The biocompatibility of BG was assessed by using dimethylthiazol diphenyl tetrazolium bromide （MTT）.The BG scaffolds were implanted in rabbit mandibles and studied histologically.The results showed that the BG with a particle size less than 100 nm was prepared successfully. The measured BET specific surface area and pore volume was 113.9 m2/g and 0.28 cm3/g respectively. Cell cultures revealed that BG has been shown to have good biocompatibility and is also beneficial to the survival of Schwann cells, which can promote cell proliferation in vivo assay indicating that the BG can promote osteoconductivity.

Broad-Spectrum Antibacterial Characteristics of Four Novel Borate-Based Bioactive Glasses

Bioactive glasses have been developed for medical applications in the body for bone and tissue repair and regeneration. We have developed a borate-containing bioactive glass (13-93B3, referred to as B3), which is undergoing clinical trials to assess its wound-healing properties. To complement the healing properties of B3, metal ion dopants have been added to enhance its antimicrobial properties. Bioactive glasses doped with silver, gallium or iodine ions were found to have broad spectrum antimicrobial effects on clinically relevant bacteria including MRSA. While the B3 glass alone was sufficient to produce antibacterial effects on select bacteria, adding dopants enhanced the broad-spectrum antibacterial properties: Live-Dead staining fluorescence microscopy suggests cell membrane integrity is disrupted in gram positive bacteria exposed to the glass compounds, but not gram negative bacteria, indicating multiple mechanisms of action for each glass formulation.

Stress Corrosion Crack Growth Behavior of Titanium Alloy/Bioactive Glasses Sandwiches in Simulated Human Physiological Environment

Based on a series of newly developed bioactive glasses having suitable thermo-mechanical properties to allow application as fixation agents between bone and titanium alloy biomedical implants, the stress corrosion crack growth (SCCG) behavior of their interfaces with Ti6AI4V was investigated in simulated body fluid (SBF) with the objective of discerning the salient mechanisms of crack advance and to assess the reliability of the bonds. Results indicated that crack growth rates in Ti6AI4V/glass/Ti6AI4V sandwich specimens were nearly the same as or slightly lower than those in the bulk glasses at comparable stress intensities; indeed, cracks would prefer to propagate off the interface, suggesting that the Ti6AI4V/glass interface has relatively good crack-growth resistance. Mechanistically, interfacial crack growth appears to be controlled by the classic stress corrosion mechanisms for silicate glasses, with no discernible effect of bioactivity on the SCCG behavior being observed.

Anti-biofilm Effect of Glass Ionomer Cements Incorporated with Chlorhexidine and Bioactive Glass

The effect of glass ionomer cement and resin-modified glass ionomer cement incorporated with chlorhexidine and bioactive glass on antimicrobial activity and physicochemical properties were investigated. The experimental results showed that groups incorporated with 1% chlorhexidine exhibited a significant reduction of optical density values of the bacterial suspension and increased the degradation of Streptococcus mutans biofilm. However, groups incorporated with 10% bioactive glass did not affect the optical density values and the biofilm formation. The mechanical properties of the materials and the polymerization were not influenced by the addition of chlorhexidine. Nevertheless, the compressive strength was lower when the materials were incorporated with bioactive glass. It can be concluded that glass ionomer cements incorporated with chlorhexidine can maintain its mechanical properties as well as reduce early S mutans biofilm formation. Controlled release/sustained release technology may be required to optimize the antibacterial activity of glass ionomer cements incorporated with bioactive glass.

Enhanced Healing of Full-thickness Diabetic Wounds Using Bioactive Glass and Yunnan Baiyao Ointments

In order to accelerate the chronic wounds healing, we investigated the healing effects of bioactive glass and Yuunan baiyao ointments in streptozotocin-induced diabetic rats. The ointments were prepared by mixing 45S5 bioactive glass powder （16% weight） with Vaseline and different weight percentages of Yurman baiyao. Full-thickness defect wounds were created on the back of 130 SD rats and were randomly divided into 8 groups. The wound healing rates were calculated at 4, 7, 10, 14 and 21 days after surgery. The samples were harvested for further observations. Considering the wound closure rate, group 6 （with 5% Yuunan baiyao） has better wound healing performance than other diabetic groups. The lower inflammatory response was observed by gross observation and confirmed by the results of H＆E staining and TEM observation. Besides, the proliferation of fibroblasts, the formation of granulation tissue, as well as the vascularization, were improved in group 6 compared to other diabetic groups. All results suggest that bioactive glass and Yunnan baiyao ointments can accelerate the recovery of diabetes-impaired skin wounds, and comparing to other diabetic groups, group 6 （with 5% Yunnan baiyao） has better healing effect.

Initial therapeutic evidence of a borosilicate bioactive glass(BSG)and Fe_(3)O_(4)magnetic nanoparticle scaffold on implant-associated Staphylococcal aureus bone infection

Implant-associated Staphylococcus aureus(S.aureus)osteomyelitis is a severe challenge in orthopedics.While antibiotic-loaded bone cement is a standardized therapeutic approach for S.aureus osteomyelitis,it falls short in eradicating Staphylococcus abscess communities(SACs)and bacteria within osteocyte-lacuna canalicular network(OLCN)and repairing bone defects.To address limitations,we developed a borosilicate bioactive glass(BSG)combined with ferroferric oxide(Fe_(3)O_(4))magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities.We conducted comprehensive assessments of the osteoinductive,immunomodulatory,antibacterial properties,and thermal response of this scaffold,with or without an alternating magnetic field(AMF).Utilizing a well-established implant-related S.aureus tibial infection rabbit model,we evaluated its antibacterial performance in vivo.RNA transcriptome sequencing demonstrated that BSG+5%Fe_(3)O_(4)enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs.Notably,BSG+5%Fe_(3)O_(4)upregulated gene expression of NOD-like receptor and TNF pathway in MSCs,alongside increased the expression of osteogenic factors(RUNX2,ALP and OCN)in vitro.Flow cytometry on macrophage exhibited a polarization effect towards M2,accompanied by upregulation of anti-inflammatory genes(TGF-β1 and IL-1Ra)and downregulation of pro-inflammatory genes(IL-6 and IL-1β)among macrophages.In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG+5%Fe_(3)O_(4)+AMF at 42 days.Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42,along with new bone formation,signifying effective control of S.aureus osteomyelitis.Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.

Engineering mesoporous bioactive glasses for emerging stimuli-responsive drug delivery and theranostic applications

Mesoporous bioactive glasses(MBGs),which belong to the category of modern porous nanomaterials,have garnered significant attention due to their impressive biological activities,appealing physicochemical properties,and desirable morphological features.They hold immense potential for utilization in diverse fields,including adsorption,separation,catalysis,bioengineering,and medicine.Despite possessing interior porous structures,excellent morphological characteristics,and superior biocompatibility,primitive MBGs face challenges related to weak encapsulation efficiency,drug loading,and mechanical strength when applied in biomedical fields.It is important to note that the advantageous attributes of MBGs can be effectively preserved by incorporating supramolecular assemblies,miscellaneous metal species,and their conjugates into the material surfaces or intrinsic mesoporous networks.The innovative advancements in these modified colloidal inorganic nanocarriers inspire researchers to explore novel applications,such as stimuli-responsive drug delivery,with exceptional in-vivo performances.In view of the above,we outline the fabrication process of calcium-silicon-phosphorus based MBGs,followed by discussions on their significant progress in various engineered strategies involving surface functionalization,nanostructures,and network modification.Furthermore,we emphasize the recent advancements in the textural and physicochemical properties of MBGs,along with their theranostic potentials in multiple cancerous and non-cancerous diseases.Lastly,we recapitulate compelling viewpoints,with specific considerations given from bench to bedside.

Nano-vibration exciter:Hypoxia-inducible factor 1 signaling pathway-mediated extracellular vesicles as bioactive glass substitutes for bone regeneration

Bioactive glasses(BG)play a vital role in angiogenesis and osteogenesis through releasing functional ions.However,the rapid ion release in the early stage will cause excessive accumulation of metal ions,which in turn leads to obvious cytotoxicity,long-term inflammation,and bone repair failure.Inspired by the vibration exciter,small extracellular vesicles(sEVs)obtained by treating mesenchymal stem cells with copper-doped bioactive glass(CuBG-sEVs),is prepared as a nano-vibration exciter.The nano-vibration exciter can convert the ion signals of CuBG into biochemical factor signals through hypoxia-inducible factor 1(HIF-1)signaling pathway and its activated autophagy,so as to better exert the osteogenic activity of BG.The results showed that CuBG extracts could significantly improve the enrichment of key miRNAs and increase the yield of CuBG-sEVs by activating HIF-1 signaling pathway and its activated autophagy.Cell experiments showed that CuBG-sEVs are favor to cell recruitment,vascularization and osteogenesis as the enrichment of key miRNAs.The animal experiments results showed that CuBG-sEVs stimulated angiogenesis mediated by CD31 and promoted bone regeneration by activating signaling pathways related to osteogenesis.These findings underscored the significant potential of sEVs as alternative strategies to better roles of BG.

Study on the Promotion of Wound Healing in Mice with Burn Injuries by Bioactive Glass 1393

Objective:To investigate the effect and mechanism of bioactive glass1393 on wound healing in mice with burn injuries.Methods:A benchtop temperature-controlled scald instrument was used to establish a mouse burn wound model,which was divided into an injury group(simple scald group)and a bioactive glass 1393treatment group.The wound healing of burn injuries in mice was observed at different times after the operation,and the formation of granulation tissue,collagen deposition and tissue proliferation in the wounds were observed by HE staining,Masson staining and Ki67 staining,and the levels of apoptosis-related proteins and the expression of wnt3a/β-catenin signaling pathway were detected in the wounds by Western blot.Results:Compared with the injury group,the bioactive glass 1393 group accelerated burn wound healing and promoted granulation tissue formation,collagen deposition,and cell proliferation.In addition,compared with the injury group,the bioactive glass 1393 group promoted the expression of Bcl-2 protein,inhibited the expression of Bax protein and up-regulated the expression of Wnt3a andβ-catenin protein.Conclusion:Bioactive glass 1393 promotes burn wound healing in mice by inhibiting apoptosis through modulation of wnt3a/β-catenin signaling pathway.

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.

A bioactive glass functional hydrogel enhances bone augmentation via synergistic angiogenesis,self-swelling and osteogenesis

Bone augmentation materials usually cannot provide enough new bone for dental implants due to the material degradation and mucosal pressure.The use of hydrogels with self-swelling properties may provide a higher bone augmentation,although swelling is generally considered to be a disadvantage in tissue engineering.Herein,a double-crosslinked gelatin-hyaluronic acid hydrogels(GH)with self-swelling properties were utilized.Meanwhile,niobium doped bioactive glasses(NbBG)was dispersed in the hydrogel network to prepare the GH-NbBG hydrogel.The composite hydrogel exhibited excellent biocompatibility and the addition of NbBG significantly improved the mechanical properties of the hydrogel.In vivo results found that GH-NbBG synergistically promoted angiogenesis and increased bone augmentation by self-swelling at the early stage of implantation.In addition,at the late stage after implantation,GH-NbBG significantly promoted new bone formation by activating RUNX2/Bglap signaling pathway.Therefore,this study reverses the self-swelling disadvantage of hydrogels into advantage and provides novel ideas for the application of hydrogels in bone augmentation.

Multifunctional zinc ion doped sol-gel derived mesoporous bioactive glass nanoparticles for biomedical applications

Mesoporous bioactive glasses have been widely investigated for applications in bone tissue regeneration and,more recently,in soft tissue repair and wound healing.In this study we produced mesoporous bioactive glass nanoparticles(MBGNs)based on the SiO2-CaO system.With the intention of adding subsidiary biological function,MBGNs were doped with Zn2+ions.Zn-MBGNs with 8 mol%ZnO content were synthesized via microemulsion assisted sol-gel method.The synthesized particles were homogeneous in shape and size.They exhibited spherical shape,good dispersity,and a size of 130±10 nm.The addition of zinc precursors did not affect the morphology of particles,while their specific surface area increased in comparison to MBGNs.The presence of Zn2+ions inhibited the formation of hydroxycarbonate apatite(HCAp)on the particles after immersion in simulated body fluid(SBF).No formation of HCAp crystals on the surface of Zn-MBGNs could be observed after 14 days of immersion.Interestingly,powders containing relatively high amount of zinc released Zn2+ions in low concentration(0.6-1.2 mg L^−1)but in a sustained manner.This releasing feature enables Zn-MBGNs to avoid potentially toxic levels of Zn2+ions,indeed Zn-MBGNs were seen to improve the differentiation of osteoblast-like cells(MG-63).Additionally,Zn-MBGNs showed higher ability to adsorb proteins in comparison to MBGNs,which could indicate a favourable later attachment of cells.Due to their advantageous morphological and physiochemical properties,Zn-MBGNs show great potential as bioactive fillers or drug delivery systems in a variety of applications including bone regeneration and wound healing.

Antibacterial,pro-angiogenic and pro-osteointegrative zein-bioactive glass/copper based coatings for implantable stainless steel aimed at bone healing

Stainless steel implants are suitable candidates for bone replacement due to their cytocompatibility and mechanical resistance,but they suffer from lack of bioactivity and are prone to bacterial infections.Accordingly,to overcome those limitations,in this study we developed by electrophoretic deposition(EPD),an innovative surface coating made of(i)zein,a natural fibroblast-friendly polymer,(ii)bioactive glass,a pro-osteogenic inorganic material and(iii)copper containing bioactive glass,an antibacterial and pro-angiogenic material.FESEM images confirmed that porous,uniform and free of cracks coatings were obtained by EPD;moreover,coatings were resistant to mechanical stress as demonstrated by the tape test,resulting in a 4B classification of adhesion to the substrate.The coatings were cytocompatible as indicated by metabolism evaluation of human fibroblasts,endothelial cells and mature or progenitor osteoblasts cultivated in direct contact with the specimens.They also maintained pro-osteogenic properties towards undifferentiated progenitor cells that expressed osteogenic genes after 15 days of direct cultivation.Copper conferred antibacterial properties as biofilm formation of the joint pathogens Staphylococcus aureus,Staphylococcus epidermidis and Escherichia coli was significantly reduced in comparison with copper-free coatings(p<0.05).Moreover,this anti-infective activity resulted as targeted towards bacteria while the cells viability was preserved when cells and bacteria were cultivated in the same environment by a co-culture assay.Finally,copper ability to recruit blood vessels and to inhibit bacterial infection was confirmed in vivo where the growth of S.aureus biofilm was inhibited and the formation of new(<50μm diameter spread)blood vessels was observed.

Hybrid gelatin/oxidized chondroitin sulfate hydrogels incorporating bioactive glass nanoparticles with enhanced mechanical properties, mineralization, and osteogenic differentiation

Biopolymer based hydrogels are characteristic of their biocompatibility and capability of mimicking extracellular matrix structure to support cellular behavior.However,these hydrogels suffer from low mechanical properties,uncontrolled degradation,and insufficient osteogenic activity,which limits their applications in bone regeneration.In this study,we developed hybrid gelatin(Gel)/oxidized chondroitin sulfate(OCS)hydrogels that incorporated mesoporous bioactive glass nanoparticles(MBGNs)as bioactive fillers for bone regeneration.Gel-OCS hydrogels could be self-crosslinked in situ under physiological conditions in the presence of borax.The incorporation of MBGNs enhanced the crosslinking and accelerated the gelation.The gelation time decreased with increasing the concentration of MBGNs added.Incorporation of MBGNs in the hydrogels significantly improved the mechanical properties in terms of enhanced storage modulus and compressive strength.The injectability of the hydrogels was not significantly affected by the MBGN incorporation.Also,the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro and rat cranial defect restoration in vivo were significantly promoted by the hydrogels in the presence of MBGNs.The hybrid Gel-OCS/MBGN hydrogels show promising potential as injectable biomaterials or scaffolds for bone regeneration/repair applications given their tunable degradation and gelation behavior as well as favorable mechanical behavior and osteogenic activities.

Injectable bone cements:What benefits the combination of calcium phosphates and bioactive glasses could bring?

Out of the wide range of calcium phosphate(CaP)biomaterials,calcium phosphate bone cements(CPCs)have attracted increased attention since their discovery in the 1980s due to their valuable properties such as bioactivity,osteoconductivity,injectability,hardening ability through a low-temperature setting reaction and moldability.Thereafter numerous researches have been performed to enhance the properties of CPCs.Nonetheless,low mechanical performance of CPCs limits their clinical application in load bearing regions of bone.Also,the in vivo resorption and replacement of CPC with new bone tissue is still controversial,thus further improvements of high clinical importance are required.Bioactive glasses(BGs)are biocompatible and able to bond to bone,stimulating new bone growth while dissolving over time.In the last decades extensive research has been performed analyzing the role of BGs in combination with different CaPs.Thus,the focal point of this review paper is to summarize the available research data on how injectable CPC properties could be improved or affected by the addition of BG as a secondary powder phase.It was found that despite the variances of setting time and compressive strength results,desirable injectable properties of bone cements can be achieved by the inclusion of BGs into CPCs.The published data also revealed that the degradation rate of CPCs is significantly improved by BG addition.Moreover,the presence of BG in CPCs improves the in vitro osteogenic differentiation and cell response as well as the tissue-material interaction in vivo.

Bioactive glass coatings on metallic implants for biomedical applications

Metallic implant materials possess adequate mechanical properties such as strength,elastic modulus,and ductility for long term support and stability in vivo.Traditional metallic biomaterials,including stainless steels,cobalt-chromium alloys,and titanium and its alloys,have been the gold standards for load-bearing implant materials in hard tissue applications in the past decades.Biodegradable metals including iron,magnesium,and zinc have also emerged as novel biodegradable implant materials with different in vivo degradation rates.However,they do not possess good bioactivity and other biological functions.Bioactive glasses have been widely used as coating materials on the metallic implants to improve their integration with the host tissue and overall biological performances.The present review provides a detailed overview of the benefits and issues of metal alloys when used as biomedical implants and how they are improved by bioactive glass-based coatings for biomedical applications.

Incorporation of bioactive glass nanoparticles in electrospun PCL/chitosan fibers by using benign solvents

The use of bioactive glass(BG)particles as a filler for the development of composite electrospun fibers has already been widely reported and investigated.The novelty of the present research work is represented by the use of benign solvents(like acetic acid and formic acid)for electrospinning of composite fibers containing BG particles,by using a blend of PCL and chitosan.In this work,different BG particle sizes were investigated,namely nanosized and micron-sized.A preliminary investigation about the possible alteration of BG particles in the electrospinning solvents was performed using SEM analysis.The obtained composite fibers were investigated in terms of morphological,chemical and mechanical properties.An in vitro mineralization assay in simulated body fluid(SBF)was performed to investigate the capability of the composite electrospun fibers to induce the formation of hydroxycarbonate apatite(HCA).