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An ideal wound dressing should create a healing environment that relieves pain, protects against infections, maintains moisture, removes debris, and speeds up wound closure and repair. However, conventional options like gauze often fall short in fulfilling these requirements, especially for chronic or nonhealing wounds. Hence there is a critical need for inventive formulations that offer efficient, cost‐effective, and eco‐friendly alternatives. This study focuses on assessing the innovative formulation based on a microbial‐derived copolymer known as poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate), P(3HB‐co‐4HB) bioactive glass and graphene particles, and exploring their biological response in vitro and in vivo—to find the best combination that promotes cell adhesion and enhances wound healing. The formulation optimized at concentration of bioactive glass (1 w/w%) and graphene (0.01 w/w%) showed accelerated degradation and enhanced blood vessel formation. Meanwhile biocompatibility was evaluated using murine osteoblasts, human dermal fibroblasts, and standard cell culture assays, demonstrating no adverse effects after 7 days of culture and well‐regulated inflammatory kinetics. Whole thickness skin defect using mice indicated the feasibility of the biocomposites for a faster wound closure and reduced inflammation. Overall, this biocomposite appears promising as an ideal wound dressing material and positively influencing wound healing rates. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effect of novel bioactive glass (BAG)-containing desensitizers on the permeability of dentin. Experimental dentin desensitizers containing 3 wt% BAG with or without acidic functional monomers (10-MDP or 4-META) were prepared. A commercial desensitizer, Seal & Protect (SNP), was used as a control. To evaluate the permeability of dentin, real-time dentinal fluid flow (DFF) rates were measured at four different time points (demineralized, immediately after desensitizer application, after two weeks in simulated body fluid (SBF), and post-ultrasonication). The DFF reduction rate (ΔDFF) was also calculated. The surface changes were analyzed using field emission scanning electron microscopy (FE-SEM). Raman spectroscopy was performed to analyze chemical changes on the dentin surface. The ΔDFF of the desensitizers containing BAG, BAG with 10-MDP, and BAG with 4-META significantly increased after two weeks of SBF storage and post-ultrasonication compared to the SNP at each time point (p < 0.05). Multiple precipitates were observed on the surfaces of the three BAG-containing desensitizers. Raman spectroscopy revealed hydroxyapatite (HAp) peaks on the dentin surfaces treated with the three BAG-containing desensitizers. Novel BAG-containing dentin desensitizers can reduce the DFF rate about 70.84 to 77.09% in the aspect of reduction of DFF through the HAp precipitations after two weeks of SBF storage. [ABSTRACT FROM AUTHOR]

Tissue engineering provides great possibilities to manage tissue damages and injuries in modern medicine. The involvement of hard biocompatible materials in tissue engineering-based therapies for the healing of soft tissue defects has impressively increased over the last few years: in this regard, different types of bioceramics were developed, examined and applied either alone or in combination with polymers to produce composites. Bioactive glasses, carbon nanostructures, and hydroxyapatite nanoparticles are among the most widely-proposed hard materials for treating a broad range of soft tissue damages, from acute and chronic skin wounds to complex injuries of nervous and cardiopulmonary systems. Although being originally developed for use in contact with bone, these substances were also shown to offer excellent key features for repair and regeneration of wounds and "delicate" structures of the body, including improved cell proliferation and differentiation, enhanced angiogenesis, and antibacterial/anti-inflammatory activities. Furthermore, when embedded in a soft matrix, these hard materials can improve the mechanical properties of the implant. They could be applied in various forms and formulations such as fine powders, granules, and micro- or nanofibers. There are some pre-clinical trials in which bioceramics are being utilized for skin wounds; however, some crucial questions should still be addressed before the extensive and safe use of bioceramics in soft tissue healing. For example, defining optimal formulations, dosages, and administration routes remain to be fixed and summarized as standard guidelines in the clinic. This review paper aims at providing a comprehensive picture of the use and potential of bioceramics in treatment, reconstruction, and preservation of soft tissues (skin, cardiovascular and pulmonary systems, peripheral nervous system, gastrointestinal tract, skeletal muscles, and ophthalmic tissues) and critically discusses their pros and cons (e.g., the risk of calcification and ectopic bone formation as well as the local and systemic toxicity) in this regard. Soft tissues form a big part of the human body and play vital roles in maintaining both structure and function of various organs; however, optimal repair and regeneration of injured soft tissues (e.g., skin, peripheral nerve) still remain a grand challenge in biomedicine. Although polymers were extensively applied to restore the lost or injured soft tissues, the use of bioceramics has the potential to provides new opportunities which are still partially unexplored or at the very beginning. This reviews summarizes the state of the art of bioceramics in this field, highlighting the latest evolutions and the new horizons that can be opened by their use in the context of soft tissue engineering. Existing results and future challenges are discussed in order to provide an up-to-date contribution that is useful to both experienced scientists and early-stage researchers of the biomaterials community. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The control of bacterial infections is of particular importance in the field of tissue engineering. Recently, much attention has been addressed toward the use of mesoporous bioactive glasses (MBGs) for antibacterial strategies, primarily because of their capability of acting as carriers for the local release of antimicrobial agents. The incorporation of antibacterial metallic ions including silver (Ag+), zinc (Zn2+), copper (Cu+ and Cu2+), cerium (Ce3+ and Ce4+), and gallium (Ga3+) cations into the MBG structure and their controlled release is proposed as one of the most attractive strategies for inhibiting bacterial growth and reproduction. Moreover, the possibility of loading and delivering various antibacterial biomolecules (e.g., antibiotics) through the porous structure of MBGs makes them as ideal candidates for antibacterial applications. In this review, we aim to present a comprehensive evaluation of MBG potential regarding antibacterial activities. For this purpose, different types of antibacterial ion-doped and drug-loaded MBGs are introduced and discussed in the light of existing knowledge, along with the significant challenges ahead. Statement of significance Prevention and treatment of infections is one of the today's greatest challenges in medical sciences, also considering the well-known issues related to increased bacterial resistance to antibiotics. The advent of mesoporous glasses led to the birth of a new class of multifunctional biomaterials acting as bioactive platforms for the local release of organic or inorganic agents eliciting an antimicrobial effect. This reviews summarizes the state of the art of MBGs in this field, highlighting the latest evolutions and the specific role played by metallic antimicrobial ions that can be incorporated in the glass composition and then properly released. Perspective for tissue engineering applications are also discussed to provide an up-to-date contribution that is useful to both experienced scientists and early-stage researchers. [ABSTRACT FROM AUTHOR]

Inducing differentiation and maturation of resident multipotent stem cells (MSCs) is an important strategy to regenerate hard tissues in mal-calcification conditions. Here we explore a co-delivery approach of therapeutic molecules comprised of ion and drug through a mesoporous bioglass nanoparticle (MBN) for this purpose. Recently, MBN has offered unique potential as a nanocarrier for hard tissues, in terms of high mesoporosity, bone bioactivity (and possibly degradability), tunable delivery of biomolecules, and ionic modification. Herein Sr ion is structurally doped to MBN while drug Phenamil is externally loaded as a small molecule activator of BMP signaling, for the stimulation of osteo/odontogenesis and mineralization of human MSCs derived from dental pulp. The Sr-doped MBN (85Si:10Ca:5Sr) sol-gel processed presents a high mesoporosity with a pore size of ∼6 nm. In particular, Sr ion is released slowly at a daily rate of ∼3 ppm per mg nanoparticles for up to 7 days, a level therapeutically effective for cellular stimulation. The Sr-MBN is internalized to most MSCs via an ATP dependent macropinocytosis within hours, increasing the intracellular levels of Sr, Ca and Si ions. Phenamil is loaded maximally ∼30% into Sr-MBN and then released slowly for up to 7 days. The co-delivered molecules (Sr ion and Phenamil drug) have profound effects on the differentiation and maturation of cells, i.e., significantly enhancing expression of osteo/odontogenic genes, alkaline phosphatase activity, and mineralization of cells. Of note, the stimulation is a result of a synergism of Sr and Phenamil, through a Trb3-dependent BMP signaling pathway. This biological synergism is further evidenced in vivo in a mal-calcification condition involving an extracted tooth implantation in dorsal subcutaneous tissues of rats. Six weeks post operation evidences the osseous-dentinal hard tissue formation, which is significantly stimulated by the Sr/Phenamil delivery, based on histomorphometric and micro-computed tomographic analyses. The bioactive nanoparticles releasing both Sr ion and Phenamil drug are considered to be a promising therapeutic nanocarrier platform for hard tissue regeneration. Furthermore, this novel ion/drug co-delivery concept through nanoparticles can be extensively used for other tissues that require different therapeutic treatment. Statement of Significance This study reports a novel design concept in inorganic nanoparticle delivery system for hard tissues – the co-delivery of therapeutic molecules comprised of ion (Sr) and drug (Phenamil) through a unique nanoparticle of mesoporous bioactive glass (MBN). The physico-chemical and biological properties of MBN enabled an effective loading of both therapeutic molecules and a subsequently sustained/controlled release. The co-delivered Sr and Phenamil demonstrated significant stimulation of adult stem cell differentiation in vitro and osseous/dentinal regeneration in vivo , through BMP signaling pathways. We consider the current combination of Sr ion with Phenamil is suited for the osteo/odontogenesis of stem cells for hard tissue regeneration, and further, this ion/drug co-delivery concept can extend the applications to other areas that require specific cellular and tissue functions. [ABSTRACT FROM AUTHOR]

Mesoporous bioactive nanoparticles (MBNs) have been developed as promising additives to various types of bone or dentin regenerative material. However, biofunctionality of MBNs as dentin regenerative additive to dental materials have rarely been studied. We investigated the uptake efficiency of MBNs-NH2 with their endocytosis pathway and the role of MBNs-NH2 in odontogenic differentiation to clarify inherent biofunctionality. MBNs were fabricated by sol-gel synthesis, and 3% APTES was used to aminate these nanoparticles (MBNs-NH2) to reverse their charge from negative to positive. To characterize the MBNs-NH2, TEM, XRD, FTIR, zeta(ξ)-potential measurements, and Brunauer–Emmett–Teller analysis were performed. After primary cultured rat dental pulp stem cells (rDPSCs) were incubated with various concentrations of MBNs-NH2, stem cell viability (24 hours) with or without differentiated media, internalization of MBNs-NH2 in rDPSCs (~4 hours) via specific endocytosis pathway, intra or extracellular ion concentration and odontoblastic differentiation (~28 days) were investigated. Incubation with up to 50 μg/mL of MBNs-NH2 had no effect on rDPSCs viability with differentiated media (p>0.05). The internalization of MBNs-NH2 in rDPSCs was determined about 92% after 4 hours of incubation. Uptake was significantly decreased with ATP depletion and after 1 hour of pre-treatment with the inhibitor of macropinocytosis (p<0.05). There was significant increase of intracellular Ca and Si ion concentration in MBNs-NH2 treated cells compared to no-treated counterpart (p<0.05). The expression of odontogenic-related genes (BSP, COL1A, DMP-1, DSPP, and OCN) and the capacity for biomineralization (based on alkaline phosphatase activity and alizarin red staining) were significantly upregulated with MBNs-NH2. These results indicate that MBNs-NH2 induce odontogenic differentiation of rDPSCs and may serve as a potential dentin regenerative additive to dental material for promoting odontoblast differentiation. [ABSTRACT FROM AUTHOR]

Bioactive nanocomposite scaffolds with cell-adhesive surface have excellent bone regeneration capacities. Fibronectin (FN)-immobilized nanobioactive glass (nBG)/polycaprolactone (PCL) (FN-nBG/PCL) scaffolds with an open pore architecture were generated by a robotic-dispensing technique. The surface immobilization level of FN was significantly higher on the nBG/PCL scaffolds than on the PCL scaffolds, mainly due to the incorporated nBG that provided hydrophilic chemical-linking sites. FN-nBG/PCL scaffolds significantly improved cell responses, including initial anchorage and subsequent cell proliferation. Although further in-depth studies on cell differentiation and the in vivo animal responses are required, bioactive nanocomposite scaffolds with cell-favoring surface are considered to provide promising three-dimensional substrate for bone regeneration. [ABSTRACT FROM AUTHOR]

In this study, a poly(ε‐caprolactone) (PCL)/bioactive glass (BG) nanocomposite was fabricated using BG nanofibers (BGNFs) and compared with an established composite fabricated using microscale BG particles. The BGNFs were generated using sol–gel precursors via the electrospinning process, chopped into short fibers and then incorporated into the PCL organic matrix by dissolving them in a tetrahydrofuran solvent. The biological and mechanical properties of the PCL/BGNF composites were evaluated and compared with those of PCL/BG powder (BGP). Because the PCL/BG composite containing 20 wt % BG showed the highest level of alkaline phosphatase (ALP) activity, all evaluations were performed at this concentration except for that of the ALP activity itself. In vitro cell tests using the MC3T3 cell line demonstrated the enhanced biocompatibility of the PCL/BGNF composite compared with the PCL/BGP composite. Furthermore, the PCL/BGNF composite showed a significantly higher level of bioactivity compared with the PCL/BGP composite. In addition, the results of the in vivo animal experiments using Sprague–Dawley albino rats revealed the good bone regeneration capability of the PCL/BGNF composite when implanted in a calvarial bone defect. In the result of the tensile test, the stiffness of the PCL/BG composite was further increased when the BGNFs were incorporated. These results indicate that the PCL/BGNF composite has greater bioactivity and mechanical stability when compared with the PCL/BG composite and great potential as a bone regenerative material. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009 [ABSTRACT FROM AUTHOR]

• Novel mesoporous Co-BGn were produced by ultrasonic-coupled sol-gel method. • Co-BGn (<100 nm) exhibited spherical morphology and high worm-like mesoporosity. • XPS confirmed the presence of Co2+ions in the glass network structure of Co-BGn. • Co-BGn showed sustained release of Co2+ ions with controlled and fast release kinetics. • Controlled release Co-BGn can be considered as hypoxia-mimic nanotherapeutics. • Fast release Co-BGn can be considered for ferroptosis killing of cancer cells. Herein, novel Co2+ ions-containing mesoporous bioactive glass nanospheres (Co-BGn) with low and high cobalt contents were prepared by a facile one-pot ultrasonic-coupled sol-gel synthesis. Structural evaluations revealed that Co-BGn are totally amorphous and cobalt ions exist as Co2+ ions in the glass structure. Notably, Co-BGn exhibited uniform spherical morphology, nanosize (< 100 nm), high worm-like mesoporosity (0.41 cm3/g) and large specific surface area ca. 787.5 m2/g. Interestingly, low and high Co-BGn showed sustained release of Co2+ ions with controlled release (8 – 32 ppm) and fast release (54 – 112.5 ppm) kinetics over 2 weeks, respectively. Furthermore, Co-BGn showed good bone-like hydroxyapatite formation in vitro. Accordingly, low Co-BGn with controlled release of Co2+ ions can be considered as hypoxia-mimic nanotherapeutics for bone/skin tissue regeneration. Whereas, high Co-BGn with fast release of high concentrations of Co2+ ions can be considered for ferroptosis killing of cancer cells including bone and skin cancers. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Fe-BGn were prepared by a facile one-pot ultrasonic-coupled sol–gel synthesis. • Adding 10% Fe 2 O 3 to BGn significantly reduced particle size from 65 nm to <20 nm. • Fe-BGn exhibited high SSA up to 288 m2/g and high total pore volume ca. 0.43 cm3/g. • Fe-BGn showed sustained release of Fe3+ ions with zero-order release kinetics. • Fe-BGn were designed for use as ferroptosis-based bone cancer nanotherapeutics. Here, Fe ions-releasing mesoporous bioactive glass ultrasmall nanoparticles (Fe-BGn) were prepared by a facile one-pot ultrasonic-coupled sol–gel synthesis designed for use as ferroptosis-based bone cancer nanotherapeutics. The addition of 10% Fe 2 O 3 to 85% SiO 2 – 15% CaO by weight significantly reduced the particle size from about 65 nm to < 20 nm along with concurrent increase of the specific surface area (SSA) from 44.7 to 288.1 m2/g. Of note, Fe-BGn showed highly sustained Fe ions release (2.20 ± 0.12 ppm/day) with almost zero-order release kinetics, while exhibiting detectable bone-like hydroxyapatite (HA) formation within 2 weeks. The Fe ions-releasing, highly mesoporous and adequately bioactive Fe-BGn could be applied for ferroptosis-based bone cancer treatment. [ABSTRACT FROM AUTHOR]

Angiogenesis (or the development of new blood vessels) is a key event in tissue engineering and regenerative medicine; thus, a number of biomaterials have been developed and combined with stem cells and/or bioactive molecules to produce three-dimensional (3D) pro-angiogenic constructs. Among the various biomaterials, electrospun nanofibrous scaffolds offer great opportunities for pro-angiogenic approaches in tissue repair and regeneration. Nanofibers made of natural and synthetic polymers are often used to incorporate bioactive components (e.g., bioactive glasses (BGs)) and load biomolecules (e.g., vascular endothelial growth factor (VEGF)) that exert pro-angiogenic activity. Furthermore, seeding of specific types of stem cells (e.g., endothelial progenitor cells) onto nanofibrous scaffolds is considered as a valuable alternative for inducing angiogenesis. The effectiveness of these strategies has been extensively examined both in vitro and in vivo and the outcomes have shown promise in the reconstruction of hard and soft tissues (mainly bone and skin, respectively). However, the translational of electrospun scaffolds with pro-angiogenic molecules or cells is only at its beginning, requiring more research to prove their usefulness in the repair and regeneration of other highly-vascularized vital tissues and organs. This review will cover the latest progress in designing and developing pro-angiogenic electrospun nanofibers and evaluate their usefulness in a tissue engineering and regenerative medicine setting. [ABSTRACT FROM AUTHOR]

Calcium phosphate cement (CPC) is a self-setting, biocompatible and osteoconductive bone cement, however its use as a bone substitute is still limited owing to its low bioactivity (i.e. its slow in vivo resorption and slow new bone formation rate) which is a challenging issue to be addressed. Herein, we report for the first time highly bioactive bone cement microspheres formulated from a cement paste containing α-tricalcium phosphate microparticles (α-TCP) and mesoporous calcium silicate bioactive glass nanoparticles (mesoporous BGn) using a water-in-oil emulsion method. Indeed, bioactive microspheres possess high potential as bone defect fillers for bone regeneration. The α-TCP microparticles were prepared by a solid state synthesis at 1400 ºC while mesoporous BGn were synthesized by template-assissted ultrasound-mediated sol-gel method. The particle size distribution of as-prepared cement microspheres was in the range of 200 – 450 µm with a sphericity index in the range of 0.92 – 0.94. The surface morphology of α-TCP microspheres revealed α-TCP micoparticles with smooth surfaces whereas α-TCP/BGn microspheres unveiled nano-roughened α-TCP microparticles. The as-prepared α-TCP/BGn cement microspheres exhibited larger specific surface area ca 18.6 m2/g, sustained release of soluble silicate (SiO 4 4-) ions (118 ppm within a week) and high protein adsorption capacity (252 mg/g). Notably, the α-TCP/BGn cement microspheres showed excellent in vitro surface bioactivity via formation of massive amounts of bone-like hydroxyapatite spherules and aggregates on their surfaces after soaking in simulated body fluid. Importantly, the in vivo implantation of as-prepared α-TCP/BGn cement microspheres in rat calvarial critical size bone defects for 6 weeks unveiled high in vivo bioactivity in terms of substantial new bone ingrowth and significant new bone formation within the bone defect as evidenced by histological analyses, X-ray radiography and micro-computed tomography evaluations. [Display omitted] • Self-hardened α-TCP/BGn cement microspheres were formulated by a water-in-oil emulsion method. • High protein adsorption capacity was achievable by the microspheres in vitro. • Sustained release of soluble silicate (SiO 4 4-) ions was detectable from microspheres in vitro. • Excellent bone-like hydroxyapatite formation ability was confirmed in vitro. • Substantial new bone ingrowth and significant new bone formation were revealed in vivo. [ABSTRACT FROM AUTHOR]

• Copper bioglass nanoparticles incorporated in ZPC (Cu-ZPC) was proposed. • Cu-ZPC exhibited therapeutic ion releases such as Zn, Cu, Ca and Si. • Cu-ZPC showed higher odontoblastic differentiation using dental pulp human cells. • Cu-ZPC inhibited the growth and attachment of E. faecalis. [Display omitted] This study was investigated the mechanophysical properties of zinc phosphate cement (ZPC) with or without the copper doped bioglass nanoparticles (Cu-BGn) and their biological effect on dental pulp human cells and bacteria. Cu-BGn were synthesized and characterized firstly and then, the experimental (Cu-ZPC) and control (ZPC) samples were fabricated with similar sizes and/or dimensions (diameter: 4 mm and height: 6 mm) based on the International Organization of Standards (ISO). Specifically, various concentrations of Cu-BGn were tested, and Cu-BGn concentration was optimized at 2.5 wt% based on the film thickness and overall setting time. Next, we evaluated the mechanophysical properties such as compressive strength, elastic modulus, hardness, and surface roughness. Furthermore, the biological behaviors including cell viability and odontoblastic differentiation by using dental pulp human cells as well as antibacterial properties were investigated on the Cu-ZPC. All data were analyzed statistically using SPSS® Statistics 20 (IBM®, USA). p < 0.05 (*) was considered significant, and 'NS' represents nonsignificant. Cu-BGn was obtained via a sol-gel method and added onto the ZPC for fabricating a Cu-ZPC composite and for comparison, the Cu-free-ZPC was used as a control. The film thickness (≤ 25 µm) and overall setting time (2.5–8 min) were investigated and the mechanophysical properties showed no significance ('NS') between Cu-ZPC and bare ZPC. However, cell viability and odontoblastic differentiation, alkaline phosphate (ALP) activity and alizarin red S (ARS) staining were highly stimulated in the extracts from the Cu-ZPC group compared to the ZPC group. Additionally, the antibacterial test showed that the Cu-ZPC extracts were more effective than the ZPC extracts (p < 0.05). Cu-ZPC showed adequate mechanophysical properties (compressive strength, hardness, and surface roughness) and enhanced odontoblastic differentiation as well as antibacterial properties compared to the ZPC-only group. Based on the findings, the fabricated Cu-ZPC might have the potential for use in the field of dental medicine and clinical applications. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel ultrasmall mesoporous Ce-BGn were prepared by ultrasound-assisted sol-gel method. • CeO 2 nanospheres (3–6 nm) were detected in the amorphous matrix of mesoporous Ce-BGn. • XPS and UV–vis DRS confirmed the presence of Ce3+/Ce4+ ions in mesoporous Ce-BGn. • Ce-BGn showed remarkable ability to act as an antioxidant (catalase-mimic). • Ce-BGn demonstrated excellent in vitro bioactivity and good in vitro cyto-biocombatiblity. The multifunctional biological properties of Ce ions including antioxidant, anti-inflammatory, antibacterial and anti-cancer effects are very encouraging for development of Ce-containing biomaterials with therapeutic properties. Herein, novel Ce3+/Ce4+ ions containing mesoporous bioactive glass ultrasmall nanoparticles (Ce-BGn) were prepared by a facile one-pot ultrasound-assisted sol-gel method. Interestingly, Ce 2 O 3 incorporation exerted a significant influence on the particle size and textural properties of mesoporous BGn (SiO 2 – CaO binary glass system). Ce-BGn exhibited ultrasmall nanoparticle size (< 30 nm), mesoporous texture (pore size up to 2.82 nm and pore volume up to 0.191 cm3/g) and large specific surface area ca. 132.9 m2/g. Notably, in situ formation of CeO 2 nanospheres (3–6 nm) was detected at the surface and in the amorphous glass matrix of mesoporous Ce-BGn. Importantly, X-ray photoelectron spectroscopy (XPS) revealed the presence of 72.57 % Ce3+ and 27.43 % Ce4+ at the surface of mesoporous Ce-BGn with Ce3+/Ce4+ ratio = 2.66. Furthermore, mesoporous Ce-BGn exhibited high catalase-mimic activity and showed sustained release of Ce (2.5–32 ppm), Ca (85–327 ppm) and Si (54–200 ppm) ions within 4 weeks along with excellent bone-like hydroxyapatite formation. Finally, the in vitro biological behavior of mesoporous Ce-BGn in cell cultures of human skin fibroblasts (HSF) revealed that mesoporous Ce-BGn (with concentrations up to 300 μg/mL) possess good cyto-biocompatibility. Taken together, novel ultrasmall mesoporous Ce-BGn showed remarkable catalase-mimic activity via surface containing Ce3+/Ce4+ ions which can scavenge ROS (Ce3+↔ Ce4+) and decompose H 2 O 2 molecules into H 2 O and O 2. In addition to that, Ce-BGn demonstrated sustained release of bioactive ions (Ce, Ca and Si), excellent bone-like hydroxyapatite formation and good cyto-biocompatibility. [ABSTRACT FROM AUTHOR]

Bone-mimetic scaffolds are receiving much interest as such scaffolds exhibit excellent biocompatibility and very close mimic to bone structure and composition. Here, novel bone-mimetic nanohydroxyapatite (nHA)/collagen (Col) porous scaffolds (nHA/Col) were prepared from surface silanized mesoporous nanobioglass (NBG)/Col hybrid scaffold by biomimetic mineralization. Surface silanized mesoporous NBG was prepared by ultrasound-assisted sol-gel method and post treatment with 3-aminopropyltriethylsilane (APTS). The surface silanized mesoporous NBG was characterized by transmission electron microscopy (TEM), transmission electron microscopy-selected area electron diffraction (TEM-SAED) and X-ray photoelectron spectroscopy (XPS). The physicochemical/mechanical characterizations of the scaffolds included scanning electron microscopy (SEM) and TEM imaging of micro/nanostructure, energy dispersive X-ray (EDX) analysis of chemical composition, TEM-SAED and X-ray diffraction/Attenuated total Reflectance-Fourier Infrared spectroscopy (XRD/ATR-FTIR) analyses of amorphous-to-crystalline transformations, thermogravimetric/differential scanning calorimetric (TGA/DSC) analyses of thermal behaviour , porosity and dynamic mechanical analyses. The presence of NBG in collagen fibrillar network enabled progressive growth of HA nanocrystals and generation of a novel bone-mimetic hybrid structures while preserving the highly porous structure of collagen scaffold. The crystallinity, crystallite size and crystal morphology of the grown HA nanocrystals were controllable by regulation of the mineralization time. Furthermore, the osteogenic properties of the non-mineralized (NBG/Col) and mineralized (nHA/Col) hybrid porous scaffolds were examined in vivo using critical-sized calvarial bone defect model in rat. Histological and micro-computed tomography (Micro-CT) analyses after 6 weeks of implantation revealed that the mineralized scaffolds possess excellent in vivo osteogenic potential compared to the non-mineralized one. Collectively, by using surface silanized mesoporous NBG hybridization with collagen fibrillar network, we successfully introduced a new approach for developing novel bone-mimetic nanohydroxyapatite/collagen hybrid scaffolds that possess significant potential for bone tissue regeneration. Unlabelled Image • Novel bone-mimetic nHA/Col porous scaffolds were prepared by biomimetic mineralization of NBG/Col hybrid porous scaffold. • The presence of NBG in collagen fibrillar network enabled growth of nHA and generation of novel bone-mimetic hybrid structures. • Crystal morphology and crystallinity of the biomimetically grown nHA were controllable by regulation of the mineralization time. • Biomimetically mineralized nHA/Col hybrid scaffolds exhibited remarkably improved physicochemical and mechanical properties. • Histology and Micro-CT analyses after 6-week implantation in rat revealed excellent bone formation ability of nHA/Col scaffolds. [ABSTRACT FROM AUTHOR]

A novel glass system 8ZnO–22Na 2 O–(24-x)CaO–46P 2 O 5 –xTiO 2 (x = 0.2, 0.4, 0.6, 0.8 and 1 mol%) was fabricated and investigated in detail for the appropriateness in the use of bone repair and regeneration applications. In this context, we explored the structural, thermal, mechanical, degradation, pH evaluation along with antibacterial assay, cytocompatability and cell proliferation by various characterization techniques like X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), Energy dispersive spectrometry (EDS) and differential thermal analysis (DTA), Vickers hardness, cell counting kit (CCK8) method and agar plates method. The obtained results of density, thermal stability and Vickers hardness increase with the increasing content of TiO 2 leads to the densification of glass structure dueto formation new linkages P–O–Ti and enters into the network in the form of either TiO 4 or TiO 5/6 structural units. The formation of a rich crystalline hydroxyl apatite (HAp) layer on the samples with incubation time (3, 7, 14 and 21days) and content of TiO 2 up to 0.6 mol% in simulated body fluid (SBF) were confirmed by in vitro analysis. Interestingly, no inhibitory effects on HAp layer formation with the addition of titanium up to 1 mol% were noticed. Lower degradation rate and pH values endorsed to hydration resistant with Ti4+ inclusion, leads to controlled ion leaching. The rat mesenchymal stem cells (rMSCs) growth on glass samples showed the enhanced biocompatibility and proliferation without toxicity. In addition, all glasses possess good antimicrobial properties against bacterial species Escherichia coli (E.coli). Finally, the results revealed that the 0.6 mol% of TiO 2 glass (T.6) showed abundant performance for bone generation applications. Image 1 • Ti4+ enters into the network in the form of either TiO 4 or TiO 5/6 units. • Density, Tg, Tc, Tm and Hv increase with content of TiO 2. • Reinforcement of glass structure ascribed to P–O–Ti linkages. • Controlled dissolution achieved by appropriate Ti4+ inclusion. • Rich HAp layer formation and high bioactivity with TiO 2 addition. [ABSTRACT FROM AUTHOR]

• Magnetic mesoporous bioactive glasses (MBGs) show great promise for cancer therapy. • Magnetic MBGs allow the controlled delivery of anti-cancer molecules and chemicals. • Incorporation of anti-tumor elements (e.g., Tb) impart anti-cancer properties to MBGs. • Photothermal therapy (PPT) using MBGs is a novel technique with promising results. • MBG-induced inhibition of angiogenesis is a new challenging issue for cancer therapy. Implementing novel approaches for cancer therapy are under continuous progress, and bioactive glasses (BGs) and glass-ceramics show excellent potential in this regard. Although these materials have been mostly used as magnetic substances in hyperthermia approach, some of their subsets, i.e., mesoporous bioactive glasses (MBGs), have been recently proposed not only as magnetic materials but also as drug delivery systems for advanced treatment of bone cancer. Different types of MBGs including granular particles and three-dimensional (3D) scaffolds can be applied for cancer therapy. Based on the results obtained from in vitro studies, MBGs seem to have a bright future in the therapeutic strategies to combat cancer; however, their application in this field is still in its beginning, and more research needs to reveal all pros and cons of this newly proposed approach. [ABSTRACT FROM AUTHOR]

Abstract Inflammation prevailing conditions delay healing processes of damaged tissues, leading to a functional impairment. Although anti-inflammatory drugs are clinically available, they often cause unwanted side effects thus being considered suboptimal. Here we report drug-free synthetic nanoparticles that target and internalize pro-inflammatory cells and release ions, ultimately demonstrating profound anti-inflammatory functions. We introduce folate-functionalized bioactive glass nanoparticle BGN(F) that can bind to pro-inflammatory cells to endocytose and release ions. The folate-conjugation significantly enhanced the nanoparticle internalization to LPS-induced pro-inflammatory cells. The direct treatment of BGN(F) at proper doses (80–160 μg/mL) substantially down-regulated pro-inflammatory molecules, including TNF-α, IL-6, iNOS and COX-2, at both gene and protein levels. The phosphorylation of intracellular signaling molecules involved in the inflammatory events, such as p38 MAPK, ERK (1/2), SAPK/JANK, IκBα, and NF-κB, were significantly suppressed by the BGN(F) treatment. Furthermore, BGN(F) was potential to switch the macrophage polarization from M1 to M2. The released ions, not the physical interactions, of nanoparticles were observed to contribute in major part to the anti-inflammatory actions of BGN(F). The BGN(F), when locally administered to a Notexin-induced myoinjury tissue in mice, significantly down-regulated IL-6 and TNF-α, switched the macrophage phenotype from M1 to M2, and accelerated tissue healing. The current findings that demonstrate profound anti-inflammatory actions of BGN(F) in vitro and in vivo support their uses as novel drug-free nanotherapeutic platform for the treatment of inflamed tissues. [ABSTRACT FROM AUTHOR]

Biomedical cements are considered promising injectable materials for bone repair and regeneration. Calcium phosphate composition sized with tens of micrometers is currently one of the major powder forms. Here we report a unique cement form made from mesoporous bioactive glass nanoparticles (BGn). The nanopowder could harden in reaction with aqueous solution at powder-to-liquid ratios as low as 0.4–0.5 ( vs . 2.0–3.0 for conventional calcium phosphate cement CPC). The cementation mechanism investigated from TEM, XRD, FT-IR, XPS, and NMR analyses was demonstrated to be the ionic (Si and Ca) dissolution and then reprecipitation to form Si-Ca-(P) based amorphous nano-islands that could network the particles. The nanopowder-derived nanocement exhibited high surface area (78.7 m 2 /g); approximately 9 times higher than conventional CPC. The immersion of nanocement in simulated body fluid produced apatite nanocrystallites with ultrafine size of 10 nm ( vs. 55 nm in CPC). The ultrafine nanocement adsorbed protein molecules (particularly positive charged proteins) at substantial levels; approximately 160 times higher than CPC. The nanocement released Si and Ca ions continuously over the test period of 2 weeks; the Si release was unique in nanocement whereas the Ca release was in a similar range to that observed in CPC. The release of ions significantly stimulated the responses of cells studied (rMSCs and HUVECs). The viability and osteogenesis of rMSCs were significantly enhanced by the nanocement ionic extracts. Furthermore, the in vitro tubular networking of HUVECs was improved by the nanocement ionic extracts. The in vivo neo-blood vessel formation in CAM model was significantly higher by the nanocement implant when compared with the CPC counterpart, implying the Si ion release might play a significant role in pro-angiogenesis. Furthermore, the early bone forming response of the nanocement, based on the implantation in a rat calvarial bone defect, demonstrated a sign of osteoinductivity along with excellent osteocondution and bone matrix formation. Although more studies remain to confirm the potential of nanocement, some of the intriguing physico-chemical properties and the biological responses reported herein support the promise of the new ‘nanopowder-based nanocement’ for hard tissue repair and regeneration. [ABSTRACT FROM AUTHOR]

Objective This study investigated the mechanical and in vitro biological properties (in immortalized human dental pulp stem cells (ihDPSCs)) of bioactive glass nanoparticle (BGN)-incorporated glass ionomer cement (GIC) with or without chitosan as a binder. Methods After the BGNs were synthesized and characterized, three experimental GICs and a control (conventional GIC) that differed in the additive incorporated into a commercial GIC liquid (Hy-bond, Shofu, Japan) were produced: BG5 (5 wt% of BGNs), CL0.5 (0.5 wt% of chitosan), and BG5 + CL0.5 (5 wt% of BGNs and 0.5 wt% of chitosan). After the net setting time was determined, weight change and bioactivity were analyzed in simulated body fluid (SBF) at 37 °C. Mechanical properties (compressive strength, diametral tensile strength, flexural strength and modulus) were measured according to the incubation time (up to 28 days) in SBF. Cytotoxicity (1 day) and biomineralization (14 days), assessed by alizarin red staining, were investigated using an extract from GIC and ihDPSCs. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test; p < 0.05. Results BGNs were sol–gel synthesized to be approximately 42 nm in diameter with a spherical morphology and amorphous structure. After the bioactivity and suspension ability of the BGNs were confirmed, all the experimental GIC groups had setting times of less than 6 min and approximately 1% weight loss after 28 days of incubation. In addition, BGNs incorporated into GIC (BG5 and BG5 + CL0.5) exhibited surface bioactivity. The mechanical properties were increased in the BGN-incorporated GICs compared to those in the control (p < 0.05). Without cytotoxicity, the biomineralization capacity was ranked in the order BG5, BG5 + CL0.5, control, and CL0.5 (p < 0.05). Significance BGN-incorporated GIC showed enhanced mechanical properties such as compressive, diametral tensile and flexural strength as well as in vitro biomineralization properties in ihDPSCs without cytotoxicity. Therefore, the developed BGN-incorporated GIC is a promising restorative dental material, although further in vivo investigation is needed before clinical application. [ABSTRACT FROM AUTHOR]