Bioactive ceramic-based materials: beneficial properties and potential applications in dental repair and regeneration.

Bioactive ceramics, primarily consisting of bioactive glasses, glass-ceramics, calcium orthophosphate ceramics, calcium silicate ceramics and calcium carbonate ceramics, have received great attention in the past decades given their biocompatible nature and excellent bioactivity in stimulating cell proliferation, differentiation and tissue regeneration. Recent studies have tried to combine bioactive ceramics with bioactive ions, polymers, bioactive proteins and other chemicals to improve their mechanical and biological properties, thus rendering them more valid in tissue engineering scaffolds. This review presents the beneficial properties and potential applications of bioactive ceramic-based materials in dentistry, particularly in the repair and regeneration of dental hard tissue, pulp-dentin complex, periodontal tissue and bone tissue. Moreover, greater insights into the mechanisms of bioactive ceramics and the development of ceramic-based materials are provided.

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Employing novel biocompatible composite scaffolds with bioglass 58S and poly L-lactic acid for effective bone defect treatment.

BACKGROUND: Bioglass materials have gained significant attention in the field of tissue engineering due to their osteoinductive and biocompatible properties that promote bone cell differentiation. In this study, a novel composite scaffold was developed using a sol-gel technique to combine bioglass (BG) 58 S with a poly L-lactic acid (PLLA). METHODS AND RESULTS: The physiochemical properties, morphology, and osteoinductive potential of the scaffolds were investigated by X-ray diffraction analysis, scanning electron microscopy, and Fourier-transform infrared spectroscopy. The results showed that the SiO2-CaO-P2O5 system was successfully synthesized by the sol-gel method. The PLLA scaffolds containing BG was found to be osteoinductive and promoted mineralization, as demonstrated by calcium deposition assay, upregulation of alkaline phosphatase enzyme activity, and Alizarin red staining data. CONCLUSIONS: These in vitro studies suggest that composite scaffolds incorporating hBMSCs are a promising substitute material to be implemented in bone tissue engineering. The PLLA/BG scaffolds promote osteogenesis and support the differentiation of bone cells, such as osteoblasts, due to their osteoinductive properties.

Fe-doped 45S5 bioactive glass compositions impair the metabolic activity and proliferation of metastatic human breast cancer cellsin vitro.

Many kinds of human tumors, including breast carcinomas, frequently metastasize to the bone, making it prone to pathologic fractures. Surgical management of bone metastases ranges from the resection of metastases to bone repair. Current surgical methods for the repair of bone defects include the use of polymethyl methacrylate (PMMA)-based bone cements. A promising alternative material are bioactive glass (BG) particles that in addition to providing physical stability can also induce bone regeneration. Moreover, BGs doped with Fe2O3may also have a negative impact on tumor cells. Here, we tested the hypothesis that BGs can affect metastatic human breast cancer cells. To this end, we assessed the effects of different BG compositions with and without Fe2O3on metastatic human MDA-MB-231 breast cancer cellsin vitro. We found that all BGs tested impaired the viability and proliferation of breast cancer cells in a concentration-dependent manner. The anti-proliferative effects inversely correlated with BG particle size, and were in general less pronounced in mesenchymal stromal cells (MSCs) that served as a control. Moreover, Fe2O3-doped BGs were more potent inhibitors of tumor cell proliferation and metabolic activity than Fe2O3-free BG. Our data therefore indicate that BGs can affect human breast cancer cells more strongly than MSCs, and suggest that the presence of Fe2O3can potentiate anti-proliferative and anti-metabolic effects of BGs. Fe2O3-doped BGs thus have the potential to be used for the surgical management of metastatic bone lesions, and may in addition to their regenerative properties also allow the local control of bone metastases.

PI3K/AKT/mTOR signaling regulates BCP ceramic-induced osteogenesis.

An increasing number of studies demonstrate that biphasic calcium phosphate (BCP) ceramics can induce bone regeneration. However, the underlying molecular mechanisms involved are still poorly understood. This work was proposed to investigate how PI3K/AKT/mTOR signaling influenced the osteogenesis mediated by BCP ceramics. The results showed that incubation with BCP ceramics promoted the proliferation of murine bone marrow-derived mesenchymal stem cells (BMSCs) in a time-dependent manner. The resulting cell proliferation was then suppressed by the selective inhibition of either PI3K, AKT, or mTOR signaling activation. Next, we confirmed that BCP ceramics up-regulated the phosphorylation levels of AKT and mTOR in BMSCs, suggesting the ability of BCP ceramics to drive the activation of PI3K/AKT/mTOR signaling in BMSCs. Furthermore, the blockade of PI3K/AKT/mTOR signaling prevented BCP ceramics-induced osteogenic differentiation and pro-angiogenesis of BMSCs by down-regulating the expression of genes encoding OPN, RUNX2 or VEGF. Moreover, the PI3K/AKT/mTOR signaling blockade suppressed stem cell infiltration and new bone formation in the implants following intra-muscular implantation of BCP ceramics in mice. Therefore, our results suggested that PI3K/AKT/mTOR signaling played a critical regulatory role in BCP ceramic-induced osteogenesis.

Cerium doping of 45S5 bioactive glass improves redox potential and cellular bioactivity.

45S5 Bioglass (BG) is composed of a glass network with silicate based on the component and can be doped with various therapeutic ions for the enhancement of hard tissue therapy. Nanoceria (CeO2) has been shown to indicate redox reaction and enhance the biological response. However, few studies focus on the proportion of CeO2-doped and its effect on the cellular bioactivity of CeO2-doped BG (CBG). In this study, we synthesized the CBG series with increasing amounts of doping CeO2 ranging (1 to 12) wt.%. The synthesized CBG series examined the characterization, mineralization capacity, and cellular activity against BG. Our results showed that the CBG series exhibited a glass structure and indicated the redox states between Ce3+ and Ce4+, thus they showed the antioxidant activity by characterization of Ce. The CBG series had a stable glass network structure similar to BG, which showed the preservation of bioactivity by exhibiting mineralization on the surface. In terms of biological response, although the CBG series showed the proliferative activity of pre-osteoblastic cells similar to BG, the CBG series augmented not only the alkaline phosphatase activity but also the osteogenic marker in the mRNA level. As stimulated the osteogenic activity, the CBG series improved the biomineralization. In conclusion, the CBG series might have a potential application for hard tissue therapeutic purposes.

Tailoring zirconia surface topography via femtosecond laser-induced nanoscale features: effects on osteoblast cells and antibacterial properties.

The performance and long-term durability of dental implants hinge on the quality of bone integration and their resistance to bacteria. This research aims to introduce a surface modification strategy for zirconia implants utilizing femtosecond laser ablation techniques, exploring their impact on osteoblast cell behavior and bacterial performance, as well as the integral factors influencing the soft tissue quality surrounding dental implants. Ultrafast lasers were employed to craft nanoscale groove geometries on zirconia surfaces, with thorough analyses conducted using x-ray diffraction, scanning electron microscopy, atomic force microscopy, and water contact angle measurements. The study evaluated the response of human fetal osteoblastic cell lines to textured zirconia ceramics by assessing alkaline phosphatase activity, collagen I, and interleukin 1ßsecretion over a 7 day period. Additionally, the antibacterial behavior of the textured surfaces was investigated usingFusobacterium nucleatum, a common culprit in infections associated with dental implants. Ciprofloxacin (CIP), a widely used antibacterial antibiotic, was loaded onto zirconia ceramic surfaces. The results of this study unveiled a substantial reduction in bacterial adhesion on textured zirconia surfaces. The fine biocompatibility of these surfaces was confirmed through the MTT assay and observations of cell morphology. Moreover, the human fetal osteoblastic cell line exhibited extensive spreading and secreted elevated levels of collagen I and interleukin 1ßin the modified samples. Drug release evaluations demonstrated sustained CIP release through a diffusion mechanism, showcasing excellent antibacterial activity against pathogenic bacteria, includingStreptococcus mutans, Pseudomonas aeruginosa, andEscherichia coli.

Development of Bioactive Hybrid Poly(lactic acid)/Poly(methyl methacrylate) (PLA/PMMA) Electrospun Fibers Functionalized with Bioglass Nanoparticles for Bone Tissue Engineering Applications.

Hybrid scaffolds that are based on PLA and PLA/PMMA with 75/25, 50/50, and 25/75 weight ratios and functionalized with 10 wt.% of bioglass nanoparticles (n-BG) were developed using an electrospinning technique with a chloroform/dimethylformamide mixture in a 9:1 ratio for bone tissue engineering applications. Neat PLA and PLA/PMMA hybrid scaffolds were developed successfully through a (CF/DMF) solvent system, obtaining a random fiber deposition that generated a porous structure with pore interconnectivity. However, with the solvent system used, it was not possible to generate fibers in the case of the neat PMMA sample. With the increase in the amount of PMMA in PLA/PMMA ratios, the fiber diameter of hybrid scaffolds decreases, and the defects (beads) in the fiber structure increase; these beads are associated with a nanoparticle agglomeration, that could be related to a low interaction between n-BG and the polymer matrix. The Young's modulus of PLA/PMMA/n-BG decreases by 34 and 80%, indicating more flexible behavior compared to neat PLA. The PLA/PMMA/n-BG scaffolds showed a bioactive property related to the presence of hydroxyapatite crystals in the fiber surface after 28 days of immersion in a Simulated Body Fluids solution (SBF). In addition, the hydrolytic degradation process of PLA/PMMA/n-BG, analyzed after 35 days of immersion in a phosphate-buffered saline solution (PBS), was less than that of the pure PLA. The in vitro analysis using an HBOF-1.19 cell line indicated that the PLA/PMMA/n-BG scaffold showed good cell viability and was able to promote cell proliferation after 7 days. On the other hand, the in vivo biocompatibility evaluated via a subdermal model in BALC male mice corroborated the good behavior of the scaffolds in avoiding the generation of a cytotoxic effect and being able to enhance the healing process, suggesting that the materials are suitable for potential applications in tissue engineering.

Gelatin Methacryloyl (GelMA) - 45S5 Bioactive Glass (BG) Composites for Bone Tissue Engineering: 3D Extrusion Printability and Cytocompatibility Assessment Using Human Osteoblasts.

3D extrusion printing has been widely investigated for low-volume production of complex-shaped scaffolds for tissue regeneration. Gelatin methacryloyl (GelMA) is used as a baseline material for the synthesis of biomaterial inks, often with organic/inorganic fillers, to obtain a balance between good printability and biophysical properties. The present study demonstrates how 45S5 bioactive glass (BG) addition and GelMA concentrations can be tailored to develop GelMA composite scaffolds with good printability and buildability. The experimental results suggest that 45S5 BG addition consistently decreases the compression stiffness, irrespective of GelMA concentration, albeit within 20% of the baseline scaffold (without 45S5 BG). The optimal addition of 2 wt % 45S5 BG in 7.5 wt % GelMA was demonstrated to provide the best combination of printability and buildability in the 3D extrusion printing route. The degradation decreases and the swelling kinetics increases with 45S5 BG addition, irrespective of GelMA concentration. Importantly, the dissolution in simulated body fluid over 3 weeks clearly promoted the nucleation and growth of crystalline calcium phosphate particles, indicating the potential of GelMA-45S5 BG to promote biomineralization. The cytocompatibility assessment using human osteoblasts could demonstrate uncompromised cell proliferation or osteogenic marker expression over 21 days in culture for 3D printable 7.5 wt % GelMA -2 wt % 45S5 BG scaffolds when compared to 7.5 wt % GelMA. The results thus encourage further investigations of the GelMA/45S5 BG composite system for bone tissue engineering applications.

3D modular bioceramic scaffolds for the investigation of the interaction between osteosarcoma cells and MSCs.

Recent advances in bone tissue engineering have shown promise for bone repair post osteosarcoma excision. However, conflicting research on mesenchymal stem cells (MSCs) has raised concerns about their potential to either promote or inhibit tumor cell proliferation. It is necessary to thoroughly understand the interactions between MSCs and tumor cells. Most previous studies only focused on the interactions between cells within the tumor tissues. It has been challenging to develop an in vitro model of osteosarcoma excision sites replicating the complexity of the bone microenvironment and cell distribution. In this work, we designed and fabricated modular bioceramic scaffolds to assemble into a co-culture model. Because of the bone-like composition and mechanical property, tricalcium phosphate bioceramic could mimic the bone microenvironment and recapitulate the cell-extracellular matrix interaction. Moreover, the properties for easy assembly enabled the modular units to mimic the spatial distribution of cells in the osteosarcoma excision site. Under this co-culture model, MSCs showed a noticeable tumor-stimulating effect with a potential risk of tumor recurrence. In addition, tumor cells also could inhibit the osteogenic ability of MSCs. To undermine the stimulating effects of MSCs on tumor cells, we present the methods of pre-differentiated MSCs, which had lower expression of IL-8 and higher expression of osteogenic proteins. Both in vitro and in vivo studies confirm that pre-differentiated MSCs could maintain high osteogenic capacity without promoting tumor growth, offering a promising approach for MSCs' application in bone regeneration. Overall, 3D modular scaffolds provide a valuable tool for constructing hard tissue in vitro models. STATEMENT OF SIGNIFICANCE: Bone tissue engineering using mesenchymal stem cells (MSCs) and biomaterials has shown promise for bone repair post osteosarcoma excision. However, conflicting researches on MSCs have raised concerns about their potential to either promote or inhibit tumor cell proliferation. It remains challenges to develop in vitro models to investigate cell interactions, especially of osteosarcoma with high hardness and special composition of bone tissue. In this work, modular bioceramic scaffolds were fabricated and assembled to co-culture models. The interactions between MSCs and MG-63 were manifested as tumor-stimulating and osteogenesis-inhibiting, which means potential risk of tumor recurrence. To undermine the stimulating effect, pre-differentiation method was proposed to maintain high osteogenic capacity without tumor-stimulating, offering a promising approach for MSCs' application in bone regeneration.

Osteoinductive and regenerative potential of premixed calcium-silicate bioceramic sealers on vascular wall mesenchymal stem cells.

AIM: The osteogenic potential of new premixed calcium-silicate-containing bioceramic sealers (Ca-Si sealers) was tested with porcine vascular wall-mesenchymal stem cells (pVW-MSCs). METHODOLOGY: Two Ca-Si-containing sealers: Ceraseal (MetaBiomed, Cheong-si, South Korea) and AH Plus Bioceramic (Maruchi, Wonju-si, South Korea), and an epoxy resin sealer (AH Plus; Dentsply, Konstanz, Germany) as a control, were prepared according to the manufacturers' indications. All samples were allowed to set for 100% of their setting time in a sterile humid cabinet at 37°C and 95% relative humidity. pVW-MSC seeding efficiency and osteogenic differentiation were analysed as marker of gene/protein expression for up to 12 days. Mineralization assay and immunofluorescence staining were performed and evaluated over a period of 21 days. Statistical analyses were conducted using one-way analysis of variance (p < .05). Additional samples were prepared and stored under the same conditions and inspected using an environmental scanning electron microscope equipped with an energy dispersive X-ray spectroscopy system. RESULTS: Significantly higher cell seeding efficiency (p < .05) was observed for both Ca-Si sealers from day 8. pVW-MSCs showed a significant shift towards the osteogenic lineage only when seeded in contact with Ca-Si sealers. Gene expression of osteopontin was upregulated significantly. Collagen I and osteocalcin were clearly expressed by cells in contact with Ca-Si sealers. Mineralization granules were observed in Alizarin red assays and confocal laser scanning microscopy analysis of both Ca-Si sealers. No gene expression or granule mineralization were observed on the epoxy resin sealer. CONCLUSIONS: Premixed Ca-Si sealers displayed a higher potential for osteogenic activity on pVW-MSCs. Epoxy resin sealer was unable to induce any osteogenic activity. The properties of both Ca-Si sealers suggest their potential as osteoinductive platforms for vascular MSCs in periapical bone.

Antibacterial and Osteogenic Doxycycline Imprinted Bioglass Microspheres to Combat Bone Infection.

Currently, postoperative infection is a significant challenge in bone and dental surgical procedures, demanding the exploration of innovative approaches due to the prevalence of antibiotic-resistant bacteria. This study aims to develop a strategy for controlled and smart antibiotic release while accelerating osteogenesis to expedite bone healing. In this regard, temperature-responsive doxycycline (DOX) imprinted bioglass microspheres (BGMs) were synthesized. Following the formation of chitosan-modified BGMs, poly N-isopropylacrylamide (pNIPAm) was used for surface imprinting of DOX. The temperature-responsive molecularly imprinted polymers (MIPs) exhibited pH and temperature dual-responsive adsorption and controlled-release properties for DOX. The temperature-responsive MIP was optimized by investigating the molar ratio of N,N'-methylene bis(acrylamide) (MBA, the cross-linker) to NIPAm. Our results demonstrated that the MIPs showed superior adsorption capacity (96.85 mg/g at 35 °C, pH = 7) than nonimprinted polymers (NIPs) and manifested a favorable selectivity toward DOX. The adsorption behavior of DOX on the MIPs fit well with the Langmuir model and the pseudo-second-order kinetic model. Drug release studies demonstrated a controlled release of DOX due to imprinted cavities, which were fitted with the Korsmeyer-Peppas kinetic model. DOX-imprinted BGMs also revealed comparable antibacterial effects against Staphylococcus aureus and Escherichia coli to the DOX (control). In addition, MIPs promoted viability and osteogenic differentiation of MG63 osteoblast-like cells. Overall, the findings demonstrate the significant potential of DOX-imprinted BGMs for use in bone defects. Nonetheless, further in vitro investigations and subsequent in vivo experiments are warranted to advance this research.

3D Printed Pedicle Screws with Microarc Oxidation Ceramic Interfaces Enhance Osteointegration and Orthopedic Fixation Feasibility.

Effective osteointegration is of great importance for pedicle screws in spinal fusion surgeries. However, the lack of osteoinductive activity of current screws diminishes their feasibility for osteointegration and fixation, making screw loosening a common complication worldwide. In this study, Ti-6Al-4V pedicle screws with full through-hole design were fabricated via selective laser melting (SLM) 3D printing and then deposited with porous oxide coatings by microarc oxidation (MAO). The porous surface morphology of the oxide coating and the release of bioactive ions could effectively support cell adhesion, migration, vascularization, and osteogenesis in vitro. Furthermore, an in vivo goat model demonstrated the efficacy of modified screws in improving bone maturation and osseointegration, thus providing a promising method for feasible orthopedic internal fixation.

Evaluating osteogenic potential of a 3D-printed bioceramic-based scaffold for critical-sized defect treatment: an in vivo and in vitro investigation.

The integration of precision medicine principles into bone tissue engineering has ignited a wave of research focused on customizing intricate scaffolds through advanced 3D printing techniques. Bioceramics, known for their exceptional biocompatibility and osteoconductivity, have emerged as a promising material in this field. This article aims to evaluate the regenerative capabilities of a composite scaffold composed of 3D-printed gelatin combined with hydroxyapatite/tricalcium phosphate bioceramics (G/HA/TCP), incorporating human dental pulp-derived stem cells (hDPSCs). Using 3D powder printing, we created cross-shaped biphasic calcium phosphate scaffolds with a gelatin layer. The bone-regenerating potential of these scaffolds, along with hDPSCs, was assessed through in vitro analyses and in vivo studies with 60 rats and critical-sized calvarial defects. The assessment included analyzing cellular proliferation, differentiation, and alkaline phosphatase activity (ALP), and concluded with a detailed histological evaluation of bone regeneration. Our study revealed a highly favorable scenario, displaying not only desirable cellular attachment and proliferation on the scaffolds but also a notable enhancement in the ALP activity of hDPSCs, underscoring their pivotal role in bone regeneration. However, the histological examination of calvarial defects at the 12-wk mark yielded a rather modest level of bone regeneration across all experimental groups. The test and cell group exhibited significant bone formation compared to all other groups except the control and cell group. This underscores the complexity of the regenerative process and paves the way for further in-depth investigations aimed at improving the potential of the composite scaffolds.

Quercetin-Loaded Bioglass Injectable Hydrogel Promotes m6A Alteration of Per1 to Alleviate Oxidative Stress for Periodontal Bone Defects.

Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, and is closely related to the occurrence and progression of various systemic diseases. However, elucidating the processes of periodontal disease and promoting periodontal bone regeneration remains a challenge. Here, quercetin is demonstrated to reduce the oxidative stress state of orofacial mesenchymal stem cells (OMSCs) in vitro and to affect the osteogenic growth of OMSCs through molecular mechanisms that mediate the m6A change in Per1. Nevertheless, the limited therapeutic efficacy of systemic medication and the limitations of local medication resulting from the small, moist, and highly dynamic periodontal environment make it challenging to treat periodontal tissues with medication. Herein, a biosafe injectable hydrogel drug-controlled delivery system is constructed as a bone-enhancing factory and loaded with quercetin to treat oxidative stress injury in periodontal tissues. This drug-carrying system made up of nanoscale bioglass microspheres and a light-cured injectable hydrogel, allows effective drug particle loading and cementation in the dynamic and moist periodontal environment. Furthermore, the system demonstrates the ability to stimulate OMSCs osteogenic differentiation in a Per1-dependent manner, which ultimately promotes periodontal bone repair, suggesting that this system has potential for clinical periodontal therapy.

Odontogenic and anti-inflammatory effects of magnesium-doped bioactive glass in vital pulp therapy.

This study aimed to investigate the effects of magnesium-doped bioactive glass (Mg-BG) on the mineralization, odontogenesis, and anti-inflammatory abilities of human dental pulp stem cells (hDPSCs). Mg-BG powders with different Mg concentrations were successfully synthesized via the sol-gel method and evaluated using x-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, and transmission electron microscopy. Apatite formation was observed on the surfaces of the materials after soaking in simulated body fluid. hDPSCs were cultured with Mg-BG powder extracts in vitro, and no evident cytotoxicity was observed. Mg-BG induced alkaline phosphatase (ALP) expression and mineralization of hDPSCs and upregulated the expression of odontogenic genes, including those encoding dentin sialophosphoprotein, dentin matrix protein 1, ALP, osteocalcin, and runt-related transcription factor 2. Moreover, Mg-BG substantially suppressed the secretion of inflammatory cytokines (interleukin [IL]-4, IL-6, IL-8, and tumor necrosis factor-alpha). Collectively, the results of this study suggest that Mg-BG has excellent in vitro bioactivity and is a potential material for vital pulp therapy of inflamed pulps.

Bioactivity and antibacterial effects of zinc-containing bioactive glass on the surface of zirconia abutments.

OBJECTIVES: This study aimed to enhance gingival fibroblast function and to achieve antibacterial activity around the implant abutment by using a zinc (Zn)-containing bioactive glass (BG) coating. METHODS: 45S5 BG containing 0, 5, and 10 wt.% Zn were coated on zirconia disks. The release of silica and Zn ions in physiological saline and their antibacterial effects were measured. The effects of BG coatings on human gingival fibroblasts (hGFs) were assessed using cytotoxicity assays and by analyzing the gene expression of various genes related to antioxidant enzymes, wound healing, and fibrosis. RESULTS: BG coatings are capable of continuous degradation and simultaneous ion release. The antibacterial effect of BG coatings increased with the addition of Zn, while the cytotoxicity remained unchanged compared to the group without coatings. BG coating enhances the expression of angiogenesis genes, while the Zn-containing BG enhances the expression of antioxidant genes at an early time point. BG coating enhances the expression of collagen genes at later time points. CONCLUSIONS: The antibacterial effect of BG improved with the increase in Zn concentration, without inducing cytotoxicity. BG coating enhances the expression of angiogenesis genes, and Zn-containing BG enhances the expression of antioxidant genes at an early time point. BG coating enhances the expression of collagen genes at later time points. CLINICAL SIGNIFICANCE: Adding 10 wt% Zn to BG could enhance the environment around implant abutments by providing antibacterial, antioxidant, and anti-fibrotic effects, having potential for clinical use.

Osteo-immunomodulatory effects of macrophage-derived extracellular vesicles treated with biphasic calcium phosphate ceramics on bone regeneration.

Literature on osteoimmunology has demonstrated that macrophages have a great influence on biomaterial-induced bone formation. However, there are almost no reports clarifying the osteo-immunomodulatory capacity of macrophage-derived extracellular vesicles (EVs). This study comprehensively investigated the effects of EVs derived from macrophages treated with biphasic calcium phosphate (BCP) ceramics (BEVs) on vital events associated with BCP-induced bone formation such as immune response, angiogenesis, and osteogenesis. It was found that compared with EVs derived from macrophages alone (control, CEVs), BEVs preferentially promoted macrophage polarization towards a wound-healing M2 phenotype, enhanced migration, angiogenic differentiation, and tube formation of human umbilical vein endothelial cells, and induced osteogenic differentiation of mesenchymal stem cells. Analysis of 15 differentially expressed microRNAs (DEMs) related to immune, angiogenesis, and osteogenesis suggested that BEVs exhibited good immunomodulatory, pro-angiogenic, and pro-osteogenic abilities, which might be attributed to their specific miRNA cargos. These findings not only deepen our understanding of biomaterial-mediated osteoinduction, but also suggest that EVs derived from biomaterial-treated macrophages hold great promise as therapeutic agents with desired immunomodulatory capacity for bone regeneration.

Enriched mesoporous bioactive glass scaffolds as bone substitutes in critical diaphyseal bone defects in rabbits.

In the field of orthopedic surgery, there is an increasing need for the development of bone replacement materials for the treatment of bone defects. One of the main focuses of biomaterials engineering are advanced bioceramics like mesoporous bioactive glasses (MBG´s). The present study compared the new bone formation after 12 weeks of implantation of MBG scaffolds with composition 82,5SiO2-10CaO-5P2O5-x 2.5SrO alone (MBGA), enriched with osteostatin, an osteoinductive peptide, (MBGO) or enriched with bone marrow aspirate (MBGB) in a long bone critical defect in radius bone of adult New Zealand rabbits. New bone formation from the MBG scaffold groups was compared to the gold standard defect filled with iliac crest autograft and to the unfilled defect. Radiographic follow-up was performed at 2, 6, and 12 weeks, and microCT and histologic examination were performed at 12 weeks. X-Ray study showed the highest bone formation scores in the group with the defect filled with autograft, followed by the MBGB group, in addition, the microCT study showed that bone within defect scores (BV/TV) were higher in the MBGO group. This difference could be explained by the higher density of newly formed bone in the osteostatin enriched MBG scaffold group. Therefore, MBG scaffold alone and enriched with osteostatin or bone marrow aspirate increase bone formation compared to defect unfilled, being higher in the osteostatin group. The present results showed the potential to treat critical bone defects by combining MBGs with osteogenic peptides such as osteostatin, with good prospects for translation into clinical practice. STATEMENT OF SIGNIFICANCE: Treatment of bone defects without the capacity for self-repair is a global problem in the field of Orthopedic Surgery, as evidenced by the fact that in the U.S alone it affects approximately 100,000 patients per year. The gold standard of treatment in these cases is the autograft, but its use has limitations both in the amount of graft to be obtained and in the morbidity produced in the donor site. In the field of materials engineering, there is a growing interest in the development of a bone substitute equivalent. Mesoporous bioactive glass (MBG´s) scaffolds with three-dimensional architecture have shown great potential for use as a bone substitutes. The osteostatin-enriched Sr-MBG used in this long bone defect in rabbit radius bone in vivo study showed an increase in bone formation close to autograft, which makes us think that it may be an option to consider as bone substitute.

Assessment of the anti-inflammatory and biological properties of Bioroot Flow: A novel bioceramic sealer.

INTRODUCTION: BioRoot Flow (BRF) is a novel premixed bioceramic sealer indicated for endodontic treatments, but the biological and immunomodulatory effects of this endodontic sealer on human periodontal ligament stem cells (hPDLSCs) have not been elucidated. METHODS: To ascertain the biological impact of BRF, TotalFill BC Sealer (TFbc), and AH Plus (AHP) on human Periodontal Ligament Stem Cells (hPDLSCs), assessments were conducted to evaluate the cytocompatibility, cellular proliferation, migratory capacity, osteo/cementogenic differentiation potential, the ability to form mineralized nodules, and the immunomodulatory characteristics of hPDLSCs following treatment with these endodontic sealers. RESULTS: Biological assays showed adequate cell metabolic activity and cell migration in BRF, while SEM assay evidenced that TFbc and BRF groups demonstrated a superior cell adhesion process, including substrate adhesion, cytoskeleton development, and spreading on the niche-like structures of the cement as compared to the AHP group. TFbc and BRF-treated groups exhibited a significantly lower IL6 and IL8 production than AHP (* p <.05). The bioceramic sealers stimulated heightened expression of BSP, CEMP-1, and CAP genes within a 7-14 day period. Notably, BRF and TFbc demonstrated a significant enhancement in the mineralization of hPDLSCs when compared to the negative control. Among these, cells treated with BRF showed a more substantial accumulation of calcium (*** p < .001). CONCLUSIONS: Taken together, these findings indicate that BRF can potentially enhance cell differentiation by promoting the expression of essential genes related to bone and cement formation. In addition, BRF and TFbc displayed anti-inflammatory effects.

Anti-inflammatory cerium-containing nano-scaled mesoporous bioactive glass for promoting regenerative capability of dental pulp cells.

AIMS: This study aimed to investigate the anti-inflammatory and odontoblastic effects of cerium-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) on dental pulp cells as novel pulp-capping agents. METHODOLOGY: Ce-MBGNs were synthesized using a post-impregnation strategy based on the antioxidant properties of Ce ions and proposed the first use of Ce-MBGNs for pulp-capping application. The biocompatibility of Ce-MBGNs was analysed using the CCK-8 assay and apoptosis detection. Additionally, the reactive oxygen species (ROS) scavenging ability of Ce-MBGNs was measured using the 2,7-Dichlorofuorescin Diacetate (DCFH-DA) probe. The anti-inflammatory effect of Ce-MBGNs on THP-1 cells was further investigated using flow cytometry and quantitative real-time polymerase chain reaction (RT-qPCR). Moreover, the effect of Ce-MBGNs on the odontoblastic differentiation of the dental pulp cells (DPCs) was assessed by combined scratch assays, RT-qPCR, western blotting, immunocytochemistry, Alizarin Red S staining and tissue-nonspecific alkaline phosphatase staining. Analytically, the secretions of tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS: Ce-MBGNs were confirmed to effectively scavenge ROS in THP-1-derived macrophages and DPCs. Flow cytometry and RT-qPCR assays revealed that Ce-MBGNs significantly inhibited the M1 polarization of macrophages (Mφ). Furthermore, the protein levels of TNF-α and IL-1ß were downregulated in THP-1-derived macrophages after stimulation with Ce-MBGNs. With a step-forward virtue of promoting the odontoblastic differentiation of DPCs, we further confirmed that Ce-MBGNs could regulate the formation of a conductive immune microenvironment with respect to tissue repair in DPCs, which was mediated by macrophages. CONCLUSIONS: Ce-MBGNs protected cells from self-produced oxidative damage and exhibited excellent immunomodulatory and odontoblastic differentiation effects on DPCs. As a pulp-capping agent, this novel biomaterial can exert anti-inflammatory effects and promote restorative dentine regeneration in clinical treatment. We believe that this study will stimulate further correlative research on the development of advanced pulp-capping agents.