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.

Unraveling the influence of channel size and shape in 3D printed ceramic scaffolds on osteogenesis.

Bone has the capacity to regenerate itself for relatively small defects; however, this regenerative capacity is diminished in critical-size bone defects. The development of synthetic materials has risen as a distinct strategy to address this challenge. Effective synthetic materials to have emerged in recent years are bioceramic implants, which are biocompatible and highly bioactive. Yet nothing suitable for the repair of large bone defects has made the transition from laboratory to clinic. The clinical success of bioceramics has been shown to depend not only on the scaffold's intrinsic material properties but also on its internal porous geometry. This study aimed to systematically explore the implications of varying channel size, shape, and curvature in tissue scaffolds on in vivo bone regeneration outcomes. 3D printed bioceramic scaffolds with varying channel sizes (0.3 mm to 1.5 mm), shapes (circular vs rectangular), and curvatures (concave vs convex) were implanted in rabbit femoral defects for 8 weeks, followed by histological evaluation. We demonstrated that circular channel sizes of around 0.9 mm diameter significantly enhanced bone formation, compared to channel with diameters of 0.3 mm and 1.5 mm. Interestingly, varying channel shapes (rectangular vs circular) had no significant effect on the volume of newly formed bone. Furthermore, the present study systematically demonstrated the beneficial effect of concave surfaces on bone tissue growth in vivo, reinforcing previous in silico and in vitro findings. This study demonstrates that optimizing architectural configurations within ceramic scaffolds is crucial in enhancing bone regeneration outcomes. STATEMENT OF SIGNIFICANCE: Despite the explosion of work on developing synthetic scaffolds to repair bone defects, the amount of new bone formed by scaffolds in vivo remains suboptimal. Recent studies have illuminated the pivotal role of scaffolds' internal architecture in osteogenesis. However, these investigations have mostly remained confined to in silico and in vitro experiments. Among the in vivo studies conducted, there has been a lack of systematic analysis of individual architectural features. Herein, we utilized bioceramic 3D printing to conduct a systematic exploration of the effects of channel size, shape, and curvature on bone formation in vivo. Our results demonstrate the significant influence of channel size and curvature on in vivo outcomes. These findings provide invaluable insights into the design of more effective bone scaffolds.

Enhancement in the induction heating efficacy of sol-gel derived SiO2-CaO-Na2O-P2O5 bioglass-ceramics by incorporating magnetite nanoparticles.

Magnetite (Fe3O4) nanoparticle (MNP)-substituted glass-ceramic (MSGC) powders with compositions of (45 - x)SiO2-24.5CaO-24.5Na2O-6P2O5-xFe3O4 (x = 5, 8, and 10 wt%) have been prepared by a sol-gel route by introducing Fe3O4 nanoparticles during the synthesis. The X-ray diffraction patterns of the as-prepared MSGC nanopowders revealed the presence of combeite (Na2Ca2Si3O9), magnetite, and sodium nitrate (NaNO3) crystalline phases. Heat-treatment up to 700 °C for 1 h resulted in the complete dissolution of NaNO3 along with partial conversion of magnetite into hematite (α-Fe2O3). Optimal heat-treatment of the MSGC powders at 550 °C for 1 h yielded the highest relative percentage of magnetite (without hematite) with some residual NaNO3. The saturation magnetization and heat generation capacity of the MSGC fluids increased with an increase in the MNP content. The in vitro bioactivity of the MSGC pellets was evaluated by monitoring the pH and the formation of a hydroxyapatite surface layer upon immersion in modified simulated body fluid. Proliferation of MG-63 osteoblast cells indicated that all of the MSGC compositions were non-toxic and MSGC with 10 wt% MNPs exhibited extraordinarily high cell viability. The MSGC with 10 wt% MNPs demonstrated optimal characteristics in terms of cell viability, magnetic properties, and induction heating capacity, which surpass those of the commercial magnetic fluid FluidMag-CT employed in hyperthermia treatment.

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.

Mineral matrix deposition of MC3T3-E1 pre-osteoblastic cells exposed to silicocarnotite and nagelschmidtite bioceramics: In vitro comparison to hydroxyapatite.

This work presents the effect of the silicocarnotite (SC) and nagelschmidtite (Nagel) phases on in vitro osteogenesis. The known hydroxyapatite of biological origin (BHAp) was used as a standard of osteoconductive characteristics. The evaluation was carried out in conventional and osteogenic media for comparative purposes to assess the osteogenic ability of the bioceramics. First, the effect of the material on cell viability at 24 h, 7 and 14 days of incubation was evaluated. In addition, cell morphology and attachment on dense bioceramic surfaces were observed by fluorescence microscopy. Specifically, alkaline phosphatase (ALP) activity was evaluated as an osteogenic marker of the early stages of bone cell differentiation. Mineralized extracellular matrix was observed by calcium phosphate deposits and extracellular vesicle formation. Furthermore, cell phenotype determination was confirmed by scanning electron microscope. The results provided relevant information on the cell attachment, proliferation, and osteogenic differentiation processes after 7 and 14 days of incubation. Finally, it was demonstrated that SC and Nagel phases promote cell proliferation and differentiation, while the Nagel phase exhibited a superior osteoconductive behavior and could promote MC3T3-E1 cell differentiation to a higher extent than SC and BHAp, which was reflected in a higher number of deposits in a shorter period for both conventional and osteogenic media.

Nanoparticulate bioceramic putty suppresses osteoclastogenesis and inflammatory bone loss in mice via inhibition of TRAF6-mediated signalling pathways: A laboratory investigation.

AIM: This study aimed to determine the effects of iRoot BP Plus on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro and inflammation-mediated bone resorption in vivo and investigated the underlying molecular mechanisms. METHODOLOGY: CCK-8 was performed to test cell viability in RANKL-induced RAW 264.7 cells and BMDMs in response to iRoot BP Plus. The effect of iRoot BP Plus on osteoclastogenesis was determined using TRAP staining and phalloidin staining, respectively. Pit formation assay was conducted to measure osteoclast resorptive capacity. Western blot and qPCR were performed to examine osteoclast-related proteins and gene expression, respectively. Western blot was also used to investigate the signalling pathways involved. For in vivo experiments, an LPS-induced mouse calvarial bone resorption model was established to analyse the effect of iRoot BP Plus on bone resorption (n = 6 per group). At 7 days, mouse calvaria were collected and prepared for histological analysis. RESULTS: We identified that iRoot BP Plus extracts significantly attenuated RANKL-induced osteoclastogenesis, reduced sealing zone formation, restrained osteolytic capacity and decreased osteoclast-specific gene expression (p < .01). Mechanistically, iRoot BP Plus extracts reduced TRAF6 via proteasomal degradation, then suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), blocked the nuclear translocation of c-Fos and diminished nuclear factor-κB (NF-κB) p65 and NFATc1 accumulation. Consistent with the in vitro results, iRoot BP Plus extracts attenuated osteoclast activity thus protecting against inflammatory bone resorption in vivo (p < .05), which was accompanied by a suppression of TRAF6, c-Fos, NFATc1 and cathepsin K expression. CONCLUSION: These findings provide valuable insights into the signalling mechanisms underlying nanoparticulate bioceramic putty-mediated bone homeostasis.

Repair of a rat calvaria defect with injectable strontium (Sr)-doped polyphosphate dicalcium phosphate dehydrate (P-DCPD) ceramic bone grafts.

The trace element strontium (Sr) enhances new bone formation. However, delivering Sr, like other materials, in a sustained manner from a ceramic bone graft substitute (BGS) is difficult. We developed a novel ceramic BGS, polyphosphate dicalcium phosphate dehydrate (P-DCPD), which delivers embedded drugs in a sustained pattern. This study assessed the in vitro and in vivo performance of Sr-doped P-DCPD. In vitro P-DCPD and 10%Sr-P-DCPD were nontoxic and eluents from 10%Sr-P-DCPD significantly enhanced osteoblastic MC3T3 cell differentiation. A sustained, zero-order Sr release was observed from 10%Sr-P-DCPD for up to 70 days. When using this BGS in a rat calvaria defect model, both P-DCPD and 10% Sr-P-DCPD were found to be biocompatible and biodegradable. Histologic data from decalcified and undecalcified tissue showed that 10%Sr-P-DCPD had more extensive new bone formation compared with P-DCPD 12-weeks after surgery and the 10%Sr-P-DCPD had more organized new bone and much less fibrous tissue at the defect margins. The new bone was formed on the surface of the degraded ceramic debris within the bone defect area. P-DCPD represented a promising drug-eluting BGS for repair of critical bone defects.

The role of integrin αvß3 in biphasic calcium phosphate ceramics mediated M2 Macrophage polarization and the resultant osteoinduction.

Calcium phosphate ceramics-based biomaterials were reported to have good biocompatibility and osteoinductivity and have been widely applied for bone defect repair and regeneration. However, the mechanism of their osteoinductivity is still unclear. In our study, we established an ectopic bone formation in vivo model and an in vitro macrophage cell co-culture system with calcium phosphate ceramics to investigate the effect of biphasic calcium phosphate on osteogenesis via regulating macrophage M1/M2 polarization. Our micro-CT data suggested that biphasic calcium phosphate had significant osteoinductivity, and the fluorescence co-localization detection found increased F4/80+/integrin αvß3+ macrophages surrounding the biphasic calcium phosphate scaffolds. Besides, our study also revealed that biphasic calcium phosphate promoted M2 polarization of macrophages via upregulating integrin αvß3 expression compared to tricalcium phosphate, and the increased M2 macrophages could subsequently augment the osteogenic differentiation of MSCs in a TGFß mediated manner. In conclusion, we demonstrated that macrophages subjected to biphasic calcium phosphate could polarize toward M2 phenotype via triggering integrin αvß3 and secrete TGFß to increase the osteogenesis of MSCs, which subsequently enhances bone regeneration.

Effects of glass-ceramic produced by the sol-gel route in macrophages recruitment and polarization into bone tissue regeneration.

Effective bone substitute biomaterials remain an important challenge in patients with large bone defects. Glass ceramics produced by different synthesis routes may result in changes in the material physicochemical properties and consequently affect the success or failure of the bone healing response. To investigate the differences in the orchestration of the inflammatory and healing process in bone grafting and repair using different glass-ceramic routes production. Thirty male Wistar rats underwent surgical unilateral parietal defects filled with silicate glass-ceramic produced by distinct routes: BS - particulate glass-ceramic produced via the fusion/solidification route, and BG - particulate glass-ceramic produced via the sol-gel route. After 7, 14, and 21 days from biomaterial grafting, parietal bones were removed to be analyzed under H&E and Massons' Trichome staining, and immunohistochemistry for CD206, iNOS, and TGF-ß. Our findings demonstrated that the density of lymphocytes and plasma cells was significantly higher in the BS group at 45, and 7 days compared to the BG group, respectively. Furthermore, a significant increase of foreign body giant cells (FBGCs) in the BG group at day 7, compared to BS was found, demonstrating early efficient recruitment of FBGCs against sol-gel-derived glass-ceramic particulate (BS group). According to macrophage profiles, CD206+ macrophages enhanced at the final periods of both groups, being significantly higher at 45 days of BS compared to the BG group. On the other hand, the density of transformation growth factor beta (TGF-ß) positive cells on 21 days were the highest in BG, and the lowest in the BS group, demonstrating a differential synergy among groups. Noteworthy, TGF-ß+ cells were significantly higher at 21 days of BG compared to the BS group. Glass-ceramic biomaterials can act differently in the biological process of bone remodeling due to their route production, being the sol-gel route more efficient to activate M2 macrophages and specific FBGCs compared to the traditional route. Altogether, these features lead to a better understanding of the effectiveness of inflammatory response for biomaterial degradation and provide new insights for further preclinical and clinical studies involved in bone healing.

Decellularized Bone Matrix/45S5 Bioactive Glass Biocomposite Hydrogel-Based Constructs with Angiogenic and Osteogenic Properties: Ex Ovo and Ex Vivo Evaluations.

Decellularized extracellular matrix is often used to create an in vivo-like environment that supports cell growth and proliferation, as it reflects the micro/macrostructure and molecular composition of tissues. On the other hand, bioactive glasses (BG) are surface-reactive glass-ceramics that can convert to hydroxyapatite in vivo and promote new bone formation. This study is designed to evaluate the key properties of a novel angiogenic and osteogenic biocomposite graft made of bovine decellularized bone matrix (DBM) hydrogel and 45S5 BG microparticles (10 and 20 wt%) to combine the existing superior properties of both biomaterial classes. Morphological, physicochemical, mechanical, and thermal characterizations of DBM and DBM/BG composite hydrogels are performed. Their in vitro biocompatibility is confirmed by cytotoxicity and hemocompatibility analyses. Ex vivo chick embryo aortic arch and ex ovo chick chorioallantoic membrane (CAM) assays reveal that the present pro-angiogenic property of DBM hydrogels is enhanced by the incorporation of BG. Histochemical stainings (Alcian blue and Alizarin red) and digital image analysis of ossification on hind limbs of embryos used in the CAM model reveal the osteogenic potential of biomaterials. The findings support the notion that the developed DBM/BG composite hydrogel constructs have the potential to be a suitable graft for bone repair.

Nano-/micro-scaled hydroxyapatite ceramic construction and the regulation of immune-associated osteogenic differentiation.

Hydroxyapatite (HA) bioceramic is a promising substitute for bone defects, and the surface properties are major factors that influence bioactivity and osteoinductivity. In this study, two kinds of HA bioceramics with nanoscale (n-HA) and microscale (m-HA) surface topography were designed to mimic the natural bone, thus enhancing the stimulation of osteogenic differentiation and revealing the potential mechanism. Compared to m-HA, n-HA owned a larger surface roughness, a stronger wettability, and reduced hardness and indentation modulus. Based on these properties, n-HA could maintain the conformation of vitronectin better than m-HA, which may contribute to higher cellular activities and a stronger promotion of osteogenic differentiation of mesenchymal stem cells (MSCs). Further RNA sequencing analysis compared the molecular expression between n-HA and m-HA. Six hundred twenty-seven differentially expressed genes were identified in MSCs, and 17 upregulated genes and 610 downregulated genes were included when n-HA compared to m-HA. The GO cluster analysis and enriched Kyoto encyclopedia of genes and genome signaling pathways revealed a close correlation with the immune process in both upregulated (chemokine signaling pathway and cytokine-cytokine receptor interaction) and downregulated pathways (osteoclasts differentiation). It suggested that the nanoscale surface topography of HA enhanced the osteoinductivity of MSCs and could not be separated from its regulation of immune function and the retention of adsorbed protein conformation.

Evaluation of In Vivo Biocompatibility in Preclinical Studies of a Finger Implant Medical Device Correlated with Mechanical Properties and Microstructure.

The aim of the experiment was to evaluate the biocompatibility of four 3D-printed biomaterials planned for use in the surgical treatment of finger amputees: Ti-6Al-4 V (Ti64), ZrO2-Al2O3 ceramic material (ATZ20), and osteoconductive (anodized Ti64) and antibacterial (Hydroxyapatite, HAp) coatings that adhere well to materials dedicated to finger bone implants. The work concerns the correlation of mechanical, microstructural, and biological properties of dedicated materials. Biological tests consisted of determining the overall cytotoxicity of the organism on the basis of in vivo tests carried out in accordance with the ISO 10993-6 and ISO 10993-11 standards. Clinical observations followed by diagnostic examinations, histopathological evaluation, and biochemical characterization showed no significant differences between control and tested groups of animals. The wound healed without complication, and no pathological effects were found. The wear test showed the fragility of the hydroxyapatite thin layer and the mechanical stability of the zirconia-based ceramic substrate. Electron microscopy observations revealed the layered structure of tested substrates and coatings.

Calcium phosphate ceramics combined with rhBMP6 within autologous blood coagulum promote posterolateral lumbar fusion in sheep.

Posterolateral spinal fusion (PLF) is a procedure used for the treatment of degenerative spine disease. In this study we evaluated Osteogrow-C, a novel osteoinductive device comprised of recombinant human Bone morphogenetic protein 6 (rhBMP6) dispersed in autologous blood coagulum with synthetic ceramic particles, in the sheep PLF model. Osteogrow-C implants containing 74-420 or 1000-1700 µm ceramic particles (TCP/HA 80/20) were implanted between L4-L5 transverse processes in sheep (Ovis Aries, Merinolaandschaf breed). In the first experiment (n = 9 sheep; rhBMP6 dose 800 µg) the follow-up period was 27 weeks while in the second experiment (n = 12 sheep; rhBMP6 dose 500 µg) spinal fusion was assessed by in vivo CT after 9 weeks and at the end of the experiment after 14 (n = 6 sheep) and 40 (n = 6 sheep) weeks. Methods of evaluation included microCT, histological analyses and biomechanical testing. Osteogrow-C implants containing both 74-420 and 1000-1700 µm ceramic particles induced radiographic solid fusion 9 weeks following implantation. Ex-vivo microCT and histological analyses revealed complete osseointegration of newly formed bone with adjacent transverse processes. Biomechanical testing confirmed that fusion between transverse processes was complete and successful. Osteogrow-C implants induced spinal fusion in sheep PLF model and therefore represent a novel therapeutic solution for patients with degenerative disc disease.

Biocompatibility and antibacterial activity of MgO/Ca3(PO4)2 composite ceramic scaffold based on vat photopolymerization technology.

Recent advancements in medical technology and increased interdisciplinary research have facilitated the development of the field of medical engineering. Specifically, in bone repair, researchers and potential users have placed greater demands on orthopedic implants regarding their biocompatibility, degradation rates, antibacterial properties, and other aspects. In response, our team developed composite ceramic samples using degradable materials calcium phosphate and magnesium oxide through the vat photopolymerization (VP) technique. The calcium phosphate content in each sample was, respectively, 80 %, 60 %, 40 %, and 20 %. To explore the relationship between the biocompatibility, antibacterial activity, and MgO content of the samples, we cultured them with osteoblasts (MC3T3-E1), Escherichia coli (a gram-negative bacterium), and Staphylococcus aureus (a gram-positive bacterium). Our results demonstrate that as the MgO content of the sample increases, its biocompatibility improves but its antibacterial activity decreases. Regarding the composite material samples, the 20 % calcium phosphate content group exhibited the best biocompatibility. However, after 0.5 h of co-cultivation, the antibacterial rates of all groups except the 20 % calcium phosphate content group co-cultured with S. aureus exceed 80 %. Furthermore, after 3 h, the antibacterial rates against E. coli exceed 95 % in all groups. This is because higher levels of MgO correspond to lower pH values and Mg2+ concentrations in the cell and bacterial culture solutions, which ultimately promote cell and bacterial proliferation. This elevates the biocompatibility of the samples, albeit at the expense of their antimicrobial efficacy. Thus, modulating the MgO content in the composite ceramic samples provides a strategy to develop gradient composite scaffolds for better control of their biocompatibility and antibacterial performance during different stages of bone regeneration.

Bioactive Glass Modified with Zirconium Incorporation for Dental Implant Applications: Fabrication, Structural, Electrical, and Biological Analysis.

Implantology is crucial for restoring aesthetics and masticatory function in oral rehabilitation. Despite its advantages, certain issues, such as bacterial infection, may still arise that hinder osseointegration and result in implant rejection. This work aims to address these challenges by developing a biomaterial for dental implant coating based on 45S5 Bioglass® modified by zirconium insertion. The structural characterization of the glasses, by XRD, showed that the introduction of zirconium in the Bioglass network at a concentration higher than 2 mol% promotes phase separation, with crystal phase formation. Impedance spectroscopy was used, in the frequency range of 102-106 Hz and the temperature range of 200-400 K, to investigate the electrical properties of these Bioglasses, due to their ability to store electrical charges and therefore enhance the osseointegration capacity. The electrical study showed that the presence of crystal phases, in the glass ceramic with 8 mol% of zirconium, led to a significant increase in conductivity. In terms of biological properties, the Bioglasses exhibited an antibacterial effect against Gram-positive and Gram-negative bacteria and did not show cytotoxicity for the Saos-2 cell line at extract concentrations up to 25 mg/mL. Furthermore, the results of the bioactivity test revealed that within 24 h, a CaP-rich layer began to form on the surface of all the samples. According to our results, the incorporation of 2 mol% of ZrO2 into the Bioglass significantly improves its potential as a coating material for dental implants, enhancing both its antibacterial and osteointegration properties.

Optimization of the Composition of Mesoporous Polymer-Ceramic Nanocomposite Granules for Bone Regeneration.

Difficult-to-treat bone damage resulting from metabolic bone diseases, mechanical injuries, or tumor resection requires support in the form of biomaterials. The aim of this research was to optimize the concentration of individual components of polymer-ceramic nanocomposite granules (nanofilled polymer composites) for application in orthopedics and maxillofacial surgery to fill small bone defects and stimulate the regeneration process. Two types of granules were made using nanohydroxyapatite (nanoHA) and chitosan-based matrix (agarose/chitosan or curdlan/chitosan), which served as binder for ceramic nanopowder. Different concentrations of the components (nanoHA and curdlan), foaming agent (sodium bicarbonate-NaHCO3), and chitosan solvent (acetic acid-CH3COOH) were tested during the production process. Agarose and chitosan concentrations were fixed to be 5% w/v and 2% w/v, respectively, based on our previous research. Subsequently, the produced granules were subjected to cytotoxicity testing (indirect and direct contact methods), microhardness testing (Young's modulus evaluation), and microstructure analysis (porosity, specific surface area, and surface roughness) in order to identify the biomaterial with the most favorable properties. The results demonstrated only slight differences among the resultant granules with respect to their microstructural, mechanical, and biological properties. All variants of the biomaterials were non-toxic to a mouse preosteoblast cell line (MC3T3-E1), supported cell growth on their surface, had high porosity (46-51%), and showed relatively high specific surface area (25-33 m2/g) and Young's modulus values (2-10 GPa). Apart from biomaterials containing 8% w/v curdlan, all samples were predominantly characterized by mesoporosity. Nevertheless, materials with the greatest biomedical potential were obtained using 5% w/v agarose, 2% w/v chitosan, and 50% or 70% w/v nanoHA when the chitosan solvent/foaming agent ratio was equal to 2:2. In the case of the granules containing curdlan/chitosan matrix, the most optimal composition was as follows: 2% w/v chitosan, 4% w/v curdlan, and 30% w/v nanoHA. The obtained test results indicate that both manufactured types of granules are promising implantable biomaterials for filling small bone defects that can be used in maxillofacial surgery.

Fracture strength and bonding interface morphology of CAD/CAM-fabricated ceramic laminate veneers on bleached enamel treated with two different antioxidants.

This study aimed to investigate the effects of two antioxidants and their application time on the fracture strength of computer-aided design and computer-aided manufacturing (CAD/CAM)-fabricated ceramic laminate veneers to bleached enamel, as well as their effects on the bonding interface micromorphology. Eight groups were set: Group NC (without bleaching and antioxidant treatment); Group NA (bleaching without antioxidant treatment); Group SA30, SA60, SA120 and Group PAC30, PAC60, PAC120 (bleaching and treating with sodium ascorbate or proanthocyanidins for 30, 60, and 120 min, respectively). After cementation of veneers, fracture strength values and failure modes were analyzed. The bonding interface morphology was observed by confocal laser scanning microscopy. The fracture strength was impaired when cementation procedure was performed immediately after bleaching. This reduction in fracture strength was reestablished with antioxidant treatment, and an extended treatment time contributed to better improvement. The resin tags at the bonding interfaces of the bleached enamel were impaired. Antioxidant treatments were able to reverse this unfavorable trend.

Enhanced bioactivity and hydrothermal aging resistance of Y-TZP ceramics for dental implant.

Although yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) ceramics have been widely used as restorative materials due to their high mechanical strength, unique esthetic effect, and good biocompatibility, their general application to implant materials is still limited by their biological inertness and hydrothermal aging phenomenon. Existing studies have attempted to investigate how to enhance the bioactivity or hydrothermal aging resistance of Y-TZP. Still, more studies need to be done on the modification that combines these two aspects. In this study, Y-TZP was prepared by 77S bioactive glass (BG) sol and akermanite (AKT) sol infiltration and microwave sintering, which provided Y-TZP with high bioactivity while maintaining resistance to hydrothermal aging. Results of phase composition evaluation, microstructural characteristics, and mechanical property tests showed that modified Y-TZP specimens exhibited little or no tetragonal-to-monoclinic (t → m) transformation and maintained relatively high mechanical properties after accelerated hydrothermal aging treatment. The in vitro biological behaviors showed that the introduction of 77S BG and AKT significantly promoted cell adhesion, spreading, viability, and proliferation on the surface of modified Y-TZP ceramics. Therefore, this modification could effectively enhance the bioactivity and hydrothermal aging resistance of Y-TZP ceramics for its application in dental implant materials.

Surface Multifunctionalization of Inert Ceramic Implants by Calcium Phosphate Biomimetic Coating Doped with Nanoparticles Encapsulating Antibiotics.

Aseptic loosening and periprosthetic infections are complications that can occur at the interface between inert ceramic implants and natural body tissues. Therefore, the need for novel materials with antibacterial properties to prevent implant-related infection is evident. This study proposes multifunctionalizing the inert ceramic implant surface by biomimetic calcium phosphate (CaP) coating decorated with antibiotic-loaded nanoparticles for bioactivity enhancement and antibacterial effect. This study aimed to coat zirconium dioxide (ZrO2) substrates with a bioactive CaP-layer containing drug-loaded degradable polymer nanoparticles (NPs). The NPs were loaded with two antibiotics, gentamicin or bacitracin. The immobilization of NPs happened by two deposition methods: coprecipitation and drop-casting. X-ray diffraction (XRD), scanning electron microscopy (SEM), and cross-section analyses were used to characterize the coatings. MG-63 osteoblast-like cells and human mesenchymal stem cells (hMSC) were chosen for in vitro tests. Antibacterial activity was assessed with S. aureus and E. coli. The coprecipitation method allowed for a favorable homogeneous distribution of the NPs within the CaP coating. The CaP coating was constituted of hydroxyapatite and octacalcium phosphate; its thickness was 3.8 ± 1 µm with cavities of around 1 µm suitable for hosting NPs with a size of 200 nm. Antibiotics were released from the coatings in a controlled manner for 1 month. The cell culture study has confirmed the excellent behavior of the coprecipitated coating, showing cytocompatibility and a homogeneous distribution of the cells on the coated surfaces. The increase in alkaline phosphatase activity showed osteogenic differentiation. The materials were found to inhibit the growth of bacteria. Newly developed coatings with antibacterial and bioactive properties are promising candidates to prevent peri-implant infectious bone diseases.

Improving the osseointegration and soft tissue sealing of zirconia ceramics by the incorporation of akermanite via sol infiltration for dental implants.

Zirconia ceramics are promising dental implant materials due to their high-grade biocompatibility, high mechanical strength, and distinctive aesthetic appearance. Nevertheless, zirconia ceramics are bio-inert with a lack of osseointegration and soft tissue sealing, which limits dental implant applications. As such, the fabrication of zirconia ceramics with high mechanical strength, excellent osseointegration and soft tissue sealing performance remains a great challenge in the dental restoration field. In this article, a novel zirconia ceramic with akermanite (AKT) modification by the negative pressure infiltration method is presented. The effects of AKT sol infiltration at different times on the morphology, phase composition, mechanical properties, bioactivity, osseointegration and soft tissue sealing of the modified zirconia ceramics have been systematically investigated. The modified zirconia ceramics feature excellent mechanical properties and significantly improved surface roughness, hydrophilia, and apatite mineralization ability as compared with unmodified zirconia ceramics. Furthermore, cell-culture experiment results indicated that the surface modification of zirconia ceramics could promote adhesion, spreading, migration, proliferation and osteogenic differentiation of mouse bone marrow stromal stem cells (mBMSCs), as well as the early adhesion, spreading, proliferation and fibroblast differentiation of human gingival fibroblasts (HGFs) in vitro. The prepared bioactive zirconia distinctively enhanced the alkaline phosphate (ALP) activity, osteogenesis-related gene expression of mBMSCs and fibroblast-related-gene expression of HGFs. The in vivo evaluation confirmed that 15-TZP ceramics could promote bone-implant osseointegration to the greatest extent as compared with pure zirconia ceramics. To conclude, our research has shown that AKT-modified zirconia ceramics can achieve bone integration and soft tissue sealing, indicating that they have a lot of potential for application as a novel dental implant material in the clinical setting.