Orthodontic resins loaded with niobium silicate particles: Impact of filler concentration on the physicochemical and biological properties.

OBJECTIVES: White spot lesions (WSL) are prevalent in patients using orthodontic appliances. The presence of ion-releasing compounds in the tooth-appliance interface may limit enamel demineralization to control WSL incidence. Thus, this study aims to evaluate the mineral formation on SiNb-containing experimental orthodontic resins and the influence of these fillers on the physicochemical and biological properties of developed materials. MATERIALS AND METHODS: The SiNb particles were synthesized via the sol-gel route and characterized by their molecular structure and morphology. Photopolymerizable orthodontic resins were produced with a 75 wt% Bis-GMA/25 wt% TEGDMA and 10 wt%, 20 wt%, or 30 wt% addition of SiNb. A control group was formulated without SiNb. These resins were tested for their degree of conversion, softening in solvent, cytotoxicity in fibroblasts, flexural strength, shear bond strength (SBS), and mineral deposition. RESULTS: The addition of 10 wt% of SiNb did not impair the conversion of monomers, cytotoxicity, and flexural strength. All groups with SiNb addition presented similar softening in solvent. The presence of these particles did not affect the bond strength between metallic brackets and enamel, with SBS values ranging from 16.41 to 18.66 MPa. The mineral deposition was observed for all groups. CONCLUSION: The use of niobium silicate as filler particles in resins may be a strategy for the adhesion of orthodontic appliances. The 10 wt% SiNb concentration resulted in a material with suitable physicochemical and biological properties while maintaining the bond strength to tooth enamel and promoting mineral deposition.

Synthesis of silver core-shell nanoparticles and their influence on an experimental resin endodontic sealer: An in vitro analysis.

AIM: To avoid root canal recontamination and endodontic treatment failure, endodontic sealers with antibacterial activity could be an alternative. Silver nanoparticles have antibacterial activity and this study aimed to synthesize Ag@SiO2 nanoparticles, incorporate them into an experimental endodontic resin sealer and evaluate their influence on physicochemical and biological properties. METHODOLOGY: Ag@SiO2 nanoparticles were produced using the sol-gel process, based on the Stöber method. The particles were characterized in terms of their chemical structure by Fourier transform-infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), UV-Vis spectral analysis, scanning electron microscopy, and transmission electron microscopy, where the particle morphology and diameter were analysed. A dual-cured experimental endodontic resin sealer was formulated using 70 wt% UDMA, 15 wt% GDMA, and 15 wt% BisEMA. The photoinitiators were added separately in two pastes. The Ag@SiO2 nanoparticles were incorporated into the endodontic sealer at the concentrations of 2.5 wt%, 5 wt%, and 10 wt%, and a control group without nanoparticles was also formulated. The endodontic sealers were evaluated for their flow, film thickness, degree of conversion, softening in solvent, radiopacity, cytotoxicity and antibacterial activity immediately and after 9 months in water storage. RESULTS: Silver was detected in the chemical characterization of Ag@SiO2 that presented a spheric regular shape and average 683.51 nm ± 93.58 diameter. Sealers presented adequate flow and film thickness while radiopacity values were below the ones required by ISO 6876. All groups underwent softening after immersion in a solvent. The 10 wt% groups showed a higher loss of subsurface hardness (∆KHN%). No reduction in cell viability was observed. Enterococcus faecalis viability in biofilm was reduced in 10 wt% groups after 24 h and 9 months. CONCLUSION: The addition of 10 wt% Ag@SiO2 reduced E. faecalis viability at immediate and longitudinal analysis while maintaining the physicochemical properties of developed sealers.

Non-thermal plasma for surface treatment of inorganic fillers added to resin-based cements.

OBJECTIVES: This study aims to evaluate the effect of non-thermal plasma (NTP) surface treatment in two composite inorganic fillers and evaluate their impact on the chemical-mechanical properties and bond strength ability of experimental resin cements. MATERIALS AND METHODS: Ytterbium fluoride (YF) and barium silicate glass (BS) were characterized and submitted to different surface treatments: non-thermal plasma (NTP); non-thermal plasma and 3-(trimethoxysilyl) propyl methacrylate silanization; and 3-(trimethoxysilyl) propyl methacrylate silanization. Untreated fillers were used as a control. The fillers were incorporated at 65wt% concentration into light-cured experimental resin cements (50wt% BisGMA; 25wt% UDMA; 25wt% TEGDMA; 1mol% CQ). The degree of conversion, the flexural strength, and the microshear bond strength (µSBS) were evaluated to characterize developed composites. RESULTS: YF and BS were successfully cleaned with NTP treatment. Nor NTP neither the silanization affected the degree of conversion of resin cements. The NTP predicted an increase in YF-containing resin cements flexural strength, reducing the storage impact in these materials. NTP treatment did not affect the µSBS when applied to YF, while silanization was effective for BS-containing materials. CONCLUSION: NTP treatment of inorganic particles was possible and was shown to reduce the amount of organic contamination of the particle surface. YF surface treatment with NTP can be an alternative to improve the organic/inorganic interaction in resin composites to obtain materials with better mechanical properties. CLINICAL RELEVANCE: Surface cleaning with NTP may be an alternative for particle surface cleaning to enhance organic-inorganic interaction in dental composites resulting in improved mechanical strength of experimental resin cements.

Alkyl trimethyl ammonium bromide for the formulation of antibacterial orthodontic resins.

OBJECTIVES: This study aimed at formulating antibacterial orthodontic resins containing alkyl trimethyl ammonium bromide (ATAB) and evaluating their physicochemical and biological properties. MATERIALS AND METHODS: The chemical composition and microstructure of ATAB was characterized through FTIR and SEM, respectively. Experimental orthodontic BisGMA/TEGDMA-based resins were formulated, and the ATAB filler was incorporated at 1wt%, 5wt%, and 10wt%, along with colloidal silica (5wt%). The degree of conversion, softening in solvent, and flexural strength of the experimental resins were analyzed. Biological properties were also assessed through cytotoxicity and antibacterial analyses. RESULTS: The incorporation of ATAB, due to the presence of ⎯N+(CH3)3 alkyl groups, had no adverse effect on the degree of conversion of the resins (p > 0.05). The %ΔKHN values at 5wt% and 10wt% were comparable to those of the control group, while the flexural strength was reduced at all concentrations of ATAB. The viability of the gingival fibroblast was reduced with the addition of ATAB (p < 0.05). The viability of biofilm and planktonic bacteria was reduced when ATAB was incorporated at 5wt% and 10wt%. CONCLUSIONS: The addition of ATAB at 5wt% resulted suitable for the formulation of orthodontic resins with the ability to control the biofilm formation and planktonic activity of S.mutans, without jeopardizing some specific physicochemical properties. CLINICAL RELEVANCE: White spot lesions in orthodontic patients may be controlled by preventive treatments. Non-patient-dependent strategies, such as the use of orthodontic resins containing ATAB, may avoid accumulation of bacteria, especially in those areas surrounding orthodontic appliances.

Biological Activity of Copaiba in Damage to the Alveolar Bone in a Model of Periodontitis Induced in Rats.

Several studies have investigated the effects of natural products in the treatment of diseases. Traditional Amazonian populations commonly use copaiba due to its well-known anti-inflammatory, antibacterial, and healing properties. In this study, we aimed to investigate the effects of systemic administration of copaiba oleoresin (Copaifera reticulata Ducke) on ligature-induced periodontitis in rats. To do so, 21 adult rats were divided into three groups (n = 7 each): a control group, ligature-induced periodontitis group, and ligature-induced periodontitis group treated with copaiba oleoresin (200 mg/kg/day). The ligature remained from day 0 to 14, and the copaiba oleoresin was administered via oral gavage during the last seven days. On day 14, the animals were euthanized, and mandibles were collected for histopathological evaluation and microcomputed tomography analysis. Our data showed that the administration of copaiba considerably reduced the inflammatory profile. Moreover, copaiba oleoresin limited alveolar bone loss, increased trabecular thickness and bone-to-tissue volume ratio, and decreased the number of trabeculae compared with those of the untreated experimental periodontitis group. Our findings provide pioneering evidence that supports the potential of copaiba oleoresin in reducing periodontitis-induced alveolar bone damage in rats.

Binge-Like Exposure During Adolescence Induces Detrimental Effects in Alveolar Bone that Persist in Adulthood.

BACKGROUND: Alcohol (EtOH) intake during adolescence has become an important public health issue. Although the detrimental effects of EtOH intake on the musculoskeletal system are well known, only a few studies have investigated its impact on the stomatognathic system of adolescents. This study aimed to investigate the effect of EtOH binge drinking on the alveolar bone and the long-term consequences after abstinence. METHODS: Adolescent female Wistar rats (35 days old) were exposed to 4 cycles of EtOH binge drinking (3 g/kg/d; 3 days On-4 days Off) or distilled water (control group). Alveolar bone micromorphology and vertical bone distance were evaluated at 1, 30, and 60 days after that last EtOH intake through X-ray computed microtomography. The mineral:matrix ratio was assessed through Raman spectroscopy. RESULTS: A decrease in both trabecular thickness and volume ratio, and an increase in trabecular separation were observed at the 1-day evaluation (immediate withdrawal). After 30 and 60 days, the alveolar bone parameters were found similar to control, except for the mineral:matrix ratio in the long-term abstinence. CONCLUSIONS: EtOH binge drinking during adolescence results in alveolar bone damage that may persist in adulthood, even after abstinence.

Embedding cells within nanoscale, rapidly mineralizing hydrogels: A new paradigm to engineer cell-laden bone-like tissue.

Bone mineralization is a highly specific and dynamic nanoscale process that has been studied extensively from a structural, chemical, and biological standpoint. Bone tissue, therefore, may be defined by the interplay of its intricately mineralized matrix and the cells that regulate its biological function. However, the far majority of engineered bone model systems and bone replacement materials have been unable to replicate this key characteristic of bone tissue; that is, the ability of cells to be gradually and rapidly embedded in a three-dimensional (3D) heavily calcified matrix material. Here we review the characteristics that define the bone matrix from a nanostructural perspective. We then revisit the benefits and challenges of existing model systems and engineered bone replacement materials, and discuss recent efforts to replicate the biological, cellular, mechanical, and materials characteristics of bone tissue on the nano- to microscale. We pay particular attention to a recently proposed method developed by our group, which seeks to replicate key aspects of the entrapment of bone cells within a mineralized matrix with precisions down to the level of individual nano-crystallites, inclusive of the bone vasculature, and osteogenic differentiation process. In summary, this paper discusses existing and emerging evidence pointing towards future developments bridging the gap between the fields of biomineralization, structural biology, stem cells, and tissue engineering, which we believe will hold the key to engineer truly functional bone-like tissue in the laboratory.

Quaternary ammonium compound as antimicrobial agent in resin-based sealants.

OBJECTIVES: The aim of this study was to evaluate the influence of [2-(methacryloyloxy)ethyl] trimethylammonium chloride (METAC) in the physico-chemical properties, antibacterial activity and cytotoxicity of an experimental resin-based sealant. MATERIALS AND METHODS: An experimental resin-based sealant was formulated with dimethacrylates and a photoinitiator system. METAC was added at 2.5 wt.% (G2.5%) and 5 wt.% (G5%) into the experimental resin-based sealant, and one group remained without METAC as control (GCTRL). The resin-based sealants were analysed for polymerization behaviour and degree of conversion (DC), Knoop hardness (KHN) and softening in solvent (ΔKHN), ultimate tensile strength (UTS), contact angle, surface free energy (SFE), immediate and long-term micro-shear bond strength (µ-SBS) and antibacterial activity and cytotoxicity against human keratinocytes. RESULTS: The experimental resin-based sealants presented different polymerization behaviours without significant differences in the DC (p > 0.05). There was no significant difference for initial KHN (p > 0.05). The ΔKHN ranged from 51.62 (±3.70)% to 62.40 (±4.14)%, with higher values for G5% (p < 0.05). G2.5% and G5% had decreased µ-SBS between immediate and long-term tests (p < 0.05) without significant differences among groups in the immediate and long-term analyses (p > 0.05). There were no significant differences for UTS, contact angle and SFE among groups (p > 0.05). G2.5% and G5% presented immediate and long-term antibacterial activity (p < 0.05) without cytotoxicity compared to GCTRL (p > 0.05). CONCLUSION: The addition of METAC provided antibacterial activity to the experimental resin-based sealant. CLINICAL RELEVANCE: METAC is an effective quaternary ammonium compound as an antibacterial agent for resin-based sealants without cytotoxic effects against human keratinocytes.

Blood Oxidative Stress Modulates Alveolar Bone Loss in Chronically Stressed Rats.

We aimed to investigate the effects of chronic stress (CS) on experimental periodontitis (EP) in rats. For this, 28 Wistar rats were divided into four groups: control, ligature-induced experimental periodontitis (EP), chronic stress (CS; by physical restraint model) and CS+EP (association of chronic stress and ligature-induced periodontitis). The experimental period lasted 30 days, including exposure to CS every day and ligature was performed on the 15th experimental day. After 30 days, the animals were submitted to the behavioral test of the elevated plus maze (EPM). Next, rats were euthanized for blood and mandible collection in order to evaluate the oxidative biochemistry (by nitric oxide (NO), reduced-glutathione activity (GSH), and thiobarbituric acid reactive substance levels (TBARS)) and alveolar bone characterization (by morphometric, micro-CT, and immunohistochemistry), respectively. The behavioral parameters evaluated in EPM indicated higher anxiogenic activity in the CS and CS+EP, groups, which is a behavioral reflex of CS. The results showed that CS was able to change the blood oxidative biochemistry in CS and CS+EP groups, decrease GSH activity in the blood, and increase the NO and TBARS concentrations. Thus, CS induces oxidative blood imbalance, which can potentialize or generate morphological, structural, and metabolic damages to the alveolar bone.

Physical and mechanical properties of dual functional cements-an in vitro study.

OBJECTIVES: The aim of this study was to evaluate the physical and mechanical properties of different dual functional cements. MATERIALS AND METHODS: Three dual functional cements (Allcem Core (FGM), Rebilda DC (VOCO), and LuxaCore Z (DMG)), a luting resin cement (Rely X ARC (3 M ESPE)), and a Core Buildup composite resin GrandioSo (VOCO) were used. Flexural strength (n = 10) and film thickness (n = 6) were evaluated according to ISO 4049:2009. Flow (n = 6) was evaluated according to ISO 6876:2001. Degree of conversion (DC) was assessed immediately and 24 h after polymerization (n = 5). For resistance to dislodgment (RD) analysis, bovine teeth were prepared to receive fiber glass posts, and a push-out test (n = 12) was used. RESULTS: Luxacore Z presented lower flexural strength when compared to GrandioSo (p < 0.001). No statistical difference was found between cements for film thickness (p = 0.66). Reduced flow values were found for Allcem Core (p = 0.006). No statistical difference was found for immediate DC for different cements (p > 0.05). After 24 h, DC increased for all groups, except for Luxacore Z (p = 0.054). The RD did not differ from the control Rely X ARC, regardless of the root third (p > 0.05). Luxacore Z showed lower mean values in the apical third compared to the coronal third (p = 0.046). CONCLUSIONS: The dual functional cements (Allcem Core and Rebilda DC) possessed similar physical and mechanical properties of luting resin cement (RelyX ARC) and Core Buildup composite resin (GrandioSo). Hence, they could be used for one-stage post and core buildup restorations. CLINICAL RELEVANCE: The dual functional cements could be used for one-stage post and core buildup restorations since they possess similar physical and mechanical properties of luting resin cements and Core Buildup composite resin.

The influence of filler load in 3D printing resin-based composites.

OBJECTIVE: To evaluate the influence of the barium glass (BG) filler in 3D printing resin-based composites for restorative structures. METHODS: Experimental 3D printing resin-based composites were formulated with UDMA 70%wt, Bis-EMA 20%wt, and TEGDMA 10%wt. Photoinitiators TPO and DFI (2%wt) were used. BG was incorporated at 40%wt and 50%wt. 0%wt BG was used as negative control and the VarseoSmile Crownplus (Bego) was used as a commercial control. Specimens were printed using a 3D printer. Subsequently, specimens were washed and submitted to post-curing with 405 nm at 60ºC for 2 × 20 min at FormCure (FormLabs). 3D printing resin-based composites were evaluated by flexural strength, degree of conversion, softening in solvent, radiopacity, and cytotoxicity against gingival fibroblasts. Data were statistically analyzed using one-way ANOVA (α = 0.05). RESULTS: No significant differences in flexural strength were showed between BG40% (90.5 ± 5,4 MPa), BG50% (102.0 ± 11.7 MPa) and VA (105.2 ± 11.7 MPa). Addition of 40% and 50% of BG showed no influence in the degree of conversion compared to VA (p > 0.05). All groups showed softening in solvent after immersion in ethanol (p < 0.05). All groups showed more than 1mmAl of radiopacity. BG50% showed significantly higher radiopacity (2.8 ± 0.3 mmAl) than other groups (p < 0,05). Cytotoxicity evaluation showed gingival cell viability higher than 80% for all groups. SIGNIFICANCE: Addition of up to 50%wt of barium glass in experimental 3D printing resin-based composites showed promising results for long-term restorative structures.

In vitro development and optimization of cell-laden injectable bioprinted gelatin methacryloyl (GelMA) microgels mineralized on the nanoscale.

Bone defects may occur in different sizes and shapes due to trauma, infections, and cancer resection. Autografts are still considered the primary treatment choice for bone regeneration. However, they are hard to source and often create donor-site morbidity. Injectable microgels have attracted much attention in tissue engineering and regenerative medicine due to their ability to replace inert implants with a minimally invasive delivery. Here, we developed novel cell-laden bioprinted gelatin methacrylate (GelMA) injectable microgels, with controllable shapes and sizes that can be controllably mineralized on the nanoscale, while stimulating the response of cells embedded within the matrix. The injectable microgels were mineralized using a calcium and phosphate-rich medium that resulted in nanoscale crystalline hydroxyapatite deposition and increased stiffness within the crosslinked matrix of bioprinted GelMA microparticles. Next, we studied the effect of mineralization in osteocytes, a key bone homeostasis regulator. Viability stains showed that osteocytes were maintained at 98 % viability after mineralization with elevated expression of sclerostin in mineralized compared to non-mineralized microgels, showing that mineralization can effectively enhances osteocyte maturation. Based on our findings, bioprinted mineralized GelMA microgels appear to be an efficient material to approximate the bone microarchitecture and composition with desirable control of sample injectability and polymerization. These bone-like bioprinted mineralized biomaterials are exciting platforms for potential minimally invasive translational methods in bone regenerative therapies.

Physical training mitigates alveolar bone and blood enzymatic antioxidants defense impairment induced by binge ethanol consumption in rats.

We aimed to investigate the effectiveness of physical training as a protective strategy to mitigate alveolar bone damage and blood antioxidant defense caused by ethanol (EtOH) consumption in a binge-drinking pattern. Male Wistar rats aged approximately 90 days were divided into four groups: control, training, EtOH, and training + EtOH. The physical training protocol was conducted on a treadmill for four consecutive weeks, while the animals in the EtOH group were administered EtOH via orogastric gavage for three consecutive days each week, following the binge drink pattern. After the training period, blood and mandibles were collected for plasma oxidative biochemistry analysis, and the alveolar bone was subjected to physicochemical composition analysis, tissue evaluation, and microtomography evaluation. Our results showed that EtOH induced oxidative stress and physical exercise promoted the recovery of antioxidant action. Physical training minimized the damage to the mineral/matrix composition of the alveolar bone due to EtOH consumption and increased the density of osteocytes in the trained group treated with EtOH than in those exposed only to EtOH. Furthermore, physical training reduced damage to the alveolar bone caused by EtOH consumption. Our findings suggest that physical training can serve as an effective strategy to reduce systemic enzymatic oxidative response damage and alleviate alveolar bone damage resulting from alcohol consumption. Further investigations are warranted to elucidate the underlying mechanisms and explore, in addition to physical training, the potential effects of other activities with varying intensities on managing alcohol-induced bone damage.

Use of Local Melatonin with Xenogeneic Bone Graft to Treat Critical-Size Bone Defects in Rats with Osteoporosis: A Randomized Study.

The aim of this study was to evaluate the effect of local administration of melatonin (MLT) on molecular biomarkers and calvaria bone critical defects in female rats with or without osteoporosis, associated or not with a xenogeneic biomaterial. Forty-eight female rats were randomly divided into two groups: (O) ovariectomized and (S) placebo groups. After 45 days of osteoporosis induction, two critical-size defects (5 mm diameter) were created on the calvaria. The groups were subdivided according to the following treatment: (C) Clot, MLT, MLT associated with Bio-Oss® (MLTBO), and Bio-Oss® (BO). After 45 days, the defect samples were collected and processed for microtomography, histomorphometry, and biomolecular analysis (Col-I, BMP-2, and OPN). All animals had one femur harvested to confirm the osteoporosis. Microtomography analysis demonstrated a bone mineral density reduction in the O group. Regarding bone healing, the S group presented greater filling of the defects than the O group; however, in the O group, the defects treated with MLT showed higher mineral filling than the other treatments. There was no difference between the treatments performed in the S group (p = 0.05). Otherwise, O-MLT had neoformed bone higher than in the other groups (p = 0.05). The groups that did not receive biomaterial demonstrated lower levels of Col-I secretion; S-MLT and S-MLTBO presented higher levels of OPN, while O-C presented statistically lower results (p < 0.05); O-BO showed greater BMP-2 secretion (p < 0.05). In the presence of ovariectomy-induced osteoporosis, MLT treatment increased the newly formed bone area, regulated the inflammatory response, and increased OPN expression.

Physical training attenuates systemic cytokine response and tissue damage triggered by apical periodontitis.

Apical periodontitis (AP) is a condition characterized by inflammatory and infectious components in the tooth canal. AP affects periradicular tissues and has systemic repercussions. Physical exercise is a structured activity that requires cardiorespiratory function, and can modulate the inflammatory profile in pathological conditions. As a result, this study aimed to determine the effects of aerobic physical training (PT) on the alveolar bone with and without AP, and its systemic inflammatory repercussions. AP was induced in the mandibular first molars, and PT was performed on a treadmill for five consecutive days over four weeks, with progressive increases in speed and activity time. Blood samples were collected to determine serum cytokine levels using immunoassays, and alveolar bone samples were collected for histopathological evaluation, lesion volume and microarchitecture assessment using computed microtomography. Animals with AP had increased pro-inflammatory cytokines levels compared to those without AP; however, these levels were attenuated or restored by PT. Compared to the AP group, the AP + PT group had a smaller lesion volume and greater preservation of the bone trabeculae in the remaining alveolar bone surrounding the lesion. In overall, PT minimized the severity of AP proving to be a valid strategy for individuals undergoing endodontic treatment.

Experimental Composite Resin with Myristyltrimethylammonium Bromide (MYTAB) and Alpha-Tricalcium Phosphate (α-TCP): Antibacterial and Remineralizing Effect.

The aim of this study was to develop an experimental composite resin with the addition of myristyltrimethylammonium bromide (MYTAB) and α -tricalcium phosphate (α-TCP) as an antibacterial and remineralizing material. Experimental composite resins composed of 75 wt% Bisphenol A-Glycidyl Methacrylate (BisGMA) and 25 wt% Triethylene Glycol Dimethacrylate (TEGDMA) were produced. Some 1 mol% Trimethyl benzoyl-diphenylphosphine oxide (TPO) was used as a photoinitiator, and butylated hydroxytoluene (BTH) was added as a polymerization inhibitor. Silica (1.5 wt%) and barium glass (65 wt%) particles were added as inorganic fillers. For remineralizing and antibacterial effect, α-TCP (10 wt%) and MYTAB (5 wt%) were incorporated into the resin matrix (α-TCP/MYTAB group). A group without the addition of α-TCP/MYTAB was used as a control. Resins were evaluated for their degree of conversion (n = 3) by Fourier Transform Infrared Spectroscopy (FTIR). The flexural strength (n = 5) was assessed based on ISO 4049:2019 requirements. Microhardness was assessed to calculate softening in solvent (n = 3) after ethanol immersion. The mineral deposition (n = 3) was evaluated after immersion in SBF, while cytotoxicity was tested with HaCaT cells (n = 5). Antimicrobial activity (n = 3) was analyzed against S. mutans. The degree of conversion was not influenced by the antibacterial and remineralizing compounds, and all groups reached values > 60%. The α-TCP/MYTAB addition promoted increased softening of polymers after immersion in ethanol and reduced their flexural strength and the viability of cells in vitro. A reduction in S. mutans viability was observed for the α-TCP/MYTAB group in biofilm formation and planktonic bacteria, with an antibacterial effect > 3log10 for the developed materials. Higher intensity of phosphate compounds on the sample's surface was detected in the α-TCP/MYTAB group. The addition of α-TCP and MYTAB promoted remineralizing and antibacterial effects on the developed resins and may be a strategy for bioactive composites.

Niobium-containing bioactive glasses modulate alkaline phosphatase activity during bone repair.

This study aimed to evaluate the pre-clinical behavior of niobium-containing bioactive glasses (BAGNb) by their ability to promote bone repair and regulate alkaline phosphatase (ALP) levels in an animal model. BAGNbs were produced as powders and as scaffolds and surgically implanted in the femur of male rats (Wistar lineage n = 10). Glasses without Nb (BAG) were produced and implanted as well. The Autogenous Bone (AB) was used as a control. After 15, 30, and 60 days of surgical implantation, blood serum samples were collected to quantify ALP activity, and femurs were removed to assess bone repair. Bone samples were histologically processed and stained with H&E to quantify the % new bone into defects. No postoperative complications were identified. Early-stage repair (15 days) resulted in increased ALP activity for all groups, with increased values ​​for powdered BAGNb. The maturation of the new bone led to a reduction in serum ALP levels. Histological sections showed the formation of immature bone tissue and vascularization with the progression of bone deposition to mature and functional tissue over time. BAG powder showed less new bone formation in 15 days, while the analysis at 30 and 60 days showed no difference between groups (p > .05). Niobium-containing bioactive glasses safely and successfully induced bone repair in vivo. The modulation of ALP activity may be a pathway to describe the ability of niobium-containing materials to contribute to new bone formation.

Controlled drug delivery from metronidazole-containing bioactive endodontic cements.

OBJECTIVES: This study aims to formulate metronidazole liquid nanocapsules (MTZLNC) and evaluate their effect on the physicochemical and biological properties of calcium silicate-based bioactive endodontic cements, in vitro. METHODS: A MTZLNC suspension was formulated by deposition of the preformed polymer and characterized by laser diffraction and high-performance liquid chromatography (HPLC). Calcium silicate (CS) was mixed with a radiopaque agent (calcium tungstate - CaWO4), at 10 wt%, to produce the cement powder. Cements liquids were used with two concentrations of MTZLNC suspension: 0.3 mg/ml and 0.15 mg/ml. Cements prepared with distilled water were used as the control. The radiopacity, setting time, and flow were evaluated following ISO 6876:2012. The compressive strength analysis was conducted according to ISO 9917:2007. pH and mineral deposition were evaluated after immersion in simulated body fluid (SBF). Cell behavior was evaluated by the viability of pre-osteoblastic cells and pulp fibroblasts by SRB and MTT and the antibacterial activity against Enterococcus faecalis was analyzed immediately and after nine months of water storage. RESULTS: MTZLNCs were formulated with a median diameter of 148 nm and 83.44 % load efficiency. Increased flow and reduced strength were observed for both MTZLNCs concentrations. The incorporation of MTZLNCs maintained the ability of cements to increase pH media and promote mineral deposition over the samples, without promoting cytotoxicity. A 2 log10 reduction in E. faecalis CFU was observed immediately and after nine months in water storage. CONCLUSION: The formulation of MTZLNCs allowed the development of antibacterial calcium silicate-based-cements with suitable physicochemical properties and bioactivity, with a reduction in mechanical strength. The 0.3 mg/ml concentration in cements liquid promoted effective and sustainable antibacterial activity.

3D printed matrix solid forms: Can the drug solubility and dose customisation affect their controlled release behaviour?

The use of 3D printing in pharmaceutics has grown over the last years, along with the number of studies on the impact of the composition of these formulations on their pharmaceutical and biopharmaceutical properties. Recently, we reported the combined effect of the infill percentage and the presence of a pore former on the drug release behaviour of 3D printed matrix solid forms prepared by fused deposition modelling. However, there are some open questions about the effect of the drug solubility and the size of these dosage forms on their controlled release properties. Therefore, we produced poly(Ɛ-caprolactone) filaments containing different soluble forms of dexamethasone (free acid, DEX; acetate ester, DEX-A; and phosphate salt, DEX-P), which showed suitable mechanical properties and printability. 3D printed solid forms were produced in two different sizes. The formulations composed of DEX-P released about 50% of drug after 10 h, while those containing DEX or DEX-A released about 9%. The drug release profiles from the 3D printed forms containing the same drug form but with different sizes were almost completely overlapped. Therefore, these 3D printed matrix solid forms can have their drug content customised by adjusting their size, without changing their controlled release behaviour.

In vitro development and optimization of cell-laden injectable bioprinted gelatin methacryloyl (GelMA) microgels mineralized on the nanoscale.

Bone defects may occur in different sizes and shapes due to trauma, infections, and cancer resection. Autografts are still considered the primary treatment choice for bone regeneration. However, they are hard to source and often create donor-site morbidity. Injectable microgels have attracted much attention in tissue engineering and regenerative medicine due to their ability to replace inert implants with a minimally invasive delivery. Here, we developed novel cell-laden bioprinted gelatin methacrylate (GelMA) injectable microgels, with controllable shapes and sizes that can be controllably mineralized on the nanoscale, while stimulating the response of cells embedded within the matrix. The injectable microgels were mineralized using a calcium and phosphate-rich medium that resulted in nanoscale crystalline hydroxyapatite deposition and increased stiffness within the crosslinked matrix of bioprinted GelMA microparticles. Next, we studied the effect of mineralization in osteocytes, a key bone homeostasis regulator. Viability stains showed that osteocytes were maintained at 98% viability after mineralization with elevated expression of sclerostin in mineralized compared to non-mineralized microgels, indicating that mineralization effectively enhances osteocyte maturation. Based on our findings, bioprinted mineralized GelMA microgels appear to be an efficient material to approximate the bone microarchitecture and composition with desirable control of sample injectability and polymerization. These bone-like bioprinted mineralized biomaterials are exciting platforms for potential minimally invasive translational methods in bone regenerative therapies.