Search Results (104)

A thermosensitive collagen-based gel (TSV gel), containing type I and III collagen, has been developed to improve the handling and stability of bone graft materials. However, its direct effect on osteoblasts is not well understood. This in vitro study evaluated the biological response of human oral osteoblasts to four bone substitutes: OsteoBiol^® GTO^® (larger granules with 20% TSV gel), Gen-OS^® (smaller granules), Gen-OS^® combined with 50% TSV gel (Gen-OS^®+TSV), and TSV gel alone. Cell proliferation, adhesion, morphology, collagen and calcium deposition, alkaline phosphatase (ALP) activity, gene expression of osteogenic markers and integrins, and changes in pH and extracellular calcium and phosphate levels were investigated. All materials supported osteoblast activity, but Gen-OS+TSV and GTO showed the most pronounced effects. These two groups promoted better cell adhesion and proliferation, higher ALP activity, and greater matrix mineralization. GTO improved cell adhesion, while the addition of TSV gel to Gen-OS enhanced biological responses compared with Gen-OS alone. Integrins α2, α5, β1, and β3, important for cell attachment to collagen, were notably upregulated in Gen-OS+TSV and GTO. Both groups also showed increased expression of osteogenic markers such as BMP-2, ALP, and osteocalcin (OCN). Higher extracellular ion concentrations and a more alkaline pH were observed, particularly in conditions without cells, suggesting active ion uptake by osteoblasts. In conclusion, combining TSV gel with collagen-based granules improves the cellular environment for osteoblast activity and may support bone regeneration more effectively than using either component alone. Full article

Bioactive glass materials have been used for decades in orthopedic surgery, traumatology, and oral and maxillofacial surgery to repair bone defects. This study aimed to evaluate in vitro the survival and proliferation of MG63 human osteosarcoma-derived cells on S53P4 bioactive glass (BonAlive^® granules). Microscopic visualization was performed to directly observe the interactions between the cells and the material. Osteoblast-like cells were examined on non-adherent test plates, on tissue culture (TC)-treated plates and on the surface of the bioglass to assess the differences. Cell survival and proliferation were monitored using a CCK-8 optical density assay. Comparing the mean OD of MG63 cells in MEM on TC-treated plates with cells on BG, we detected a significant difference (p < 0.05), over each time of observation. The sustained cell proliferation confirmed the non-cytotoxic property of the bioglass, as the cell number increased continuously at 48, 72, 96, and 168 h and even did not plateau after 168 h. Since the properties of bioglasses can vary significantly depending on their composition and environment, a thorough characterization of their biocompatibility is crucial to ensure their effective and appropriate application—for example, during hip and knee prosthesis insertion. Full article

Innovation in oral implantology is constantly on the move, with a constant search for new biomaterials to overcome many of the limitations of the biomaterials used in current implantable medical devices. This study explores the biocompatibility of an innovative 5% calcium-to-zirconia (Ca-SZ) coating deposited by PVD on TA6V substrates for use in oral implantology. In order to determine the contribution of the Ca-SZ coating, an in vitro biocompatibility study was carried out to assess the potential influence of the Ca-SZ coating (1) on the viability and proliferation of saos-2 and HaCaT cells over a short-term exposure period of 96 h, (2) on the synthesis of pro-inflammatory cytokines, and (3) on the synthesis of osteogenic differentiation markers over a long-term exposure period of 21 days, in comparison with reference biomaterials. The sampling consisted of n = 3 biological replicates, and a p-value of <0.05 was used as the threshold for statistical significance. Viability and proliferation kinetics to WST-1 and CyQUANT NF, respectively, showed improved viability/proliferation of Ca-SZ exposed to both cell lines independently. The TNF-alpha and IL-6 assays revealed reduced levels of cytokines compared with the reference biomaterials, including the control groups. In parallel, in Saos-2 cells exposed to Ca-SZ for 21 days under osteogenic conditions increased expression of osteogenic markers, such as the synthesis of soluble collagens, alkaline phosphatase (ALP), osteopontin, and osteocalcin, reflecting dynamic and facilitated osteoblastic differentiation, which was supported by the formation of hydroxyapatite (HA) crystals observed by SEM micrograph and confirmed by EDS mapping. In conclusion, Ca-SZ demonstrates an overall better biocompatibility compared with reference biomaterials, linked to a bioactive interaction of calcium, promoting cell proliferation and differentiation for optimal osteointegration, underlining its potential as a relevant innovation for next-generation implants. Full article

Negative-pressure wound therapy (NPWT) using vacuum-assisted closure (VAC) is a well known tissue defect bridging method that applies a vacuum pump to sterile, open-cell foam dressings via suction tubes. Although it has mostly been described for soft tissue use, there are also a few studies concerning its use on hard tissue. However, as oral and maxillofacial surgery has to deal with both soft and hard tissue, which lie next to each other in these regions, there is a particular need to assess the influence of negative pressure on bone. Therefore, the effects of different negative pressure levels (530 mbar and 725 mbar) and atmospheric pressure (1013 mbar) on bone tissue cultures and osteoblast cell cultures were investigated over periods of 1, 3, and 6 weeks. During the culture period, osteoblast growth and the tissue regeneration of bone defects were studied in vitro using tissue cultures that were histologically supplemented by cytological investigations and quantitative RNA expression studies. In the bone defect model, there was a faster defect reduction using NPWT; the effect was especially strong for 530 mbar. Compared to the control group, up to 30% more newly generated bone tissue was detected. This effect on the mineralization capacity was assessed by the mRNA expression of osteogenic marker genes, as well as the receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG), two multifaceted cytokines that regulate bone metabolism. The influence of negative pressure consequently resulted in a decreased RANKL/OPG ratio in osteoblasts. Associated with the upregulation of marker genes to up to 400%, including Col1, BMP4, OCN, and RUNX2, the decrease in the RANKL/OPG ratio to 41% indicates the stimulation of osteogenesis. Since VAC has been shown to be a safe and effective method to close wounds in general, these data suggest that patients suffering from compound bone and soft tissue defects in the maxillofacial area may benefit from an adapted therapy approach accelerating both soft and hard tissue regeneration. Full article

Background and clinical significance: Osteonecrosis of the femoral head (ONFH) is a disease of the epiphysis caused by the death of osteocytes and osteoblasts, resulting in debilitating pain. ONFH can be traumatic or nontraumatic, with prolonged glucocorticoid use being the leading cause of nontraumatic ONFH. Atopic dermatitis (AD) is a chronic inflammatory skin condition typically treated with topical corticosteroids. ONFH following topical corticosteroid treatment is exceedingly rare, with limited documentation in the literature. We present a case of an under-recognized complication of prolonged topical corticosteroid treatment. Case presentation: We report a case of a 29-year-old Caucasian male patient with sharp right hip pain. Plain radiographs, a CT scan, and an MRI indicated Ficat and Arlet stage 3 ONFH. The patient reported the prolonged uncontrolled use of topical mometasone furoate for five years due to AD. Following the diagnosis, topical corticosteroids were discontinued, and the treatment was shifted to tacrolimus and, subsequently, to oral methotrexate with folic acid. The patient underwent a total hip arthroplasty in June 2022. Given his young age and poor response to previous treatments, he was transitioned to upadacitinib, which led to significant improvement without skin flare-ups or postoperative hip pain. Conclusions: This case highlights the rare, but serious, risk of ONFH associated with long-term topical corticosteroid use. It underscores the importance of monitoring systemic side effects in dermatological therapies and educating patients on proper corticosteroid use. Alternative treatments, such as upadacitinib, should be considered in young male patients to prevent severe complications. Full article

Periodontitis is a chronic inflammatory disease characterized by the destruction of tooth-supporting structures, influenced by immune system dysregulation, oxidative stress, and imbalances in bone metabolism. Given its multifactorial pathogenesis, bioactive compounds such as vitamin D, melatonin, and omega-3 fatty acids have emerged as potential adjuncts to periodontal therapy due to their immunomodulatory, anti-inflammatory, and antioxidative properties. This narrative review explores the role of these three supplements in periodontal health, their potential in synergistic effects, and existing research gaps, providing a foundation for future studies on their clinical applications. Vitamin D is essential for calcium homeostasis, bone remodeling, and immune function. It modulates both innate and adaptive immune responses, enhancing antimicrobial peptide production and reducing inflammatory cytokine expression. Omega-3 fatty acids reduce the production of pro-inflammatory eicosanoids while promoting the synthesis of pro-resolving lipid mediators, contributing to bone preservation and immune balance. Melatonin, known for its antioxidant and osteogenic properties, supports bone remodeling by stimulating osteoblast proliferation and inhibiting osteoclast activity, while also regulating circadian rhythms, which may influence oral health. Although these bioactive compounds show promising effects in preclinical and clinical studies, significant knowledge gaps remain regarding optimal dosages, long-term efficacy, combined use, and standardized treatment protocols. Further clinical trials are necessary to elucidate their therapeutic value in periodontal disease management, especially those focused on their potential synergistic mechanisms. Understanding their synergistic mechanisms may open new avenues for adjunctive strategies in periodontal therapy. Full article

Diabetes-related osteoporosis has been known to be a consequence of oxidative stress caused by excessive reactive oxygen species (ROS) production in the tissues. Despite the increase in the number of individuals with diabetes-related osteoporosis year on year, there is still no effective drug that does not induce adverse side effects. Glabridin, which exerts hypoglycemic effects and possesses antioxidant properties, may have beneficial effects in the treatment of diabetes-related osteoporosis. In this study, we aimed to investigate the preventive effects of glabridin in counteracting oxidative stress-induced bone loss and its underlying mechanisms. A diabetic rat model was established by a single intraperitoneal injection of streptozotocin into male Wistar rats. The diabetic rats were orally gavaged daily with glabridin or glyburide for 8 weeks. The presence of diabetes significantly decreased the rats’ tibia length, bone thickness, epiphyseal plate length, and collagen deposition compared to the control rats; in comparison, treatment with glabridin for 8 weeks significantly reversed these effects. In our in vitro study, the treatment of MC3T3-E1 preosteoblasts with glabridin up to 7.5 µM for 48 h showed no cytotoxic effect. However, pretreatment with glabridin significantly prevented oxidative stress-induced inhibition of cell proliferation. In addition, glabridin significantly diminished ROS production, restored antioxidant enzyme activity, and mitigated cellular apoptosis. These effects occurred by stimulating the phosphorylation of Akt, GSK-3β, and P65 NF-ĸB proteins. The above results show that glabridin alleviated oxidative stress-induced bone loss and osteoblast cell apoptosis by modulating the expression of the Akt/NF-ĸB and Akt/GSK-3β pathways. Full article

Background/objective: In orthodontic therapy, the periodontal ligament plays a critical role in the bone remodeling process by stimulating osteoblasts in tension zones and promoting bone resorption through osteoclasts in compression zones in response to mechanical stress. These processes are regulated by key cytokines, such as RANKL and IL-1, which are influenced by factors such as patient age and force application. This work evaluates the effectiveness of clear aligners versus traditional braces on periodontal health in patients with periodontitis, following PRISMA guidelines and utilizing specific inclusion and exclusion criteria. Methods: A systematic review of 1664 records was conducted, leading to the inclusion of eight studies that focus on the impact of orthodontic treatments on periodontal health. The review identifies various biases present in the literature. Results: The findings reveal that clear aligners, in contrast to fixed appliances, improve oral hygiene and reduce inflammation, leading to better periodontal outcomes. Fixed appliances, on the other hand, may exacerbate plaque accumulation and inflammation, which can worsen periodontal health. Conclusions: Clear aligners offer advantages over fixed appliances in terms of enhancing periodontal health, improving patient compliance, and providing long-term benefits, particularly in patients with severe periodontitis. The effectiveness of clear aligners is linked to better management of periodontal complications and overall oral hygiene. Treatment decisions should be based on patient-specific criteria to optimize outcomes. Full article

Inflammation significantly influences cellular communication in the oral environment, impacting tissue repair and regeneration. This study explores the role of small extracellular vesicles (sEVs) derived from lipopolysaccharide (LPS)-treated stem cells from the apical papilla (SCAP) in modulating macrophage polarization and osteoblast differentiation. SCAPs were treated with LPS for 24 h, and sEVs from untreated (SCAP-sEVs) and LPS-treated SCAP (LPS-SCAP-sEVs) were isolated via ultracentrifugation and characterized using transmission electron microscopy, Western blot, and Tunable Resistive Pulse Sensing. LPS-SCAP-sEVs exhibited characteristic exosome morphology (~100 nm diameter) and expressed vesicular markers (CD9, CD63, CD81, and HSP70). Functional analysis revealed that LPS-SCAP-sEVs promoted M1 macrophage polarization, as evidenced by the increased pro-inflammatory cytokines (IL-6 and IL-1β) and the reduced anti-inflammatory markers (IL-10 and CD206), while impairing the M2 phenotype. Additionally, LPS-SCAP-sEVs had a minimal impact on SCAP metabolic activity or osteogenic gene expression but significantly reduced mineralization capacity in osteogenic conditions. These findings suggest that sEVs mediate the inflammatory interplay between SCAP and macrophages, skewing macrophage polarization toward a pro-inflammatory state and hindering osteoblast differentiation. Understanding this sEV-driven communication axis provides novel insights into the cellular mechanisms underlying inflammation in oral tissues and highlights potential therapeutic targets for modulating extracellular vesicle activity during acute inflammatory episodes. Full article

Despite treatment, prostate cancer commonly progresses into castration-resistant prostate cancer (CRPC), which remains largely incurable, requiring the development of new interventions. Darolutamide is an orally administered second-generation androgen receptor inhibitor indicated for patients with non-metastatic CRPC or metastatic hormone-sensitive prostate cancer. Here, we evaluated the effect of androgen receptor (AR) inhibition by darolutamide in combination with DNA double-strand-break-inducing targeted radium-223 alpha therapy in vitro and in an intratibial LNCaP xenograft model mimicking prostate cancer metastasized to bone. The results highlight the synergistic antitumor efficacy of darolutamide in combination with radium-223 both in vitro and in vivo. This effect was most likely driven by the downregulation of genes involved in DDR signaling, which was demonstrated in vitro by a gene set enrichment analysis. The combination treatment also reduced pathological tumor-induced effects in bone by decreasing the number of osteoblasts and osteoclasts and reducing abnormal bone formation in tumor-bearing bone. Additionally, it was shown that darolutamide does not affect the uptake of radium-223 into bone tissue. These results support the investigation of darolutamide in combination with radium-223 for the treatment of patients with CRPC metastasized to bone. Full article

Background: Alcohol-induced osteoporosis is a significant health concern, impairing bone formation and enhancing resorption, thereby weakening skeletal integrity. This study examines the effects of palm vitamin E on bone histomorphometry in a male rat model of alcohol-induced osteoporosis. Methods: Three-month-old Sprague–Dawley rats were randomized into seven groups, with one baseline control group (BC) and six experimental groups undergoing a two-phase treatment. In the first month, the control group received normal saline, while experimental groups received intraperitoneal alcohol (3 g/kg) three times weekly. For the subsequent two months, alcohol treatment continued in one group (A), while others received olive oil (C), saline (AN), alpha-tocopherol (AA), or palm vitamin E (AE) orally. Results: Femur histomorphometric analysis post-sacrifice showed that alcohol exposure significantly decreased osteoblastic activity and impaired bone microarchitecture, evidenced by reduced Ob.S/BS, OS/BS, OV/BV, Tb.Th, BV/TV, and Tb.N, alongside increased Oc.S/BS, ES/BS, and Tb.Sp. Both alpha-tocopherol and palm vitamin E improved bone parameters, with palm vitamin E showing superior efficacy except in OV/BV. Conclusions: These findings suggest that palm vitamin E may offer a therapeutic benefit for mitigating alcohol-induced bone damage. Full article

The machining of implants and parts for dental prostheses to eliminate biofilm in the implantoplasty process causes a loss of mechanical properties and also characteristics of the surfaces, making tissue regeneration difficult. In the present work, treatments consisting of elements that can reduce infection, such as citric acid and magnesium, together with elements that can improve cell adhesion and proliferation, such as collagen, are proposed for implant–crown assembly. Titanium, zirconia, composite (PMMA + feldspar) and cobalt–chromium discs were immersed in four different solutions: 25% citric acid, 25% citric acid with the addition of collagen 0.25 g/L, 25% citric acid with the addition of 0.50 g/L and the latter with the addition of 1% Mg (NO₃)₂. After immersion was applied for 2 and 10 min, the roughness was determined by interferometric microscopy and the contact angle (CA) was evaluated. Human fibroblastic and osteoblastic line cells (HFFs and SaOS-2) were used to determine cell viability and proliferation capacity. Cell binding and cytotoxicity were determined by resazurin sodium salt assay (Alamar Blue) and cell morphology by confocal assay (immunofluorescence F-actin (phalloidin)) after 3 days of incubation. For the evaluation of bacterial activity, the bacterial strains Sptreptococcus gordonii (Gram+) and Pseudomonas aeruginosa (Gram−) were used. The antibacterial properties of the proposed treatments were determined by means of the resazurin sodium salt (Alamar Blue) assay after 1 day of incubation. The treatments considerably decreased the contact angle of the treated samples with respect to the control samples. The treatments endowed the surfaces of the samples with a hydrophilic/super-hydrophilic character. The combination of elements proposed for this study provided cell viability greater than 70%; considering the absence of cytotoxicity, it therefore promotes the adhesion and proliferation of fibroblasts and osteoblasts. In addition, it also endows the surface with antibacterial characteristics against from Gram+ and Gram− bacteria without damaging the cells. These results show that this mouthwash can be useful in oral applications to produce a new passivation layer that favors the hydrophilicity of the surface and promotes cellular activity for the formation of fibroblasts and osteoblasts, as well as showing bactericidal activity. Full article

Although fine dust is linked to numerous health issues, including cardiovascular, neurological, respiratory, and cancerous diseases, research on its effects on oral health remains limited. In this study, we investigated the protective effects of mature hemp stem extract-induced exosomes (MSEIEs) on periodontal cells exposed to fine dust. Using various methods, including microRNA profiling, PCR, flow cytometry, immunocytochemistry, ELISA, and Alizarin O staining, we found that MSE treatment upregulated key microRNAs, such as hsa-miR-122-5p, hsa-miR-1301-3p, and hsa-let-7e-5p, associated with vital biological functions. MSEIEs exhibited three primary protective functions: suppressing inflammatory genes while activating anti-inflammatory ones, promoting the differentiation of periodontal ligament stem cells (PDLSCs) into osteoblasts and other cells, and regulating LL-37 and MCP-1 expression. These findings suggest that MSEIEs have potential as functional biomaterials for applications in pharmaceuticals, cosmetics, and food industries. Full article

In adverse environments, fine dust is linked to a variety of health disorders, including cancers, cardiovascular, neurological, renal, reproductive, motor, systemic, and respiratory diseases. Although PM10 is associated with oral inflammation and cancer, there is limited research on biomaterials that prevent damage caused by fine dust. In this study, we evaluated the effects of biomaterials using microRNA profiling, flow cytometry, conventional PCR, immunocytochemistry, Alizarin O staining, and ELISA. Compared to SBE (Scutellaria baicalensis extract), the preventive effectiveness of SBEIEs (SBE-induced exosomes) against fine dust was approximately two times higher. Furthermore, SBEIEs promoted cellular differentiation of periodontal ligament stem cells (PDLSCs) into osteoblasts, periodontal ligament cells (PDLCs), and pulp progenitor cells (PPCs), enhancing immune modulation for oral health against fine dust. In terms of immune modulation, SBEIEs activated the secretion of cytokines such as IL-10, LL-37, and TGF-β in T cells, B cells, and macrophages, while attenuating the secretion of MCP-1 in macrophages. MicroRNA profiling revealed that significantly modulated miRNAs in SBEIEs influenced four biochemical categories: apoptosis, cellular differentiation, immune activation, and anti-inflammation. These findings suggest that SBEIEs are an optimal biomaterial for developing oral health care products. Additionally, this study proposes functional microRNA candidates for the development of pharmaceutical liposomes. Full article

Implantoplasty is one of the most common techniques to remove peri-implantitis from the surface of dental implants. It is a process of mechanization of the titanium surface, causing the loss of the roughness of the dental implant, which leads to difficulty in tissue regeneration. The aim of this research is to apply a decontaminant based on citric acid and add collagen and magnesium cations to promote tissue formation and have a bactericidal character. Eighty commercially pure grade 3 titanium discs were used to perform the implantoplasty protocol, like the one used in dental clinics. They were treated with four different solutions: 25% citric acid, 25% citric acid with the addition of collagen 0.25 g/L, 25% citric acid with the addition of 0.50 g/L and the latter with the addition of 1% Mg (NO₃)₂. The roughness was determined by confocal microscopy, the contact angle, adhesion and proliferation of HFFs fibroblasts, proliferation of SaOS-2 osteoblasts and bactericidal behavior by culturing very common bacteria in the oral cavity, Gram-positive Streptococcus sanguinis and gordonii and as Gram-negative Pseudomonas aeruginosa. The results showed that the treatment with citric acid slightly increases the roughness and decreases the contact angle from 78 to 13°, making the surface superhydrophilic. Fibroblast proliferation studies show a very significant increase at 24 h, the most favorable solution being the one containing 0.50 g/L of collagen with the presence of magnesium in a 25% citric acid solution. This same solution shows the highest cytocompatibility and osteoblastic proliferation with statistically significant differences with respect to the control and the rest of the solutions. Microbiological studies show a bactericidal effect due to the presence of citric acid, which is especially effective on Gram-positive bacteria. The results allow us to have mouthwashes that can be applied in the patient’s mouth, which will help the regeneration of tissues and avoid new bacterial colonization. Full article