Search Results (1,636)

Cell population and vascular vessel distribution analysis in membrane-based scaffolds for tissue engineering is crucial. Biomimetic nanostructured membranes of methyl methacrylate/hydroxyethyl methacrylate and methyl acrylate/hydroxyethyl acrylate (MMA)1-co-(HEMA)1/(MA)3-co-(HEA)2 loaded with 5% wt SiO2-nanoparticles (Si-M) were doped with zinc (Zn-M) or doxycycline (Dox-M). Critical bone defects were effectuated on six New Zealand-bred rabbit skulls and then they were covered with the membrane-based scaffolds. After six weeks, bone cell population in terms of osteoblasts, osteoclasts, osteocytes, fibroblasts, and M1 and M2 macrophages and vasculature was determined. The areas of interest were the space above (over) and below (under) the membrane, apart from the interior (inner) compartment. All membranes showed that vasculature and most cell types were more abundant under the membrane than in the inner or above regions. Quantitatively, osteoblast density increased by approximately 35% in Zn-M and 25% in Si-M compared with Dox-M. Osteoclast counts decreased by about 78% in Dox-M, indicating strong inhibition of bone resorption. Vascular structures were nearly twofold more frequent under the membranes, particularly in Si-M, while fibroblast presence remained moderate and evenly distributed. The M1/M2 macrophage ratio was higher in Zn-M, reflecting a transient pro-inflammatory state, whereas Dox-M favored an anti-inflammatory, pro-regenerative profile. These results indicate that the biomimetic electrospun membranes functioned as architectural templates that provided favorable microenvironments for cell colonization, angiogenesis, and early bone regeneration in a preclinical in vivo model. Zn-M membranes appear suitable for early osteogenic stimulation, while Dox-M membranes may be advantageous in clinical contexts requiring modulation of inflammation and osteoclastic activity. Full article

Background: Oxidative stress and inflammation contribute to osteoporosis. Berries provide polyphenols especially anthocyanins that may modulate bone remodeling. This review is the first to synthesize evidence specifically on berries and bone health, integrating human, animal, and in vitro data under the GRADE framework. Methods: We systematically searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library through 23 April 2025 for human, animal, and in vitro studies on berries or berry-derived compounds and bone outcomes. Risk of bias was assessed with RoB 2.0, ROBINS-I, SYRCLE, and an adapted ToxRTool; certainty of human evidence was appraised with GRADE. Results: Forty-six studies were included (12 human, 20 animal, 14 in vitro). Observational cohorts linked higher anthocyanin intake with greater BMD. Small randomized trials suggested modest benefits of blackcurrant and blueberry on whole-body BMD, bone turnover markers, and calcium retention, while results for biomarkers were mixed. Animal models generally showed attenuation of ovariectomy- or age-related bone loss, and in vitro experiments indicated inhibition of osteoclastogenesis with stimulation of osteoblast activity. By GRADE, certainty was low–moderate for BMD, low for biomarkers, and very low for fractures. Conclusions: Berry polyphenols may support skeletal health via antioxidant and anti-resorptive mechanisms, but current clinical evidence is limited by small samples, heterogeneity, and lack of fracture outcomes. Larger, longer, standardized RCTs with exposure profiling are needed before dietary recommendations can be made. Full article

Background: Tooth extraction is often accompanied by bone tissue loss. This systematic review aims to compare osteoplastic materials for socket preservation. Methods: This systematic review was carried out with the PRISMA statement. To identify relevant studies, a thorough literature search was executed in several databases, such as Medline, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. The inclusion criteria were restricted to randomized controlled trials, and their methodological quality was evaluated with the Cochrane Risk of Bias tool (ROB 2). Results: Based on the predefined inclusion and exclusion criteria, nine randomized clinical trials published before 2024 were selected for analysis, all of them investigating the application of osteoplastic materials. Six studies performed xenogenic bone augmentation; one of them compared alloplastic and xenogenic materials; two studies described synthetic osteoplastic materials; and one described autogenic bone material. Conclusion: Socket augmentation with osteoplastic materials demonstrates effectiveness in preserving alveolar ridge dimensions and creating favorable conditions for further implant placement, though differences in clinical performance highlight the need for careful material selection. Full article

Background/Objectives: Osteoporosis is caused by excessive osteoclast activation via the receptor activator nuclear factor kappa B ligand (RANKL), which is released from osteoblasts or osteocytes. RANKL regulates osteoclast activity by binding to the receptor activator of nuclear factor kappa B (RANK) in the canonical pathway or leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) in the non-canonical pathway. In this study, we attempted to develop an intact small-fragment protein based on RANKL by removing the RANK-binding site and transforming the amino acid residues at crucial sites to inhibit osteoclast activity and treat osteoporosis. Methods: We expressed a small-fragment variant of RANKL as a soluble glutathione S-transferase (GST) or 6x histidine (His)-tagged fusion protein using a GST- or His-binding domain tag expression vector system. To generate an intact form of small-fragment RANKL, ribosome-inactivating protein–His-fusion RANKL was purified using HisTrap affinity chromatography and treated with tobacco etch virus nuclear inclusion endopeptidase to remove the His-tag fusion protein. Tartrate-resistant acid phosphatase (TRAP) and bone resorption pit formation assays were performed to analyze the inhibitory effects on osteoclast differentiation and activation. Results: The intact forms of 225RANKL295P and 225RANKL295A showed the strongest inhibitory effects on TRAP activity and bone resorption pit formation. Conclusions: Using an optimal construct design, a large and diverse range of small RANKL fragments could be generated. This suggests that the generation of small-fragment RANKL provides a promising avenue for the advancement of novel therapeutic approaches to osteoporosis. Full article

Background and Objectives: Heterotopic ossification (HO) involves abnormal bone growth in soft tissues. Current treatments are ineffective and prone to adverse effects, suggesting the need for new HO therapies. Intramembranous bone growth is led by osteoblasts. Since osteoblastogenesis and adipogenesis are opposed and mutually controlled processes, this study aims to identify a new repurposed therapeutic tool to inhibit osteoblastogenesis through adipogenesis promotion. Methods: We performed docking experiments between peroxisome proliferator-activated receptor-γ and bone metabolism-affecting drugs, namely, thiazolidinediones (rosiglitazone, pioglitazone), indomethacin, and dexamethasone, to test tritherapy antiosteoblastogenic effect. Mouse mesenchymal stem cells (C3H10T1/2), human osteoblast-like cells (SaOS2 and primary preosteoblasts), and mouse chondrocytes (ATDC5) were differentiated in the presence of these compounds. The effects on osteoblastogenesis, adipogenesis, and endochondral ossification were analysed through marker gene expression via RT–qPCR. Additionally, primary human HO cells and a congenital HO patient were treated with the selected drug combination (P-tritherapy). Results: Tritherapy significantly and synergistically promoted the expression of an adipogenic marker (fatty acid-binding protein 4) and decreased the expression of an osteoblastogenic marker (osteopontin). In an endochondral ossification model, it reduced ossification markers (collagen-2α1) expression, and in HO cells, it increased adipogenesis markers’ expression. Clinically, P-tritherapy administration prompted bone resorption in a patient with progressive osseous heteroplasia. Conclusions: Tritherapy induced adipogenesis while inhibiting osteoblastogenesis and endochondral ossification, demonstrating its potential as a new therapeutic tool to prevent abnormal bone growth. These results were consistent with bone turnover modification observed in a congenital HO patient. This concordance underscores tritherapy potential for rapid and safe translation to prevent HO. Full article

Background: Bone defects resulting from trauma, infection, or benign tumors pose major challenges in orthopedic surgery. Traditional approaches, such as autologous bone grafting, are limited by donor site morbidity and graft availability. CERAMENT™, a synthetic bone substitute composed of calcium sulfate and hydroxyapatite, offers an alternative with osteoconductive properties, controlled resorption, and injectability. Methods: A scoping review was conducted in accordance with PRISMA-ScR guidelines. Literature searches were performed in PubMed, Embase, and Scopus through 3 July 2025, using the terms “CERAMENT™” and “Orthopedics.” Studies were selected based on the PICO framework, focusing on clinical applications of CERAMENT™ in human orthopedic procedures. Results: Out of 480 initial records, 22 studies met the inclusion criteria. CERAMENT™ demonstrated favorable outcomes in a range of orthopedic settings. In the CERTiFy trial, it was non-inferior to autologous grafting in tibial plateau fractures. CERAMENT™ achieved full wound healing and bone remodeling in chronic osteomyelitis. Additional studies reported positive outcomes in tumor-related defect reconstruction, spinal augmentation, and foot and ankle surgery, highlighting reduced surgical morbidity and faster recovery. Conclusions: CERAMENT™ offers a versatile, effective solution for bone reconstruction across multiple orthopedic domains. Its clinical performance, ease of use, and antimicrobial capabilities support its integration into routine orthopedic practice. Further research may refine its indications and long-term benefits. Full article

Oxidative stress brought on by prolonged glucocorticoid therapy reduces bone growth, structure, and mechanical qualities. Free radicals promote osteoclastic activity and are harmful to osteoblasts. As an antioxidant, tocotrienol offers protection against illnesses linked to free radicals. Annatto tocotrienol (ATT) is a tocopherol-free tocotrienol, and palm tocotrienol (PTT) is a tocotrienol mixture. Finding out how ATT and PTT protect against glucocorticoid-induced osteoporosis was the aim of this study. In this study, 32 mature male Sprague-Dawley rats were employed. Twenty-four rats were divided into three groups: Dex, Dex + PTT, and Dex + ATT, after being adrenalectomized. A sham surgery was performed on the remaining eight rats. The Dex group received oral vehicle palm olein (0.1 mL/kg/day) and intramuscular injection of dexamethasone (120 µg/kg/day). Dexamethasone 120 µg/kg/day was administered intramuscularly to the Dex + PTT and Dex + ATT group, and palm tocotrienol (PTT) and annatto tocotrienol (ATT) 60 mg/kg/day were added as a supplement. Vehicle palm olein was administered intramuscularly to the sham-operated rats, 0.05 mL/kg/day and 0.1 mL/kg/day orally. The treatments were administered for two months before the rats were euthanized. The biomechanical strength of the femoral bones was evaluated, and the structural characteristics of bone histomorphometry were examined. According to the findings, prolonged glucocorticoid therapy resulted in decreased superoxide dismutase (SOD) activity, increased lipid peroxidation, and bone carboxy-terminal collagen cross-linkages (CTX). Bone Volume/Tissue Volume (BV/TV) and Trabecular Number (Tb.N) were drastically reduced, which severely reduced bone biomechanical strength. There were also alterations in the bone formation and resorption gene expressions. Lipid peroxidation, CTX levels, and SOD activity were all considerably maintained at control levels by PTT and ATT intake. Additionally, it preserved the biomechanical strength and bone structure, as well as maintaining the gene expressions. According to the study’s findings, ATT and PTT may have anabolic and anti-resorptive properties and have the potential to be utilized as a prophylactic for individuals receiving long-term glucocorticoid therapy. Full article

Background: Jawbone invasion is a common and prognostically unfavorable feature of oral squamous cell carcinoma (OSCC). Although cancer-associated fibroblasts (CAFs) are recognized for their role in tumor progression, their spatial dynamics at the tumor–bone interface remain poorly understood. Methods: We analyzed 14 OSCC specimens with confirmed jawbone invasion using histopathological and immunohistochemical techniques. Digital pathology combined with AI-assisted image analysis was employed to quantify and visualize the spatial distribution of OSCC cells (RANKL-positive), CAFs (α-SMA and FAP-positive), and osteoclasts (cathepsin K-positive) within defined regions of interest at the tumor–bone invasive front. Results: A consistent laminar stromal region enriched in CAFs was observed between the tumor nests and jawbone. CAFs were spatially clustered near OSCC cells and osteoclasts, with 81% and 74% residing within 50 μm, respectively. On average, 11.4 CAFs were present per OSCC cell and 23.2 per osteoclast. These spatial proximities were largely preserved irrespective of stromal thickness, suggesting active bidirectional cellular interactions. Conclusions: Our findings demonstrate that CAFs are strategically positioned to facilitate intercellular signaling between tumor cells and osteoclasts, potentially coordinating OSCC proliferation and bone resorption. This study highlights the utility of AI-assisted spatial histology in unraveling tumor microenvironmental dynamics and proposes CAFs as potential therapeutic targets in OSCC-induced osteolytic invasion. Full article

Acromegaly is associated with a higher risk of certain malignancies, but not hematological neoplasia, although multiple myeloma (MM) was found in very limited cases. We aim to present such a case, adding a particular presentation with co-occurrence of a plasmocytoma. A 52-year-old male with acromegaly confirmed at 46 (MRI: pituitary macroadenoma of 12 × 11 × 10 mm) underwent hypophysectomy followed by 3 years of octreotide LAR then lanreotide depot. After another 6 months, he experienced a rapidly growing, painful lump in the right lateral thoracic area confirmed by CT as a 9-cm osteolytic lesion at the third rib. Core biopsy revealed plasmocytoma of the bone and medullary biopsy confirmed MM. Plasmacytoma was managed with 10 radiotherapy sessions, with favorable outcome and mass resorption; MM was managed with a VRD regimen, followed by autologous hematopoietic stem-cell transplantation. Six months after sFLC normalization and plasmacytoma resorption, complete remission was reported. In the meantime, lanreotide was continued, with complete acromegaly control. To conclude, what started as a rather typical scenario for an otherwise rare condition, as is acromegaly in the general population (but not so rare for endocrinologists), turned into an unexpected and more severe outcome. Noting this exceptional association, we pinpoint that further research is needed for understanding the dual acromegaly–MM relationship. Full article

Background: During maxillary sinus floor augmentation, the elevated sinus mucosa may come into close contact with the pristine mucosa. The presence of xenograft granules can lead to unintended mechanical and biological interactions between the two layers, and the resulting tissue damage remains poorly understood. The aim of this study was to perform a focused histological evaluation of graft-mediated interactions between the elevated and pristine sinus mucosae. Methods: Histological slides from five previously published rabbit sinus augmentation studies using grafts with different resorption rates were retrospectively analyzed. The following main patterns of tissue alteration were identified: (1) Proximity stage, characterized by epithelial thickening, goblet cell hyperactivity, and ciliary shortening; (2) Fusion stage, with epithelial interpenetration and loss of distinct mucosal boundaries; (3) Synechiae stage, featuring connective tissue bridges linking the two mucosae; and (4) Pristine mucosa lesions, caused by direct contact between residual graft particles and the pristine sinus mucosa. Results: A total of 192 sinuses were evaluated. Sinuses augmented with slowly resorbable grafts showed proximity stage in 22.3% of cases, fusion in 7.7%, direct lesions in 9.6%, and only one instance of synechia. In contrast, the faster resorbable xenograft presented only 11.1% of proximity stage, without further alterations. Conclusions: In this rabbit model, xenografts were associated with histological alterations of the sinus mucosa, while synechiae formation was rare. These preclinical findings should not be directly extrapolated to humans but may provide a basis for future investigations. Full article

Background: Traditional parameters such as bone-to-implant contact percentage (BIC%) provide only static insights into implant integration and do not reflect the temporal dynamics of bone regeneration. The concept of Dynamic Regenerative Balance (DRB) was introduced to represent the biological equilibrium between bone formation and graft resorption. The break-even point serves as a measurable approximation of this equilibrium. This study aimed to illustrate the usefulness of the break-even point in expressing the balance between graft resorption and new bone formation, rather than to define definitive values for specific biomaterials. Methods: Four preclinical studies on sinus floor elevation in rabbits were selected. Each reported histomorphometric data on new bone formation and graft resorption at two or more time points. Six biomaterials were analyzed: autogenous bone, Bio-Oss^®, Bio-Oss Collagen^®, Gen-Os^®, Maxresorb^®, and Maxresorb^® Inject. The break-even point was calculated by linear extrapolation as the time at which new bone equals residual graft percentage. Results: The break-even point varied significantly among biomaterials (expressed in days/area %): autogenous bone reached equilibrium fastest (18.4 days/13.5%), followed by Gen-Os^® (40.4 d/19.1%). Bio-Oss Collagen^® (62.3 d/28.3%), Maxresorb^® (73.9 d/36.4%), and Maxresorb^® Inject (96.1 d/34.1%). For Bio-Oss^®, it occurred at 81.8 days (33.6%) in one study, while in another, it was not reached within 6 months. These differences reflect distinct regenerative kinetics and resorption profiles among materials. Conclusions: The break-even point offers a simple and informative parameter to describe the balance between graft resorption and new bone formation, providing a useful complement to conventional histomorphometric measures and a framework for future studies. Full article

Background: Periodontally accelerated osteogenic orthodontics (PAOO) is a surgical procedure to accelerate orthodontic tooth movement and minimize periodontal complications. This study surveyed U.S. periodontists to assess various aspects of the procedure as regards prevalence, training, and execution. Methods: The authors developed a unique questionnaire, the first national study of this type, housed on the Qualtrics^® survey platform, to analyze trends in PAOO training and use. Unique recruitment emails were sent to 3154 members of the American Academy of Periodontology. 449 U.S. periodontists/3154 surveyed (14.2%) responded to this web-based, anonymized survey. IBM statistical software (SPSS V28) was used for data analysis. Results: Among respondents, PAOO training was received during residency (32.7%) and by continuing education (CE) (50.8%), with higher CE (57.3%) by those who did not receive PAOO residency training (p < 0.001). 38.5% of periodontists perform PAOO, and those most likely to perform PAOO had both PAOO residency training and CE, with 78.5% performing 1–5 cases/year. Most (87.7%) received 1–2 PAOO referrals/year from orthodontists or general dentists. Differences in techniques and materials were the type of bone graft or membrane used, the position of corticotomies, and the timing of orthodontic movement. The primary PAOO goal was “rapid tooth movement” (41.1%) and to “increase the alveolar housing” (37.2%). The secondary (38%) and tertiary (37.2%) ranked goals were “augment dehiscence or fenestration”, with the “prevention of apical root resorption” ranked as their quaternary goal. Conclusions: The results of this survey provide data on the trends, training, and use of PAOO among U.S. periodontists. This information may aid in developing residency curriculum and performing PAOO research. Full article

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for degenerative diseases due to their ability to modulate disease progression through paracrine mechanisms. Among various MSC sources, placenta-derived MSCs (PD-MSCs) offer significant advantages, including high proliferation capacity, reduced senescence, and low immunogenicity, making them ideal for allogeneic applications. In this study, we investigated the therapeutic effects of PD-MSC transplantation in an estrogen-deficiency-induced osteoporosis mouse model. Mice were divided into three groups: a normal control group, a non-transplanted osteoporosis group, and a PD-MSC-transplanted group. Our findings demonstrated that PD-MSC transplantation significantly improved osteoporosis-related parameters, including increased femur weight, bone volume, bone mineral density, and calcium deposition. Additionally, estrogen levels were elevated, bone formation markers were upregulated, and bone resorption markers were downregulated. PD-MSCs also reduced inflammatory cytokine levels while enhancing anti-inflammatory factors. Notably, the BMP/SMAD signaling pathway, crucial for bone formation, was significantly upregulated. These results suggest that PD-MSC transplantation effectively restores bone homeostasis by inhibiting osteoclast activity, promoting osteogenesis, and modulating inflammation. This study provides strong evidence supporting the potential of PD-MSCs as a novel therapeutic strategy for osteoporosis, offering a regenerative and anti-inflammatory approach to bone disease management. Full article

Background: Peri-implantitis is the leading cause of implant failure, with a reported prevalence of 22–45%. Effective removal of bacterial biofilm from the implant surface is critical to non-surgical therapy. This study aimed to assess the efficacy of different implant surface cleaning methods across various bone defect configurations, considering operator experience. Methods: Thirty-six dental implants were coated to simulate biofilm, mounted in resin blocks with bone defects of varying geometries, and covered with silicone to simulate soft tissue. Three operators with differing levels of experience treated the implant surfaces using four instruments: a titanium curette (TiCu), ultrasonic scaler (US), titanium brush (TiBr), and air abrasion with erythritol (AirPo). Each combination was tested in triplicate. Implants were photographed and analyzed with dedicated software to quantify cleaning efficacy. Results: The expert dentist achieved the highest average cleaning efficacy (36.6%). The most effective tools were the titanium brush (37.2%) and ultrasonic scaler (35.0%), followed by the titanium curette (28.1%) and air-abrasion (22.9%). The first two instruments were the least operator-dependent. Among the defect types, the 60° defect was the easiest to clean. Complete implant surface decontamination was not achieved in any scenario. Conclusions: Ultrasonic scalers and titanium brushes demonstrated the highest and most consistent cleaning efficacy, independent of operator skill level. Sixty-degree defects were the most amenable to cleaning. These findings underscore the need to tailor decontamination approaches based on defect geometry and to consider combining non-surgical methods with adjunctive or surgical interventions, which may ultimately enhance clinical decision-making and improve treatment outcomes. Full article

Background: Peri-implantitis is an inflammatory condition caused by bacterial plaque and several factors like diabetes, smoking, titanium bio-tribocorrosion, implant–abutment micromovements, occlusal overload, cement remnants, and poor oral hygiene, resulting in bone resorption. The aim of this review was to evaluate the relationship between titanium metal particles and the development of peri-implantitis, specifically the characterisation of the inflammatory response regarding cytokine profile, immune cell infiltration, and transcription factors up-regulated in the peri-implant sites. Methods: A systematic review was conducted following the PRISMA guidelines, from January 2004 to January 2025, in three databases: PubMed, Web of Science, and Wiley Library. The inclusion criteria included in vivo human studies and in vitro studies with a focus on bio-tribocorrosion of titanium particles in peri-implant tissues, and their immunological and cellular implications. Quality assessment of in vivo transversal and case–control studies used Joanna Briggs Institute Critical Appraisal Tools, and, for in vitro studies, the modified CONSORT checklist. Results: A total of 27 studies were included, 20 in vitro and 7 in vivo. Titanium particles induced the secretion of IL-1β, IL-6, and TNF-α by peri-implant cells, activation of the NLRP3 inflammasome, and RANKL/OPG bone resorption, further stimulating an exacerbated inflammatory response, LPS independent. There was a significant increase in IL-33, an alarmin, possibly associated with implant–pillar micromovements. IL-8 production by gingival stromal cells and fibroblasts, and downregulation of CCR7 can explain an altered leukocyte migration and the mixture of M1/M2 macrophage populations in peri-implantitis. Conclusions: Titanium particle bio-tribocorrosion stimulates a chronic inflammatory response impacting immune cell composition and cytokine secretion in peri-implant tissue, leading, ultimately, to osteolysis. Modulation of the immune response may contribute to the development of therapeutic strategies and the prevention of implant failure. Full article