Bone Research Articles

Synthesis and characterization of gelzan nanocomposite scaffold incorporating Ag/Fe2+ co-doped hydroxyapatite for antibacterial bone tissue regeneration

Abstract A nanocomposite scaffold was developed using gelzan, a natural extracellular polysaccharide, as the biopolymer matrix. Gelzan (GZ) was combined with Ag/Fe2⁺ co-doped hydroxyapatite (HAp) particles to enhance the scaffold’s biological properties. The aim of incorporating Ag/Fe2⁺ co-doped HAp was to utilize the combined antibacterial and bioactive properties of these components. The synthesized Ag/Fe2⁺ co-doped HAp nanoparticles, along with the gelzan-based nanocomposite scaffold produced via freeze-drying, underwent comprehensive analyses. These included Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and biological assessments for antibacterial activity and bioactivity. The results demonstrated that the Ag/Fe2⁺ co-doped HAp nanocomposite scaffold possessed favourable physicochemical properties. Furthermore, the integration of Ag and Fe2⁺ co-doped HAp into the gelzan matrix was confirmed, revealing the scaffold’s structural and compositional characteristics. Tests of apatite formation in simulated body fluid (SBF) indicated the development of layered apatite precipitates after 7 days. The scaffold also exhibited significant antibacterial activity, with inhibition zones of 7.35 ± 0.70 mm and 5.54 ± 0.60 mm against Staphylococcus aureus and Escherichia coli, respectively. These findings suggest the scaffold’s promising potential as a biomaterial for bone tissue regeneration.

Abstract C050: Leveraging ECM deposition by CAF-like Ewing sarcoma tumor cells to target micrometastases with matrix-binding VHHs

Abstract Ewing sarcoma (EwS) is an aggressive bone and soft tissue tumor and EwS patients often succumb to their disease years after initial treatment due to relapses at metastatic sites. Novel therapeutic strategies are needed that can successfully eliminate microscopic residual disease foci that persist at the end of primary therapy. Extracellular matrix (ECM) proteins in the tumor microenvironment (TME) provide critical pro-survival and pro-invasion signals to tumor cells. Our published and unpublished data show that the glycoprotein tenascin-C (TNC) is enriched in EwS metastases and that TNC and other pro-tumorigenic ECM proteins are deposited by subpopulations of CAF-like tumor cells that are activated in response to tumor and TME-derived TGF-beta ligands. TNC is abundantly produced by multiple human tumors of epithelial and non-epithelial lineage but is otherwise rarely expressed outside of development and wound healing. Importantly, TNC is specifically enriched in metastatic lesions where it has been implicated as a mediator of metastatic competence and treatment resistance. In the current work we have tested whether the TNC-rich TME of disseminated EwS tumor foci could be leveraged to direct therapies to sites of residual micrometastatic disease. To achieve this, we generated monovalent and bivalent anti-human TNC VHHs (hTNC-VHH) using a mammalian expression platform. Camelid-derived hTNC-VHH sequences were sourced from published literature. VHHs are single domain heavy chain only antibody fragments with higher stability and tissue penetration than conventional monoclonal antibodies. Using EwS tumor spheroids in collagen-rich 3D culture, hTNC-VHH penetrated dense ECM matrices and bound through multiple cell layers in under 10 minutes. hTNC-VHH accumulated in TNC-positive but not TNC-knockout EwS spheroids and were retained beyond 96 hours. To assess their potential to drive protein and immune therapies to TNC-rich TMEs, we fused hTNC-VHH to immune modulating CD3- and CD28-activating VHHs. These hTNC-VHH-CD3/CD28-conjugates promoted immune cell activation and tumor cell death in PBMC-tumor co-culture assays as determined by CD25 flow cytometry and fluorescence microscopy, respectively. To assess in vivo localization, fluorescently-tagged hTNC-VHH were intravenously injected into mice that had been xenografted with EwS cells. Tissue microscopy confirmed selective binding of hTNC-VHH to small lung and liver EwS micrometastases in less than 4 hours. VHHs were not retained in non-tumor bearing organs including the brain and heart or in tumor-free lung and liver regions. Experiments are ongoing to assess anti-tumor efficacy and pharmacodynamics of hTNC-VHH conjugates in EwS xenografts. Together these findings suggest that the ECM-remodeling properties of CAF-like EwS cells can be exploited to recruit novel ECM-targeting protein therapeutics to micrometastases. If successful, this innovative approach could eradicate microscopic residual disease and prevent metastatic EwS recurrence. Citation Format: Emma D. Wrenn, Jason P. Price, Raymond O. Ruff, Nicolas M. Garcia, James M. Olson, Elizabeth R. Lawlor. Leveraging ECM deposition by CAF-like Ewing sarcoma tumor cells to target micrometastases with matrix-binding VHHs [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C050.

Subchondral Bone Degeneration and Pathology 3-15 Years Following Ankle Sprain Injury in Adolescent Sport.

Sport-related ankle sprains (SASs) are prevalent in adolescents (ages 10-19), increasing the risk of developing posttraumatic osteoarthritis (PTOA). Although early ankle osteoarthritis (OA) is not well defined, OA eventually includes alterations in bone mineral density (BMD), structural changes, and soft tissue pathology. This study examined the impact of SAS sustained in adolescent sport on bone and soft tissue structural outcomes 3-15 years postinjury. Participants (n = 10) with prior unilateral SAS in adolescent sport (HxAI) were compared to age- and sex-matched controls. To assess injury-related pathologies and BMD, 1.5-tesla (T) extremity magnetic resonance imaging (MRI) and computed tomography scans were used. Semiquantitative scores for injury patterns and OA features from MRI scans were summed and compared between groups. The talus, calcaneus, navicular, and 5% distal tibia were segmented, and BMD was measured for each bone. All HxAI participants exhibited MRI injury pathology (median 2; IQR 1-6), whereas only 1 of 10 controls showed pathology (median 0; IQR 0-0), χ2(1, n = 20) = 16.36, P < .001. Both the injured and uninjured ankles in HxAI displayed injury pattern pathology. Additionally, 3 of 10 injured ankles and 2 of 10 uninjured ankles in the HxAI group (median 0; IQR 0-3), but none of the controls (median 0; IQR 0-0), exhibited OA features. In the HxAI group, talus BMD was lower in the injured ankle (502.4 ± 67.9 g/cm3) compared with the uninjured ankle (515.6 ± 70.1 g/cm3) (F = 13.33, P = .002), with no significant BMD differences at the calcaneus, navicular, or 5% distal tibia. No differences were observed between the ankles of the control group. The presence of injury pattern pathology, structural changes, and reduced talus BMD suggest that degenerative changes may occur in individuals as early as 3-15 years following ankle injury.

3D Printing Hierarchical Porous Nanofibrous Scaffold for Bone Regeneration.

Current limitations in 3D printing pose significant challenges for the fabrication of hierarchical 3D scaffolds with nanofibrous structures that simulate the natural bone extracellular matrix (ECM) for enhanced bone regeneration. This study presents an innovative approach to 3D printing customized hierarchical porous scaffolds with nanofiber structures using biodegradable nanofibrous microspheres as the bio-ink. In vitro investigations demonstrate that the hierarchical porous architecture substantially enhances cell infiltration and proliferation rates, while the nanofiber topology provides physical cues to guide osteogenic differentiation and ECM deposition. When serving as a cell carrier, the 3D-printed nanofibrous scaffold promotes bone tissue regeneration and integration in vivo. Additionally, the facile and versatile chemical modification facilitates the precise tailoring of the scaffold's functionality. Using nanofibrous microspheres with highly biomimetic and versatile modification properties as the foundational constituent in this universal 3D printing methodology enables comprehensive manipulation of scaffolding biological properties, spanning from macroscopic external morphology to molecular-scale biochemical kinetics, thereby addressing a diverse spectrum of clinical requisites.

A delphi-based model for prognosis of femoral head collapse in osteonecrosis: a multi-factorial approach.

Osteonecrosis of the femoral head (ONFH) is a progressive and debilitating condition characterized by the death of bone tissue due to inadequate blood supply. Despite advances in diagnostic imaging and treatment strategies, predicting the risk of femoral head collapse remains a significant clinical challenge. This study seeks to address this gap by developing a robust prognostic model that integrates clinical, imaging, and laboratory data to improve early diagnosis and guide therapeutic decision-making. We conducted a qualitative systematic review and employed the Delphi method to select key prognostic factors from clinical data, imaging findings, and laboratory indicators. The study included ONFH patients treated from January 2014 to December 2021. We used univariate and multivariate Cox regression analyses to develop a nomogram for predicting the risk of femoral head collapse. The model's performance was evaluated using the concordance index (C-index), calibration plots, and decision curve analysis (DCA). The study included 297 patients (454 hips) with ONFH. Key prognostic factors identified included pain presence (p < 0.001, RR = 0.185, 95% CI: 0.11-0.31), JIC classification (C1: p < 0.001, RR = 0.096, 95% CI: 0.054-0.171; C2: p < 0.001, RR = 0.323, 95% CI: 0.215-0.487), necrotic area (3 < MNAI < 6: p < 0.001, RR = 0.107, 95% CI: 0.061-0.190; MNAI ≥ 6: p < 0.001, RR = 0.466, 95% CI: 0.314-0.692), weight-bearing reduction (p < 0.001, RR = 0.466, 95% CI: 0.323-0.672), preservation of the anterolateral pillar (p < 0.001, RR = 0.223, 95% CI: 0.223-0.473), and subchondral bone fracture on CT (p < 0.001, RR = 0.32, 95% CI: 0.217-0.472). The nomogram demonstrated a high C-index of 0.88, indicating excellent predictive accuracy. Calibration plots showed good agreement between predicted and observed outcomes, and DCA confirmed the model's clinical utility. The prognostic model developed in this study provides a reliable tool for predicting femoral head collapse in ONFH patients. It allows for early identification of high-risk patients, guiding personalized treatment strategies to improve patient outcomes and reduce the need for invasive surgical procedures.

EL HÁBITO DE FUMAR Y SU INFLUENCIA EN LA CONSOLIDACIÓN ÓSEA: UNA REVISIÓN INTEGRADORA

Smoking is considered one of the risk factors for various diseases, not only related to the respiratory system but also influencing the physiological processes of various organs and body systems. This article aims to deepen the understanding of the effects of smoking on bone healing by analyzing its molecular, cellular, and clinical bases. This process is subject to possible direct or indirect interferences from chemical substances such as nicotine. It is important to note that, besides conventional cigarettes, there is also indiscriminate use of electronic cigarettes, which, according to an analysis conducted by Pérez and Duarte (2022), have considerably higher nicotine levels than traditional cigarettes. Another study conducted by González et al. (2021) highlights the increasing popularity of these devices among young people, underscoring the importance of preventive measures. According to the National Institute of Traumatology and Orthopedics (INTO), inhaling tobacco smoke increases bone tissue healing time by 60%, thus delaying the body's ability to heal injuries and compromising bone absorption. The clinical repercussions of smoking on the quality and speed of bone recovery after fractures and orthopedic procedures are identified to improve understanding and develop specific clinical strategies and interventions for smoking patients. The specific objectives of this research were to: investigate the molecular and cellular mechanisms of the bone healing process, analyze the effects of smoking on the quality of the formed tissue, evaluate the influence of smoking on the bone healing time in patients after fracture or orthopedic surgery, and finally propose therapeutic strategies and preventive measures to improve bone healing. To this end, a bibliographic search was conducted on articles relevant to the topic using various means. The selection of articles was based on three stages, choosing those that met the inclusion criteria. During the development of this article, it is observed that smoking is an extended and ancestral practice, being a constant and emerging health problem. Additionally, it is considered a modifiable risk factor for decreasing bone density. In conclusion, the need for specific strategies to address complications in bone healing in smoking patients is highlighted.

Role of R-spondin 2 on osteogenic differentiation of bone marrow mesenchymal stem cells and bone metabolism in ovariectomized mice

To investigate the effects of R-spondin 2 (Rspo2) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and bone mineral content in ovariectomized mice. BMSCs were extracted from the bone marrow of the long bones of 7 4-week-old female C57BL/6 mice using whole bone marrow culture and passaged. After the cell phenotype was identified by flow cytometry, the 3rd generation cells were co-cultured with 10, 20, 40, 80, and 100 nmol/L Rspo2. Then, the cell activity and proliferative capacity were determined by cell counting kit 8 (CCK-8), and the intervention concentration of Rspo2 was screened for the subsequent experiments. The osteogenic differentiation ability of BMSCs was detected by alkaline phosphatase (ALP) staining, and the mRNA levels of osteogenesis-related genes [RUNX family transcription factor 2 (Runx2), collagen type Ⅰ alpha 1 (Col1), osteocalcin (OCN)] were detected by real-time fluorescence quantitative PCR (RT-qPCR). In addition, 18 10-week-old female C57BL/6 mice were randomly divided into sham operation group (sham group), ovariectomy group (OVX group), and OVX+Rspo2-intervention group (OVX+Rspo2 group), with 6 mice in each group. The sham group only underwent bilateral back incision and suturing, while the other two groups established osteoporosis mouse models by bilateral ovarian castration. Then, the mice were given a weekly intraperitoneal Rspo2 (1 mg/kg) treatment in OVX+Rspo2 group and saline at the same dosage in sham group and OVX group. After 12 weeks of treatment, the body mass and uterus mass of the mice were weighed in the 3 groups to assess whether the OVX model was successfully prepared; the tibia bones were stained with HE and immunohistochemistry staining to observe the changes in tibial bone mass and the expression level of Runx2 protein in the bone tissues. Blood was collected to detect the expressions of bone metabolism markers [ALP, OCN, type Ⅰ procollagen amino-terminal peptide (PINP)] and bone resorption marker [β-collagen degradation product (β-CTX)] by ELISA assay. Micro-CT was used to detect the bone microstructure changes in the tibia, and three-dimensional histomorphometric analyses were performed to analyze the trabeculae thickness (Tb.Th), trabeculae number (Tb.N), trabeculae separation (Tb.Sp), and bone volume fraction (BV/TV). CCK-8 assay showed that Rspo2 concentrations below 80 nmol/L were not cytotoxic ( P>0.05), and the cell viability of 20 nmol/L Rspo2 group was significantly higher than that of the control group ( P<0.05). Based on the above results, 10, 20, and 40 nmol/L Rspo2 were selected for subsequent experiments. ALP staining showed that the positive cell area of each concentration of Rspo2 group was significantly larger than that of the control group ( P<0.05), with the highest showed in the 20 nmol/L Rspo2 group. The expression levels of the osteogenesis-related genes (Runx2, Col1, OCN) significantly increased, and the differences were significant between Rspo2 groups and control group ( P<0.05) except for Runx2 in the 40 nmol/L Rspo2 group. In animal experiments, all groups of mice survived until the completion of the experiment, and the results of the body mass and uterus mass after 12 weeks of treatment showed that the OVX model was successfully prepared. Histological and immunohistochemical staining showed that the sparseness and connectivity of bone trabecula and the expression of Runx2 in the OVX group were lower than those in the sham group, whereas they were reversed in the OVX+Rspo2 group after treatment with Rspo2, and the differences were significant ( P<0.05). ELISA assay showed that compared with the sham group, the serum bone metabolism markers in OVX group had an increase in ALP and a decrease in PINP ( P<0.05). After Rspo2 intervention, PINP expression significantly reversed and increased, with significant differences compared to the sham group and OVX group ( P<0.05). The bone resorption marker (β-CTX) was significantly higher in the OVX group than in the sham group ( P<0.05), and it was significantly decreased in the OVX+Rspo2 group when compared with the OVX group ( P<0.05). Compared with the sham group, Tb.Th, Tb.N, and BV/TV significantly decreased in the OVX group, while Tb.Sp significantly increased ( P<0.05); after Rspo2 intervention, all of the above indexes significantly improved in the OVX+Rspo2 group ( P<0.05) except Tb.Th. Rspo2 promotes differentiation of BMSCs to osteoblasts, ameliorates osteoporosis due to estrogen deficiency, and promotes bone formation in mice.

Technical note: Effects of chemical, radiational, and thermal treatment of bone tissue on material stiffness and anisotropy.

We evaluated the effects of four treatments for pathogen inactivation in bone tissue (ethanol storage, formalin fixation, gamma irradiation, and heat treatment via autoclave) on stiffness and anisotropy values in bone samples. Cortical bone samples from the humerus of 14 bovine specimens were subjected to Knoop microindentation analysis in longitudinal and transverse planes of section and four indenter orientations within each section. From each specimen, individual samples were assigned to one of five treatment conditions: 50% ethanol-saline solution, formalin immersion, gamma irradiation, autoclave, and buffered saline (controls). Each sample was microindented 100 times and the resultant stiffness data were analyzed by a resampled factorial analysis of variance. First- and second-order interactions as well as main effects of indenter orientation, treatment, and specimen were significant for both transverse and longitudinal sections, with the sole exception that indenter orientation-treatment interaction was nonsignificant for longitudinal sections. Interaction plots reveal that thermal (autoclave) and irradiation treatments depress stiffness values the most, while patterns of indentation stiffness at different orientations are relatively unaffected. Patterns of anisotropy are relatively unaffected by preservative treatments, but elastic modulus changes are consistent and unambiguous. Formalin and ethanol treatments are most comparable to controls and represent the best preservative media for mechanical testing. These options, however, are likely to be the least effective for ensuring the inactivation or sterilization of potentially contaminated samples.

Diagnostic and Therapeutic Challenges of Focal Cortical Dysplasia in Mali: A Case Report

Focal Cortical Dysplasias (FCDs) are a common cause of pharmaco-resistant epilepsy. FCDs are rare conditions, and their pathogenesis remains poorly understood. We report a 12-year-old patient seen in our clinic for focal onset epileptic seizures. Neurological examination and brain CT-scan were nearly normal. However, an electroencephalogram (EEG) revealed a slightly slow background rhythm with slow spikes in the medial and right parietal regions and a brain magnetic resonance imaging (MRI) showed a focal cortical thickening in the right parietal lobe with FLAIR hypersignal, indicating a focal cortical dysplasia. Ongoing seizures marked the disease course under antiepileptic polytherapy after 15 months of treatment. Keywords: Focal cortical dysplasia, pharmaco-resistant epilepsy, Mali, Africa.

Biocompatible nanocomposite hydroxyapatite-based granules with increased specific surface area and bioresorbability for bone regenerative medicine applications.

Hydroxyapatite (HA) granules are frequently used in orthopedics and maxillofacial surgeries to fill bone defects and stimulate the regeneration process. Optimal HA granules should have high biocompatibility, high microporosity and/or mesoporosity, and high specific surface area (SSA), which are essential for their bioabsorbability, high bioactivity (ability to form apatite layer on their surfaces) and good osseointegration with the host tissue. Commercially available HA granules that are sintered at high temperatures (≥ 900°C) are biocompatible but show low porosity and SSA (2-5 m2/g), reduced bioactivity, poor solubility and thereby, low bioabsorbability. HA granules of high microporosity and SSA can be produced by applying low sintering temperatures (below 900°C). Nevertheless, although HA sintered at low temperatures shows significantly higher SSA (10-60 m2/g) and improved bioabsorbability, it also exhibits high ion reactivity and cytotoxicity under in vitro conditions. The latter is due to the presence of reaction by-products. Thus, the aim of this study was to fabricate novel biomaterials in the form of granules, composed of hydroxyapatite nanopowder sintered at a high temperature (1100°C) and a biopolymer matrix: chitosan/agarose or chitosan/β-1,3-glucan (curdlan). It was hypothesized that appropriately selected ingredients would ensure high biocompatibility and microstructural properties comparable to HA sintered at low temperatures. Synthesized granules were subjected to the evaluation of their biological, microstructural, physicochemical, and mechanical properties. The obtained results showed that the developed nanocomposite granules were characterized by a lack of cytotoxicity towards both mouse preosteoblasts and normal human fetal osteoblasts, and supported cell adhesion to their surface. Moreover, produced biomaterials had the ability to induce precipitation of apatite crystals after immersion in simulated body fluid, which, combined with high biocompatibility, should ensure good osseointegration after implantation. Additionally, nanocomposite granules possessed microstructural parameters similar to HA sintered at a low temperature (porosity approx. 50%, SSA approx. 30m²/g), Young's modulus (5-8 GPa) comparable to cancellous bone, and high fluid absorption capacity. Moreover, the nanocomposites were prone to biodegradation under the influence of enzymatic solution and in an acidic environment. Additionally, it was noted that the hydroxyapatite nanoparticles remaining after the physicochemical dissolution of the biomaterial were easily phagocytosed by mouse macrophages, mouse preosteoblasts, and normal human fetal osteoblasts (in vitro studies). The obtained materials show great potential as bone tissue implantation biomaterials with improved bioresorbability. The obtained materials show great potential as bone tissue implantation biomaterials with improved bioresorbability.

Biomaterial Cues for Regulation of Osteoclast Differentiation and Function in Bone Regeneration

AbstractTissue regeneration involves dynamic dialogue between and among different cells and their surrounding matrices. Bone regeneration is specifically governed by reciprocity between osteoblasts and osteoclasts within the bone microenvironment. Osteoclast‐directed resorption and osteoblast‐directed formation of bone are essential to bone remodeling, and the crosstalk between these cells is vital to curating a sequence of events that culminate in the creation of bone tissue. Among bone biomaterial strategies, many have investigated the use of different material cues to direct the development and activity of osteoblasts. However, less attention has been given to exploring features that similarly target osteoclast formation and activity, with even fewer strategies demonstrating or integrating biomaterial‐directed modulation of osteoblast‐osteoclast coupling. This review aims to describe various biomaterial cues demonstrated to influence osteoclastogenesis and osteoclast function, emphasizing those that enhance a material construct's ability to achieve bone healing and regeneration. Additionally discussed are approaches that influence the communication between osteoclasts and osteoblasts, particularly in a manner that takes advantage of their coupling. Deepening the understanding of how biomaterial cues may dictate osteoclast differentiation, function, and influence on the microenvironment may enable the realization of bone‐replacement interventions with enhanced integrative and regenerative capacities.

Research progress on bone repair biomaterials with the function of recruiting endogenous mesenchymal stem cells

To review the research progress on bone repair biomaterials with the function of recruiting endogenous mesenchymal stem cells (MSCs). An extensive review of the relevant literature on bone repair biomaterials, particularly those designed to recruit endogenous MSCs, was conducted, encompassing both domestic and international studies from recent years. The construction methods and optimization strategies for these biomaterials were summarized. Additionally, future research directions and focal points concerning this material were proposed. With the advancement of tissue engineering technology, bone repair biomaterials have increasingly emerged as an ideal solution for addressing bone defects. MSCs serve as the most critical "seed cells" in bone tissue engineering. Historically, both MSCs and their derived exosomes have been utilized in bone repair biomaterials; however, challenges such as limited sources of MSCs and exosomes, low survival rates, and various other issues have persisted. To address these challenges, researchers are combining growth factors, bioactive peptides, specific aptamers, and other substances with biomaterials to develop constructs that facilitate stem cell recruitment. By optimizing mechanical properties, promoting vascular regeneration, and regulating the microenvironment, it is possible to create effective bone repair biomaterials that enhance stem cell recruitment. In comparison to cytokines, phages, and metal ions, bioactive peptides and aptamers obtained through screening exhibit more specific and targeted recruitment functions. Future development directions for bone repair biomaterials will involve the modification of peptides and aptamers with targeted recruitment capabilities in biological materials, as well as the optimization of the mechanical properties of these materials to enhance vascular regeneration and adjust the microenvironment.

Glial maturation factor-β deficiency prevents oestrogen deficiency-induced bone loss by remodelling the actin network to suppress adipogenesis of bone marrow mesenchymal stem cells.

An imbalance between the adipogenesis and osteogenesis of bone marrow mesenchymal stem cells (BMSCs) is considered the basic pathogenesis of osteoporosis. Although actin cytoskeleton remodelling plays a crucial role in the differentiation of BMSCs, the role of actin cytoskeleton remodelling in the adipogenesis of BMSCs and postmenopausal osteoporosis (PMOP) has remained elusive. Glia maturation factor-beta (GMFB) has a unique role in remodelling the polymerization/depolymerization cycles of actin. We observed that GMFB expression was increased in bone tissue from both ovariectomized (OVX) rats and PMOP patients. GMFB knockout inhibited the accumulation of bone marrow adipocytes and increased bone mass in the OVX rat model. The inhibition of adipocyte differentiation in GMFB knockout BMSCs was mediated via actin cytoskeleton remodelling and the Ca2+-calcineurin-NFATc2 axis. Furthermore, we found that GMFB shRNA treatment in vivo had favourable effects on osteoporosis induced by OVX. Together, these findings suggest a pathological association of the GMFB with PMOP and highlight the potential of the GMFB as a therapeutic target for osteoporosis patients.

Clinical and radiographic assessment of the association between orthodontic mini-screws and periodontal health.

Proper anchorage control is crucial for predictable tooth movement and preventing inadequate torque during orthodontic treatment. Through clinical and radiographic parameters; this study assesses the association between mini-screws and periodontal health. A prospective observational study included 16 systemically healthy non-smoking individuals requiring mini-screws. Mini-screws with a rough, titanium oxide-coated surface were placed. Periodontal assessments (Plaque index, gingival index, probing pocket depth, gingival recession, bleeding on probing, mucosal discomfort, mucosal redness, keratinized tissue width, supracrestal tissue height, and transmucosal soft tissue thickness) were performed at 2nd week and 3 months post-placement. Radiographic evaluations measured distances between mini-screws and adjacent teeth using Image J software. The study included 13 females and 3 males (mean age 21.9 ± 1.8 years) with 24 mini-screws. Early mini-screw loss was not observed. Significant reductions in site-level Gingival Index and bleeding on probing (p < 0.05) and full-mouth bleeding on probing (p < 0.05) were noted over time. Absence of significant differences was found in mucosal discomfort and redness, keratinized tissue width, or transmucosal soft tissue thickness, but supracrestal tissue height decreased significantly (p < 0.05). Radiographically, significant bone reduction around mini-screws was observed at 3 months, with torque gauge values significantly decreased as well (p < 0.05). Orthodontic mini-screws can be effectively utilized in orthodontic treatment with proper planning and monitoring. While improvements in gingival health were observed with targeted oral care, the study underscores the need for careful consideration of potential risks to periodontal tissues, such as reductions in supracrestal tissue height and bone levels. A balanced approach that integrates preventive strategies with precise screw placement is essential to maximize the benefits of mini-screws while minimizing potential periodontal complications. While proper oral hygiene can help control inflammation around mini-screw sites, clinicians must also be mindful of potential risks, such as reductions in bone levels and tissue height. Careful patient selection, precise placement, and regular follow-up are crucial to ensure the stability of mini-screws' stability and to prevent complications, ultimately contributing to better treatment outcomes in orthodontic care. This study was registered on ClinicalTrials.gov with the registration number NCT06491849 on June 28, 2024.

An Algorithm for Management of Radial Longitudinal Deficiency.

Lack of specific guidelines in the literature renders management of radial longitudinal deficiency (RLD) exceedingly diverse. This diversity in treatment approaches can lead to variability in outcomes and pose a challenge in determining the most effective interventions for each individual case of RLD. Surgeons must carefully consider the unique characteristics and needs of each patient when developing a treatment plan for this complex condition. Around 40% of cases are linked to syndromes like Holt-Oram syndrome, thrombocytopenia absent radius (TAR) syndrome, Fanconi anaemia and VACTERL. Hand surgeons must be knowledgeable about these conditions, as they may be the first to identify these syndromes in children. Associated elbow stiffness can also be a crucial factor in treatment decision-making. Although this condition has been studied for more than 10 decades, the surgical treatment that is currently available is not completely successful in restoring 'normal' wrist function and appearance. Centralisation and radialisation procedures continue to be the cornerstones of surgical treatment. Many innovative approaches include altering the biomechanics of this condition with bony or soft tissue procedures and microvascular techniques. Understanding the proximal limb changes is crucial in the holistic management of this challenging malformation. This article presents a treatment algorithm based on literature evidence and our clinical experience. Level of Evidence: Level V (Therapeutic).

Macrophage migration inhibitory factor promotes heterotopic ossification by mediating ROS/HIF-1α positive feedback loop and activating Wnt/β-catenin signaling pathway.

Heterotopic ossification (HO) refers to the development of bone tissue in areas other than the skeletal system. The development and maturation of the skeletal system are significantly influenced by macrophage migration inhibitory factor (MIF). The objective of this study was to examine the impact of MIF on the in vitro osteogenic differentiation and mineralization of tendon-derived stem cells (TDSCs), mediated by a positive feedback loop involving ROS/HIF-1α/MIF. TDSCs were isolated and identified from the hind limbs of C57/BL6 mice. The functional and procedural roles of MIF in HO, focusing on the impact of MIF on the differentiation of TDSCs into bone-forming cells were investigated in vitro. Seventy-five mice were randomly assigned to five groups. Gene expression and histological analyses of MIF and its receptors, and determine the expression of osteogenic markers in vivo. The results revealed a positive and concentration-dependent effect of MIF on the osteogenic differentiation of TDSCs. Furthermore, an ROS/HIF-1α/MIF positive loop was detected in the simulated early trauma hypoxic microenvironment, resulting in a 3 to 4 folds increase in MIF expression levels. MIF was also found to enhance double the expression levels of markers associated with bone and cartilage at the site of injury, consequently facilitating the development of HO, which was thought to be associated with the activation of the Wnt/β-catenin pathway. MIF, which mediates the ROS/HIF-1α/MIF positive feedback loop during the hypoxic phase of HO, triggers the Wnt/β-catenin signaling pathway to enhance the osteogenic differentiation and formation of HO in TDSCs.

Nanotechnology-Enhanced Orthopaedic Surgery

Nanomaterials hold significant promise for the future of orthopaedic implants due to their ability to mimic the nanoscale components of the bone, such as collagen fibrils and hydroxyapatite. Nanomaterials can regulate cell behaviour while offering mechanical strength and biocompatibility, making them ideal for bone repair and tissue regeneration. This comprehensive review explores the key existing and potential applications of nanotechnology in orthopaedics, including bone tissue engineering, drug delivery systems, systems combatting implant-related infections, and the surface preparation of implants to enhance osseointegration. These innovations are poised to revolutionise orthopaedic care by improving implant durability, reducing infection risks, and promoting bone regeneration to deliver personalised treatment and create better patient outcomes.

The circulatory levels and bone expression of MIR21, 34a, 155 and their target genes in a section of Egyptian Population.

Bone tissue is constantly regenerated and repaired through a finely balanced process known as bone remodeling. Many miRNAs act as regulators of the signaling pathways involved in bone metabolic processes to maintain tissue homeostasis. This study aimed to assess the circulating levels of MIR21, MIR34a, and MIR155 in human serum and their bone expression, and the expression of bone turnover-related genes which can reflect the bone quality. This prospective study was conducted on 60 patients (30 males and 30 females) indicated for surgical interventions for neural decompression +/- fixation. Relative quantification of expression of MIR21, miR34a, and MIR155 and bone related genes was assayed using PCR. The serum levels of osteocalcin and Serum Bone Alkaline Phosphatase (sBAP) were assayed using a human ELISA kit. The main finding of the present work was the strong positive association between the circulating levels of only miR21 and MIR155 and their bone expression in the population under study and with bone markers and target genes Also, a positive association was found between both bone expression and circulating MIR21 levels with age and sBAP. These results suggest that the circulating levels of these microRNAs as early markers for the predication of bone quality.

EDI&amp;S SO04 Accuracy of Outsourced Radiology Reports in Emergency Surgical Care; Do they provide a high-quality cost-effective service?

Abstract Background Computed Tomography (CT) scans play a crucial role in emergency surgical care enabling proper management and prompt decision making. In our study we aimed to compare abdominal CT scan reports created by inhouse radiologists to those created by outsourced radiology reporting service for patients admitted with acute surgical pathologies. The study also looked at the impact of the reporting style (free text or structured format) on the quality of scan reports. Method The study was conducted in a busy general surgery unit located in the North West of England. Patients who were admitted acutely under the surgical specialty and had abdominal CT scans over a period of three months from August 2023 to October 2023 were included. Patients who were admitted following trauma or had non abdominal CT scans have been excluded. Statistical analysis was conducted to compare inhouse radiology reports to outsourced ones. Scan reports were thoroughly scrutinised to identify whether they included all relevant information needed and whether they were written in structured or free text format. Results A total of 192 patients were identified with a median age of 59 years. Outsourced radiology reports were found to be significantly underreporting comments on the biliary system (OR=0.369, P=0.046), spleen (OR=0.414, P=0.044), kidneys (OR=0.354, P=0.027), lymph nodes (OR=0.412, P=0.011), mesentery and peritoneum (OR=0.364, P=0.004), vasculature (OR=0.381, P=0.002), bones and soft tissues (OR=0.273, P=0.003), as well as lung bases (OR=0.300, P=0.009). Structured format was found to outperform free text style on comments on spleen (OR=8.064, P=0.044), adrenals (OR=8.468, P=0.039), mesentery and peritoneum (OR=4.618, P=0.000), as well as bone and soft tissues (OR=9.295, P=0.031). Conclusion CT scans reported by outsourced radiology service were found to be significantly underreporting certain key elements. Additionally, free style reporting format was found to miss some crucial aspects of abdominal scan reports. That adds further challenges to clinicians assessing and managing acute surgical patients. Further studies auditing different outsourced companies are recommended to ensure patients are provided with high-quality cost-effective emergency service.

Prospective Screening of Cancer Syndromes in Patients with Mesenchymal Tumors

Background: The etiology of most mesenchymal tumors is unknown, and knowledge about syndromes with an increased risk of tumors in bone or soft tissue is sparse. Methods: We present a prospective germline analysis of 312 patients with tumors suspected of being sarcomas at a tertiary sarcoma center. Germline and tumor whole genome sequencing, tumor transcriptome, and methylome analyses were performed. Results: Germline pathogenic or likely pathogenic variants associated with an increased risk of tumors were detected in 24 patients (8%), of which 11 (4%) harbored a detectable second hit in the tumor. Second hits were confirmed in genes with (NF1, RB1, TP53, EXT2, and SDHC) and without (ATM, CDC73, MLH1, MSH6, POLG, and KCNQ1) known association with mesenchymal tumor predisposition. Sarcomas from two Lynch syndrome patients showed mismatch repair deficiency, predicting a treatment response to immune checkpoint inhibitors (Level 1 biomarker according to the FDA (Federal Drug Administration) and ESMO (European Society for Medical Oncology)). None of the three CHEK2 carriers had a second hit in the tumor, suggesting a weak link to sarcoma. Conclusions: We conclude that second-hit analyses can be used in standard of care to identify syndrome-related tumors. This approach can help distinguish true manifestations of tumor syndromes from unrelated germline findings and enhance the understanding of germline predisposition in soft tissue tumors. Prospective screening using germline whole genome sequencing should be considered when comprehensive somatic sequencing is introduced into clinical practice.