Bone Healing Research Articles

Platelet-Rich Fibrin (PRF) Analyzed for Cytokine Profiles - A Misguided Hope for Osteogenesis in Jawbone Defects? Research and Clinical Observational Study.

Platelet-rich fibrin (PRF) blood concentrates are used in oral implantology and defect surgery to promote osteoneogenesis in Bone Marrow Defects in Jawbone (BMDJ), according to the morphology of fatty-degenerative osteonecrosis also called FDOJ. Can the benefit of PRF on alveolar osteoneogenesis be confirmed by cytokine analysis?. The cytokine expressions of the PRF samples in 26 patients undergoing BMDJ/FDOJ surgery in the same session were analysed for seven cytokines (RANTES/CCL5; FGF-2; IL-1RA; Il-6; IL-8; MCP-1; TNF-a) by multiplex (Luminex). The FDOJ samples of these 26 BMDJ/FDOJ patients were analysed for the RANTES/CCL5 expression only. Cytokine expression in PRF is compared to reference values for healthy medullary bone of the jaw and BMDJ/FDOJ and shows that the cytokine expressions of the PRF samples do not compensate or counteract prima vista for the cytokine dysregulations present in the BMDJ/FDOJ areas. To define the aid of cytokines studied in PRF in the restoration of the immunological dysregulation in areas of BMDJ/FDOJ, literature is reviewed comparing RANTES/CCL5, IL-1ra, TNF-α and MCP-1/CCL2 expression in PRF and BMDJ/FDOJ. Immunoregulatory properties of PRF in alveolar bone restoration are evaluated. PRF was mistakenly thought to be a cure for bone healing, which is here shown to be incorrect. Enoral Ultrasound Sonography of bone density is available for the clinical measurement of individually developed osteoneogenesis by PRF. The multiplex analysis of PRF shows a dynamic and cytokine-based interaction with osteoneogenesis that is not yet fully clarified.

Meta-analysis of proteomics data from osteoblasts, bone, and blood: Insights into druggable targets, active factors, and potential biomarkers for bone biomaterial design

Non-healing bone defects are a pressing public health concern accounting for one main cause for decreased life expectancy and quality. An aging population accompanied with increasing incidence of comorbidities, foreshadows a worsening of this socio-economic problem. Conventional treatments for non-healing bone defects prove ineffective for 5%–10% of fractures. Those challenges not only increase the patient’s burden but also complicate medical intervention, underscoring the need for more effective treatment strategies and identification of patients at risk before treatment selection. To address this, our proteomic meta-analysis aims to identify universally affected proteins and functions in the context of bone regeneration that can be utilized as novel bioactive biomaterial functionalizations, drug targets or therapeutics as well as analytical endpoints, or biomarkers in implant design and testing, respectively. We compiled 29 proteomic studies covering cellular models, extracellular vesicles, extracellular matrix, bone tissue, and liquid-biopsies to address different tissue hierarchies and species. An innovative, integrated framework consisting of data harmonization, candidate protein selection, network construction, and functional enrichment as well as drug repurposing and protein scoring metrics was developed. To make this framework widely applicable to other research questions, we have published a detailed tutorial of our meta-analysis process. We identified 51 proteins that are potentially important for bone healing. This includes well-known ECM components such as collagens, fibronectin and periostin, and proteins less explored in bone biology like YWHAE, HSPG2, CCN1, HTRA1, IGFBP7, LGALS1, TGFBI, C3, SERPINA1, and ANXA1 that might be utilized in future bone biomaterial development. Furthermore, we discovered the compounds trifluoperazine, phenethyl isothiocyanate, quercetin, and artenimol, which target key proteins such as S100A4, YWHAZ, MMP2, and TPM4 providing the option to manipulate undesired processes in bone regeneration. This may open new ways for treatment options to face the increasing socio-economic pressure of non-healing bone defects.

Application of botulinum toxin A in tissue repair and regeneration

Tissue repair and regeneration present significant clinical challenges. Despite the array of treatments currently available in this domain, the urgent demand for innovative therapies persists, with the goal of enhancing patient quality of life. Recently, the application of botulinum neurotoxin type A (BoNT/A) has expanded within the realm of tissue repair and regeneration. This review critically examines the utilization of BoNT/A, specifically focusing on its vascular effects, potential in nerve regeneration, and contributions to bone healing. This analysis not only offers fresh insights into the diverse mechanisms of action of BoNT/A but also explores additional therapeutic possibilities for patients.

Constructing bone organoids based on endochondral ossification model via endogenous enzyme-induced mineralization

Regenerative strategies based on the utilization of bone organoids have been effective. The mineralization of bone organoids, in particular, is a crucial step that not only validates their functionality but also their potential for clinical applications in bone regeneration and disease modeling. However, the mechanisms underlying mineralization in bone organoids is unclear. Here, we recapitulated the differentiation and mineralization processes of natural bone development, through the mineralization of cartilaginous pellets (CPs) by utilizing the concept of endogenous enzyme-induced mineralization. An endogenous enzyme-induced mineralization system based on the encapsulation of CPs, calcium glycerophosphate (CaGP), and 6,8-dimethyl-3-(4-phenyl-1H-imidazol-5-yl)-quinolin-2(1H)-one (DIPQUO) in a methacrylated gelatin (GelMA) hydrogel was reconstructed. DIPQUO significantly enhanced the expression of alkaline phosphatase (ALP) in CPs, hydrolyzed CaGP to provide calcium and phosphate ions, and synchronously accelerated the mineralization of CPs and the hydrogel. The mineralization of CPs exhibited a stage-specific gene expression pattern highly consistent with the process of endochondral ossification, which was mediated by the Wnt/β-catenin and MAPK/ERK signaling pathways confirmed by RNA sequencing. Electron microscopy-based ultrastructural analysis showed that the number of mitochondria, lysosomes, and vesicles increased markedly during mineralization. Furthermore, bone organoids constructed via endogenous enzyme-induced mineralization led to rapid bone healing within 4 weeks in a rat model with a distal femoral condyle defect. Our findings have important implications for elucidating the bone formation process and bone-defect regeneration.

Impact of Porosity and Stiffness of 3D Printed Polycaprolactone Scaffolds on Osteogenic Differentiation of Human Mesenchymal Stromal Cells and Activation of Dendritic Cells.

Despite the potential of extrusion-based printing of thermoplastic polymers in bone tissue engineering, the inherent nonporous stiff nature of the printed filaments may elicit immune responses that influence bone regeneration. In this study, bone scaffolds made of polycaprolactone (PCL) filaments with different internal microporosity and stiffness was 3D-printed. It was achieved by combining three fabrication techniques, salt leaching and 3D printing at either low or high temperatures (LT/HT) with or without nonsolvent induced phase separation (NIPS). Printing PCL at HT resulted in stiff scaffolds (modulus of elasticity (E): 403 ± 19 MPa and strain: 6.6 ± 0.1%), while NIPS-based printing at LT produced less stiff and highly flexible scaffolds (E: 53 ± 10 MPa and strain: 435 ± 105%). Moreover, the introduction of porosity by salt leaching in the printed filaments significantly changed the mechanical properties and degradation rate of the scaffolds. Furthermore, this study aimed to show how these variations influence proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBMSC) and the maturation and activation of human monocyte-derived dendritic cells (Mo-DC). The cytocompatibility of the printed scaffolds was confirmed by live-dead imaging, metabolic activity measurement, and the continuous proliferation of hBMSC over 14 days. While all scaffolds facilitated the expression of osteogenic markers (RUNX2 and Collagen I) from hBMSC as detected through immunofluorescence staining, the variation in porosity and stiffness notably influenced the early and late mineralization. Furthermore, the flexible LT scaffolds, with porosity induced by NIPS and salt leaching, stimulated Mo-DC to adopt a pro-inflammatory phenotype marked by a significant increase in the expression of IL1B and TNF genes, alongside decreased expression of anti-inflammatory markers, IL10 and TGF1B. Altogether, the results of the current study demonstrate the importance of tailoring porosity and stiffness of PCL scaffolds to direct their biological performance toward a more immune-mediated bone healing process.

Safety of vertical osteotomies in segmental Le Fort I procedures: a one-year radiological follow-up study

The aim of this study was to evaluate the frequency of dental and periodontal injuries, as well as radiological bone healing, at the vertical osteotomies in patients treated with segmental Le Fort I (LFI) osteotomy, as observed on cone beam computed tomography (CBCT) scans. This retrospective study analysed 105 patients who underwent segmental LFI osteotomy, in whom vertical osteotomies between the lateral incisor and canine were performed using a bur and extended in depth with an osteotome. CBCT scans were obtained preoperatively and at the 1-week and 1-year follow-ups. Measurements at the 1-week follow-up included interdental distances, root injuries, and periodontal detachment, while assessment at the 1-year follow-up included endodontic treatment and healing of the vertical osteotomies. The results showed no damage to the 420 roots at risk adjacent to the osteotomies; however, the osteotomy extended into the periodontal ligament in 38 roots. The mean preoperative minimum distance between roots differed significantly between osteotomy sites with intact periodontal ligament and those with periodontal ligament detachment (P < 0.001). One tooth was endodontically treated at the 1-year follow-up. Incomplete healing of the vertical osteotomy occurred more frequently in female patients than in male patients (P = 0.012). The study findings suggest that segmental LFI osteotomy is safe when performed with a bur and osteotome, provided a minimum distance of 2.5 mm between roots is maintained.

Obesity Prolongs the Pro-Inflammatory Response and Attenuates Bone Healing on Titanium Implants

Obesity is a metabolic disease resulting from excess body fat accumulation associated with chronic systemic inflammation. Obesity has been shown to impact the function and activity of neutrophils, macrophages, and T cells, contributing to higher circulating levels of pro-inflammatory cytokines. Biomaterial surface properties such as roughness and hydrophilicity can influence the behavior of immune cells in the peri-implant microenvironment. This study aimed to determine how obesity induced by a high-fat diet (HFD) affects the inflammatory response to modified titanium (Ti) implants and subsequent bone formation. Obese mice had significantly more neutrophils, pro-inflammatory macrophages, and T cells and fewer anti-inflammatory macrophages and mesenchymal stem cells (MSCs) in the peri-implant tissue than lean mice. Obesity also increased circulating adipokines and pro-inflammatory cytokines when compared to lean animals. Bone formation around Ti implants was reduced in obese mice compared to controls. Adoptive transfer of bone marrow cells isolated from obese mice into wild-type mice demonstrated the localized impact of obesity on immune cell function and phenotype, promoting a pro-inflammatory peri-implant microenvironment and attenuating bone formation post-implantation. These results show that obesity significantly affects the inflammatory response to modified Ti implants, prolonging the pro-inflammatory response to the implanted biomaterial and compromising bone formation. Statement of SignificanceObesity has been shown to significantly alter physiological processes, including the behavior of immune cells, inducing a state of systemic chronic inflammation. Our study demonstrates that obesity-induced via a high-fat diet alters immune cell response to implanted biomaterials, with increased pro-inflammatory response and attenuated immunomodulation resulting in decreased biomaterial integration.

Accelerating Fracture Healing in Delayed Uniting Fractures: A Clinical Study

Background: Delayed union fractures pose a significant clinical challenge, often requiring enhanced treatment modalities to accelerate healing and improve patient outcomes. Various techniques, including autologous bone grafting and biologic agents like platelet-rich plasma (PRP) and bone morphogenetic proteins (BMPs), have been employed to stimulate bone regeneration. However, the optimal approach remains debated. Objective: This study aimed to compare the efficacy of autologous bone grafting, biologic agents, and combined therapies in promoting fracture healing, reducing pain, improving functional outcomes, and enhancing patient satisfaction in delayed union fractures. Methods: A prospective study was conducted on 80 patients with delayed union fractures. Patients were randomly assigned to one of four groups: standard care (control), autologous bone grafting, biologic agents (PRP and BMPs), or a combination of bone grafting and biologic agents. Radiographic healing was assessed at 6, 12, and 24 weeks. Pain intensity was measured using the Visual Analog Scale (VAS), functional outcomes were assessed using the AAOS lower limb function scale, and patient satisfaction was evaluated using a Likert scale. Results: The combined therapy group exhibited significantly faster radiographic healing, with 80% of patients showing callus formation at 6 weeks and 95% achieving complete union at 24 weeks, compared to 35% in the control group. The combined group also reported the greatest reduction in VAS pain scores, with a mean decrease from 7.8 to 1.5 at 24 weeks (p&lt;0.001). Functional outcomes were significantly improved in the combined group, with a mean AAOS score of 100 at 24 weeks, compared to 70 in the control group (p&lt;0.001). Additionally, 90% of patients in the combined group reported high satisfaction, compared to 40% in the control group. Conclusion: The combination of autologous bone grafting and biologic agents, such as PRP and BMPs, significantly accelerates ..........

Controversies in the Management of Type II Odontoid Fractures.

The management of type II odontoid fractures in the elderly is controversial, as these patients often have numerous medical comorbidities that increase the risks of surgery, but they may also fail to achieve fracture healing with nonsurgical management. Recent changes in technology and surgeon attitudes may influence the preferred approach to both surgical and nonsurgical treatments for many clinicians. While bony fracture healing remains the goal of management, a stable fibrous union is increasingly considered a satisfactory outcome. The optimal surgical approach remains debated, with some authors raising concerns about the risk of swallowing dysfunction being particularly problematic with odontoid screw placement in the elderly. The use of BMP-2 applied either anteriorly into the fracture site or posteriorly in the interlaminar space and placement of temporary posterior fixation to be removed upon demonstration of anterior bony healing are novel surgical techniques that are presently the subject of investigation. A clearer understanding of the currently available treatment options and the associated controversies may improve clinician decision-making and potentially better patient outcomes in the management of type II odontoid fractures for the growing geriatric population.

The inhibitory effect of salidroside on RANKL-induced osteoclast formation via NFκB suppression.

Bone fractures are a prevalent clinical issue, and recent studies highlighted the promising potential of natural bone healing agents in enhancing fracture repair and regeneration. The regulatory interaction mechanism between osteoblasts and osteoclasts is crucial for bone cell biology and bone disease. In Mongolian medicine, people have used the Rhodiola rosea (R. rosea) extract to accelerate bone healing in bone fractures. Salidroside is a bioactive compound of R. rosea. Salidroside is known to regulate bone metabolism and inhibit the activation of osteoclast cells, but how it affects the differentiation of osteoclasts is unknown. We examined the effect of R. rosea extract and its bioactive compound salidroside on the RANKL-induced osteoclast formation in RAW264.7 cells. The present study observed that salidroside directly inhibits RANKL-induced TRAP-positive osteoclast formation. Immunoblotting analysis revealed that salidroside inhibited the expression of c-Fos and NFATc1, osteoclastogenic key transcription factors, by suppressing late activation of p65 NFκB. Further, the ethanol extracts of R. rosea significantly reduced the RANKL-induced osteoclasts in a dose-dependent manner. In conclusion, salidroside inhibits RANKL-induced osteoclast formation via suppressing the NFκB/c-Fos/NFATc1 signalling pathway. R. rosea, a primary source of salidroside, is helpful for bone healing via its inhibitory effect on osteoclast formation.

3D Bioprinting Strategies for Melatonin‐Loaded Polymers in Bone Tissue Engineering

AbstractBone pathologies are still among the most challenging issues for orthopedics. Over the past decade, different methods are developed for bone repair. In addition to advanced surgical and graft techniques, polymer‐based biomaterials, bioactive glass, chitosan, hydrogels, nanoparticles, and cell‐derived exosomes are used for bone healing strategies. Owing to their variation and promising advantages, most of these methods are not translated into clinical practice. Three dimensonal (3D) bioprinting is an additive manufacturing technique that has become a next‐generation biomaterial technique adapted for anatomic modeling, artificial tissue or organs, grafting, and bridging tissues. Polymer‐based biomaterials are mostly used for the controlled release of various drugs, therapeutic agents, mesenchymal stem cells, ions, and growth factors. Polymers are now among the most preferable materials for 3D bioprinting. Melatonin is a well‐known antioxidant with many osteoinductive properties and is one of the key hormones in the brain–bone axis. 3D bioprinted melatonin‐loaded polymers with unique lipophilic, anti‐inflammatory, antioxidant, and osteoinductive properties for filling large bone gaps following fractures or congenital bone deformities may be developed in the future. This study summarized the benefits of 3D bioprinted and polymeric materials integrated with melatonin for sustained release in bone regeneration approaches.

019. Craniofacial Fracture and Secretome: A Systematic Review

Background: The challange in craniofacial fracture management is restore the morphology and physiology of the carniofacial features to pre-injury remains a challenge. Tissue engginering such as secretome become a great hope as a modern and comprehensive therapy for handling craniofacial fractures. To evaluate the effectiveness of application of secretome in craniofacial bone regeneration in animal and human models. Methods: We conducted in August 2024 through several online databases, including PubMed (MEDLINE), The Cochrane Library, and Google Scholar. The inclusion criteria include methodological research (in vivo, in vitro, or clinical studies) which provided a complete set of data and full-text articles. We omitted studies of non-craniofacial bone fracture repair. COCHRANE RoB 2.0 checklist to analyze the risk of bias. Results: Twenty articles selected, 16 investigated animal models and four conducted clinical studies. Two animal studies researched on rabbits (n=34), one on dogs (n=4) and 13 on rats (n=281). There are 48 participants on the clinical studies. Secretome in animal and humans model increase titer which had effect to bone regeneration such as IGF, VEGF, TGF-B-1, osteocalcin, Runx2, PCNA, ANG1, ANG2, MMP8, BMP2, IBSP, MMP13 and ICAM-1. In radiology and histology evaluation, secretome reported increase rate of bone regeneration. Conclusion: Secretome promotes the expression of cytokines required for bone healing. secretome can enhace craniofacial bone regeneration by speeding up healing and increasing the areas of repair. Analysis is done through morphological studies, CT scan results, and histological findings.

Transcutaneous CO2 application combined with low-intensity pulsed ultrasound accelerates bone fracture healing in rats

BackgroundLow-intensity pulsed ultrasound (LIPUS) is a non-invasive therapy that accelerates fracture healing. As a new treatment method for fracture, we recently reported that the transcutaneous application of CO2 accelerated fracture healing in association with promoting angiogenesis, blood flow, and endochondral ossification. We hypothesized that transcutaneous CO2 application, combined with LIPUS, would promote bone fracture healing more than the single treatment with either of them.MethodsFemoral shaft fractures were produced in 12-week-old rats. Animals were randomly divided into four groups: the combination of CO2 and LIPUS, CO2, LIPUS, and control groups. As the transcutaneous CO2 application, the limb was sealed in a CO2-filled bag after applying hydrogel that promotes CO2 absorption. Transcutaneous CO2 application and LIPUS irradiation were performed for 20 min/day, 5 days/week. At weeks 1, 2, 3, and 4 after the fractures, we assessed the fracture healing process using radiography, histology, immunohistochemistry, real-time PCR, and biomechanical assessment.ResultsThe fracture healing score using radiographs in the combination group was significantly higher than that in the control group at all time points and those in both the LIPUS and CO2 groups at weeks 1, 2, and 4. The degree of bone fracture healing in the histological assessment was significantly higher in the combination group than that in the control group at weeks 2, 3, and 4. In the immunohistochemical assessment, the vascular densities of CD31- and endomucin-positive microvessels in the combination group were significantly higher than those in the control and LIPUS groups at week 2. In the gene expression assessment, significant upregulation of runt-related transcription factor 2 (Runx2) and vascular endothelial growth factor (VEGF) was detected in the combination group compared to the LIPUS and CO2 monotherapy groups. In the biomechanical assessment, the ultimate stress was significantly higher in the combination group than in the LIPUS and CO2 groups.ConclusionThe combination therapy of transcutaneous CO2 application and LIPUS had a superior effect in promoting fracture healing through the promotion of angiogenesis and osteoblast differentiation compared to monotherapy.

Local Delivery of Exosomes and Antibiotics in Hydroxyapatite-Based Nanocement for Osteomyelitis Management.

The management of bone and joint infections is a formidable challenge in orthopedics and poses a global health concern. While clinical management emphasizes infection prevention and complete eradication, an effective strategy for stabilizing skeletal tissue with adequate soft tissue coverage remains limited. In this study, we have employed a novel approach of using the local delivery of exosomes and antibiotics (rifampicin) using a hydroxyapatite-based nanocement carrier to manage the residual space created during debridement effectively. Additionally, we synthesized a periosteum-guiding antioxidant herbal membrane to leverage the inherent periosteum regeneration capability of the bone, facilitating bone callus repair and natural healing. The synthesized scaffolds were biocompatible and demonstrated potent antibacterial activity in vitro. When evaluated in vivo in the Staphylococcus aureus-induced rat tibial osteomyelitis model, the released drugs successfully cleared the residual bacteria and the released exosome promoted bone healing, resulting in 3-fold increase in bone volume as analyzed via micro-CT analysis. Immunofluorescence staining of periosteum-specific markers also indicated the complete formation of periosteal layers, thus highlighting the complete bone repair.

Functional Mechanism and Clinical Implications of lncRNA LINC-PINT in Delayed Fracture Healing

Background Fracture healing can be impeded or even compromised by various factors, resulting in a growing number of patients suffering. The lncRNA LINC-PINT has garnered attention for its latent role in enhancing fracture healing, but its specific functions in this process remain unclear. Objectives The primary objective of this study is to investigate the clinical relevance and underlying molecular mechanisms of LINC-PINT in delayed fracture healing (DFH), while also assessing its potential as an early diagnostic biomarker. Materials and methods The expression levels of LINC-PINT were measured in the serum of DFH patients and those with normal fracture healing using RT-qPCR. In MC3T3-E1 cells, the study investigated the influence on the expression of differentiation-related protein, cell viability, and apoptosis through the modulation of LINC-PINT and miR-324-3p. To elucidate the targeting relationship between LINC-PINT, miR-324-3p, and BMP2, a dual-luciferase reporter assay was employed. Results The findings revealed a significant downregulation of LINC-PINT expression in DFH patients. LINC-PINT showed high sensitivity and specificity as a diagnostic marker for DFH. In MC3T3-E1 cells, LINC-PINT overexpression markedly enhanced the expression levels of ALP, OCN, Runx2, and OPN, improved cell viability, and inhibited apoptosis. LINC-PINT negatively regulated miR-324-3p, and the effects of LINC-PINT were counteracted by miR-324-3p. LINC-PINT was found to regulate BMP2 by targeting miR-324-3p. Conclusion LINC-PINT could serve as an early diagnostic biomarker for DFH and slow the progression of DFH by modulating BMP2 through the targeted regulation of miR-324-3p. This research presents new molecular targets for the diagnosis and treatment of DFH.

Elastic stable intramedullary nailing in paediatric diaphyseal forearm fractures – a retrospective analysis of 201 cases

BackgroundForearm shaft fractures are common injuries, often caused by falling from a fully-upright position or falling off a bike. They can be treated nonoperatively or surgically with intramedullary nailing or plates. The method of choice for treating pediatric forearm shaft fractures is the application of elastic stable intramedullary nailing (ESIN)|. The aim of the study was to evaluate ESIN in pediatric patients with forearm shaft fractures based on radiological images, and determine the etiology and complication rate associated with the injury.MethodsThe study included 201 patients, 30.5% female 69.5% male, aged 1 to 17 years (mean 9.1 years; SD = 3.2), all had been diagnosed with a fracture of the forearm shaft and had been treated surgically with ESIN. In addition, all possessed a complete set of X-ray images and had attended a minimum six-month follow-up examination of the forearm. Axial alignment was evaluated retrospectively in the anatomical (AP) and lateral (LAT) positions. In total, 402 radiographs were examined. Of the injuries, 68% occurred during sports activity and 75% involved both the radius and the ulna.ResultsUnion was observed in all cases. Mean axial alignment values in AP and LAT X-ray or both the ulna and radius were satisfactory. Axial alignment values were not influenced significantly by age, type of surgery, type of fracture or etiology. Plaster cast application (9.8% of cases) significantly influenced radius axial alignment. The complication rate was 11.4% (n = 23). Significantly more complications were observed in patients receiving open reduction internal fixation (ORIF) (p = 0.0025).ConclusionThe ESIN technique is an effective treatment for forearm diaphyseal fractures in children, with good results regarding reduction and bone healing, indicated by x-ray.

Wnt/β-catenin signaling pathway: proteins' roles in osteoporosis and cancer diseases and the regulatory effects of natural compounds on osteoporosis.

Osteoblasts are mainly derived from mesenchymal stem cells in the bone marrow. These stem cells can differentiate into osteoblasts, which have the functions of secreting bone matrix, promoting bone formation, and participating in bone remodeling. The abnormality of osteoblasts can cause a variety of bone-related diseases, including osteoporosis, delayed fracture healing, and skeletal deformities. In recent years, with the side effects caused by the application of PTH drugs, biphosphonate drugs, and calmodulin drugs, people have carried out more in-depth research on the mechanism of osteoblast differentiation, and are actively looking for natural compounds for the treatment of osteoporosis. The Wnt/β-catenin signaling pathway is considered to be one of the important pathways of osteoblast differentiation, and has become an important target for the treatment of osteoporosis. The Wnt/β-catenin signaling pathway, whether its activation is enhanced or its expression is weakened, will cause a variety of diseases including tumors. This review will summarize the effect of Wnt/β-catenin signaling pathway on osteoblast differentiation and the correlation between the related proteins in the pathway and human diseases. At the same time, the latest research progress of natural compounds targeting Wnt/β-catenin signaling pathway against osteoporosis is summarized.

Enhancing biomechanical outcomes in proximal femoral osteotomy through optimised blade plate sizing: A neuromusculoskeletal-informed finite element analysis

Proximal femoral osteotomy (PFO) is a frequently performed surgical procedure to correct hip deformities in the paediatric population. The optimal size of the blade plate implant in PFO is a critical but underexplored factor influencing biomechanical outcomes. This study introduces a novel approach to refine implant selection by integrating personalized neuromusculoskeletal modelling with finite element analysis. Using computed tomography scans and walking gait data from six paediatric patients with various pathologies and deformities, we assessed the impact of four distinct implant width-to-femoral neck diameter (W-D) ratios (30 %, 40 %, 50 %, and 60 %) on surgical outcomes. The results show that the risk of implant yield generally decreases with increasing W-D ratio, except for Patient P2, where the yield risk remained below 100 % across all ratios. The implant factor of safety (FoS) increased with larger W-D ratios, except for Patients P2 and P6, where the highest FoS was 2.60 (P2) and 0.49 (P6) at a 60 % W-D ratio. Bone-implant micromotion consistently remained below 40 µm at higher W-D ratios, with a 50 % W-D ratio striking the optimal balance for mechanical stability in all patients except P6. Although interfragmentary and principal femoral strains did not display consistent trends across all patients, they highlight the need for patient-specific approaches to ensure effective fracture healing. These findings highlight the importance of patient-specific considerations in implant selection, offering surgeons a more informed pathway to enhance patient outcomes and extend implant longevity. Additionally, the insights gained from this study provide valuable guidance for manufacturers in designing next-generation blade plates tailored to improve biomechanical performance in paediatric orthopaedics.

Supplemental Magnesium Gluconate Enhances Scaffold-Mediated New Bone Formation and Natural Bone Healing by Angiogenic- and Wnt Signal-Associated Osteogenic Activation.

Local implantation or supplementation of magnesium gluconate (MgG) is being investigated as an effective approach to bone repair. Although studies have highlighted the possible mechanisms in Mg ion-stimulated new bone formation, the role of MgG in healing bone defects and the signaling mechanisms are not yet completely understood. In this study, we explored how supplemental MgG has bone-specific beneficial effects by delivering MgG locally and orally in animal models. We fabricated MgG-incorporated (CMC-M) and -free chitosan (CMC) scaffolds with good microstructures and biocompatible properties. Implantation with CMC-M enhanced bone healing in rat model of mandible defects, compared with CMC, by activating Wnt signals and Wnt-related osteogenic and angiogenic molecules. Oral supplementation with MgG also stimulated bone healing in mouse model of femoral defects along with the increases in Wnt3a and angiogenic and osteogenic factors. Supplemental MgG did not alter nature bone accrual and bone marrow (BM) microenvironment in adult mouse model, but enhanced the functioning of BM stromal cells (BMSCs). Furthermore, MgG directly stimulated the induction of Wnt signaling-, angiogenesis-, and osteogenesis-related molecules in cultures of BMSCs, as well as triggered the migration of endothelial cells. These results suggest that supplemental MgG improves bone repair in a way that is synergistically enhanced by Wnt signal-associated angiogenic and osteogenic molecules. Overall, this study indicates that supplemental MgG might ameliorate oxidative damage in the BM, improve the functionality of BM stem cells, and maintain BM-microenvironmental homeostasis.

Local muscle or myocutaneous flap transfer for emergent repair of Gustilo IIIB open tibiofibular fractures

This study aimed to investigate the clinical outcomes of local muscle or myocutaneous flap transfer for emergent repair of Gustilo IIIB open tibiofibular fractures. This retrospective case series study included patients with Gustilo IIIB open tibiofibular fractures treated by local muscle or myocutaneous flap transfer in Weifang People’s Hospital between May 2016 and April 2021. Fifteenpatients (11 males aged 19–72 years) were included. The follow-up ranged from 8 to 24 months. The ranges of bone healing time and wound healing time were 6–17 months and 1–3 weeks, respectively. The length of hospital stay was 26 days (11–50 days). All patients reported acceptable functional recovery and satisfactory leg appearance, with Johner-Wruhs scores of excellent, good, and fair in 10, four, and one patients, respectively. The excellent-good rate was 93.3%. The complications included one case of infection and one case of nonunion. In conclusion, local muscle or myocutaneous flap transfer for emergent repair of Gustilo IIIB open tibiofibular fractures may be useful in providing adequate soft tissue coverage and fracture healing with low complication and infection rates.