Bone Fracture Model Research Articles

Clinical usability and efficacy of a robotic bone fracture reduction system: A pilot animal study

Challenges in minimally invasive surgeries, such as intramedullary nailing for long bone fractures, include radiation overexposure for patients and surgeons, potential malreduction, and physical burden on surgeons in maintaining the reduction status. A robotic bone fracture reduction system was developed in this study to address these problems. The system consists of a hexapod with six degrees of freedom, with a fracture reduction device and a master device. This study aimed to evaluate the novel system in a preclinical setting. The length of the six axes in the system can be adjusted to precisely control the length, angle, and rotation so that no additional traction is required. Fluoroscopic images can be remotely examined to reduce the risk of radiation exposure for surgeons. In this study, alignment accuracy and radiation exposure were measured using 32 bovine bone fracture models, and these surgical outcomes were compared to those of conventional manual surgery to verify the clinical usability and effectiveness of the system. The alignment accuracy was assessed by analyzing length, angulation, and rotation. The four surgeons participating in this study were divided into two groups (expert and novice) according to their clinical experience. All parameters in robotic surgery significantly decreased by approximately 4 mm and 8° on average (p≤0.05) compared to conventional surgery. The mean radiation exposure in robot-assisted surgery was 0.11 mSv, showing a significant decrease compared to conventional surgery (p<0.05). Reduction accuracy was higher in robotic surgery performed by the novice group than in conventional surgery performed by the expert group; however, standard deviation values were inversed. In conclusion, the bone fracture reduction robot system increased the alignment accuracy through precise control while reducing radiation exposure in surgeons, as the surgery was performed remotely. The use of this system is predicted to improve the accuracy and reproducibility of the surgery and the safety of medical staff.11Abbreviations: CT, computed tomography; FRD, fracture reduction device; FRMD, fracture reduction master device; SD, standard deviation

Ballistic Gels in Experimental Fracture Setting.

Biomechanical tests typically involve bending, compression, or shear stress, while fall tests are less common. The main challenge in performing fall tests is the non-reproducible directionality of bone when tested with soft tissue. Upon removal of the soft tissue, the explanted bone's resistance to impact diminishes. Therefore, ballistic gels can fix specimens in reproducible directions and simulate periosteal soft tissue. However, the use of ballistic gels in biomechanical studies is neither standardized nor widespread. This study aimed to optimize a ballistic gel consistency that mimics the upper thigh muscle in sheep. Our results suggest a standardized and flexible evaluation method by embedding samples in ballistic gel. Compression tests were conducted using cylindrical pieces of gluteal muscle from sheep. Various compositions of agarose and gelatin mixtures were tested to achieve a muscle-like consistency. The muscle-equivalent ballistic gel was found to consist of 29.5% gelatin and 0.35% agarose. Bones remained stable within the ballistic gel setup after freeze-thaw cycles between -20 °C and +20 °C. This method reduces the variability caused by muscle and improves storage quality, allowing for tests to be conducted under consistent conditionsBallistic gels of agarose and gelatin are suitable for bone fracture models. They have muscle-like strength, fix fractures simultaneously, are inexpensive to produce, and can be stored to allow repeated measurements of the same object with changing questions.

Preliminary osteogenic and antibacterial investigations of wood derived antibiotic-loaded bone substitute for the treatment of infected bone defects.

Introduction: The development of reliable treatments for infected or potentially infected bone loss resulting from open fractures and non-unions is extremely urgent, especially to reduce the prolonged courses of antimicrobial therapy to which affected patients are subjected. Numerous bone graft substitutes have been used over the years, but there are currently no effective solutions to treat critical bone loss, especially in the presence of infection. The present study evaluated the use of the biomorphic calcium phosphate bone scaffold b. Bone™, based on a next-generation resorbable biomimetic biomaterial, in bone reconstruction surgery in cases of infection. Methods: Using an "in vitro 3D bone fracture model" to predict the behavior of this drug delivery system during critical bone loss at an infected (or potentially infected) site, the effects of scaffolds loaded with gentamicin or vancomycin on the viability and differentiation capacity of human mesenchymal stem cells (hMSCs) were evaluated. Results: This scaffold, when loaded with gentamicin or vancomycin, exhibits a typical drug release curve that determines the inhibitory effects on the growth of Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli, as well as relative biofilm formation. Discussion: The study demonstrates that b.bone scaffolds can effectively address key challenges in orthopedic surgery and patient care by inhibiting bacterial growth and biofilm formation through rapid, potent antibiotic release, reducing the risk of treatment failure due to resistance, and providing a promising solution for bone infections and improved patient outcomes. Future studies could explore the combination of different antibiotics on these scaffolds for more tailored and effective treatments against post-traumatic osteomyelitis pathogens.

Force/position tracking control of fracture reduction robot based on nonlinear disturbance observer and neural network

AbstractBackgroundFor the fracture reduction robot, the position tracking accuracy and compliance are affected by dynamic loads from muscle stretching, uncertainties in robot dynamics models, and various internal and external disturbances.MethodsA control method that integrates a Radial Basis Function Neural Network (RBFNN) with Nonlinear Disturbance Observer is proposed to enhance position tracking accuracy. Additionally, an admittance control is employed for force tracking to enhance the robot's compliance, thereby improving the safety.ResultsExperiments are conducted on a long bone fracture model with simulated muscle forces and the results demonstrate that the position tracking error is less than ±0.2 mm, the angular displacement error is less than ±0.3°, and the maximum force tracking error is 26.28 N. This result can meet surgery requirements.ConclusionsThe control method shows promising outcomes in enhancing the safety and accuracy of long bone fracture reduction with robotic assistance.

Patient-specific numerical simulation of the bone healing process including implant materials and gait conditions

Numerical simulations in biomechanics, particularly in bone healing, present a cost-effective option compared to experiments that demand prolonged observations with human or with animal models. However, to define in-silico simulations of the bone healing process requires considering multiple factors, such as the implant design and patient’s characteristics. As a result, the current challenge is integrating different numerical methodologies to simulate bone healing, aiming to facilitate the emergence of innovative clinical treatments and new implant designs.In this paper, we present a patient-specific numerical methodology to simulate the bone healing process, able to consider patient’s load conditions and bone density distribution provided by CT-scans. The main novelty is the combination of the Cartesian grid Finite Element Method (cgFEM) with a bone callus healing model, complemented by a load-condition optimisation scheme to relate implant materials and load conditions while ensuring successful healing outcome.This numerical methodology creates a finite element model based on the patient’s medical image, serving as a virtual testing tool for investigating the influence of implant materials on gait pattern requirements to ensure an optimal healing outcome. In practice, a personalised bone fracture model was employed to evaluate four distinct implant materials: two conventional materials (stainless steel and titanium) and two bioabsorbable candidates (polylactic acid plastic (PLA) and magnesium). The results offer personalised optimal load conditions for each studied material, showcasing the potential of in-silico studies in minimising uncertainties associated with exploring new clinical treatments.

Echinacoside promotes osteogenesis and angiogenesis and inhibits osteoclast formation.

The purpose of this research is to demonstrate echinacoside promotes osteogenesis and angiogenesis and inhibits osteoclast formation. We conducted a cell experiment invitro to study how echinacoside affects angiogenesis, osteogenesis and osteoclast formation. We used polymerase chain reaction and Western blotting to detect the expression levels of proteins and genes related to angiogenesis, osteogenesis and osteoclast formation. We established a bone fracture model with rats to test angiogenesis, osteogenesis and osteoclast formation of echinacoside. We labelled osteogenic markers, blood vessels and osteoclastic markers in fracture sections of rats. The invitro cell experiments showed echinacoside improved the osteogenic activity of mouse embryo osteoblast precursor cells and promoted the migration and tube formation of human umbilical vein endothelial cells. In addition, it inhibited differentiation of mouse leukaemia cells of monocyte macrophage. Echinacoside increased the expression of related proteins and genes and improved angiogenesis and osteogenesis while inhibiting osteoclast formation by repressing the expression of related proteins and genes. From invivo experiments, the results of IHC and HE experiments demonstrated echinacoside significantly decreased the content of MMP-9 and improved the content of VEGF and OCN. The fluorescence immunoassay showed echinacoside promoted the activities of RUNX2 and VEGF and inhibited CTSK. Echinacoside reduced the content of TNF-α, IL-1β and IL-6, thus demonstrating its anti-inflammatory activity. Echinacoside improved angiogenesis and osteogenesis and inhibited osteoclast formation to promote fracture healing.

Accuracy Analysis of 3D Bone Fracture Models: Effects of Computed Tomography (CT) Imaging and Image Segmentation

The introduction of three-dimensional (3D) printed anatomical models has garnered interest in pre-operative planning, especially in orthopedic and trauma surgery. Identifying potential error sources and quantifying their effect on the model dimensional accuracy are crucial for the applicability and reliability of such models. In this study, twenty radii were extracted from anatomic forearm specimens and subjected to osteotomy to simulate a defined fracture of the distal radius (Colles’ fracture). Various factors, including two different computed tomography (CT) technologies (energy-integrating detector (EID) and photon-counting detector (PCD)), four different CT scanners, two scan protocols (i.e., routine and high dosage), two different scan orientations, as well as two segmentation algorithms were considered to determine their effect on 3D model accuracy. Ground truth was established using 3D reconstructions of surface scans of the physical specimens. Results indicated that all investigated variables significantly impacted the 3D model accuracy (p < 0.001). However, the mean absolute deviation fell within the range of 0.03 ± 0.20 to 0.32 ± 0.23 mm, well below the 0.5 mm threshold necessary for pre-operative planning. Intra- and inter-operator variability demonstrated fair to excellent agreement for 3D model accuracy, with an intra-class correlation (ICC) of 0.43 to 0.92. This systematic investigation displayed dimensional deviations in the magnitude of sub-voxel imaging resolution for all variables. Major pitfalls included missed or overestimated bone regions during the segmentation process, necessitating additional manual editing of 3D models. In conclusion, this study demonstrates that 3D bone fracture models can be obtained with clinical routine scanners and scan protocols, utilizing a simple global segmentation threshold, thereby providing an accurate and reliable tool for pre-operative planning.

Comparison of antegrade and retrograde cross pin fixation in the surgical treatment of pediatric supracondylar femur fractures: A biomechanical study

PurposeThe aim of this study is to compare biomechanical stability of Kirschner wires (K-wires) sent with antegrade and retrograde technique in the fixation of pediatric supracondylar femur fractures. Materials and MethodsA transverse fracture model was created two centimeters above the physis in 24 synthetic bone models suitable for the pediatric femur bone structure. The models were randomly divided into two groups as 12 bones each. In the first group (Group 1), 12 bone fracture models were retrogradely fixed with two cross K-wires. In the second group (Group 2), the fracture was fixed antegradely. In Group 2, both wire ends were allowed to protrude three millimeters from the femoral condyles. The stability of the groups was tested biomechanically by exposing them to varus and extension forces. The forces corresponding to 1 mm, 2 mm, 3 mm and 4 mm displacement and failure loads were calculated in two groups. ResultsAccording to the test results regarding displacements and failure loads, the retrograde group was found to be significantly stronger than the antegrade group against varus loads (p < 0.05). When the groups were compared in terms of extension strength, the results of the two groups were similar and there was no statistical difference between them (p > 0.05). ConclusionRetrograde cross K-wires fixation provides a more stable fixation against varus forces. This is important to prevent varus deformity, which is a clinically less tolerable deformity. However, considering that full-weight mobilization of patients is not allowed after surgery in pediatric supracondylar femur fractures, the surgeon should consider that K-wires can also be sent antegrade to decrease the risk of septic arthritis.

Biomechanical Variability and Usability of a Novel Customizable Fracture Fixation Technique.

A novel in situ customizable osteosynthesis technique, Bonevolent™ AdhFix, demonstrates promising biomechanical properties under the expertise of a single trained operator. This study assesses inter- and intra-surgeon biomechanical variability and usability of the AdhFix osteosynthesis platform. Six surgeons conducted ten osteosyntheses on a synthetic bone fracture model after reviewing an instruction manual and completing one supervised osteosynthesis. Samples underwent 4-point bending tests at a quasi-static loading rate, and the maximum bending moment (BM), bending stiffness (BS), and AdhFix cross-sectional area (CSA: mm²) were evaluated. All constructs exhibited a consistent appearance and were suitable for biomechanical testing. The mean BM was 2.64 ± 0.57 Nm, and the mean BS was 4.35 ± 0.44 Nm/mm. Statistically significant differences were observed among the six surgeons in BM (p < 0.001) and BS (p = 0.004). Throughout ten trials, only one surgeon demonstrated a significant improvement in BM (p < 0.025), and another showed a significant improvement in BS (p < 0.01). A larger CSA corresponded to a statistically significantly higher value for BM (p < 0.001) but not for BS (p = 0.594). In conclusion, this study found consistent biomechanical stability both across and within the surgeons included, suggesting that the AdhFix osteosynthesis platform can be learned and applied with minimal training and, therefore, might be a clinically viable fracture fixation technique. The variability in BM and BS observed is not expected to have a clinical impact, but future clinical studies are warranted.

Evaluating rearing behaviour as a model-specific pain indicator in mouse osteotomy models.

To assess pain in mouse models of bone fractures, currently applied assessment batteries use combinations of clinical signs with spontaneous behaviours and model-specific behaviours, including walking and weight-bearing behaviour. Rearing behaviour - an upright position on the hindlimbs - has a motivational and an ambulatory component. Thus, rearing behaviour might have the potential to be an indicator for model-specific pain in mouse fracture models. To date, the assessment of rearing behaviour in bone fracture models using mice is only scarcely described. In this study, we aimed to determine whether the duration of rearing behaviour is affected by osteotomy of the femur in male and female C57BL/6N mice with external fixation (rigid vs. flexible) and could be an additional sign for model-specific pain, such as the presence of limping. Rearing duration was significantly decreased after osteotomy in male and female mice at 24 h, 48 h and 72 h, but was not affected by anaesthesia/analgesia alone. In male mice, the relative rearing duration increased over 72 h (both fixations) and at 10 days in the rigid fixation group but remained significantly lower in the flexible fixation group. In contrast, in female mice, no increase in rearing duration was observed within 72 h and at 10 days post-osteotomy, independent of the fixation. We did not identify any association between relative rearing time and presence or absence of limping. In summary, our results do not provide sufficient evidence that altered rearing behaviour might be an indicative sign for pain in this model.

Does intramedullary elastic nail augmentation increase resistance to bending stress in plate fixation of long bones? A biomechanical study on lamb cadaveric femurs.

The aim of this study was to evaluate the bending strength of plate-screw fixation augmented with titanium elastic nails (TENs) in a simple long bone fracture model using lamb cadaver femurs. A total of 24 lamb cadaveric femurs that were osteotomized transversely from the mid-diaphysis with a bone saw were used to obtain a simple fracture model. The femurs were divided randomly into three groups. In Group 1, only plate-screw was used for fixation. In Group 2, plate-screw fixation was augmented with a 2.5-mm TEN. In Group 3, plate-screw fixation was augmented with two 2.5-mm TENs. Each bone model was positioned on a mechanical testing machine. Subsequently, three-point bending loads were applied to each bone to measure the force required for failure at the osteotomy site. The data were recorded on a computer connected to the test device and the bending strengths of all samples were calculated. There was no statistically significant difference in the bending strength (megapascals) between Groups 1 and 2 or between Groups 2 and 3 (p>0.05). However, the bending strength in Group 3 was significantly higher than in Group 1 (p<0.05). The application of intramedullary TEN during surgery in long bone fractures, combined with a bridge plate, may be helpful to strengthen the fixation stability.

Effects of Piper sarmentosum on Bone Health and Fracture Healing: A Scoping Review.

Piper sarmentosum (PS) is a traditional herb used by Southeast Asian communities to treat various illnesses. Recent pharmacological studies have discovered that PS possesses antioxidant and anti-inflammatory activities. Since oxidative stress and inflammation are two important processes driving the pathogenesis of bone loss, PS may have potential therapeutic effects against osteoporosis. This review systematically summarised the therapeutic effects of PS on preventing osteoporosis and promoting fracture healing. A systematic literature search was performed in November 2021 using 4 electronic databases and the search string "Piper sarmentosum" AND (bone OR osteoporosis OR osteoblasts OR osteoclasts OR osteocytes). Nine unique articles were identified from the literature. The efficacy of PS has been studied in animal models of osteoporosis induced by ovariectomy and glucocorticoids, as well as bone fracture models. PS prevented deterioration of bone histomorphometric indices, improved fracture healing and restored the biomechanical properties of healed bone in ovariectomised rats. PS also prevented osteoblast/osteocyte apoptosis, increased bone formation and mineralisation and subsequently improved trabecular bone microstructures and strength of rats with osteoporosis induced by glucocorticoids. Apart from its antioxidant and anti-inflammatory activity, PS also suppressed circulating and skeletal expression of corticosterone and skeletal expression of 11β hydroxysteroid dehydrogenase type 1 but increased the enzyme activity in the glucocorticoid osteoporosis model. This review also identified several research gaps about the skeletal effects of PS and suggested future studies to bridge these gaps. PS may be of therapeutic benefit to bone health. However, further research is required to validate this claim.

Adiponectin overexpression promotes fracture healing through regulating the osteogenesis and adipogenesis balance in osteoporotic mice.

Osteoporosis invariably manifests as loss of bone, which is replaced by adipose tissue; this can easily lead to fractures, accompanied by delayed and poor healing. Adiponectin (APN) balances osteogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMSCs). Therefore, this study explored whether adiponectin promotes bone fracture healing by regulating the balance between osteogenesis and adipogenesis. We used adenovirus overexpression vectors carrying APN (Ad-APN-GFP) to treat ovariectomized (OVX) mouse BMSCs and osteoporotic bone fractures to investigate the role of APN in bone microenvironment metabolism in osteoporotic fractures. We subsequently established an OVX mice and bone fracture model using Ad-APN-GFP treatment to investigate whether APN could promote bone fracture healing in osteoporotic mice. The experimental results showed that APN is a critical molecule in diverse differentiation directions in OVX mouse BMSCs, with pro-osteogenesis and anti-adipogenesis properties. Importantly, our study revealed that Ad-APN-GFP treatment facilitates bone generation and healing around the osteoporotic fracture ends. Moreover, we identified that Sirt1 and Wnt signaling were closely related to the pro-osteogenesis and anti-adipogenesis commitment of APN in OVX mouse BMSCs and femoral tissues. We demonstrated that APN overexpression facilitates bone fracture healing in osteoporosis. Furthermore, APN overexpression promoted bone formation in OVX mouse BMSCs and bone fracture ends by regulating the balance between osteogenesis and adipogenesis both in vitro and in vivo.

Extracellular Vesicles Secreted by TGF-β1-Treated Mesenchymal Stem Cells Promote Fracture Healing by SCD1-Regulated Transference of LRP5.

Bone fracture repair is a multiphased regenerative process requiring paracrine intervention throughout the healing process. Mesenchymal stem cells (MSCs) play a crucial role in cell-to-cell communication and the regeneration of tissue, but their transplantation is difficult to regulate. The paracrine processes that occur in MSC-derived extracellular vesicles (MSC-EVs) have been exploited for this study. The primary goal was to determine whether EVs secreted by TGF-β1-stimulated MSCs (MSCTGF-β1-EVs) exhibit greater effects on bone fracture healing than EVs secreted by PBS-treated MSCs (MSCPBS-EVs). Our research was conducted using an in vivo bone fracture model and in vitro experiments, which included assays to measure cell proliferation, migration, and angiogenesis, as well as in vivo and in vitro gain/loss of function studies. In this study, we were able to confirm that SCD1 expression and MSC-EVs can be induced by TGF-β1. After MSCTGF-β1-EVs are transplanted in mice, bone fracture repair is accelerated. MSCTGF-β1-EV administration stimulates human umbilical vein endothelial cell (HUVEC) angiogenesis, proliferation, and migration in vitro. Furthermore, we were able to demonstrate that SCD1 plays a functional role in the process of MSCTGF-β1-EV-mediated bone fracture healing and HUVEC angiogenesis, proliferation, and migration. Additionally, using a luciferase reporter assay and chromatin immunoprecipitation studies, we discovered that SREBP-1 targets the promoter of the SCD1 gene specifically. We also discovered that the EV-SCD1 protein could stimulate proliferation, angiogenesis, and migration in HUVECs through interactions with LRP5. Our findings provide evidence of a mechanism whereby MSCTGF-β1-EVs enhance bone fracture repair by regulating the expression of SCD1. The use of TGF-β1 preconditioning has the potential to maximize the therapeutic effects of MSC-EVs in the treatment of bone fractures.

MLK3 silence suppressed osteogenic differentiation and delayed bone formation via influencing the bone metabolism and disturbing MAPK signaling.

Mixed lineage kinase 3 (MLK3) is a member of a serine/threonine MAP3K family, and it has been demonstrated to play critical roles in various biological activities and disease progression. Previous studies showed that impaired skeletal mineralization and spontaneous tooth fracture in the MLK3-deficient mice, suggesting MLK3 actively participated in the bone formation. However, the detailed function and underlying mechanisms remain obscure. The MLK3 knockout (KO) mouse was applied in the present study, and multi-omics were performed to compare the metabolites and gene expression between wild type (WT) and KO mice. The bone fracture model was successfully established, and the healing process was evaluated by X-ray, micro-CT examination, histomorphometry and immunohistochemistry (IHC) staining. On the other hand, the effects of MLK3 on osteogenic differentiation were assessed by alkaline phosphatase (ALP) activity, Alizarin red S (ARS) staining and qRT-PCR examination. Finally, the downstream signaling pathways were screened out by RNA-sequencing (RNA-seq) and then validated by Western blotting. In the present study, imbalanced bone metabolism was observed in these MLK3 KO mice, suggesting MLK3 may participate in bone development. Moreover, MLK3 -/- mice displayed abnormal bone tissues, impaired bone quality, and delayed fracture healing. Further investigation showed that the inhibition of MLK3 attenuated osteoblast differentiation in vitro. According to the RNA-seq data, MAPK signaling was screened out to be a downstream pathway, and its subfamily members extracellular signal-regulated kinase (ERK), p38 and Jun N-terminal protein kinase (JNK) were subjected to Western blotting examination. The results revealed that although no differences in their expression were observed between MSCs derived from WT and KO mice, their phosphorylated protein levels were all suppressed in MLK3 -/- MSCs. In conclusion, our results demonstrated that loss of MLK3 suppressed osteoblast differentiation and delayed bone formation via influencing metabolism and disturbing MAPK signaling. The findings based on the current study demonstrated that MLK3 promoted osteogenesis, stimulated new bone formation and facilitated fracture healing, suggesting that MLK3 may serve as a potential therapeutic target for bone regeneration. MLK3 activator therefore may be developed as a therapeutic strategy for bone fracture.

The Comparison of Clinical Efficacy of Minimally Invasive Tarsal Sinus Approach and L-Type Incision Approach Combined with 3D Printing Technology in Calcaneal Fracture.

Purpose To explore the comparison of the reduction of the subtalar articular surface and other postoperative effects of the minimally invasive tarsal sinus approach and lateral L-shaped incision conventional approach for the treatment of calcaneal fracture with 3D printing technology. Methods Patients who received surgical treatment for calcaneal fractures in the First Affiliated Hospital of Henan University of Science and Technology from June 2019 to December 2020 were collected. 3D printing equipment produced the affected side reduction heel bone fracture model and navigation template model. The tarsal sinus approach was used in the experimental group, and the lateral L-shaped incision approach was used in the control group. Patients were followed up 3 days, 1 month, 3 months, 6 months, and 12 months after the operation. Imaging indicators were measured 12 months after surgery, and scores from American Foot and Ankle Orthopaedic Society (AOFAS) and MSF were performed. Results Operation time was 70.52 ± 13.16 in the control group and 55.24 ± 12.25 minutes in the experimental group (P < 0.001). Intraoperative blood loss was 98.77 ± 18.65 in the control group and 89.56 + 17.54 in the experimental group (P > 0.05). The duration of antibiotic use was 5.53 ± 3.24 days in the control group and 5.48 ± 4.18 days in the experimental group (P > 0.05). The frequency of fluoroscopy was 6.56 ± 1.72 in the control group and 3.88 ± 1.05 in the experimental group (P < 0.001). Fracture healing time was 3.24 ± 0.52 months in the control group and 3.08 ± 0.58 months in the experimental group (P > 0.05). The postoperative Böhler angle was 28.31 ± 3.14 in the control group and 29.24 ± 2.76 in the experimental group (P > 0.05). Postoperative subtalar articular displacement (step > 2 mm) was observed in 4 patients in the control group and 1 in the experimental group (P < 0.05). MSF score was 90.12 ± 4.85 in the control group and 91.36 ± 2.58 in the experimental group (P > 0.05). Conclusion The study found that the experimental group was significantly better than the control group in terms of the operation time, intraoperative fluoroscopy times, and success rate of reduction of the subtalar articular surface. 3D printing technology can shorten the operation time, accurately reduce the fracture block, and reduce the secondary trauma, which is conducive to the functional recovery of the affected foot.

MicroRNA-146a mediates distraction osteogenesis via bone mesenchymal stem cell inflammatory response

Distraction osteogenesis (DO) is a widely used surgical technique to repair bone defects, partly owing to its high efficiency in inducing osteogenesis; however, the process of osteogenesis is complex, and the precise mechanism is still unclear. Among the factors identified for an effective DO procedure, well-controlled inflammation is essential. We aimed to explore how microRNA(miR)−146a, a negative regulator of inflammation, influences osteogenesis in DO. First, we established canine right mandibular DO and bone fracture models to evaluate the expression level of miR-146a in response to these procedures. Second, bone marrow mesenchymal stem cells (BMSCs) were isolated from healthy puppies and cultured with lipopolysaccharide (LPS) to observe how inflammation affects osteogenesis. Finally, the osteogenesis activity of BMSCs transfected with lentiviral vector either overexpressing (miR-146a-up) or inhibited for miR-146a expression was evaluated. miR-146a-up-transfected BMSCs were injected locally into the distraction gaps of the DO model canines. On days 42 and 56 post-surgery, the bone volume/tissue volume and bone mineral density values were evaluated via using micro-computed tomography, and newly formed tissues were harvested and evaluated via histological staining. The expression of miR-146a in both the DO canine model and LPS-stimulated BMSCs increased. Overexpression of miR-146a enhanced cell proliferation, migration, and osteogenic differentiation. Additionally, the newly formed callus was improved in canine mandibles injected with miR-146a-up-transfected BMSCs. In summary, miR-146a regulates mandibular DO by improving osteogenesis, and can serve as a potential target to shorten the therapy period of DO.

High Fluoride Ingestion Impairs Bone Fracture Healing by Attenuating M2 Macrophage Differentiation.

Fluorosis is still endemic in at least 25 countries around the world. In this study, we investigated the effect of high fluoride intake on fracture healing. Our in vitro experiments found that fluoride inhibited the osteogenic and angiogenic differentiation of MSCs in a dose-dependent manner. By constructing a bone fracture model, we found that high fluoride intake influences bone fracture by attenuating endochondral ossification and angiogenesis. In the mechanism, we clarified that high fluoride inhibits M2 differentiation rather than M1 differentiation in the fracture area, which may contribute to the delayed healing of the fracture. These findings provide an essential reference for the clinical treatment of bone fracture patients with a history of high fluoride intake or skeletal fluorosis patients.

Sesamin Promotes Osteoporotic Fracture Healing by Activating Chondrogenesis and Angiogenesis Pathways.

Osteoporotic fracture has been regarded as one of the most common bone disorders in the aging society. The natural herb-derived small molecules were revealed as potential treatment approaches for osteoporotic fracture healing. Sesamin is a member of lignan family, which possesses estrogenic activity and plays a significant role in modulating bone homeostasis. Our previous study reported the promoting effect of sesamin on postmenopausal osteoporosis treatment. However, the role of sesamin in osteoporotic fracture healing has not been well studied yet. In this study, we further investigated the putative treatment effect of sesamin on osteoporotic fracture healing. Our study indicated that sesamin could activate bone morphogenetic protein 2 (BMP2) signaling pathway and further promotes in vitro chondrogenesis and angiogenesis activities. This promoting effect was abolished by the treatment of ERα inhibitor. In the osteoporotic bone fracture model, we demonstrated that sesamin markedly improves the callus formation and increases the cartilaginous area at the early-stage, as well as narrowing the fracture gap, and expands callus volume at the late-stage fracture healing site of the OVX mice femur. Furthermore, the angiogenesis at the osteoporotic fracture site was also significantly improved by sesamin treatment. In conclusion, our research illustrated the therapeutic potential and underlying regulation mechanisms of sesamin on osteoporotic fracture healing. Our studies shed light on developing herb-derived bioactive compounds as novel drugs for the treatment of osteoporotic fracture healing, especially for postmenopausal women with low estrogen level.

STING inhibition accelerates the bone healing process while enhancing type H vessel formation.

The stimulator of interferon genes (STING), one of the critical factors of innate immunity, is indicated to be closely related to angiogenesis. This study examined STING's role in angiogenesis and the formation of type H vessels, a specific subtype of bone vessels that regulates bone healing. Different concentrations of 2',3'-cGAMP, and H-151 or C-176 were applied to activate or inhibit STING, respectively. Human umbilical vein endothelial cells were used to examine the effect of STING on angiogenesis in vitro; cell viability, cell migration, and quantitative real-time polymerase chain reactions were performed. Also, the metatarsal experiment was applied as ex vivo proof. Bone fracture or defect mice models were used to examine the effect of STING in vivo; the bone healing process was evaluated by radiography weekly and by μCT on the 14th day after surgery. The formation of type H vessels (CD31hi Emcnhi endothelial cells) and osteogenesis (OCN-positive cells) was assessed using the cryosection and paraffin section. STING activation inhibited angiogenesis both in vitro and ex vivo and slowed down the bone healing process in vivo. Histological analysis showed an increased callus formation, fewer type H vessels, and almost no callus mineralization in the STING activation group compared to the control group. By contrast, H-151 (a hsSTING inhibitor) promoted angiogenesis at a low dose. Moreover, inhibition of mmSTING by C-176 enhanced type H vessels' formation, implying osteogenesis promotion in bone healing (higher bone volume density and more OCN-positive cells). Our data suggested that STING inhibition accelerates the bone healing process while enhancing type H vessel formation.