The effect of Ding's screws and tension band wiring for treatment of olecranon fractures: a biomechanical study.

Although tension band wiring (TBW) is popular and recommended by the AO group, the high rate of complications such as skin irritation and migration of the K-wires cannot be ignored. Ding's screw tension band wiring (DSTBW) is a new TBW technique that has shown positive results in the treatment of other fracture types. The objective of this study was to evaluate the stability of DSTBW in the treatment of olecranon fractures by biomechanical testing. We conducted a Synbone biomechanical model by using three fixation methods: DSTBW, intramedullary screw and tension band wiring (IM-TBW), and K-wire TBW, were simulated to fix the olecranon fractures. We compared the mechanical stability of DSTBW, IM-TBW, and TBW in the Mayo Type IIA olecranon fracture Synbone model using a single cycle loading to failure protocol or pullout force. During biomechanical testing, the average fracture gap measurements were recorded at varying flexion angles in three different groups: TBW, IM-TBW, and DSTBW. The TBW group exhibited measurements of 0.982 mm, 0.380 mm, 0.613 mm, and 1.285 mm at flexion angles of 0°, 30°, 60°, and 90° respectively. The IM-TBW group displayed average fracture gap measurements of 0.953 mm, 0.366 mm, 0.588 mm, and 1.240 mm at each of the corresponding flexion angles. The DSTBW group showed average fracture gap measurements of 0.933 mm, 0.358 mm, 0.543 mm, and 1.106 mm at the same flexion angles. No specimen failed in each group during the cyclic loading phase. Compared with the IM-TBW and TBW groups, the DSTBW group showed significant differences in 60° and 90° flexion angles. The mean maximum failure load was 1229.1 ± 110.0 N in the DSTBW group, 990.3 ± 40.7 N in the IM-TBW group, and 833.1 ± 68.7 N in the TBW group. There was significant difference between each groups (p < 0.001).The average maximum pullout strength for TBW was measured at 57.6 ± 5.1 N, 480.3 ± 39.5 N for IM-TBW, and 1324.0 ± 43.8 N for DSTBW. The difference between maximum pullout strength of both methods was significant to p < 0.0001. DSTBW fixation provides more stability than IM-TBW and TBW fixation models for olecranon fractures.

A novel technique of a new cannulated screw for treatment of inferior pole patellar fractures: a finite element study.

OBJECTIVE: We invented a new cannulated screw with holes on the tail, which called Ding's screw. The goal of this study was to evaluate the biomechanical outcomes of this new screw with tension band wiring for the treatment of inferior pole patellar fractures in a finite element model. METHODS: We conducted a finite element biomechanical study using two fixation methods: Ding's screw and tension band wiring (DSTBW) and cannulated screws and tension band wiring (CSTBW). Two methods were simulated to fix the inferior pole patellar fracture in a finite element model. The relative displacement and stress distribution were analyzed and compared. RESULT: There were less displacement and stress distribution of DSTBW in different knee movement (30°, 60°, 90°, 120°) when compared to CSTBW. The highest value of displacement of the fracture and von Mises stress of the internal fixation happened in 120° knee movement in both groups. The highest displacement of the DSTBW was less than that of the CSTBW (1.92 mm to 2.12 mm). The highest value of the stress on the screws was 110.60 MPa in DSTBW group, and 132.90 MPa in CSTBW group. The highest value of the stress on the titanium cable was 38.51 MPa in DSTBW group, and 41.91 MPa in CSTBW group. CONCLUSION: DSTBW fixation provides more stability than CSTBW fixation model in a finite element study.

Identification and validation of FPR1, FPR2, IL17RA and TLR7 as immunogenic cell death related genes in osteoarthritis.

Immunogenic cell death (ICDs) has gained increasing attention for its significant clinical efficacy in various diseases. Similarly, more and more attention has been paid in the role of immune factors in the pathological process of osteoarthritis (OA). The objective of this study is to reveal the relationship between ICD-related genes and the process of OA at the gene level through bioinformatics analysis. In this study, Limma R package was applied to identify differentially expressed genes (DEG), and OA related module genes were determined by weighted gene co-expression network analysis. The ICD-related genes were extracted from a previous study. The module genes related to DEGs and ICD were overlapped. Then, hub genes were identified by a series of analyses using the Least absolute shrinkage and selection operator and random forest algorithm, the expression level and diagnostic value of hub genes were evaluated by Logistic regression. In addition, we used Spearman rank correlation analysis to clarify the relationship between hub genes and infiltrating immune cells and immune pathways. The expression levels of FPR1, FPR2, IL17RA, and TLR7 was verified in SD rat knee joint model of OA by immunohistochemistry. The expression levels of FPR1, FPR2, IL17RA, and TLR7 mRNA were detected in the IL-1ß induced rat chondrocytes in qPCR experiment in vitro. Four hub genes (FPR1, FPR2, IL17RA, and TLR7) were ultimately identified as OA biomarkers associated with ICD. And knockdown of TLR7 reversed collagen II and ADAMTS-5 degradation in IL-1ß-stimulated chondrocytes. This research may provide new immune related biomarkers for the diagnosis of OA and serve as a reference for disease treatment monitoring.

The effect of ding's screw and tension band wiring for treatment of olecranon fractures: a finite element study.

BACKGROUND: Tension band wiring (TBW) is a common surgical intervention for olecranon fractures. However, high rate of complications such as loss of reduction, skin irritation, and migration of the K-wires were reported up to 80%. Ding's screw tension band wiring (DSTBW) is a new TBW technique that has shown positive results in the treatment of other fracture types. The objective of this study was to evaluate the stability of DSTBW in the treatment of olecranon fractures by finite element analysis. METHOD: We used Ding's screw tension band fixation (DSTBW) and K-wire tension band fixation (TBW) to establish a finite element model to simulate and fix olecranon fractures. The stress distribution, opening angle, twisting angle, and pullout strength of K-wires or screws were analyzed and compared. RESULTS: The maximum von Mises stress was observed on the internal fixation for 90° elbow motion in both groups. The von Mises value of the screw in DSTBW was 241.2 MPa, and the von Mises value of k-wire in TBW was 405.0 MPa. Opening angle: TBW was 0.730° and DSTBW was 0.741° at 45° flexion; TBW was 0.679° and DSTBW was 0.693° at 90° flexion. Twisting angle: TBW was 0.146° and DSTBW was 0.180° at 45° flexion; TBW was 0.111° and DSTBW was 0.134° at 90° flexion. The pullout strength of DSTBW was significantly higher than that of TBW. Maximum pullout strength of Ding's screw was 2179.1 N, maximum pullout strength of K-wire was 263.6 N. CONCLUSION: DSTBW technology provides stable fixation for olecranon fractures, reducing the risk of internal fixation migration and failure.

The effect of Ding's screws and tension band wiring for treatment of inferior pole patellar fractures.

OBJECTIVES: We developed a cannulated screw with holes in the tail, named the Ding's screw. The objective of this study was to evaluate the clinical effect of Ding's screw in the treatment of inferior pole patellar fracture. METHODS: From March 2017 to October 2021, 68 patients with inferior pole patellar fracture in our department were retrospectively reviewed. According to different treatment methods, they were divided into Ding's screw and tension band wiring group (DSTBW) and cannulated screws and tension band wiring group (CSTBW). Radiological and clinical outcomes were evaluated and compared. RESULTS: There were 33 cases in DSTBW group and 35 cases in CSTBW group. The mean follow-up duration was 14.5 ± 2.6 months in the DSTBW group and 15.0 ± 2.3 months in the CSTBW group. No significant differences in age, sex, operative side or time to surgery were present between the two groups. Skin breakdown and infection were not significantly different among the groups (P > 0.05). At the last follow-up, the average Bostman score of the DSTBW group was 28.5 ± 1.3(excellent) and that of the CSTBW group was 27.8 ± 1.6(good), with statistical significance (P = 0.045). The average Lysholm score of the DSTBW group was 94.1 ± 3.4 (good), and that of the CSTBW group was 90.1 ± 4.4 (good), and the difference was statistically significant (P < 0.001). The average knee joint ROM of the DSTBW group was 135.6 ± 6.8˚, and that of the CSTBW group was 130.1 ± 6.7˚, and the difference between the two groups was statistically significant (P = 0.001). CONCLUSIONS: DSTBW is an effective method for the treatment of inferior pole patellar fractures with stable fixation and good functional effect.

Small Extracellular Vesicles Released from Bioglass/Hydrogel Scaffold Promote Vascularized Bone Regeneration by Transferring miR-23a-3p.

Background: The treatment of critical-size bone defect is a great difficulty in orthopedics. Osteogenesis and angiogenesis are critical issue during the process of bone repair and remodeling. Mesenchymal stem cells (MSCs)-derived exosomes have the same therapeutic effect to MSCs-based therapies. The effect of human umbilical cord MSCs-derived sEVs (hUC-MSCs-sEVs) on vascularized bone regeneration and the potential mechanism remains to be investigated. Herein, we aimed to explore the therapeutic effect and the mechanism of hUC-MSCs-sEVs on critical-size bone defect. Methods: To investigate the potential osteogenesis and angiogenesis effects of sEVs in vitro, we extracted sEVs from hUC-MSCs, and then sEVs were co-incubated with BMSCs and HUVECs. We next investigated the effect and potential mechanism of sEVs on the effects of osteogenesis and angiogenesis. We fabricated 3D-printed bioglass scaffold with Gelma/nanoclay hydrogel coatings to load sEVs (BG-gel-sEVs) to ensure in vivo sustained efficacy of sEVs. Finally, the skull defect model was used to evaluate the capacity of vascularized bone regeneration of the composited scaffolds. Results: hUC-MSCs-sEVs facilitated calcium deposition and the endothelial network formation, inducing osteogenic differentiation and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway. Additionally, the BG-gel-sEVs composited scaffold achieved vascularized bone regeneration in vivo. Conclusion: This finding illuminated that hUC-MSCs-sEVs promoted osteogenesis and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway, achieving vascularized bone regeneration.

Minimally invasive technique of monoaxial percutaneous screws and instrumentational maneuvers in thoracolumbar and lumbar fractures.

OBJECTIVES: Percutaneous pedicle screw fixation (PPSF) has been a common surgery for treating thoracolumbar and lumbar fractures. Many studies have reported PPSF is associated with poor reduction. We present a reliable method by using short-segment monoaxial percutaneous screws and instrumentational maneuvers to reduce the spine. This study aimed to evaluate radiological and clinical results of this method of reduction compared to traditional polyaxial screws method in treating thoracolumbar and lumbar fractures. METHODS: From February 2015 to February 2021, 64 patients with thoracolumbar and lumbar fractures in our department were retrospectively reviewed and divided into experimental group and control group according to different treatment methods. The experimental group was treated with short-segment monoaxial percutaneous screws (which were inserted at the adjacent vertebrae one level above, one level below the fracture, and the fractured vertebra) and instrumentational maneuvers method, while the control group was treated with traditional polyaxial screws method. The operation time was recorded. Visual analogue scale (VAS) and Oswestry disability index (ODI) were assessed as the clinical outcomes. The anterior height of the injured vertebra (AVH), the kyphosis cobb angle and the vertebral wedge angle were used to evaluate the fracture radiological reduction. RESULTS: A total of 64 patients were enrolled including 31 in the experimental group and 33 in the control group. There were no significant difference in operation time, AVH, the kyphosis cobb angle,the wedge angle of injured vertebra,VAS and ODI score between the two groups in preoperation. In each group, there were significant differences in the AVH, the kyphosis cobb angle and wedge angle of injured vertebra between preoperation and immediate postoperation. In each group, there were significant differences in VAS and ODI score between the preoperation and last follow-up. The total correction rates of AVH,the kyphosis cobb angle and the wedge angle of injured vertebra were significantly higher in the experimental group than those in the control group, while the loss of correction was significantly lower than the control. CONCLUSIONS: The reduction technique using monoaxial percutaneous screws and instrumentational maneuvers for thoracolumbar and lumbar fractures exhibited better radiological results and satisfying functional outcomes when compared to traditional polyaxial screws.

Nanofiber/hydrogel core-shell scaffolds with three-dimensional multilayer patterned structure for accelerating diabetic wound healing.

Impaired angiogenesis is one of the predominant reasons for non-healing diabetic wounds. Herein, a nanofiber/hydrogel core-shell scaffold with three-dimensional (3D) multilayer patterned structure (3D-PT-P/GM) was introduced for promoting diabetic wound healing with improved angiogenesis. The results showed that the 3D-PT-P/GM scaffolds possessed multilayered structure with interlayer spacing of about 15-80 µm, and the hexagonal micropatterned structures were uniformly distributed on the surface of each layer. The nanofibers in the scaffold exhibited distinct core-shell structures with Gelatin methacryloyl (GelMA) hydrogel as the shell and Poly (D, L-lactic acid) (PDLLA) as the core. The results showed that the porosity, water retention time and water vapor permeability of the 3D-PT-P/GM scaffolds increased to 1.6 times, 21 times, and 1.9 times than that of the two-dimensional (2D) PDLLA nanofibrous scaffolds, respectively. The in vitro studies showed that the 3D-PT-P/GM scaffolds could significantly promote cell adhesion, proliferation, infiltration and migration throughout the scaffolds, and the expression of cellular communication protein-related genes, as well as angiogenesis-related genes in the same group, was remarkably upregulated. The in vivo results further demonstrated that the 3D-PT-P/GM scaffolds could not only effectively absorb exudate and provide a moist environment for the wound sites, but also significantly promote the formation of a 3D network of capillaries. As a result, the healing of diabetic wounds was accelerated with enhanced angiogenesis, granulation tissue formation, and collagen deposition. These results indicate that nanofiber/hydrogel core-shell scaffolds with 3D multilayer patterned structures could provide a new strategy for facilitating chronic wound healing.

Pulmonary thromboembolism after distal ulna and radius fractures surgery: A case report and a literature review.

BACKGROUND: Pulmonary thromboembolism (PTE) is a serious postoperative complication that can occur after a fracture. Generally, PTE is caused by the falling off of lower extremity deep vein thrombosis (LEDVT) after lower limb fracture surgery. LEDVT and PTE after upper extremity fracture surgery are very rare. PTE is one of the most common clinical causes of sudden death. Venous thromboembolism includes PTE and DVT. We experienced one case of LEDVT and PTE after distal ulna and radius fracture surgery. The purpose of our report is to raise awareness for orthopedic surgeons that PTE can occur after distal ulna and radius fracture surgery, and patients with high risk factors should be considered for prevention and treatment of thrombosis in a timely manner. CASE SUMMARY: We report a 51-year-old Chinese male who had severe fractures of the left distal ulna, radius and little finger after a motorcycle accident. The patient underwent external fixation, open reduction and internal fixation. On the third post-operative day, computed tomographic pulmonary angiography showed PTE. Doppler ultrasonography showed thrombus formation in the bilateral posterior tibial veins. After a period of anticoagulation therapy, on the 25th d after the PTE, computed tomographic pulmonary angiography showed that thrombus in both sides of the pulmonary artery disappeared. Furthermore, about 4 mo after the PTE, thrombosis in the deep veins of the lower limbs disappeared. About 1 year after the surgery, X-rays showed good fracture healing, and the function of the wrist joint recovered well. CONCLUSION: Though rare, PTE can occur after distal ulna and radius fracture surgery and patients with high risk factors should be considered for prevention and treatment of thrombosis in a timely manner.

Platelet-rich plasma enhances the repair capacity of muscle-derived mesenchymal stem cells to large humeral bone defect in rabbits.

Mesenchymal stem cell-based therapy is a highly attractive strategy that promotes bone tissue regeneration. The aim of the present study was to evaluate the combination effect of muscle-derived mesenchymal stem cells (M-MSCs) and platelet-rich plasma (PRP) on bone repair capacity in rabbits with large humeral bone defect. Precise cylindrical bone defects of 10 mm diameter and 5 mm depth were established in rabbit humeral bones, which were unable to be repaired under natural conditions. The rabbits received treatment with M-MSCs/PRP gel, M-MSCs gel, or PRP gel, or no treatment. The bone tissue regeneration was evaluated at day 0-90 after surgery by HE morphological staining, Lane-Sandhu histopathological scoring, tetracycline detection, Gomori staining and micro-computed tomography. Beyond that, Transwell assay, CCK8 assay, Western blot analysis and ALP activity detection were performed in M-MSCs in vitro with or without PRP application to detect the molecular effects of PRP on M-MSCs. We found that the repair effect of M-MSCs group or PRP group was limited and the bone defects were not completely closed at post-operation 90 d. In contrast, M-MSCs/PRP group received obvious filling in the bone defects with a Lane-Sandhu evaluation score of 9. Tetracycline-labeled new bone area in M-MSCs/PRP group and new mineralized bone area were significantly larger than that in other groups. Micro-computed tomography result of M-MSCs/PRP group displayed complete recovery of humeral bone at post-operation 90 d. Further in vitro experiment revealed that PRP significantly induced migration, enhanced the growth, and promoted the expression of Cbfa-1 and Coll I in M-MSCs. In conclusion, PRP application significantly enhanced the regeneration capacity of M-MSCs in large bone defect via promoting the migration and proliferation of M-MSCs, and also inducing the osteogenic differentiation.

MiR-135-5p promotes osteoblast differentiation by targeting HIF1AN in MC3T3-E1 cells.

BACKGROUND: MicroRNAs (miRNAs or miRs) serve crucial roles in the progression of osteoporosis. This study investigated the role and specific molecular mechanism of miR-135-5p in regulating osteoblast differentiation and calcification. METHODS: Bone morphogenetic protein 2 (BMP2) was employed to interfere with the differentiation of MC3T3-E1. Then, miR-135-5p mimic or miR-135-5p inhibitor was transfected into MC3T3-E1, and quantitative RT-PCR was used to measure the expression of miR-135-5p. The expressions of runt-related transcription factor 2 (Runx2), osterix (OSX), osteopontin (OPN), and osteocalcin (OCN) were determined using western blot. Alkaline phosphatase (ALP) activity was measured using an appropriate kit assay. Calcium nodule staining was evaluated with alizarin red staining. A luciferase reporter assay was used to verify the target of miR-135-5p. Hypoxia-inducible factor 1 α inhibitor (HIF1AN) overexpression was applied to investigate its own role in the mechanism and a miR-135-5p rescue experiment was also performed. RESULTS: Overexpression of miR-135-5p promoted osteogenic differentiation and calcification, as shown by the increase in ALP activity, calcification and osteogenic marker levels, including Runx2, OSX, OPN and OCN. Knockdown of miR-135-5p yielded the opposite results. HIF1AN was confirmed as a direct target of miR-135-5p. HIF1AN overexpression inhibited osteogenic differentiation and calcification while miR-135-5p reversed these effects. CONCLUSIONS: These results indicate that miR-135-5p might have a therapeutic application related to its promotion of bone formation through the targeting of HIF1AN.

Inhibition of Nf-ҝb prevents trauma-induced heterotopic ossification in rat model.

PURPOSE: To investigate the pathogenesis and find a better prophylactic method of acquired heterotopic ossification (HO). MATERIALS AND METHODS: In the first part, we designed the brain-traumatic/burn/tenotomy rat model and testified its efficacy as HO model. 44 rats were randomly divided into experimental group and control group. After operation, the bilateral tendons of 2 rats were collected at the 2nd, 3rd, 4th, 6th, 8th, and 10th weeks to determine the expression levels of p65. Additionally, the remaining rats were exposed to X-Ray examination at the 10th week. In the second part, 124 rats were randomly divided into four groups based on the administration dosage of Ammonium pyrrolidinedithiocarbamate (PDTC). Then, three rats of each group were euthanized every week in the first seven weeks to collect tendon to detect the expression levels of p65 by qRT-PCR and Western Blot. The remaining rats were exposed to X-Ray examination at the 10th week to assess the size of HO before being euthanized for HE staining. RESULTS: The success rate of Brain-traumatic/Burn/Tenotomy model was 100%. Pharmacologic inhibition of Nf-ҝb signaling pathway by PDTC could significantly reduce the expression levels of p53 and the size of HO, and the reduction was most significant in the 0.6mg dosage group. CONCLUSIONS: Brain-traumatic/Burn/Tenotomy model was highly reliable HO model. Inhibition of Nf-ҝb signaling pathway by PDTC could significantly reduce HO formation, and the most effective concentration was 6 mg/ml for local injection.

Dynamics of MMP­9, MMP­2 and TIMP­1 in a rat model of brain injury combined with traumatic heterotopic ossification.

The present study aimed to detect early changes in the concentration of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase­2 (MMP­2) and tissue inhibitor of metalloproteinase­1 (TIMP­1) in a rat model of brain injury combined with traumatic heterotopic ossification (HO). A total of 132 male Sprague­Dawley rats were used to establish the experimental and control groups. Anatomy and sample collection were conducted on postoperative days 1, 2, 3, 4, 5, 6 and 7. Hematoxylin and eosin and immunohistochemical staining were performed for local tissues. MMP­9, MMP­2 and TIMP­1 levels and gene expression level were measured by ELISA and reverse transcription­quantitative polymerase chain reaction. Radiological investigation of the rat lower limbs was conducted at weeks 5 and 10 following modeling to observe the occurrence of HO. The incidence of HO for rats in the experimental group was higher compared with the control group. The serum MMP­9 levels of the experimental group were notably higher on postoperative days 5­7 compared with the control group. The MMP­9 gene expression of the experimental group was higher on postoperative days 3­7 compared with the control group. The TIMP­1 gene expression levels were markedly higher compared with the control group at each time point. Thus, an increase in inflammatory response is closely associated with brain injury, in addition to an increase in the number of inflammatory cells with the incidence of HO. The pathological elevation of MMP­9 and the altered dynamic equilibrium between MMP­9 and TIMP­1 contributed to the degradation, remodeling and calcification of the extracellular matrix, resulting in the induction of osteoblast precursor cells in HO. MMP­9 is a predictive marker of HO.

[EXPRESSION AND SIGNIFICANCE OF HYPOXIA INDUCIBLE FACTOR 1α IN RAT MODEL OF HETEROTOPIC OSSIFICATION AFTER Achilles TENOTOMY].

OBJECTIVE: To explore the role and significance of hypoxia inducible factor lα (HIF-lα) and hypoxia microenvironment in the pathogenesis of post-traumatic heterotopic ossification by detecting the expression of HIF-lα in rat model of heterotopic ossification after Achilles tenotomy. METHODS: A total of 140 male Sprague Dawley rats, aged 8-10 weeks, and weighing (210.1±10.6) g, were randomly divided into experimental group (n=70) and control group (n=70). In experimental group, the Achilles tendon was cut off and clamped to prepare post-traumatic heterotopic ossification model; in control group, only Achilles tendon was exposed. The general condition of rats was observed after operation, and at 2, 3, 4, 5, 6, 7, 8, 10, 12, and 14 days after operation, the Achilles tendon tissue was harvested from 6 rats for gross observation, histological observation, and immunohistochemical staining observation, and real-time fluorescence quantitative PCR and Western blot were used to detect the expressions of HIF-lα gene and protein at different time points in 2 groups. The X-ray films were taken and histological examination was done at 10 weeks after operation to evaluate the formation of heterotopic ossification. RESULTS: During the experiment, 1 rat died in experimental group at 3 days after operation, and the other rats survived to the end of the experiment. Gross and histological staining showed that the Achilles tendon had no obvious change, with normal tendon structure in control group at each time point. In experimental group, atrophy and necrosis of Achilles tendon stump were observed, with infiltration of inflammatory cells; and the hardness of Achilles tendon tissue gradually increased with the time; there were a large number of irregular connective tissue and cartilage cells. When compared with control group, the HIF-lα mRNA and protein expressions were significantly increased in experimental group at each time point (P<0.05). Immunohistochemical staining showed that HIF-lα was positive in experimental group. According to the results of X-ray films and histological examination at 10 weeks after operation, heterotopic ossification was found in experimental group, but no heterotopic ossification in control group. CONCLUSIONS: The expression of HIF-lα significantly increases at early stage of post-traumatic heterotopic ossification after Achilles tenotomy, suggesting that the local hypoxia microenvironment plays an important role in the pathogenesis of heterotopic ossification.