A novel degradable PCL/PLLA strapping band for internal fixation of fracture.

Early fracture fixation is the critical factor in fracture healing. Common internal fracture implants are made of metallic materials, which often affects the imaging quality of CT and MRI. Most patients will choose secondary surgery to remove the internal fixation implants, which causes secondary damage to them. The development of new degradable internal fracture implants has attracted more and more attention from orthopedic surgeons and researchers. Based on these problems, we improved the various properties of medical grade polycaprolactone (PCL) by adding poly(L-lactide) (PLLA). We produced PCL/PLLA strapping bands with different mass ratios by injection molding. We compared the mechanical properties, degradation properties, cell biocompatibility, bone marrow mesenchymal stem cells (BMSCs) adhesion, proliferation, osteogenic differentiation and fracture fixation effect of these strapping bands. The results showed that the tensile strength and yield force of the strapping bands increased with the increase of the content of PLLA. The addition of PLLA could significantly improve the mechanical strength in the early stage and accelerate the degradation rate of the strapping band. PCL/PLLA (80/20) strapping band had no significant cytotoxicity toward rBMSCs and could promote osteogenic differentiation of rBMSCs. The strapping band could ensure femoral fracture healing of beagles in 3 months and didn't cause damage to the surrounding tissues and main organs. This study will provide some new insights into the biodegradable products of PCL/PLLA blends for internal fixation of fracture. We produced novel degradable PCL/PLLA strapping bands with different mass ratios by injection molding. We tested the biological safety of the prepared internal fixation strapping bands for fracture, such as cell experiment in vitro and animal experiment, and studied the degradation behavior in vitro. The strapping bands could ensure femoral fracture healing of beagles. This study will provide some new insights into the biodegradable products of PCL/PLLA blends for internal fixation of fracture. A Immunofluorescence staining of rBMSCs (live cells: green; dead cells: red). B Young's modulus change curve during strapping bands degradation. C The implantation process of strapping bands. D Micro-CT images of the beagle's fracture recovery after the operation.

Mesenchymal stem cells encapsulation in chitosan and carboxymethyl chitosan hydrogels to enhance osteo-differentiation.

BACKGROUND: Recently biomaterials utilized for designing scaffolds in tissue engineering are not cost-effective and eco-friendly. As a result, we design and develop biocompatible and bioactive hydrogels for osteo-tissue regeneration based on the natural polysaccharide chitosan. Three distinct hydrogel components were used for this. METHODS: Hydrogels networks were created using chitosan 2% (CTS 2%), carboxymethyl chitosan 2% (CMC 2%), and 50:50 mixtures of CTS and CMC (CTS/CMC 50:50). Furthermore, scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR), degradation, and swelling behavior of design hydrogels were studied. Also, the cytocompatibility and osteo-differentiation potency were examined by encapsulating mesenchymal stem cells derived from adipose tissue (AMSCs) on the designed hydrogels. RESULTS: According to the findings, our results showed an acceptable pore structure, functional groups, and degradation rate of the designed hydrogels for in vitro evaluation. In addition, employing CMC instead of CTS or adding 50% CMC to the hydrogel component could improve the hydrogel's osteo-bioactivity without the use of external osteogenic differentiation agents. CONCLUSION: The CMC-containing hydrogel not only caused early osteogenesis but also accelerated differentiation to the maturity phase of osteoblasts.

Cytisine attenuates bone loss of ovariectomy mouse by preventing RANKL-induced osteoclastogenesis.

Postmenopausal Osteoporosis (PMOP) is oestrogen withdrawal characterized of much production and activation by osteoclast in the elderly female. Cytisine is a quinolizidine alkaloid that comes from seeds or other plants of the Leguminosae (Fabaceae) family. Cytisine has been shown several potential pharmacological functions. However, its effects on PMOP remain unknown. This study designed to explore whether Cytisine is able to suppress RANKL-induced osteoclastogenesis and prevent the bone loss induced by oestrogen deficiency in ovariectomized (OVX) mice. In this study, we investigated the effect of Cytisine on RAW 264.7 cells and bone marrow monocytes (BMMs) derived osteoclast culture system in vitro and observed the effect of Cytisine on ovariectomized (OVX) mice model to imitate postmenopausal osteoporosis in vivo. We found that Cytisine inhibited F-actin ring formation and tartrate-resistant acid phosphatase (TRAP) staining in dose-dependent ways, as well as bone resorption by pit formation assays. For molecular mechanism, Cytisine suppressed RANK-related trigger RANKL by phosphorylation JNK/ERK/p38-MAPK, IκBα/p65-NF-κB, and PI3K/AKT axis and significantly inhibited these signalling pathways. However, the suppression of PI3K-AKT-NFATc1 axis was rescued by AKT activator SC79. Meanwhile, Cytisine inhibited RANKL-induced RANK-TRAF6 association and RANKL-related gene and protein markers such as NFATc1, Cathepsin K, MMP-9 and TRAP. Our study indicated that Cytisine could suppress bone loss in OVX mouse through inhibited osteoclastogenesis. All data provide the evidence that Cytisine may be a promising agent in the treatment of osteoclast-related diseases such as osteoporosis.

SP1-mediated upregulation of lncRNA LMCD1-AS1 functions a ceRNA for miR-106b-5p to facilitate osteosarcoma progression.

Growing studies have indicated the involvements of long noncoding RNAs (lncRNAs) in the initiation and progression of various tumors. We aimed to investigated the role of lncRNA LMCD1 antisense RNA 1 (LMCD1-AS1) in osteosarcoma development. We found that LMCD1-AS1 and SP1 were highly expressed in osteosarcoma tissues and cell lines. High levels of LMCD1-AS1 were correlated with positively metastasis and poor clinical prognosis. Moreover, we showed that SP1 can bind to the promoter region of LMCD1-AS1, resulting in its overexpression in osteosarcoma. Functionally, silencing of LMCD1-AS1 suppressed the proliferation, migration, invasion and EMT progress of osteosarcoma cells. Mechanistic studies revealed that LMCD1-AS1 was a sponge of miR-106b-5p activity. LMCD1-AS1 modulated survival of osteosarcoma via targeting miR-106b-5p. Overall, we firstly indicated that LMCD1-AS1 overexpression contributes to osteosarcoma development and poor clinical outcome, suggesting that LMCD1-AS1 may be a novel diagnostic and prognostic biomarker for osteosarcoma and a target for osteosarcoma therapy.

Mitochondrion-mediated iron accumulation promotes carcinogenesis and Warburg effect through reactive oxygen species in osteosarcoma.

BACKGROUND: Iron metabolism disorder is closely associated with several malignant tumors, however the mechanisms underlying iron and the carcinogenesis in osteosarcoma are not yet well understood. METHODS: Cell proliferation ability of osteosarcoma cell lines was measured by CCK-8, EdU incorporation and colony formation assays. Cell cycle analysis was detected by flow cytometry. The carcinogenesis of osteosarcoma was measured by soft-agar formation, trans-well and Wound healing-scratch assay. Warburg effect was detected by Seahorse respirometry assays. Reactive oxygen species (ROS) level was measured by Dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probes. Western blotting was used to measure the expression of mitoferrin 1 (SLC25A37) and mitoferrin 2 (SLC25A28). Iron level in vitro and vivo was detected by iron assay kit. RNAi stable cell lines was generated using shRNA. RESULTS: Iron promoted proliferation, carcinogenesis and Warburg effect of osteosarcoma cells. Iron-induced reactive oxygen species (ROS) played an important role in these processes. Iron accumulated more in mitochondrion than in cytoplasm, suggesting mitochondrion-mediated iron accumulation was involved in the development of osteosarcoma. Moreover, iron upregulated the expression of mitoferrin 1 (SLC25A37) and mitoferrin 2 (SLC25A28). Knock-down of mitoferrin 1 (SLC25A37) and mitoferrin 2 (SLC25A28) decreased the production of ROS. In addition, iron increased the expression of Warburg key enzymes HK2 and Glut1, and affected AMPK/mTORC1 signaling axis. CONCLUSIONS: Mitochondrion-mediated iron accumulation promotes carcinogenesis and Warburg effect of osteosarcoma cells. Meanwhile, iron deprivation might be a novel effective strategy in the treatment of osteosarcoma.

A comparison of deltopectoral versus Judet approach for glenoid exposure.

BACKGROUND: Open reduction-internal fixation via an anterior or posterior approach is a widely used method for treating displaced glenoid fractures. This study aimed to identify the exposure range of the glenoid rim by these 2 approaches (deltopectoral and Judet approaches) and provide reference data for the choice of surgical approach. METHODS: Twelve cadaveric shoulders were dissected. Both deltopectoral and Judet approaches were performed on each shoulder to mark the glenoid fracture. In addition, the shoulder was disarticulated to record the exposure range of the glenoid rim. RESULTS: For the deltopectoral approach, the range of the exposed glenoid rim was from 5:50 to 11:30, which accounted for about 47.2% of the clock face. For the Judet approach, the range of the exposed glenoid rim was from 1:30 to 6:20, which accounted for about 40.3% of the clock face. Along the inferior glenoid, there was an area of partial overlap for the 2 approaches. The superior glenoid rim located from 11:30 to 1:30 was considered inaccessible, as it could not be exposed by the 2 approaches. CONCLUSION: Less than 50% of the glenoid rim can be exposed by the deltopectoral or Judet approach. With a single approach, it may be difficult to expose and fix some complex glenoid fractures. The superior part of the glenoid fracture is the non-access area via the deltopectoral or Judet approach.

miR-21 and miR-19b delivered by hMSC-derived EVs regulate the apoptosis and differentiation of neurons in patients with spinal cord injury.

BACKGROUND: In this study, we aimed to evaluate the therapeutic effects of extracellular vesicles (EVs), which were collected from differentiated PC12 cells and mesenchymal cells (MSCs), on the treatment of spinal cord injury (SCI). In addition, we aimed to identify miRNAs related to the inhibitory effect of EVs against cell apoptosis. METHODS: Electron microscopy was used to observe the distributions of EVs in the samples. Real-time PCR, western blot, thiazolyl blue tetrazolium bromide (MTT) assay, and flow cytometry were performed to establish the molecular signaling pathway underlying the effect of EVs in SCI. In addition, a Basso-Beattie-Bresnahan (BBB) score system, Nissl staining, immunohistochemistry assay, and TdT-mediated dUTP nick-end labeling (TUNEL) assay were conducted to validate the molecular signaling pathway established above. RESULTS: The expression of miR-21 and miR-19b was upregulated in EVs isolated from induced PC12 cells and MSCs, along with decreased expression of phosphatase and tensin homolog (PTEN) messenger RNA (mRNA)/protein and a lower level of cell apoptosis. The transfection of miR-21/miR-19b precursors into the cells also exhibited an inhibitory effect on cell apoptosis. In addition, in-silicon analysis and luciferase assays validated the role of PTEN as a virtual target of miR-21/miR-19b. Finally, the BBB scores and Nissl staining also validated the therapeutic effects of EVs derived from differentiated P12 cells/MSCs in SCI rats. Accordingly, the negative correlations between miR-21/miR-19b and PTEN mRNA/protein were implicated in the post-SCI recovery. CONCLUSIONS: The increased levels of miR-21/miR-19b in the EVs derived from differentiated PC12 cells and MSCs suppresses the apoptosis of neuron cells by downregulating the expression of PTEN.

Melatonin ameliorates spinal cord injury by suppressing the activation of inflammasomes in rats.

BACKGROUND: The activation of inflammasomes plays an important role in the pathogenesis of spinal cord injury (SCI). In addition, the administration of melatonin (MT) has been shown to suppress the activation of inflammasomes. In this study, we aimed to investigate the molecular mechanisms underlying the therapeutic effect of MT in the treatment of SCI. METHODS: Basso-Beattie-Bresnahan (BBB) locomotion scaling was conducted to evaluate the therapeutic effect of MT on post-SCI locomotion recovery. In addition, the measurement of spinal cord water content was performed together with Nissl staining to evaluate the protective effect of MT against SCI. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemistry (IHC) assay, Western blot analysis, and real-time polymerase chain reaction (PCR) were also conducted to clarify the molecular mechanisms underlying the therapeutic effect of MT in the treatment of SCI. RESULTS: BBB scores of SCI + MT rats were increased compared with the BBB scores of SCI rats, thus confirming the beneficial role of MT treatment in post-SCI functional recovery. Meanwhile, the administration of MT could alleviate SCI by reducing spinal cord water content and by exerting a neuroprotective effect on motor neurons. Furthermore, in the treatment of SCI, MT also attenuated cell apoptosis. Moreover, the relative expression of NLRP3, interleukin-1ß (IL-1ß), and caspase-1 were markedly elevated in the SCI group compared with that in the sham group, while the administration of MT reduced the expression of NLRP3 in SCI rats. CONCLUSIONS: MT treatment accelerated the recovery of SCI by suppressing the activation of inflammasomes.

Does isolated greater trochanter implication affect hip abducent strength and functions in intertrochanteric fracture?

BACKGROUND: A fracture in the isolated greater trochanter is an infrequent type of femoral intertrochanteric fracture. The gluteus medius and gluteus minimus are abducent muscle groups with attachments located on the greater trochanter. Thus, a fracture of the greater trochanter could cause avulsion injury of these attachment points and eventually affect the abducent function of the hip joint and cause chronic pain. Despite these prospects, the impact of a greater trochanter fracture on abducent strength and hip joint function have yet to be investigated. METHODS: Patients who were diagnosed with an isolated greater trochanter fracture (via computed tomography scan and X-ray) and underwent conservative treatment from June 2013 to October 2016 were included in the present study. Magnetic resonance imaging (MRI) was used to verify the morbidity of recessive fractures. Patients' Harris Hip Scores were determined at 3 months, 6 months, and 12 months and the abducent strength and range of motion of the hip joint on the injured side were analyzed and compared to those on the healthy side. RESULT: Among 32 patients, there were 7 individuals diagnosed with isolated greater trochanter fractures by MRI, and 25 individuals whose fractures were found to have extended into the intertrochanteric region, wherein the recessive intertrochanteric region fractures had no relationship with patients' age, gender, or weight. After 12 months of conservative treatment, 7 patients still complained of pain in the hip joint. The average Harris Hip Score was 87.84 ± 4.83, and the abducent range of the hip joint on the injured side (42.02 ± 13.93°) was not significantly different from that of the healthy side (46.24 ± 7.93°). The abducent strength of the hip joint of the injured side was 121.32 ± 41.06 N which was significantly lower than that of healthy side (137.44 ± 42.21 N). CONCLUSION: Results from this investigation suggest that an isolated greater trochanter fracture attenuates the abducent strength of the hip joint, which may be related to injuries of the ligaments and muscles around the greater trochanter. The surgical skills and methods of addressing isolated greater trochanter fractures merit further investigation.

A new anatomic locking plate for the treatment of posterolateral tibial plateau fractures.

BACKGROUND: Posterolateral tibial plateau fractures have become more common, and their treatment is of great importance to knee function. Additionally, there is no available literature detailing specialized anatomic locking plate for tibial plateau fractures. Therefore, the aim of the study was to evaluate the safety and clinical efficacy of an innovative anatomic locking plate for treatment of posterolateral tibial plateau fractures. METHODS: Between March 2014 and January 2016, 12 patients with posterolateral tibial plateau fracture underwent surgery with the anatomic locking plate for the posterolateral tibial plateau via the posterolateral approach. Relevant operational data for clinical evaluation were collected. RESULTS: The mean follow-up time was 26 months, and the mean age was 35 years for 12 patients. The mean interval between the time of injury and the surgery was 6.1 days. Radiological fracture union was evident in all patients at 12 weeks. During surgery, the blood loss ranged from 100 to 300 mL, and the duration ranged from 55 to 90 min. The Tegner-Lysholm functional score ranged from 85 to 97 at the final follow-up. Moreover, the final Rasmussen functional score ranged from 25 to 29, and Rasmussen anatomical score ranged from 13 to 18. CONCLUSIONS: The newly designed anatomic locking plate for the posterolateral tibial plateau provided adequate fixation along the posterolateral tibial plateau. It proved to be safe and effective in a small-sample-size population (12 patients) during a 12- to 34-month follow-up.

Locking plate for treating traumatic sternoclavicular joint dislocation: a case series.

BACKGROUND: Traumatic sternoclavicular joint dislocations are rare; closed reduction is the primary treatment. The failure of closed reduction or a prominent insult to the skin may require surgery to ensure the best possible outcome. METHODS: The records of 5 patients operated at our institution for sternoclavicular joint dislocation were reviewed. All patients were treated with open reduction and single 3.5-mm locking plate was used for fixation. Outcomes were evaluated with the Constant Shoulder Score (CSS) and Disability of the Arm, Shoulder, and Hand (DASH) questionnaire. Intraoperative and postoperative complications were recorded. RESULTS: All the patients had an average follow-up of 14 months (range, 11-16 months). At the final follow-up, the mean CSS score was 89.5 (range, 78-98) and the mean DASH score was 9.0 (range, 4-16). There were no early complications, including wound infection or neurologic or vascular deficits; there were also no broken or loosened screws or plates. No case of redislocation or arthrosis was observed. CONCLUSION: Our study indicates that open reduction and fixation with a single locking plate for the treatment of traumatic sternoclavicular joint dislocation is a safe, relatively simple surgical procedure that can lead to satisfactory outcomes.

Single lateral versus medial and lateral plates for treating displaced scapular body fractures: a retrospective comparative study.

BACKGROUND: This study compared the outcomes and complications of single lateral plating vs. dual plating for treating displaced scapular body fractures. METHODS: Open reduction and internal fixation using locking plates was performed in 45 patients with displaced scapular fractures. A single lateral plate fixed in the lateral border was used in 22 patients (group A), and dual plates fixed in both the lateral and medial borders were used in 23 (group B). RESULTS: The average follow-up duration in both groups was 20 months. A remarkable difference was seen between the 2 groups in mean operative time and blood loss, although the Disabilities of the Arm, Shoulder and Hand and Constant Shoulder scores at the final follow-up were similar. The prominence rate of the hardware was 27.3% (6 of 22) in group A and 65.2% (15 of 23) in group B. The plate removal rate was 31.8% (7 of 22) in group A and 78.3% (18 of 23) in group B. CONCLUSIONS: Open reduction using a single plate on the lateral border for treating displaced scapular body fractures can lead to good functional outcomes, shorter operative time, less blood loss, and fewer plate-related complications compared with the dual-plating technique.

What is the optimal sequence of decompression for multilevel noncontinuous spinal cord compression injuries in rabbits?

BACKGROUND: In recent years, multilevel spinal cord injuries (SCIs) have gained a substantial amount of attention from clinicians and researchers. Multilevel noncontinuous SCI patients cannot undergo the multiple steps of a one-stage operation because of a poor general condition or a lack of proper surgical approaches. The surgeon subsequently faces the decision of whether to initially relieve the rostral or caudal compression. In this study, we established a spinal cord compression model involving two noncontinuous segments in rabbits to evaluate the effects of differences in decompression order on the functional recovery of the spinal cord. METHODS: A Fogarty catheter was inserted into the epidural space through a hole in T6-7 and advanced 3 cm rostrally or caudally. Following successful model establishment, which was demonstrated by an evaluation of evoked potentials, balloons of different volumes (40 µl or 50 µl) were inflated in the experimental groups, whereas no balloons were inflated in the control group. The experimental groups underwent the first decompression in the rostral or caudal area at 1 week post-injury; the second decompression was performed at 2 weeks post-injury. For 6 weeks post-injury, the animals were tested to determine behavioral scores, somatosensory evoked potentials (SEPs) and radiographic imaging changes; histological and apoptosis assay results were subsequently analyzed. RESULTS: The behavioral test results and onset latency of the SEPs indicated that there were significant differences between priority rostral decompression (PRD) and priority caudal decompression (PCD) in the 50-µl compression group at 6 weeks post-injury; however, there were no significant differences between the two procedures in the 40-µl group at the same time point. Moreover, there were no significant peak-to-peak amplitude differences between the two procedures in the 50-µl compression group. CONCLUSIONS: The findings of this study suggested that preferential rostral decompression was more beneficial than priority caudal decompression with respect to facilitating spinal cord functional recovery in rabbits with severe paraplegia and may provide clinicians with a reference for the clinical treatment of multiple-segment spinal cord compression injuries.

The Bare Area of the Proximal Ulna: An Anatomic Study With Relevance to Chevron Osteotomy.

PURPOSE: A chevron osteotomy of the ulna is widely used to obtain intra-articular access to the elbow in the treatment of type C distal humerus fractures. The trochlear notch of the proximal ulna is divided into 2 articular parts by the "bare area." Ideally, the olecranon osteotomy should be centered on the bare area to minimize damage to the joint cartilage. The goals of this study were to describe the anatomy of the bare area and design an ideal chevron-shaped osteotomy. METHODS: We dissected 38 cadaver elbows and measured the width of the bare area, the distance between the tip of the triceps insertion and the area on the olecranon cortex corresponding to the bare area. We then designed a chevron osteotomy to stay within the bare area and measured the distance from the tip of the triceps insertion to the osteotomy apex as well as the angle of the osteotomy plane and the angle of the chevron cuts. RESULTS: The bare area existed in all 38 cadavers. The mean longitudinal and transverse widths were 4.0 mm (range, 1.0-8.6 mm) and 19.0 mm (range, 16.9-23.8 mm), respectively. The mean distance between the tip of the triceps insertion and the area on the olecranon cortex corresponding to the bare area was 19.0 mm (range, 16.0-23.0 mm). The mean transverse and longitudinal widths of the cortical notch were 3.0 mm (range, 1.6-4.5 mm) and 8.0 mm (range, 6.5-14.8 mm), respectively. The mean distance between the tip of the triceps insertion and the osteotomy apex was 22.0 mm (range, 18.0-24.0 mm) and the mean angle between the osteotomy surface and the vertical plane corresponding to the tangent plane was 20° (range, 10° to 25°). The mean angle of the V shape was 140° (range, 130° to 150°). CONCLUSIONS: Using the narrowest edge lacking cartilage (lateral or medial side) as a point of reference to locate the bare area, the designed chevron osteotomy entered the joint in the bare area in most specimens and decreased associated damage to the joint cartilage. CLINICAL RELEVANCE: This study describes the anatomy of the bare area and the design of the ideal chevron-shaped osteotomy to treat type C distal humerus fractures.

Augmented Repair of Acute Achilles Tendon Rupture Using an Allograft Tendon Weaving Technique.

Achilles tendon rupture is a common injury, especially in those who are physically active. Although open surgery is a widely used option for the treatment of acute Achilles tendon rupture, the optimal treatment is still disputed. In our study, 59 patients with unilateral, closed, acute rupture of the Achilles tendon were treated by open surgery using an allograft weave to augment the repair. All the surgeries were performed within 1 to 4 days after injury. The mean American Orthopaedic Foot and Ankle Society ankle-hindfoot score was recorded as 91.20 (range 88 to 95), 95.34 (range 92 to 98), and 98.27 (range 97 to 99) at the 3-, 6-, and 12-month follow-up visit, respectively. At the final follow-up visit, the mean difference between the mid-calf circumference of the injured and uninjured legs was 0.19 (range -0.03 to 1.50) cm (p = .43). At the final follow-up visit, the mean difference between the vertical distances from the plantar surface of the heel to the ground for the injured and uninjured lower extremities was 0.44 (range -0.03 to 0.5) cm (p = .17). Augmented repair using the allograft tendon weaving technique provided satisfactory tendon strength and functional outcomes and a timely return to the patients' activities.

A-769662 protects osteoblasts from hydrogen dioxide-induced apoptosis through activating of AMP-activated protein kinase (AMPK).

Here we report that 5'-monophosphate (AMP)-activated protein kinase (AMPK) agonist A-769662 inhibited hydrogen peroxide (H2O2)-induced viability loss and apoptosis of human and mouse osteoblast cells. H2O2-induced moderate AMPK activation in osteoblast cells, which was enhanced by A-769662. Inactivation of AMPK by its inhibitor compound C, or by target shRNA-mediated silencing and kinase dead (KD) mutation exacerbated H2O2-induced cytotoxicity in osteoblast cells. A-769662-mediated protective effect against H2O2 was also blocked by AMPK inhibition or depletion. A-769662 inhibited reactive oxygen species (ROS) accumulation by H2O2 in osteoblast cells. Meanwhile, H2O2-induced ATP depletion was inhibited by A-769662, but was aggravated by compound C. Further, H2O2 induced AMPK-dependent and pro-survival autophagy in cultured osteoblast cells, which was enhanced by A-769662. Our results suggested that activation of AMPK by H2O2 is anti-apoptosis and pro-survival in osteoblast cells, probably due to its anti-oxidant, pro-autophagy and ATP preservation abilities, and A-769662-mediated cell-protective effect in osteoblast cells requires AMPK activation. Our study suggests that A-769662 might be further investigated as a novel anti-osteonecrosis agent.

Numerical study of pedicle screw construction and locking compression plate fixation in posterior pelvic ring injuries: Analyzed by finite element method.

BACKGROUND: The aim of this study was to compare the biomechanical performance of pedicle screw construction and locking compression plate fixation in posterior pelvic ring injuries analyzed by finite element method. METHODS: A 3-dimensional finite element model of the spine-pelvis-femur complex with ligaments was reconstructed from computed tomography images. An unstable posterior pelvic ring injury was created, which was fixed with a pedicle screw construction or locking compression plate. A follower load of 400 N was applied to the upper surface of the vertebrae to simulate the upper body weight, while the ends of the proximal femurs were fixed. The construct stiffness, the maximum vertical displacement, the maximum posterior displacement, the maximum right displacement, and the overall maximum displacement of the sacrum, and stress distributions of the implants and pelvises were assessed. RESULTS: The construct stiffness of the pedicle screw model (435.14 N/mm) was 2 times that of the plate model (217.01 N/mm). The maximum vertical displacement, the maximum posterior displacement, the maximum right displacement, and the overall maximum displacement of the sacrum in the pedicle screw model were smaller than those in the plate model (0.919, 1.299, 0.259, and 1.413 mm in the pedicle screw model, and 1.843, 2.300, 1.053, and 2.895 mm in the plate model, respectively). The peak stresses of the implant and pelvis in the pedicle screw model decreased by 80.4% and 25% when compared with the plate model (44.57 and 34.48 MPa in the pedicle screw model, and 227.47 and 45.97 MPa in the plate model, respectively). CONCLUSION: The study suggested that the pedicle screw construction could provide better fixation stability than the locking compression plate and serves as the recommended fixation method for the treatment of posterior pelvic ring injuries.

Finite element analysis of a novel anatomical plate in posterolateral plateau fractures.

Objective: This study aims to analyze the biomechanical characteristics of posterolateral plateau fractures fixed by a novel anatomical plate using finite element analysis. Methods: A three-dimensional digital model of the full length of right tibiofibula was obtained by CT scanning. A posterolateral tibial plateau fracture model was then created. The acquired fracture model was assembled with 4 groups of internal fixations: Group A, novel anatomical plate; Group B, straight buttress plate; Group C, oblique T-shaped locking plate; Group D, two lag screws. Axial loads of 500, 1,000 and 1,500 N perpendicular to the horizontal plane were used to simulate the stress on the lateral plateau of a 65 kg person standing, walking and fast running. Results: Vertical displacements of the posterolateral fragments in each of the four groups gradually increased under loads from 500 N to 1,500 N. The maximum displacement of the fracture fragment in four groups were all located on the lateral side of the proximal part, and the displacement gradually decreased from the proximal part to the distal end. The maximum displacement values under the axial load of 1,500 N was in the following order: novel anatomical plate (1.2365 mm) < oblique T-shaped locking plate (1.314 mm) < two lag screws (1.3747 mm) < straight buttress plate (1.3932 mm). As the axial load increased, the stress value of the different internal fixation models gradually increased. The stress behavior of the same internal fixation model under different loads was similar. The maximum stress value under the axial load of 1,500 N was in the following order: novel anatomical plate (114.63 MPa) < oblique T-shaped locking plate (277.17 MPa) < two lag screws (236.75 MPa) < straight buttress plate (136.2 MPa). Conclusion: The patients with posterolateral plateau fractures fixed with a novel anatomical plate in standing, walking and fast running can achieve satisfactory biomechanical results, which lays the foundation for future applications. At the same time, clinical fracture types are often diverse and accompanied by damage to the soft tissue. Therefore, the ideal surgical approach and appropriate internal fixation must be selected based on the patient's injury condition.

Biomechanical comparison of an intramedullary nail combined with a reconstruction plate combination versus a single intramedullary nail in unstable intertrochanteric fractures with lateral femoral wall fracture: A finite element analysis.

This study aimed to compare the biomechanical performance of an intramedullary nail combined with a reconstruction plate and a single intramedullary nail in the treatment of unstable intertrochanteric femoral fractures with a fracture of the lateral femoral wall (LFW). A three-dimensional finite element (FE) femur model was established from computed tomography images of a healthy male volunteer. A major reverse obliquity fracture line, associated with a lesser trochanteric fragment defect and a free bone fragment of the LFW, was developed to create an AO/OTA type 31-A3.3 unstable intertrochanteric fracture mode. Two fixation styles were simulated: a long InterTAN nail (ITN) with or without a reconstruction plate (RP). A vertical load of 2100 N was applied to the femoral head to simulate normal walking. The construct stiffness, von Mises stress, and model displacement were assessed. The ITN with RP fixation (ITN/RP) provided higher axial stiffness (804 N/mm) than the ITN construct (621 N/mm). The construct stiffness of ITN/RP fixation was 29% higher than that of ITN fixation. The peak von Mises stress of the implants in the ITN/RP and ITN models was 994.46 MPa and 1235.24 MPa, respectively. The peak stress of the implants in the ITN/RP model decreased by 24% compared to that of the ITN model. The peak von Mises stress of the femur in the ITN/RP model was 269.06 MPa, which was lower than that of the ITN model (331.37 MPa). The peak stress of the femur in the ITN/RP model was 23% lower than that of the ITN model. The maximum displacements of the ITN/RP and ITN models were 12.12 mm and 13.53 mm, respectively. The maximum displacement of the ITN/RP model decreased by 12% compared with that of the ITN model. The study suggested that an additional plate fixation could increase the construct stiffness, reduce the stresses in the implant and femur, and decrease displacement after intramedullary nailing. Therefore, the intramedullary nail and reconstruction plate combination may provide biomechanical advantages over the single intramedullary nail in unstable intertrochanteric fractures with a fractured LFW.

siRNA incorporated in slow-release injectable hydrogel continuously silences DDIT4 and regulates nucleus pulposus cell pyroptosis through the ROS/TXNIP/NLRP3 axis to alleviate intervertebral disc degeneration.

Aims: In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. Methods: An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel's mechanism in IVDD. Results: A correlation between DDIT4 expression levels and disc degeneration was shown with human nucleus pulposus and needle-punctured rat disc specimens. We confirmed that DDIT4 was responsible for activating the ROS-TXNIP-NLRP3 axis during oxidative stress-induced pyroptosis in rat nucleus pulposus in vitro. Mitochondria were damaged during oxidative stress, and DDIT4 contributed to mitochondrial damage and ROS production. In addition, siDDIT4@G5-P-HA hydrogels showed good delivery activity of siDDIT4 to NPCs. In vitro studies illustrated the potential of the siDDIT4@G5-P-HA hydrogel for alleviating IVDD in rats. Conclusion: DDIT4 is a key player in mediating pyroptosis and IVDD in NPCs through the ROS-TXNIP-NLRP3 axis. Additionally, siDDIT4@G5-P-HA hydrogel has been found to relieve IVDD in rats. Our research offers an innovative treatment option for IVDD.