Biomechanical investigation of S2 alar-iliac screw and S1 pedicle screw fixation in the treatment of Denis type II sacral fractures.

Although S2 alar-iliac screw technique has been widely used in spinal surgery, its applicability to pelvic fractures is largely unknown. This study aimed to evaluate the biomechanical stability of S2 alar-iliac screw and S1 pedicle screw fixation in the treatment of Denis II sacral fractures. Twenty-eight artificial pelvic fracture models were treated with unilateral lumbopelvic fixation, sacroiliac screw fixation, S2 alar-iliac screw and S1 pedicle screw fixation, and S2 alar-iliac screw and contralateral S1 pedicle screw fixation (Groups 1-4, respectively; N = 7 per group). Each model was cyclically tested under increasing axial compression. Optical motion-tracking was used to assess relative displacement and gap angle, and the number of failure cycles. Relative displacement was significantly smaller in Group 3 than in Groups 1 (p = 0.004) and 4 (p < 0.001) but not significantly different between Groups 3 and 2 (p = 0.290). The gap angle in Group 3 was significantly smaller than that in Group 1 (p = 0.009) on the sagittal plane but significantly larger than that in Group 4 (p = 0.006) on the horizontal plane. A number of failure cycles was significantly higher in Group 3 than in Groups 1 (p = 0.002) and 4 (p = 0.004) but not significantly different between Groups 3 and 2 (p = 0.910). From a biomechanical perspective, S2 alar-iliac screw and S1 pedicle screw fixation can provide good stability in the treatment of Denis II sacral fractures.

Biomechanical comparison of the undercut thread design versus conventional buttress thread for the lag screw of the dynamic hip screw system.

Objective: To compare the fixation stability of the lag screw with a undercut thread design for the dynamic hip screw (DHS) system versus the lag screw with the conventional buttress thread. Methods: The lag screws with the undercut thread (a flat crest feature, a tip-facing undercut feature) and buttress thread were both manufactured. Fixation stability was investigated using cyclic compressive biomechanical testing on custom osteoporotic femoral head sawbone. The forces required for the same vertical displacement in the two types of lag screw were collected to evaluate the resistance to migration. Varus angle was measured on X-ray images to assess the ability in preventing varus collapse. Finite element analysis (FEA) was performed to analyze the stress and strain distribution at the bone-screw interface of the two types of lag screws. Results: The biomechanical test demonstrated that the force required to achieve the same vertical displacement of the lag screw with the undercut thread was significantly larger than the lag screw with conventional buttress thread (p < 0.05). The average varus angles generated by the undercut and buttress threads were 3.38 ± 0.51° and 5.76 ± 0.38°, respectively (p < 0.05). The FEA revealed that the region of high-stress concentration in the bone surrounding the undercut thread was smaller than that surrounding the buttress thread. Conclusion: The proposed DHS system lag screw with the undercut thread had higher migration resistance and superior fixation stability than the lag screw with the conventional buttress thread.

Fixation stability comparison of bone screws based on thread design: buttress thread, triangle thread, and square thread.

BACKGROUND: The influence of thread profile on the fixation stability of bone screws remains unclear. This study aimed to compare the fixation stability of screws with different thread profiles under several loading conditions. METHODS: Bone screws that differed in thread profile (buttress, triangle, and square thread) only were made of stainless steel. Their fixation stabilities were evaluated individually by the axial pullout test and lateral migration test, besides, they were also evaluated in pairs together with a dynamic compression plate and a locking plate in polyurethane foam blocks under cyclic craniocaudal and torsional loadings. RESULTS: The triangle-threaded and square-threaded screws had the highest pullout forces and lateral migration resistance. When being applied to a dynamic compression plate, higher forces and more cycles were required for both triangle- and square-threaded screws to reach the same displacement under cyclic craniocaudal loading. On the other hand, the triangle-threaded screws required a higher torque and more cycles to reach the same angular displacement under cyclic torsional loading. When being applied to a locking plate, the square-threaded screws needed higher load, torque, and more cycles to reach the same displacement under both cyclic craniocaudal and torsion loadings. CONCLUSIONS: The triangle-threaded screws had superior pullout strength, while square-threaded screws demonstrated the highest lateral migration resistance. Moreover, dynamic compression plate fixation with triangle- and square-threaded screws achieved more favorable fixation stability under craniocaudal loading, while triangle-threaded screws demonstrated superior fixation stability under torsional loading. Locking plate fixation with a square-threaded screw achieved better fixation stability under both loading types.

Development and initial validation of a novel thread design for nonlocking cancellous screws.

High failure rates have been associated with nonlocking cancellous screws with a typical buttress thread in patients with osteoporotic bone. This study aimed to develop a novel thread design and compare its fixation stability with that of a typical buttress thread. Nonlocking cancellous screws with a novel thread design (proximal flank angle of 120 degrees, a flat crest feature, a tip-facing undercut feature) and nonlocking cancellous screws with a typical buttress thread were manufactured using stainless steel. Fixation stabilities were evaluated individually by the axial pullout and lateral migration tests, and they were evaluated in pairs together with a dynamic compression plate in an osteoporotic bone substitute (10 PCF polyurethane foam per ASTM F1839) under cyclic craniocaudal and torsional loadings. Pullout strength and lateral migration resistance for the individual screw test and the force, torque, and number of cycles required to achieve specific displacement and torsion for the multi-screw test were comparatively analyzed between both screw types. A finite element analysis model was constructed to analyze the stress distributions in the bone tissue adjacent to the threads. The biomechanical test revealed the novel undercut thread had superior axial pullout strength, lateral migration resistance, and superior fixation stability when applied to a dynamic compression plate under cyclic craniocaudal loading and torsional loading than those in the typical buttress thread. The finite element analysis simulation revealed that the novel thread can distribute stress more evenly without high-stress concentration at the adjacent bone tissue when compared to that of a typical buttress thread.

Development and initial validation of a novel undercut thread design for locking screws.

BACKGROUND: Locking screws with a typical buttress thread have high levels of failure in patients with osteoporotic bones. This study aims to develop a novel thread design for the locking screw and compare its fixation stability with the typical buttress thread. METHODS: Locking screws with a novel thread design that possess an undercut feature and locking screws with a typical buttress thread were manufactured from stainless steel. Their fixation stabilities were then evaluated individually under a lateral migration test and evaluated in pairs together with a locking plate (LP) in an osteoporotic bone substitute under cyclic craniocaudal and torsional loadings. A finite element analysis (FEA) model was constructed to analyze the stress distributions present in the bone tissue adjacent to the novel thread versus the buttress thread. RESULTS: The biomechanical test revealed that the novel thread had a significantly higher lateral migration strength than the buttress thread. When applied to a LP, the locking screw with the novel thread requires more cycles and higher forces or torque to resist migration up to 5 mm or 10° than the buttress thread. The FEA simulation showed that the novel thread can make the stress distribute more evenly at the adjacent bone tissue when compared with the buttress thread. CONCLUSIONS: The locking screw with the novel undercut thread had superior lateral migration resistance during both initial and continued migration and superior fixation stability when applied to a LP under both cyclic craniocaudal loading and torsional loading than the locking screw with a typical buttress thread.

Stenotic intercondylar notch is not a risk factor for posterior cruciate ligament rupture: a morphological analyses using magnetic resonance imaging.

PURPOSE: The present study aimed to examine the factors related to the morphological characteristics of the femoral condyle in posterior cruciate ligament rupture in female and male populations. METHODS: One hundred and three patients (41 females, 62 males) with posterior cruciate ligament rupture from 2010 to 2020 were included in this retrospective case-control study. The sex and age of the posterior cruciate ligament rupture group were matched to those of the control group (41 females, 62 males; age range 16-69 years). Magnetic resonance imaging was used to measure the intercondylar notch width, femoral condylar width, and intercondylar notch angle in both the axial and coronal images. The 'α' angle was also measured using magnetic resonance imaging. The notch width index is the ratio of the intercondylar notch width to the femoral condylar width. Three types of intercondylar notch shapes (types A, U, and W) were evaluated in the axial magnetic resonance imaging images. RESULTS: The difference in the mean coronal notch width index between the study groups was statistically significant in the female population. The difference in the mean coronal femoral condylar width between the study groups was statistically significant in the male population. CONCLUSIONS: A larger coronal notch width index was the greatest risk factor for posterior cruciate ligament rupture in the female population. In the male population, decreased coronal condylar width was the greatest risk factor for posterior cruciate ligament rupture. The results did not indicate that patients with a PCL rupture have a stenotic intercondylar notch. Posterior cruciate ligament injury prevention strategies could be applied to females with a larger coronal notch width index and males with a decreased condylar width. LEVELS OF EVIDENCE: Level III.

Treatment of Unstable Posterior Pelvic Ring Injury with S2-Alar-Iliac Screw and S1 Pedicle Screw Fixation.

OBJECTIVE: The S2-alar-iliac (S2AI) screws have been described as an alternative method for lumbosacropelvic fixation in place of iliac screws. However, the clinical effect of the short-segment S2AI screw fixation technique in the treatment of unstable posterior pelvic ring injuries remains unclear. In this study, we report the preliminary clinical results of the internal fixation connecting a S2-alar-iliac screw and a S1 pedicle screw (i.e., S2AI-S1 fixation) in the treatment of unstable pelvic posterior ring injuries. METHODS: Twenty-five patients with unstable posterior pelvic ring injury were treated with S2AI-S1 fixation from February 2019 to June 2020. The incision length, surgical time, blood loss, frequency of intraoperative fluoroscopy, quality of reduction, complications, and functional outcome were analyzed. RESULTS: A total of 29 groups of S2AI-S1 fixation were used in 25 patients. The mean incision length was 8.3 (6.2 - 10.3) cm, mean operative time was 86.4 (60 - 142) minutes, mean frequency of intraoperative fluoroscopy was 7.9 (4 - 12) times, and mean blood loss was 148 (50 - 500) mL. The mean postoperative follow-up time was 17.8 (10 - 26) months. The satisfaction rate of pelvic reduction quality was 25/29, and the satisfactory rate of functional outcome was 23/25. There were no obvious signs of screw prominence, screw loosening, or implant failure. CONCLUSIONS: The case series presented in this study show the successful use of S2AI-S1 fixation to treat unstable posterior pelvic ring injuries. The S2AI-S1 fixation, not including the lumbar spine in the fixation range, is a simple, safe, and effective fixation method.

Applicable safety analysis and biomechanical study of iliosacral triangular osteosynthesis.

BACKGROUND: The aim of this study was to investigate the applicable safety and biomechanical stability of iliosacral triangular osteosynthesis (ITO) through 3D modeling and finite element (FE) analysis. METHODS: Pelvic CT imaging data from 100 cases were imported into Mimics software for the construction of 3D pelvic models. The S2-alar-iliac (S2AI) screws and S2 sacroiliac screws were placed in the S2 segment with optimal distribution and their compatibility rate on the S2 safe channel was observed and analyzed. In the FE model, the posterior pelvic ring was fixed with two transsacral screws (TTS), triangular osteosynthesis (TO) and ITO, respectively. Four different loading methods were implemented in sequence to simulate the force in standing, flexion, right bending, and left twisting, respectively. The relative displacement and change in relative displacement of the three fixing methods were recorded and analyzed. RESULTS: The theoretical compatibility rate of S2AI screw and S2 sacroiliac screw in S2 segment was 94%, of which 100% were in males and 88% in females. In the FE model, in terms of overall relative displacement, TTS group showed the smallest relative displacement, the ITO group showed the second smallest, and the TO group the largest relative displacement. The change in relative displacement of the TTS group displayed the smaller fluctuations in motion. The change in relative displacement of the TO group under right bending and left twisting displayed larger fluctuations, while the ITO group under flexion displayed larger fluctuations. CONCLUSIONS: The simultaneous placement of S2AI screw and S2 sacroiliac screw in the S2 segment is theoretically safe. Although the biomechanical stability of ITO is slightly lower than TTS, it is better than TO, and can be used as a new method for the treatment of posterior pelvic ring injuries.

Development and validation of a modularized external fixator for generating standardized fracture healing micromotions in rats.

AIMS: To fully verify the reliability and reproducibility of an experimental method in generating standardized micromotion for the rat femur fracture model. METHODS: A modularized experimental device has been developed that allows rat models to be used instead of large animal models, with the aim of reducing systematic errors and time and money constraints on grouping. The bench test was used to determine the difference between the measured and set values of the micromotion produced by this device under different simulated loading weights. The displacement of the fixator under different loading conditions was measured by compression tests, which was used to simulate the unexpected micromotion caused by the rat's ambulation. In vivo preliminary experiments with a small sample size were used to test the feasibility and effectiveness of the whole experimental scheme and surgical scheme. RESULTS: The bench test showed that a weight loading < 500 g did not affect the operation of experimental device. The compression test demonstrated that the stiffness of the device was sufficient to keep the uncontrollable motion between fracture ends, resulting from the rat's daily activities, within 1% strain. In vivo results on 15 rats prove that the device works reliably, without overburdening the experimental animals, and provides standardized micromotion reproductively at the fracture site according to the set parameters. CONCLUSION: Our device was able to investigate the effect of micromotion parameters on fracture healing by generating standardized micromotion to small animal models. Cite this article: Bone Joint Res 2021;10(11):714-722.

S2-alar-iliac screw and S1 pedicle screw fixation for the treatment of non-osteoporotic sacral fractures: a finite element study.

BACKGROUND: Five different sacral fracture fixation methods were compared using finite element (FE) analysis to study their biomechanical characteristics. METHODS: Denis type I sacral fractures were created by FE modeling. Five different fixation methods for the posterior pelvic ring were simulated: sacroiliac screw (SIS), lumbopelvic fixation (LPF), transiliac internal fixator (TIFI), S2-alar-iliac (S2AI) screw and S1 pedicle screw fixation (S2AI-S1) and S2AI screw and contralateral S1 pedicle screw fixation (S2AI-CS1). Four different loading methods were implemented in sequence to simulate the force in standing, flexion, right bending and left twisting, respectively. Vertical stiffness, relative displacement and change in relative displacement were recorded and analyzed. RESULTS: As predicted by the FE model, the vertical stiffness of the five groups in descending order was S2AI-S1, SIS, S2AI-CS1, LPF and TIFI. In terms of relative displacement, groups S2AI-S1 and S2AI-CS1 displayed a lower mean relative displacement, although group S2AI-CS1 exhibited greater displacement in the upper sacrum than group S2AI-S1. Group SIS displayed a moderate mean relative displacement, although the displacement of the upper sacrum was smaller than the corresponding displacement in group S2AI-CS1, while groups LPF and TIFI displayed larger mean relative displacements. Finally, in terms of change in relative displacement, groups TIFI and LPF displayed the greatest fluctuations in their motion, while groups SIS, S2AI-S1 and S2AI-CS1 displayed smaller fluctuations. CONCLUSION: Compared with SIS, unilateral LPF and TIFI, group S2AI-S1 displayed the greatest biomechanical stability of the Denis type I sacral fracture FE models. When the S1 pedicle screw insertion point on the affected side is damaged, S2AI-CS1 can be used as an appropriate alternative to S2AI-S1.

Lateral migration resistance of screw is essential in evaluating bone screw stability of plate fixation.

Conventional evaluation of the stability of bone screws focuses on pullout strength, while neglecting lateral migration resistance. We measured pullout strength and lateral migration resistance of bone screws and determined how these characteristics relate to screw stability of locking plate (LP) and dynamic compression plate (DCP) fixation. Pullout strength and lateral migration resistance of individual bone screws with buttress, square, and triangular thread designs were evaluated in polyurethane foam blocks. The screw types with superior performance in each of these characteristics were selected. LP and DCP fixations were constructed using the selected screws and tested under cyclic craniocaudal and torsional loadings. Subsequently, the association between individual screws' biomechanical characteristics and fixation stability when applied to plates was established. Screws with triangular threads had superior pullout strength, while screws with square threads demonstrated the highest lateral migration resistance; they were selected for LP and DCP fixations. LPs with square-threaded screws required a larger force and more cycles to trigger the same amount of displacement under both craniocaudal and torsional loadings. Screws with triangular and square threads showed no difference in DCP fixation stability under craniocaudal loading. However, under torsional loading, DCP fixation with triangular-threaded screws demonstrated superior fixation stability. Lateral migration resistance is the primary contributor to locking screw fixation stability when applied to an LP in resisting both craniocaudal and torsional loading. For compression screws applied to a DCP, lateral migration resistance and pullout strength work together to resist craniocaudal loading, while pullout strength is the primary contributor to the ability to resist torsional loading.

Can barb thread design improve the pullout strength of bone screws?

AIMS: To draw a comparison of the pullout strengths of buttress thread, barb thread, and reverse buttress thread bone screws. METHODS: Buttress thread, barb thread, and reverse buttress thread bone screws were inserted into synthetic cancellous bone blocks. Five screw-block constructs per group were tested to failure in an axial pullout test. The pullout strengths were calculated and compared. A finite element analysis (FEA) was performed to explore the underlying failure mechanisms. FEA models of the three different screw-bone constructs were developed. A pullout force of 250 N was applied to the screw head with a fixed bone model. The compressive and tensile strain contours of the midsagittal plane of the three bone models were plotted and compared. RESULTS: The barb thread demonstrated the lowest pullout strength (mean 176.16 N (SD 3.10)) among the three thread types. It formed a considerably larger region with high tensile strains and a slightly smaller region with high compressive strains within the surrounding bone structure. The reverse buttress thread demonstrated the highest pullout strength (mean 254.69 N (SD 4.15)) among the three types of thread. It formed a considerably larger region with high compressive strains and a slightly smaller region with high tensile strains within the surrounding bone structure. CONCLUSION: Bone screws with a reverse buttress thread design will significantly increase the pullout strength. Cite this article: Bone Joint Res 2021;10(2):105-112.

The Effect of Knee Flexion on Length Changes and Stress Distribution of Ligaments: A Displacement Controlled Finite Element Analysis.

The use of dynamic finite element analysis to investigate the biomechanical behavior of the knee joint is mainly based on movement of the joint. Challenges are associated with simulation of knee joint flexion-extension activity. This study investigated changes in the length and stress state of ligaments during lunge with a displacement controlled finite element analysis of the knee joint based on in vivo fluoroscopic kinematic data. The geometric center axis (GCA) was used to represent knee kinematics to quantify femoral motion relative to the tibia. Because the GCA was considered as a functional flexion axis, 2 degrees of freedom could be reduced. Published data on the in vivo fluoroscopic kinematic features of the GCA were used to establish the equations for degrees of freedom. Data for 4 degrees of freedom were obtained simultaneously at every 5° of knee flexion. Displacement and rotation were applied to the femur and tibia to produce relative displacement, and the elongation and stress state of the knee ligaments were computed. The predictions confirmed that lunge affected the biomechanical behavior of ligaments. Displacement controlled finite element analysis of knee flexion can be simulated on the basis of fluoroscopic kinematic data to achieve physiologic movement. [Orthopedics. 2021;44(1):e61-e67.].

Infra-acetabular screw exited between ischial tuberosity and ischial spine is more suitable for Asian population: a 3D morphometric study.

BACKGROUND: Recently, the infra-acetabular screw has been proposed for use in treatment of acetabular fractures as a part of a periacetabular fixation frame. Biomechanical studies have shown that an additional infra-acetabular screw placement can enhance the fixation strength of acetabular fracture internal fixation. Currently, the reported exit point of the infra-acetabular screw has been located at the ischial tuberosity (Screw I). However, our significant experience in placement of the infra-acetabular screw has suggested that when the exit point is located between the ischial tuberosity and the ischial spine (Screw II), the placement of a 3.5 mm infra-acetabular screw may be easier for some patients. We conducted this study in order to determine the anatomical differences between the two different IACs. METHODS: The raw datasets were reconstructed into 3D models using the software MIMICS. Then, the models, in the STL format model, were imported into the software Geomagic Studio to delete the inner triangular patches. Additionally, the STL format image processed by Geomagic Studio was imported again into MIMICS. Finally, we used an axial perspective based on 3D models in order to study the anatomical parameters of the two infra-acetabular screw corridors with different exit points. Hence, we placed the largest diameter virtual screw in the two different screw corridors. The data obtained from this study presents the maximum diameter, length, direction, and distances between the entry point and center of IPE. RESULTS: In 65.31% males and 40.54% females, we found a screw I corridor with a diameter of at least 5 mm, while a screw II corridor was present in 77.55% in males and 62.16% in females. Compared to screw I, the length of screw II is reduced, the angle with the coronal plane is significantly reduced, and the angle with the transverse plane is significantly increased. CONCLUSIONS: For East Asians, changing the exit point of the infra-acetabular screw can increase the scope of infra-acetabular screw use, especially for females.

A novel mechanical parameter to quantify the microarchitecture effect on apparent modulus of trabecular bone: A computational analysis of ineffective bone mass.

BACKGROUND: One of the characteristics of osteoporotic bone is the deterioration of trabecular microarchitecture. Previous studies have shown microarchitecture alone can vary the apparent modulus of trabecular bone significantly independent of bone volume fraction (BV/TV) from morphological and topological perspectives. However, modulus is a mechanical quantity and there is a lack of mechanical explanatory parameters. This study aims to propose a novel mechanical parameter to quantify the microarchitecture effect on the apparent modulus of trabecular bone. MATERIALS AND METHODS: Fourteen human female cadaveric vertebrae were scanned with a dual-energy X-ray (DXA) equipment followed by a micro-CT (µCT) system at 18 µm isotropic resolution. Four trabecular bone specimens (3.46 × 3.46 × 3.46 mm) were obtained from each vertebral body and converted to voxel-based micro finite element (µFE) models. The apparent modulus (E) of the µFE model was computed using a linear micro finite element analysis (µFEA). The normalized apparent modulus (E*) was computed as E divided by BV/TV. The relationship between E and BV/TV was analyzed by linear, power-law and exponential regressions. Linear regression was performed between E* and BV/TV. Ineffective bone mass (InBM) was defined as the bone mass with a negligible contribution to the load-resistance and represented by elements with von Mises stress less than a certain stress threshold. InBM was quantified as the low von Mises stress ratio (LSVMR), which is the ratio of the number of InBM elements to the total number of elements in the µFE model. An incremental search technique with coarse and fine search intervals of 10 and 1 MPa, respectively, was adopted to determine the stress threshold for calculating LSVMR of the µFE model. Correlation between E* and LSVMR was analyzed using linear and power-law models for each stress threshold. The threshold producing the highest coefficient of determination (R2) in the correlation between E* and LSVMR was taken as the optimal stress threshold for calculating LSVMR. Linear regression was performed between E and LSVMR. Multiple linear regression of E against both BV/TV and LSVMR was further analyzed. RESULTS: E significantly (p < .001) correlates to BV/TV whereas E* has no significant (p = .75) correlation with BV/TV. Incremental search suggests 59 MPa to be the optimal stress threshold for calculating LSVMR. BV/TV alone can explain 59% of the variation in E using power-law regression model (E = 2254.64BV/TV1.04, R2 = 0.59, p < .001). LSVMR alone can explain 48% of the variation in E using linear regression model (E = 1696.4-1647.1LSVMR, R2 = 0.48, p < .001). With these two predictors taken into consideration, 95% of the variation in E can be explained in a multiple linear regression model (E = 1364.89 + 2184.37BV/TV - 1605.38LSVMR, adjusted R2 = 0.95, p < .001). CONCLUSION: LSVMR can be adopted as the mechanical parameter to quantify the microarchitecture effect on the apparent modulus of trabecular bone.

The role of ginsenoside Rb1, a potential natural glutathione reductase agonist, in preventing oxidative stress-induced apoptosis of H9C2 cells.

BACKGROUND: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study. METHODS: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein. RESULTS: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (-6.426 kcal/mol), and the binding was stable. GRb1 significantly reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity in vitro, with a half-maximal effective concentration of ≈2.317 µM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells. CONCLUSION: GRb1 is a potential natural GR agonist that protects against oxidative stress-induced apoptosis of H9C2 cells.

Effect of the screw tightening sequence on the stress distribution of a dynamic compression plate: A pilot finite element study.

OBJECTIVE: Although the optimal screw tightening sequence is a common question orthopaedists encounter during fractures fixation with a dynamic compression plate (DCP), the effect of the screw tightening sequence on the stability of the plate has never been explored. This study explores the effect of the screw tightening sequence on the stress distribution of a DCP using a finite element method. METHODS: Idealized finite element analysis models of the femoral diaphysis with six-hole or eight-hole DCPs were constructed. The screw tightening preload was simulated using 'bolt load' in ABAQUS. Two screw tightening sequences were studied for the six-hole plate and six sequences were studied for the eight-hole plate. U magnitude and Von Mises stress were used to evaluate the deformation and stress distribution of the plate, respectively. Deformation and stress distribution plots from different sequences were compared. RESULTS: The different screw tightening sequences showed different deformation processes, while all had the same final deformation after all the screws were tightened. Each screw tightening step of different tightening sequences showed different stress distributions in the plate, while all had the same stress distribution after all the screws were tightened. CONCLUSION: Using different screw tightening sequences to fix the same DCP can produce the same stability, which means in terms of fixation stability, after the two screws nearest to the fracture line are tightened, surgeons do not need to hesitate about the order in which the rest screws should be inserted during the surgery.

A Biomimicking Polymeric Cryogel Scaffold for Repair of Critical-Sized Cranial Defect in a Rat Model.

Mineralized polymeric cryogels with interconnective macroporous structure have demonstrated their potential as promising scaffolding material in bone tissue engineering. However, their capability in inducing osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro and osteogenesis in vivo has not been explored yet. In this work, the roles of the mineralized cryogel on osteogenesis are systematically studied. Mineralized macroporous poly(ethylene glycol)-co-2-hydroxyethyl methacrylate cryogel promotes osteogenic differentiation of rat MSCs, particularly in upregulating the activity of alkaline phosphatase (ALP, ∼5.7-folds) and expression of related osteogenic gene markers (ALP ∼16-folds, osteocalcin ∼133-folds) at 14 days. In vivo implantation reveals that mineralized cryogels could promote fast osteogenesis and angiogenesis in critical-sized cranial bone defect of a Sprague-Dawley rat model in 4 weeks. The adsorption, entrapment, and concentration of osteogenic growth factors (bone morphogenetic protein 2) and angiogenesis growth factor (vascular endothelial growth factor [VEGF]) in the matrices in vivo may possibly participate in the process of osteogenesis and angiogenesis. Notably, the adsorption of larger amount of VEGF in nonmineralized cryogels facilitates obvious angiogenesis and comparable osteogenesis in bone defect in 8 weeks. Graphical abstract [Figure: see text] Impact Statement The current work reported the fabrication and characterization of a biomimicking mineralized polymeric cryogel as scaffolding material in bone regeneration. In addition to its three dimensional porous structure and the osteogenic potential, this biomimicking scaffold was also found to enhance the adsorption of biochemical cues, which in turn greatly promoted the angiogenesis as well as the tissue regeneration.

Bone resorption triggered by high radial stress: The mechanism of screw loosening in plate fixation of long bone fractures.

Screw loosening is a common complication in plate fixation. However, the underlying mechanism is unclear. This study investigated screw loosening mechanisms by finite element analysis (FEA) simulation and clinical X-ray feature analysis. Two FEA models incorporated bone heterogeneity and orthotropy, representing fracture fixation using dynamic compression plate (DCP) and locking compression plate (LCP), were developed. These models were used to examine the volume of bone exceeding a certain stress value around each screw under physiologically-relevant loading conditions. These damaged bone was then separated and compared by the axial stress and radial stress of each screw. In addition, features of patients' X-ray images showing screw loosening were analyzed to validate the loosening features simulated by the models. The FEA study showed that more damaged bone was found at the central two screws which gradually decreased toward the two end screws in all groups. More bone was damaged by the radial stress of each screw than by the axial stress. The radiological analysis of screw loosening showed that bone loss occurred at the screw closest to the fracture line first then subsequent bone loss at the screws further away from the fracture line occurred. This study found that the two screws nearest to the fracture line are more vulnerable to loosening. The radial stress of the screw plays a larger role in screw loosening than the axial stress. Bone resorption triggered by the high radial stress of screws is indicated as the mechanism of screw loosening in the diaphyseal plate fixation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1498-1507, 2019.

pH-Sensitive Nanocarrier-Mediated Codelivery of Simvastatin and Noggin siRNA for Synergistic Enhancement of Osteogenesis.

The inexpensive hypolipidemic drug simvastatin (SIM), which promotes bone regeneration by enhancing bone morphogenetic protein 2 (BMP-2) expression, has been regarded as an ideal alternative to BMP-2 therapy. However, SIM has low bioavailability and may induce the upregulation of the BMP-2-antagonistic noggin protein, which greatly limits the osteogenic effect. Here, a pH-sensitive copolymer, monomethoxy-poly(ethylene glycol)- b-branched polyethyleneimine- b-poly( N-( N', N'-diisopropylaminoethyl)- co-benzylamino)aspartamide (mPEG-bPEI-PAsp(DIP-BzA)) (PBP), was synthesized and self-assembled into a cationic micelle. SIM and siRNA targeting the noggin gene (N-siRNA) were loaded into the PAsp(DIP-BzA) core and the cationic bPEI interlayer of the micelle via hydrophobic and electrostatic interactions, respectively. The SIM-loaded micelle effectively delivered SIM into preosteoblast MC3T3-E1 cells and rapidly released it inside the acidic lysosome, resulting in the elevated expression of BMP-2. Meanwhile, the codelivered N-siRNA effectively suppressed the expression of noggin. Consequently, SIM and N-siRNA synergistically increased the BMP-2/noggin ratio and resulted in an obviously higher osteogenetic effect than did simvastatin or N-siRNA alone, both in vitro and in vivo.