Mechanically sensitive HSF1 is a key regulator of left-right symmetry breaking in zebrafish embryos.

The left-right symmetry breaking of vertebrate embryos requires nodal flow. However, the molecular mechanisms that mediate the asymmetric gene expression regulation under nodal flow remain elusive. Here, we report that heat shock factor 1 (HSF1) is asymmetrically activated in the Kupffer's vesicle of zebrafish embryos in the presence of nodal flow. Deficiency in HSF1 expression caused a significant situs inversus and disrupted gene expression asymmetry of nodal signaling proteins in zebrafish embryos. Further studies demonstrated that HSF1 is a mechanosensitive protein. The mechanical sensation ability of HSF1 is conserved in a variety of mechanical stimuli in different cell types. Moreover, cilia and Ca2+-Akt signaling axis are essential for the activation of HSF1 under mechanical stress in vitro and in vivo. Considering the conserved expression of HSF1 in organisms, these findings unveil a fundamental mechanism of gene expression regulation by mechanical clues during embryonic development and other physiological and pathological transformations.

Preventing Disused Bone Loss through Inhibition of Advanced Glycation End Products.

Bone loss occurs in astronauts during long-term space flight, but the mechanisms are still unclear. We previously showed that advanced glycation end products (AGEs) were involved in microgravity-induced osteoporosis. Here, we investigated the improvement effects of blocking AGEs formation on microgravity-induced bone loss by using the AGEs formation inhibitor, irbesartan. To achieve this objective, we used a tail-suspended (TS) rat model to simulate microgravity and treated the TS rats with 50 mg/kg/day irbesartan, as well as the fluorochrome biomarkers injected into rats to label dynamic bone formation. To assess the accumulation of AGEs, pentosidine (PEN), non-enzymatic cross-links (NE-xLR), and fluorescent AGEs (fAGEs) were identified in the bone; 8-hydroxydeoxyguanosine (8-OHdG) was analyzed for the reactive oxygen species (ROS) level in the bone. Meanwhile, bone mechanical properties, bone microstructure, and dynamic bone histomorphometry were tested for bone quality assessment, and Osterix and TRAP were immunofluorescences stained for the activities of osteoblastic and osteoclastic cells. Results showed AGEs increased significantly and 8-OHdG expression in bone showed an upward trend in TS rat hindlimbs. The bone quality (bone microstructure and mechanical properties) and bone formation process (dynamic bone formation and osteoblastic cells activities) were inhibited after tail-suspension, and showed a correlation with AGEs, suggesting the elevated AGEs contributed to the disused bone loss. After being treated with irbesartan, the increased AGEs and 8-OHdG expression were significantly inhibited, suggesting irbesartan may reduce ROS to inhibit dicarbonyl compounds, thus suppressing AGEs production after tail-suspension. The inhibition of AGEs can partially alter the bone remodeling process and improve bone quality. Both AGEs accumulation and bone alterations almost occurred in trabecular bone but not in cortical bone, suggesting AGEs effects on bone remodeling under microgravity are dependent on the biological milieu.

Nonlinear dynamics of membrane skeleton in osteocyte.

Osteocytes play an important role in mechanosensation and conduction in bone tissue, and the change of mechanical environment can affect the sensitivity of osteocytes to external stimulation. The structure of osteocytes will be changed when they are subjected to vibrations, which influence the mechanosensitivity of osteocytes and alter the regulation of bone remodeling process. As an important mechanotransduction structure in osteocytes, the membrane skeleton greatly affects the mechanosensation and conduction of osteocytes. However, the dynamic responses of membrane skeleton to the vibration and the structural changes of membrane skeleton are unclear. Therefore, we applied a nonlinear dynamics method to explain the time-dependent changes of membrane skeleton. The semi-ellipsoidal reticulate shell structure of membrane skeleton is built based on the experimental observation in our previous work. Then, the nonlinear dynamic equations of membrane skeleton are established according to the theory of plate and shell dynamics, and the displacement-time curves, phase portraits, and Poincaré maps of membrane skeleton structure were obtained. The numeration results show that under the vibration stimulation of 15 Hz, 30 Hz, 60 Hz, and 90 Hz, the membrane skeleton is destroyed after a transient equilibrium position vibration. The vibration of 15 Hz has the most destructive effect on the membrane skeleton, the natural frequency of membrane skeleton may be less than 15 Hz. In addition, the chaos phenomenon occurs to the membrane skeleton during vibration. As a damping factor, the existence of viscosity alleviates the damage of structure. This study can help us to understand the oscillation characteristic of membrane skeleton in osteocyte.

Cells respond to space microgravity through cytoskeleton reorganization.

Decades of spaceflight studies have provided abundant evidence that individual cells in vitro are capable of sensing space microgravity and responding with cellular changes both structurally and functionally. However, how microgravity is perceived, transmitted, and converted to biochemical signals by single cells remains unrevealed. Here in this review, over 40 cellular biology studies of real space fights were summarized. Studies on cells of the musculoskeletal system, cardiovascular system, and immune system were covered. Among all the reported cellular changes in response to space microgravity, cytoskeleton (CSK) reorganization emerges as a key indicator. Based on the evidence of CSK reorganization from space flight research, a possible mechanism from the standpoint of "cellular mechanical equilibrium" is proposed for the explanation of cellular response to space microgravity. Cytoskeletal equilibrium is broken by the gravitational change from ground to space and is followed by cellular morphological changes, cell mechanical properties changes, extracellular matrix reorganization, as well as signaling pathway activation/inactivation, all of which ultimately lead to the cell functional changes in space microgravity.

Effects of advanced glycation end products on osteocytes mechanosensitivity.

Osteocytes are extremely sensitive to mechanical loading and govern bone remodeling process. Advanced glycation end products (AGEs) have the capacity to induce osteocyte apoptosis. In order to investigate the effects of AGEs on the mechanosensitivity of osteocytes, the osteocytic-like cells (MLO-Y4) were treated with low (50 µg/ml) and high (400 µg/ml) concentrations of AGEs for 1day and exposed to 15 dyne/cm2 of fluid shear stress. Then the F-actin cytoskeleton, prostaglandin E2(PGE2), Nitric oxide (NO), the Wnt/ß-catenin signaling pathway activity mRNA expressions were detected for osteocytes mechanical response changes; osteocalcin (OCN) and receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) were detected for the regulation on bone remodeling function of osteocytes. The results showed that AGEs accumulation inhibited the sense of osteocytes to external mechincal loading, promoted shear-induced NO and PGE2 release, suppressed the mechanosensitivity of Wnt/ß-catenin signaling pathway, and furthermore promoted OCN and RANKL/OPG mRNA expressions. These indicated AGEs had an adverse impact on the mechanosensitivity of osteocytes, and led to a negative effect on their regulation of bone remodeling process under mechanical stimulation. This work provides a new perspective to interpret the alteration mechanism of osteocytes mechanosensitivity and provides a novel clue for exploring the mechanism of osteoporosis.

Extracellular Matrix Stiffness Regulates DNA Methylation by PKCα-Dependent Nuclear Transport of DNMT3L.

Extracellular matrix (ECM) stiffness has profound effects on the regulation of cell functions. DNA methylation is an important epigenetic modification governing gene expression. However, the effects of ECM stiffness on DNA methylation remain elusive. Here, it is reported that DNA methylation is sensitive to ECM stiffness, with a global hypermethylation under stiff ECM condition in mouse embryonic stem cells (mESCs) and embryonic fibroblasts compared with soft ECM. Stiff ECM enhances DNA methylation of both promoters and gene bodies, especially the 5' promoter regions of pluripotent genes. The enhanced DNA methylation is functionally required for the loss of pluripotent gene expression in mESCs grown on stiff ECM. Further experiments reveal that the nuclear transport of DNA methyltransferase 3-like (DNMT3L) is promoted by stiff ECM in a protein kinase C α (PKCα)-dependent manner and DNMT3L can be binding to Nanog promoter regions during cell-ECM interactions. These findings unveil DNA methylation as a novel target for the mechanical sensing mechanism of ECM stiffness, which provides a conserved mechanism for gene expression regulation during cell-ECM interactions.

Non-amputated limb muscle coordination of unilateral transfemoral amputees.

Unilateral transfemoral amputees rely heavily on non-amputated limb muscles to regulate the prosthetic gait. In this study, we compared the non-amputated limb muscle coordination of eight unilateral transfemoral amputees to eight able-bodied controls. Inverse dynamics approach was conducted via a musculoskeletal model to obtain lower limb joint moments and muscle forces. In addition to the muscle forces at the instants of peak joint moments and the maximum muscle forces, the peak joint moments of the lower limbs were also investigated. The results showed that there were significant differences of muscle forces between the non-amputated limbs and the controls at the instant of peak hip extension moment, although the peak hip extension moments themselves were not significantly different between the two groups. The non-amputated limbs had significantly smaller peak hip flexion moment and peak knee extension moment, with significant differences between the muscle forces of non-amputated limbs and controls at the two instants. There was no significant difference between the muscle forces of the non-amputated limbs and controls at the peak knee flexion moment instant, despite the fact that the non-amputated limbs had significantly higher peak knee flexion moments. In addition, the non-amputated limbs had significantly smaller maximum muscle forces than the controls. These results demonstrate that amputees modify their muscle coordination to adapt to the specific joint requirements of the prosthetic gait. Our findings suggest the possibility of non-amputated limb muscle atrophy due to the decrease in the peak muscle forces during walking.

SIRT1 Inhibits High Shear Stress-Induced Apoptosis in Rat Cortical Neurons.

INTRODUCTION: Sirtuin1 (SIRT1), one of NAD+-dependent protein deacetylases, is proved to be neuroprotective in aging diseases, but its effect on neuronal apoptosis has not been clarified. To investigate the role of SIRT1 in inhibiting neuronal apoptosis, SIRT1 was interfered or overexpressed in cortical neurons. METHODS: We exerted overloading laminar shear stress with 10 dyn/cm2 for 4, 8, and 12 h on neurons to cause cortical neuronal apoptosis, and the apoptosis percentage was tested by TUNEL assay. The adenovirus plasmids containing SIRT1 RNA interference or SIRT1 wild type gene were transfected into neurons before shear stress loading. SIRT1 mRNA and protein level were tested by Real-time PCR, immunofluorescence and western blots assay. RESULTS: SIRT1 was primarily expressed in nucleus of cortical neurons, and its mRNA level was significantly increased after 4 h stimulation. SIRT1 RNAi cortical neurons had higher TUNEL positive cells, while SIRT1 overexpression significantly decreased the percentage of died cells induced by shear stress compared to control group. CONCLUSIONS: SIRT1 plays a neuroprotective role in shear stress induced apoptosis and could be as potential pharmacological targets against neuronal degeneration in future.

Pharmacological Regulation of Primary Cilium Formation Affects the Mechanosensitivity of Osteocytes.

Primary cilia are responsible for sensing mechanical loading in osteocytes. However, the underlying working mechanism of cilia remains elusive. An osteocyte model is necessary to reveal the role of cilia. Furthermore, the osteocyte model should be with upregulated or downregulated primary cilium expression. Herein, we used a pharmacological method to regulate the cilium formation of osteocytes. After screening, some pharmacological agents can regulate the cilium formation of osteocytes. We performed a CCK-8 assay to analyze the optimal working conditions of the drugs for MLO-Y4 cells. The agents include chloral hydrate (CH), Gd3+, Li+, and rapamycin. The expression of cilia affects the cellular functions, including mechanosensitivity, of osteocytes. Results showed that CH downregulated the cilium formation and ciliogenesis of osteocytes. In addition, Gd3+, Li+, and rapamycin upregulated the cilium expression of osteocytes. Moreover, the cilium expression positively correlated with the mechanosensitivity of osteocytes. This work reveals the role of primary cilia in the mechanosensing of osteocytes.

The microgravity induces the ciliary shortening and an increased ratio of anterograde/retrograde intraflagellar transport of osteocytes.

It is hard to explain the decrease in mechanosensitivity of osteocytes under microgravity. Primary cilia are essential mechanosensor for osteocytes. The cilia become shorter under the simulated microgravity (SMG) environment. The cilia change may be the reason for the mechanosensitivity decrease of osteocytes under SMG. To reveal the role of primary cilia in weightless-induced osteocyte dysfunction, we investigate intraflagellar transport (IFT) to understand the mechanism of the decreased cilia length of osteocytes when subjected to SMG. We measure the number of anterograde IFT particles with GFP::IFT88 and retrograde IFT particles with OFP::IFT43 that occur at a particular transverse plane of the cilia. We also measure the expression of IFT88 and IFT43 and the size of IFT particles under SMG. Herein, the ratio of anterograde/retrograde particle number and the ratio of protein expression of IFT88/IFT43 increase under SMG. The size of anterograde IFT particles with GFP::IFT88 gets a significant decrease under SMG. Fundamentally, SMG has broken the balanced operating state of IFT and makes the IFT particles smaller. The phenomenon under SMG is intriguing.

The Biomechanical Relationship between Hallux Valgus Deformity and Metatarsal Pain.

Metatarsal pain is a common pathological outcome in patients with a hallux valgus (HV) deformity. However, the relationship between the degree of HV deformity and metatarsal pain has not been systematically examined. The purpose of the present study was to investigate the correlation between metatarsal pain and the degree of HV deformity. Between October 2017 and September 2018, 512 HV patients (944 feet) participated in an evaluation of their HV angle (HVA) using X-ray images. The participants were divided into four groups corresponding to their HVA (<15°, 15° to 20°, 21° to 40°, or >40°). Load rate, impulse, contact duration, and contact area were measured and recorded as dynamic gait parameters using the RsScan system. Data were evaluated using SPSS statistical software. The visual analog scale (VAS) was used to assess metatarsal pain. For the four HV deformity groups, the peak value of impulse and contact duration was concentrated on the second and third metatarsals (Meta2 and Meta3) (P < 0.05); contact area was also shown on metatarsals 1, 2, and 5 (P < 0.05). Metatarsal pain on Meta2 had the highest VAS score (VAS: 6.57), followed by Meta3 (Mean VAS: 5.72). In the HV > 40° group, the load location on Meta2 was transferred to Meta1. The percent of pain attributed to Meta2 and Meta3 was also increased in this group. These findings illustrated that metatarsal pain was primarily located on Meta2 and Meta3 in the different degrees of HV deformity. This information can provide the location to target for pain relief and help guide further rehabilitation.

Spontaneous cellular vibratory motions of osteocytes are regulated by ATP and spectrin network.

Vibration at high frequency has been demonstrated to be anabolic for bone and embedded osteocytes. The response of osteocytes to vibration is frequency-dependent, but the mechanism remains unclear. Our previous computational study using an osteocyte finite element model has predicted a resonance effect involving in the frequency-dependent response of osteocytes to vibration. However, the cellular spontaneous vibratory motion of osteocytes has not been confirmed. In the present study, the cellular vibratory motions (CVM) of osteocytes were recorded by a custom-built digital holographic microscopy and quantitatively analyzed. The roles of ATP and spectrin network in the CVM of osteocytes were studied. Results showed the MLO-Y4 osteocytes displayed dynamic vibratory motions with an amplitude of ~80 nm, which is relied both on the ATP content and spectrin network. Spectrum analysis showed several frequency peaks in CVM of MLO-Y4 osteocytes at 30 Hz, 39 Hz, 83 Hz and 89 Hz. These peak frequencies are close to the commonly used effective frequencies in animal training and in-vitro cell experiments, and show a correlation with the computational predictions of the osteocyte finite element model. These results implicate that osteocytes are dynamic and the cellular dynamic motion is involved in the cellular mechanotransduction of vibration.

Titanium clasp fabricated by selective laser melting, CNC milling, and conventional casting: a comparative in vitro study.

PURPOSE: This study aimed to investigate the effects of selective laser melting (SLM), milling methods, and casting on the behavior of titanium clasp. METHODS: The clasp and its die simulating the molar were designed using 3D software. Clasp specimens were fabricated using SLM approaches (SLM Ti) and computerized numerical control (CNC) milling technology (Milling CPTi). Cast clasps of the same forms were also prepared as controls using titanium alloy powder (Cast Ti) and commercial pure titanium (Cast CPTi), following the conventional casting methods. The surface roughness and accuracy of clasps were analyzed. The changes in retentive force and permanent deformation were measured up to 10,000 insertion/removal cycles. One-way analysis of variance and Tukey's test or Kruskal-Wallis H test were performed for data analysis and comparisons. RESULTS: The Milling CPTi clasps had a smoother inner surface than the other groups (p<0.05). The accuracy of the inner surface showed no significant difference among the groups, whereas that of the outer surface showed significant differences (p<0.05). The SLM Ti clasp had significantly higher retentive forces than the other groups (p<0.05), but it rapidly reduced after 2000 insertion/removal cycles until the fracture of all specimens was at 4000 cycles. The Milling CPTi clasps had more permanent deformation, but the rate of reduction of retentive force was only 9.5% (at 10,000 cycles). CONCLUSIONS: Milling has the potential to replace casting for fabricating removable partial denture (RPD) titanium clasps. However, SLM should be further improved for fabricating RPD titanium clasps before clinical application.

Potential Maintenance Mechanism in Atrial Fibrillation Patients Subject to Different Treatment Procedures: A Preliminary Study Based on a Human Atrial Model.

Two clinical ablation protocols, 2C3L and stepwise, have been routinely used in our group to treat atrial fibrillation (AF), but with a less than 60% long-term arrhythmia-free outcome achieved in patients. The goal of this study was to examine the underlying mechanism of low success in clinical outcome. MRI images from one patient were used to reconstruct a human atrial anatomical model, and fibrotic tissue was manually added to represent the arrhythmia substrate. AF was induced with standard protocols used in clinical practice. 2C3L and stepwise were then used to test the efficacy of arrhythmia termination in our model. The results showed that re-entries induced in our model could not be terminated by using either 2C3L or the stepwise protocol. Although some of the induced re-entries were terminated, others emerged in new areas. Ablation using only the 2C3L or stepwise method was not sufficient to terminate all re-entries in our model, which may partially explain the poor long-term arrhythmiafree outcomes in clinical practice. Our findings also suggest that computational heart modelling is an important tool to assist in the establishment of optimal ablation strategies.

Effect of Long-Term Systolic Blood Pressure Trajectory on Kidney Damage in the Diabetic Population: A Prospective Study in a Community-Based Chinese Cohort.

BACKGROUND: Previous studies have shown that hypertension is an important factor contributing to the occurrence and progression of diabetic kidney damage. However, the relationship between the patterns of blood pressure (BP) trajectory and kidney damage in the diabetic population remains unclear. This prospective study investigated the effect of long-term systolic BP (SBP) trajectory on kidney damage in the diabetic population based on an 8-year follow-up community-based cohort. METHODS: This study included 4556 diabetic participants among 101,510 participants. BP, estimated glomerular filtration rate (eGFR), and urinary protein were measured every 2 years from 2006 to 2014. SBP trajectory was identified by the censored normal modeling. Five discrete SBP trajectories were identified according to SBP range and the changing pattern over time. Kidney damage was evaluated through eGFR and urinary protein value. A multivariate logistic regression model was used to analyze the influence of different SBP trajectory groups on kidney damage. RESULTS: We identified five discrete SBP trajectories: low-stable group (n = 864), moderate-stable group (n = 1980), moderate increasing group (n = 609), elevated decreasing group, (n = 679), and elevated stable group (n = 424). The detection rate of kidney damage in the low-stable group (SBP: 118-124 mmHg) was the lowest among the five groups. The detection rate of each kidney damage index was higher in the elevated stable group (SBP: 159-172 mmHg) compared with the low-stable group. For details, the gap was 4.14 (11.6% vs. 2.8%) in eGFR <60 ml·min-1·1.73 m-2 and 3.66 (17.2% vs. 4.7%), 3.38 (25.0% vs. 7.4%), and 1.8 (10.6% vs. 5.9%) times in positive urinary protein, eGFR <60 ml·min-1·1.73 m-2 and/or positive urinary protein, and eGFR decline ≥30%, respectively (P < 0.01). CONCLUSION: An elevated stable SBP trajectory is an independent risk factor for kidney damage in the diabetic population.

Accuracy and reproducibility of 3D digital tooth preparations made by gypsum materials of various colors.

PURPOSE: The study aimed to identify the accuracy and reproducibility of preparations made by gypsum materials of various colors using quantitative and semi-quantitative three-dimensional (3D) approach. MATERIALS AND METHODS: A titanium maxillary first molar preparation was created as reference dataset (REF). Silicone impressions were duplicated from REF and randomized into 6 groups (n=8). Gypsum preparations were formed and grouped according to the color of gypsum materials, and light-scanned to obtain prepared datasets (PRE). Then, in terms of accuracy, PRE were superimposed on REF using the best-fit-algorithm and PRE underwent intragroup pairwise best-fit alignment for assessing reproducibility. Root mean square deviation (RMSD) and degrees of similarity (DS) were computed and analyzed with SPSS 20.0 statistical software (α=.05). RESULTS: In terms of accuracy, PREs in 3D directions were increased in the 6 color groups (from 19.38 to 20.88 µm), of which the marginal and internal variations ranged 51.36 - 58.26 µm and 18.33 - 20.04 µm, respectively. On the other hand, RMSD value and DS-scores did not show significant differences among groups. Regarding reproducibility, both RMSD and DS-scores showed statistically significant differences among groups, while RMSD values of the 6 color groups were less than 5 µm, of which blue color group was the smallest (3.27 ± 0.24 µm) and white color group was the largest (4.24 ± 0.36 µm). These results were consistent with the DS data. CONCLUSION: The 3D volume of the PREs was predisposed towards an increase during digitalization, which was unaffected by gypsum color. Furthermore, the reproducibility of digitalizing scanning differed negligibly among different gypsum colors, especially in comparison to clinically observed discrepancies.

Developing transmission line equations of oxygen transport for predicting oxygen distribution in the arterial system.

The oxygen content in the arterial system plays a significant role in determining the physiological status of a human body. Understanding the oxygen concentration distribution in the arterial system is beneficial for the prevention and intervention of vascular disease. However, the oxygen concentration in the arteries could not be noninvasively monitored in clinical research. Although the oxygen concentration distribution in a vessel could be obtained from a three-dimensional (3D) numerical simulation of blood flow coupled with oxygen transport, a 3D numerical simulation of the systemic arterial tree is complicated and requires considerable computational resources and time. However, the lumped parameter model of oxygen transport derived from transmission line equations of oxygen transport requires fewer computational resources and less time to numerically predict the oxygen concentration distribution in the systemic arterial tree. In this study, transmission line equations of oxygen transport are developed according to the theory of oxygen transport in the vessel, and fluid transmission line equations are used as the theoretical reference for the development. The transmission line equations of oxygen transport could also be regarded as the theoretical basis for developing lumped parameter models of other substances in blood.

Matrix stiffness determines the phenotype of vascular smooth muscle cell in vitro and in vivo: Role of DNA methyltransferase 1.

Cells perceive the physical cues such as perturbations of extracellular matrix (ECM) stiffness, and translate these stimuli into biochemical signals controlling various aspects of cell behavior, which contribute to the physiological and pathological processes of multiple organs. In this study, we tested the hypothesis that during arterial stiffening, vascular smooth muscle cells (SMCs) sense the increase of ECM stiffness, which modulates the cellular phenotype through the regulation in DNA methyltransferases 1 (DNMT1) expression. Moreover, we hypothesized that the mechanisms involve intrinsic stiffening and deficiency in contractility of vascular SMCs. Substrate stiffening was mimicked in vitro with polyacrylamide gels. A contractile-to-synthetic phenotypic transition was induced by substrate stiffening in vascular SMCs through the down-regulation of DNMT1 expression. DNMT1 repression was also observed in the tunica media of mice aortas in an acute aortic injury model and a chronic kidney failure model, as well as in the tunica intima of human carotid arteries with calcified atherosclerotic lesions. DNMT1 inhibition facilitates arterial stiffening in vivo and promotes osteogenic transdifferentiation, calcification and cellular stiffening of vascular SMCs in vitro. These effects may be attributable, at least in part, to the role of DNMT1 in regulating the promoter activities of Transgelin (SM22α) and α-smooth muscle actin (SMA) and the functional contractility of SMCs. We conclude that DNMT1 is a critical regulator that negatively regulates arterial stiffening via maintaining the contractile phenotype of vascular SMCs. This research may facilitate elucidation of the complex crosstalk between vascular SMCs and their surrounding matrix in healthy and in pathological conditions and provide new insights into the implications for potential targeting of the phenotypic regulatory mechanisms in material-related therapeutic applications.

Percutaneous Sacroiliac Screw Placement: A Prospective Randomized Comparison of Robot-assisted Navigation Procedures with a Conventional Technique.

BACKGROUND: Sacroiliac (SI) screw fixation is a demanding technique, with a high rate of screw malposition due to the complex pelvic anatomy. TiRobot™ is an orthopedic surgery robot which can be used for SI screw fixation. This study aimed to evaluate the accuracy of robot-assisted placement of SI screws compared with a freehand technique. METHODS: Thirty patients requiring posterior pelvic ring stabilization were randomized to receive freehand or robot-assisted SI screw fixation, between January 2016 and June 2016 at Beijing Jishuitan Hospital. Forty-five screws were placed at levels S1 and S2. In both methods, the primary end point screw position was assessed and classified using postoperative computed tomography. Fisher's exact probability test was used to analyze the screws' positions. Secondary end points, such as duration of trajectory planning, surgical time after reduction of the pelvis, insertion time for guide wire, number of guide wire attempts, and radiation exposure without pelvic reduction, were also assessed. RESULTS: Twenty-three screws were placed in the robot-assisted group and 22 screws in the freehand group; no postoperative complications or revisions were reported. The excellent and good rate of screw placement was 100% in the robot-assisted group and 95% in the freehand group. The P value (0.009) showed the same superiority in screw distribution. The fluoroscopy time after pelvic reduction in the robot-assisted group was significantly shorter than that in the freehand group (median [Q1, Q3]: 6.0 [6.0, 9.0] s vs. median [Q1, Q3]: 36.0 [21.5, 48.0] s; χ2 = 13.590, respectively, P < 0.001); no difference in operation time after reduction of the pelvis was noted (χ2 = 1.990, P = 0.158). Time for guide wire insertion was significantly shorter for the robot-assisted group than that for the freehand group (median [Q1, Q3]: 2.0 [2.0, 2.7] min vs. median [Q1, Q3]: 19.0 [15.5, 45.0] min; χ2 = 20.952, respectively, P < 0.001). The number of guide wire attempts in the robot-assisted group was significantly less than that in the freehand group (median [Q1, Q3]: 1.0 [1.0,1.0] time vs. median [Q1, Q3]: 7.0 [1.0, 9.0] times; χ2 = 15.771, respectively, P < 0.001). The instrumented SI levels did not differ between both groups (from S1 to S2, χ2 = 4.760, P = 0.093). CONCLUSIONS: Accuracy of the robot-assisted technique was superior to that of the freehand technique. Robot-assisted navigation is safe for unstable posterior pelvic ring stabilization, especially in S1, but also in S2. SI screw insertion with robot-assisted navigation is clinically feasible.