Depth-dependent ratcheting strains of young and adult articular cartilages by experiments and predictions.

BACKGROUND: Ratcheting strain is produced due to the repeated accumulation of compressive strain in cartilage and may be a precursor to osteoarthritis. The aim of this study was to investigate the ratcheting behaviors of young and adult articular cartilages under cyclic compression by experiments and theoretical predictions. METHODS: A series of uniaxial cyclic compression tests were conducted for young and adult cartilage, and the effects of different loading conditions on their ratcheting behaviors were probed. A theoretical ratcheting model was constructed and applied to predict the ratcheting strains of young and adult cartilages with different loading conditions. RESULTS: Ratcheting strains of young and adult cartilages rapidly increased at the initial stage, followed by a slower increase in subsequent stages. The strain accumulation value and its rate for young cartilage were greater than them for adult cartilage. The ratcheting strains of the two groups of cartilage samples decreased with increasing stress rate, while they increased with increasing stress amplitude. As the stress amplitude increased, the gap between the ratcheting strains of young and adult cartilages increased gradually. The ratcheting strains of young and adult cartilages decreased along the cartilage depth from the surface to the deep layer. The ratcheting strains of different layers increased with the compressive cycle, and the difference among the three layers was noticeable. Additionally, the theoretical predictions agreed with the experimental data. CONCLUSIONS: Overall, the ratcheting behavior of articular cartilage is affected by the degree of articular cartilage maturation.

Structure-dependent mitochondrial dysfunction and hypoxia induced with single-walled carbon nanotubes.

Cytotoxicity of nanomaterials on living systems is known to be affected by their size, shape, surface chemistry, and other physicochemical properties. Exposure to a well-characterized subpopulation of specific nanomaterials is therefore desired to reveal more detailed mechanisms. This study develops scalable density gradient ultracentrifugation sorting of highly dispersed single-walled carbon nanotubes (SWNTs) into four distinct bands based on diameter, aggregation, and structural integrity, with greatly improved efficiency, yield, and reproducibility. With guarantee of high yield and stability of four SWNT fractions, it is possible for the first time, to investigate the structure-dependent bioeffects of four SWNT fractions. it is possible Among these, singly-dispersed integral SWNTs show no significant effects on the mitochondrial functions and hypoxia. The aggregated integral SWNTs show more significant effects on the mitochondrial dysfunction and hypoxia compared to the aggregated SWNTs with poor structure integrity. Then, it is found that the aggregated integral SWNTs induced the irregular mitochondria respiratory and pro-apoptotic proteins activation, while aggregated SWNTs with poor structure integrity greatly enhanced reactive oxygen species (ROS) levels. This work supports the view that control of the distinct structure characteristics of SWNTs helps establish clearer structure-bioeffect correlation and health risk assessment. It is also hoped that these results can help in the design of nanomaterials with higher efficiency and accuracy in subcellular translocation.

USP26 suppresses type I interferon signaling by targeting TRAF3 for deubiquitination.

Deubiquitinating enzymes (DUBs) play a pivotal role in regulating the antiviral immune response by targeting members of the RLR signaling pathway. As a pivotal member of the RLR pathway, TRAF3 is essential for activating the MAVS/TBK-1/IRF3 signaling pathway in response to viral infection. Despite its importance, the function of DUBs in the TRAF3-mediated antiviral response is poorly understood. Ubiquitin-specific protease 26 (USP26) regulates the RLR signaling pathway to modulate the antiviral immune response. The results demonstrate that EV71 infection upregulates the expression of USP26. Knockdown of USP26 significantly enhances EV71-induced expression of IFN-ß and downstream interferon-stimulated genes (ISGs). Deficiency of USP26 not only inhibits EV71 replication but also weakens the host's resistance to EV71 infection. USP26 physically interacts with TRAF3 and reduces the K63-linked polyubiquitination of TRAF3, thereby promoting pIRF3-mediated antiviral signaling. USP26 physically interacts with TRAF3 and reduces the K63-linked polyubiquitination of TRAF3, thereby promoting pIRF3-mediated antiviral signaling. Conversely, knockdown of USP26 leads to an increase in the K63-linked polyubiquitination of TRAF3. These findings unequivocally establish the essential role of USP26 in RLR signaling and significantly contribute to the understanding of deubiquitination-mediated regulation of innate antiviral responses.

Failure mechanical properties of lumbar intervertebral disc under high loading rate.

BACKGROUND: Lumbar disc herniation (LDH) is the main clinical cause of low back pain. The pathogenesis of lumbar disc herniation is still uncertain, while it is often accompanied by disc rupture. In order to explore relationship between loading rate and failure mechanics that may lead to lumbar disc herniation, the failure mechanical properties of the intervertebral disc under high rates of loading were analyzed. METHOD: Bend the lumbar motion segment of a healthy sheep by 5° and compress it to the ultimate strength point at a strain rate of 0.008/s, making a damaged sample. Within the normal strain range, the sample is subjected to quasi-static loading and high loading rate at different strain rates. RESULTS: For healthy samples, the stress-strain curve appears collapsed only at high rates of compression; for damaged samples, the stress-strain curves collapse both at quasi-static and high-rate compression. For damaged samples, the strengthening stage becomes significantly shorter as the strain rate increases, indicating that its ability to prevent the destruction is significantly reduced. For damaged intervertebral disc, when subjected to quasi-static or high rates loading until failure, the phenomenon of nucleus pulposus (NP) prolapse occurs, indicating the occurrence of herniation. When subjected to quasi-static loading, the AF moves away from the NP, and inner AF has the greatest displacement; when subjected to high rates loading, the AF moves closer to the NP, and outer AF has the greatest displacement. The Zhu-Wang-Tang (ZWT) nonlinear viscoelastic constitutive model was used to describe the mechanical behavior of the intervertebral disc, and the fitting results were in good agreement with the experimental curve. CONCLUSION: Experimental results show that, both damage and strain rate have a significant effect on the mechanical behavior of the disc fracture. The research work in this article has important theoretical guiding significance for preventing LDH in daily life.

Strain rate-dependent failure mechanics of the intervertebral disc under tension/compression and constitutive analysis.

BACKGROUND: The intervertebral disc exhibits not only strain rate dependence (viscoelasticity), but also significant asymmetry under tensile and compressive loads, which is of great significance for understanding the mechanism of lumbar disc injury under physiological loads. OBJECTIVE: In this study, the strain rate sensitive and tension-compression asymmetry of the intervertebral disc were analyzed by experiments and constitutive equation. METHOD: The Sheep intervertebral disc samples were divided into three groups, in order to test the strain rate sensitive mechanical behavior, and the internal displacement as well as pressure distribution. RESULTS: The tensile stiffness is one order of magnitude smaller than the compression stiffness, and the logarithm of the elastic modulus is approximately linear with the logarithm of the strain rate, showing obvious tension-compression asymmetry and rate-related characteristics. In addition, the sensitivity to the strain rate is the same under these two loading conditions. The stress-strain curves of unloading and loading usually do not coincide, and form a Mullins effect hysteresis loop. The radial displacement distribution is opposite between the anterior and posterior region, which is consistent with the stress distribution. By introducing the damage factor into ZWT constitutive equation, the rate-dependent viscoelastic and weakening behavior of the intervertebral disc can be well described.

Extracellular matrix of mechanically stretched cardiac fibroblasts improves viability and metabolic activity of ventricular cells.

BACKGROUND: In heart, the extracellular matrix (ECM), produced by cardiac fibroblasts, is a potent regulator of heart's function and growth, and provides a supportive scaffold for heart cells in vitro and in vivo. Cardiac fibroblasts are subjected to mechanical loading all the time in vivo. Therefore, the influences of mechanical loading on formation and bioactivity of cardiac fibroblasts ECM should be investigated. METHODS: Rat cardiac fibroblasts were cultured on silicone elastic membranes and stimulated with mechanical cyclic stretch. After removing the cells, the ECMs coated on the membranes were prepared, some ECMs were treated with heparinase II (GAG-lyase), then the collagen, glycosaminoglycan (GAG) and ECM proteins were assayed. Isolated neonatal rat ventricular cells were seeded on ECM-coated membranes, the viability and lactate dehydrogenase (LDH) activity of the cells after 1-7 days of culture was assayed. In addition, the ATPase activity and related protein level, glucose consumption ratio and lactic acid production ratio of the ventricular cells were analyzed by spectrophotometric methods and Western blot. RESULTS: The cyclic stretch increased collagen and GAG levels of the ECMs, and elevated protein levels of collagen I and fibronectin. Compared with the ECMs produced by unstretched cardiac fibroblasts, the ECMs of mechanically stretched fibroblasts improved viability and LDH activity, elevated the Na⁺/K⁺-ATPase activity, sarco(endo)plasmic reticulum Ca²âº-ATPase (SERCA) activity and SERCA 2a protein level, glucose consumption ratio and lactic acid production ratio of ventricular cells seeded on them. The treatment with heparinase II reduced GAG levels of these ECMs, and lowered these metabolism-related indices of ventricular cells cultured on the ECMs. CONCLUSIONS: Mechanical stretch promotes ECM formation of cardiac fibroblasts in vitro, the ECM of mechanically stretched cardiac fibroblasts improves metabolic activity of ventricular cells cultured in vitro, and the GAG of the ECMs is involved in regulating metabolic activity of ventricular cells.

Cardiac fibroblast-derived extracellular matrix produced in vitro stimulates growth and metabolism of cultured ventricular cells.

Cardiac fibroblasts (CFs) produce extracellular matrix (ECM) which is a potent regulator of heart cell function and growth, and provides a supportive microenvironment for heart cells. Therefore, CF-derived ECM produced in vitro is very suitable for heart-cell culturing and cardiac tissue engineering. The aim of this study was to investigate the effect of CF-derived ECM produced in vitro on the growth and metabolism of cultured ventricular cells. CF-derived ECM-coated cell culture dishes were prepared by culturing rat CFs and then decellularizing the cultures. Isolated neonatal rat ventricular cells were seeded on ECM-coated, collagen I-coated or uncoated dishes, and the growth of cells after 1-5 days of culture was assayed with MTT reagent. In addition, cellular metabolic activity was analyzed by spectrophotometric methods and protein levels of sarco(endo)plasmic reticulum Ca(2+)-ATPase type 2a (SERCA2a) by Western blotting. The relative growth of ventricular cells was better on ECM-coated than on uncoated or collagen I-coated dishes. Furthermore, the glucose consumption ratio, lactic acid production ratio, Na(+)/K(+)-ATPase activity, SERCA activity and protein levels of SERCA2a were all higher in cells on the ECM-coated dishes. In conclusion, cardiac fi broblast-derived ECM produced in vitro stimulates the growth and metabolism of cultured ventricular cells. This study indicates that the bioactivity of the ECM supports heart cell growth in vitro, and this might be useful for cardiac tissue engineering.

Irrigating degradation properties of silk fibroin-collagen type II composite cartilage scaffold in vitro and in vivo.

Silk fibroin-collagen type II scaffolds are promising in cartilage tissue engineering due to their suitable biological functionality to promote proliferation of chondrocytes in vitro. However, their degradation properties, which are of crucial importance as scaffold degradation should consistent with the new tissue formation process, are still unknown. In this study, degradability of silk fibroin-collagen type II cartilage scaffolds was probed both in vitro and in vivo. In vitro degradation experiments show that the scaffolds decreased 32.25 % ± 0.62 %, 34.27 % ± 0.96 %, 36.27 % ± 2.39 % in weight after 8 weeks of degradation at the irrigation velocity of 0 mL/min, 7.89 mL/min and 15.79 mL/min. The degradation ratio, which increases with time and increasing irrigation velocity, is described by combining the built mathematic model and finite element modeling method. The scaffolds after 8 weeks of degradation in vitro keep their mechanical structural integrity to support new tissues. In vivo degradation experiments conducted in rabbits further show that the scaffolds degrade gradually, be absorbed with time and finally collapse in structure. The degradation process is accompanied by the growth of fibrous tissues and the scaffold is filled by fibrous tissues after 12 weeks of implantation. Immunohistology analysis shows that the inflammation caused by scaffolds is controllable and gradually alleviates with time. To sum up, silk fibroin-collagen type II cartilage scaffolds, which show suitable mechanical properties and biocompatibility during degradation in vitro and in vivo, have great potential in cartilage repair. The novelty of the study is that it not only introduces a mathematical model to predict the irrigation degradation ratio, but also provides experimental degradation data support for clinical application of silk fibroin-collagen type II cartilage scaffolds.

Mechanical strain promotes osteoblast ECM formation and improves its osteoinductive potential.

BACKGROUND: The extracellular matrix (ECM) provides a supportive microenvironment for cells, which is suitable as a tissue engineering scaffold. Mechanical stimulus plays a significant role in the fate of osteoblast, suggesting that it regulates ECM formation. Therefore, we investigated the influence of mechanical stimulus on ECM formation and bioactivity. METHODS: Mouse osteoblastic MC3T3-E1 cells were cultured in cell culture dishes and stimulated with mechanical tensile strain. After removing the cells, the ECMs coated on dishes were prepared. The ECM protein and calcium were assayed and MC3T3-E1 cells were re-seeded on the ECM-coated dishes to assess osteoinductive potential of the ECM. RESULTS: The cyclic tensile strain increased collagen, bone morphogenetic protein 2 (BMP-2), BMP-4, and calcium levels in the ECM. Compared with the ECM produced by unstrained osteoblasts, those of mechanically stimulated osteoblasts promoted alkaline phosphatase activity, elevated BMP-2 and osteopontin levels and mRNA levels of runt-related transcriptional factor 2 (Runx2) and osteocalcin (OCN), and increased secreted calcium of the re-seeded MC3T3-E1 cells. CONCLUSION: Mechanical strain promoted ECM production of osteoblasts in vitro, increased BMP-2/4 levels, and improved osteoinductive potential of the ECM. This study provided a novel method to enhance bioactivity of bone ECM in vitro via mechanical strain to osteoblasts.

Simulation of the mechanical behavior of osteons using artificial gravity devices in microgravity.

Aviation medical research shows that disuse osteoporosis will occur after long-term space flight. Even with countermeasures such as exercise and drug treatments, this outcome cannot be avoided in flight. In recent years, the application of artificial gravity devices that change the mechanical microenvironment of bone in microgravity have shown promise in mitigating the risk of disuse osteoporosis. Considering the existence of osteocytes, a fluid-solid coupling finite element model for osteons with two-stage pore structure (Haversian canal, lacunar-canalicular system) was established. In order to study the changes in the mechanical behavior of osteocytes under the action of various artificial gravity (AG) devices, including long-arm centrifuge (LAC), short-arm centrifuge (SAC), and a lower body negative pressure (LBNP) chamber. In addition, the difference in pulsating pressure and static pressure stress caused by the gravity gradient under the AG devices was examined. The simulation results showed that the AG devices could effectively improve the stress level of osteocytes in microgravity. The mechanical microenvironment of osteocytes that was provided by the LAC was closest to that of the Earth's gravitational field. The mechanical stimulation on osteocytes was not significantly improved by the SAC, but from a practical viewpoint, it occupied less space than the LAC. The LBNP chamber created a higher level of stress for osteocytes. Therefore, the LAC was an ideal device for replacing Earth's gravitational field, except for the practical limitations of its physical size. In contrast, the LBNP device had the greatest application potential in training for its expansibility and convenience.

Does oblique lumbar interbody fusion promote adjacent degeneration in degenerative disc disease: A finite element analysis.

BACKGROUND: The number of oblique lumbar interbody fusion (OLIF) procedures has continued to rise over recent years. Adjacent segment degeneration (ASD) is a common complication following vertebral body fusion. Although the precise mechanism remains uncertain, ASD has gradually become more common in OLIF. Therefore, the present study analyzed the association between disc degeneration and OLIF to explore whether adjacent degeneration was promoted by OLIF in degenerative disc disease. METHODS: A three-dimensional nonlinear finite element (FE) model of the L3-S1 lumbar spine was developed and validated. Three lumbar spine degeneration models with different degrees of degeneration (mild, moderate and severe) and a model of OLIF surgery were constructed at the L4-L5 level. When subjected to a follower compressive load (500 N), hybrid moment loading was applied to all models of the lumbar spine and the range of motion (ROM), intradiscal pressure (IDP), facet joint force (FJF), average mises stress in the annulus (AMSA), average tresca stress in the annulus (ATSA) and average endplate stress (AES) were measured. RESULTS: Compared with the healthy lumbar spine model, the ROM, IDP, FJF, AMSA, ATSA and AES of the segments adjacent to the degenerated segment increased in each posture as the degree of disc degeneration increased. In different directions of motion, the ROM, IDP, FJF, AMSA, ATSA and AES in the OLIF model in the L3-L4 and L5-S1 segments were higher than those of the healthy model and each degenerated model. Compared with the healthy model, the largest relative increase in biomechanical parameters above (ROM, IDP, FJF, AMSA, ATSA or AES) was observed in the L3-L4 segment in the OLIF model, of 77.13%, 32.63%, 237.19%, 45.36%, 110.92% and 80.28%, respectively. In the L5-S1 segment the corresponding values were 68.88%, 36.12%, 147.24%, 46.00%, 45.88% and 51.29%, respectively. CONCLUSIONS: Both degenerated discs and OLIF surgery modified the pattern of motion and load distribution of adjacent segments (L3-L4 and L5-S1 segments). The increases in the biomechanical parameters of segments adjacent to the surgical segment in the OLIF model were more apparent than those of the degenerated models. In summary, OLIF risked accelerating the degeneration of segments adjacent to those of a surgical segment.

Research on solute transport behaviors in the lacunar-canalicular system using numerical simulation in microgravity.

BACKGROUND: The lack of mass transfer in microgravity might be the underlying cause of disuse osteoporosis in astronauts after long-term space flights. The osteons are cylindrical structures and are the main structural units of the diaphysis in long bones. METHODS: A multi-scale 3D fluid-solid coupled finite element model of osteon with a two-stage pore structure was developed using COMSOL software in order to investigate solute transport behaviors in the lacunar-canalicular system (LCS) induced by physiological strain loading. Certain small molecules that are necessary as solutes in tissue fluid for osteocyte metabolism were simplified to micro-particles. A comparative analysis of solute transport behaviors in the LCS induced by physiological strain loading was conducted with a frequency of 0.2-2.5 Hz in microgravity and the Earth's gravitational fields. RESULTS: The average velocity of solute transport in lacunae in microgravity was 2-3 orders of magnitude lower than in Earth's gravitational field. The number of particles that represented solute transport quantity in the middle and deep lacunae increased steadily with a load frequency within the Earth's gravitational field. However, it differed based on the load frequency in microgravity, with the number of particles increasing with frequencies in the range of 0.2-0.5 Hz and 0.8-2 Hz, and decreasing with frequencies in the range of 0.5-0.8 Hz. CONCLUSIONS: A moving load with appropriate frequency could promote solute transport to the middle and deep lacunae, effectively preventing apoptosis of deep osteocytes due to a lack of nutrients. The results of this study provided theoretical guidance for preventing bone loss in astronauts during long-term space flights.

Effect of Strain Rates on Failure of Mechanical Properties of Lumbar Intervertebral Disc Under Flexion.

OBJECTIVE: To evaluate the strain-rate-dependent viscoelastic properties of the intervertebral disc by in vitro experiments. METHOD: The biomechanical experiments were conducted from September 2019 to December 2019. The lumbar spines of sheep were purchased within 4-6 hours from the local slaughterhouse, and the intervertebral disc samples were divided into three groups. In rupture group, the samples were used to test the mechanical behavior of the intervertebral disc rupture at different strain rates. In fatigue injury group, the samples were used to test the mechanical behavior of fatigue injury on the intervertebral disc under different strain rates. In internal displacement group, the samples were used to test the internal displacement distribution of the intervertebral disc at different strain rates by applying an optimized digital image correlation (DIC) technique. RESULTS: Both the yielding and cracking phenomenon occurs at fast and medium loading rates, while only the yielding phenomenon occurs at a slow loading rate. The yield stress, compressive strength, and elastic modulus all increase with the increase of the strain rate, while the yield strain decreases with the increase of the strain rate. The logarithm of the elastic modulus in the intervertebral disc is approximately linear with the logarithm of the strain rate under different strain rates. Both before and after fatigue loading, the stiffness in the loading and unloading curves of the intervertebral disc is inconsistent, forming a hysteresis loop, which is caused by the viscoelastic effect. The strain rate has no significant effect on the internal displacement distribution of the intervertebral disc. Based on the experimental data, the constitutive relationship of the intervertebral disc at different strain rates is obtained. The fitting curves are well coupled with the experimental data, while the fitting parameters are approximately linear with the logarithm of the strain rate. CONCLUSIONS: These experiments indicate that the strain rate has a significant effect on the mechanical behavior of the intervertebral disc rupture and fatigue injury, while the constitutive equation can predict the rate-dependent mechanical behavior of lumbar intervertebral disc under flexion very well. These results have important theoretical guiding significance for preventing lumbar disc herniation in daily life.

Comparative analysis of the biomechanics of the adjacent segments after minimally invasive cervical surgeries versus anterior cervical discectomy and fusion: A finite element study.

PURPOSE: Percutaneous full-endoscopic anterior cervical discectomy (PEACD) and posterior cervical foraminotomy (PCF) as alternatives to anterior cervical discectomy and fusion (ACDF) are extensively used in the treatment of patients with cervical spondylotic radiculopathy. The possibility of avoiding the risk of accelerated degeneration of the adjacent segments caused by fusion is claimed to be the theoretical advantage of these approaches; however, there is a paucity of supportive evidence from biomechanical data. Therefore, this study investigated and compared the effects of PCF, PEACD, and ACDF on the adjacent segments and operative segments of the cervical spine from a biomechanical standpoint. METHOD: A normal and intact three-dimensional finite element digital model of C4-C7 was constructed and validated, and the finite element models of PEACD, PCF, and ACDF were obtained by modifying the C4-C7 model. All models were exposed to identical conditions of load during flexion, extension, axial rotation, and lateral bending. We calculated the range of motion (ROM), intervertebral disc pressure (IDP), and facet joint contact force (FJCF) of the operative segment and the adjacent segment in different motion conditions. RESULT: The conventional ACDF had a remarkable influence on the ROM and IDP of the operative segment and the adjacent segments. In the PEACD model, the change of ROM was not noticeable; the IDP of the operative segment was significantly smaller, whereas the change of IDP of the adjacent segment was insignificant. In the PCF model, the ROM and IDP of all segments remained unaffected.During extension, the facet joint contact force changed significantly after ACDF, and it changed slightly after PECAD and PCF. CONCLUSION: By comparatively analyzing the biomechanical changes of the cervical spine after PCF, PEACD, and ACDF using the finite element method, we suggested that PCF and PEACD were more suitable for surgical intervention of cervical spondylotic radiculopathy than ACDF from a biomechanical point of view and PCF may outperform PEACD.

Ratcheting Behavior of Intervertebral Discs Under Cyclic Compression: Experiment and Prediction.

OBJECTIVE: To evaluate the ratcheting behavior of intervertebral discs (IVD) by experiments and theoretical study. METHOD: The lumbar spines of sheep were obtained at a local slaughterhouse, and the IVD was processed with upper and lower vertebral bodies (about 5 mm) to ensure the mechanical state of the IVD in situ. The ratcheting tests of uniaxial cyclic compression loading for disc samples is carried out using the Electronic Universal Fatigue Testing System at room temperature. The effects of different stress variations, stress rates, as well as different segments on ratcheting behavior of discs were investigated. RESULTS: The ratcheting strain evolution of lumbar IVD include stages of sharp increase and asymptotic stability. Both the ratcheting strain and ratcheting strain rate increase with an increase of stress variation (R = 0.962, P = 0.004) but decrease with an increase of the stress rate (R = -0.876, P = 0.019 ). Compression stiffness increases with an increase of the stress rate (R = 0.964, P = 0.004 ) or stress variation (R = 0.838, P = 0.037). Compared with L5 - 6 , the L6 - 7 disc showed less ratcheting strain (P = 0.04 ), indicating that the disc at this segment was more resistant to the impact of the ratcheting cycle. In addition, ratcheting strain evolution was predicted using a ratcheting evolution constitutive equation, and the predicted results were in good agreement with experimental data. CONCLUSIONS: The ratcheting behavior occurs in IVD, and this cumulative deformation is consistent with the general ratcheting behavior. The constitutive equation can predict the ratcheting strain evolution of IVD very well. These results are of great significance for the analysis of defects and the development of repair in IVD.

Mechanical property and biocompatibility of silk fibroin-collagen type II composite membrane.

Osteoarthritis is caused by injuries and cartilage degeneration. Cartilage tissue engineering provides new ideas for the treatment of osteoarthritis. Herein, the different ratios composite membranes of silk fibroin/collagen type II were constructed (SF50-50:50, SF70-70:30, SF90-90:10). The surface properties of the composite membranes and chondrocyte morphology were observed by SEM (scanning electron microscopy). Physical functionality as well as stability of composite membranes was evaluated from tensile mechanical properties, the percentage of swelling and degradation. The tensile mechanical behavior of SF70 composite membranes was also predicted based on the constitutive model established in this study, and it is found that the experimental results and predictions were in good agreement. Biocompatibility was evaluated using chondrocytes (ADTC-5) culture. Cell proliferation was analyzed and the treatment of live/dead double staining was performed to assess the viability on chondrocytes. To sum up, SF70 showed the suitable morphology, physical stability, and biological functionality to promote proliferation of chondrocytes. This indicates that the mixing ratio of SF70 shows promise in the future as a scaffold material for cartilage repair.

Analysis of the mechanical effects of defect shape on damage evolution of articular cartilage under rolling load.

To study the mechanical effects of defect shape on the damage evolution of knee cartilage and find the causes of fragments, so as to obtain damage evolution rules and determine the most appropriate shape used in a clinical repair. A porous viscoelasticity fiber-reinforced 2D numerical model with different micro-defect shapes was established which considered the depth-dependent Young's modulus, fiber distribution, porosity and permeability. The stress-strain relationship, interstitial hydraulic and interstitial flow velocity was obtained under rolling load. The results showed that damage developed at the bottom corner of the defect, preferentially deep within the cartilage tangential to the fibers direction, and then extended to the surface along adjacent fibers, finally forming fragments. In the early stages of damage, the shear stress and interstitial flow velocity within cartilage with a rectangular cross-sectional defect were the lowest, while interstitial hydraulic pressure was the highest, followed by 100° trapezoid and semicircle, and finally 80° trapezoid defects. In the later stage of damage, the results were very similar. The shear strain, interstitial flow velocity and interstitial hydraulic pressure decreased with increasing defect depth. Therefore, defect shape only affected damage evolution in the early stages. The fragments in cartilage were the result of the damage evolution which sizes were correlated with the initial defect depth. The damage velocity of cartilage with a rectangular section-incision was the slowest. Finally, we concluded that cylindrical incisions are optimal in clinical surgery. These results provide a theoretical basis for the clinical interpretation of pathological degeneration and repair therapy.

The Combination of icariin and constrained dynamic loading stimulation attenuates bone loss in ovariectomy-induced osteoporotic mice.

Osteoporosis is a disease characterized by low bone mass and progressive destruction of bone microstructure, resulting in increasing the risk of fracture. Icariin (ICA) as a phytoestrogen shows osteogenic effects, and the mechanical stimulation has been demonstrated the improving effect on osteoporosis. The objective of this study was to investigate the effect of ICA in combination with constrained dynamic loading (CDL) stimulation on osteoporosis in ovariectomized (OVX) mice. The serum hormone levels, bone turnover markers, trabecular architecture, ulnar biomechanical properties, and the expression of osteoblast-related gene (alkaline phosphatase, ALP; osteocalcin, OCN; bone morphogenetic protein-2, BMP-2; Collagen I (α1), COL1; osteoprotegerin, OPG) and osteoclast-related genes (receptor activators of NF-κB ligand, RANKL; tartrate-resistant acid phosphatase, TRAP) were analyzed. The results showed that ICA + CDL treatment could increase the osteocalcin (20.85%), estradiol levels (20.61%) and decrease the TRAP activity (26.27%) significantly than CDL treatment. The combined treatment attenuated bone loss and biomechanical decrease more than single use of CDL treatment. ICA + CDL treatment significantly up-regulated the level of osteoblast-related gene expression and down-regulated the osteoclast-related genes expression; moreover, the combined treatment increased the ratio of OPG/RANKL significantly compared to ICA (72.83%) or CDL (65.63%) treatment alone. The present study demonstrates that icariin in combination with constrained dynamic loading treatment may have a therapeutic advantage over constrained dynamic loading treatment alone for the treatment of osteoporosis, which would provide new evidence for the clinical treatment of osteoporosis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1415-1424, 2018.

[The establishment of a new mechanobiology model of bone and functional adaptation studies in vivo].

OBJECTIVES: to study the functional adaptation in response to artificial loading in vivo. METHODS: A single element strain gauge of < 2 mm x 3 mm in size was attached in longitudinal alignment to the medial surface of the ulnar midshaft, in vivo recordings of ulnar strains during locomotion were obtained. The ulnae of natural female rats were subjected to dynamic axial loading in vivo simulate strains during locomotion using INSTRON materials-testing machine. The left ulna of adult female rats were subjected to applied loading at frequencies of 5 Hz, 10 Hz, 15 Hz for 10 min/d with a haversian, low-magnitude (1mm peak to peak) waveform for a two weeks period, the peak strains at the Left ulnar midshaft is 2000 microepsilon and 3000 microepsilon, the right ulna of each rat served as a paired internal control. Dual Energy X-ray Absorptiometry (DXA) was used to measure bone mineral density (BMD) at the ulnar; 3-point bending was used to test mechanical characteristics; the ulna's response to loading was traced by subcutaneously injecting each rat twice with 7.5 mg/kg calcein and 30 mg/kg Tetracycline Hcl on days 3 and 12 of the loading period, and analyzed by histomorphometry; immunohistochemistry as an effect of elevated strain in the bone matrix. RESULTS: at frequencies of 10 Hz, 15 Hz groups, loading promoted obviously secreted of alkaline phosphatase (ALP), osteocalcin (OCN) and collagen I; a relative benefit in BMD was found compare to the control (P < 0.05) followed the decline of material mechanical properties (modulus of elasticity, ultimate stress) (P < 0.01). CONCLUSION: These data show that a new bionics mechanobiology model of the axial ulna loading technique had be established successfully in rat. A short daily period of low-magnitude, high-frequency mechanical stimuli results in an osteogenic response related to peak strain magnitude.

Study of the Mechanical Environment of Chondrocytes in Articular Cartilage Defects Repaired Area under Cyclic Compressive Loading.

COMSOL finite element software was used to establish a solid-liquid coupling biphasic model of articular cartilage and a microscopic model of chondrocytes, using modeling to take into account the shape and number of chondrocytes in cartilage lacuna in each layer. The effects of cyclic loading at different frequencies on the micromechanical environment of chondrocytes in different regions of the cartilage were studied. The results showed that low frequency loading can cause stress concentration of superficial chondrocytes. Moreover, along with increased frequency, the maximum value of stress response curve of chondrocytes decreased, while the minimum value increased. When the frequency was greater than 0.2 Hz, the extreme value stress of response curve tended to be constant. Cyclic loading had a large influence on the distribution of liquid pressure in chondrocytes in the middle and deep layers. The concentration of fluid pressure changed alternately from intracellular to peripheral in the middle layer. Both the range of liquid pressure in the upper chondrocytes and the maximum value of liquid pressure in the lower chondrocytes in the same lacunae varied greatly in the deep layer. At the same loading frequency, the elastic modulus of artificial cartilage had little effect on the mechanical environment of chondrocytes.