Noncontact elasticity measurement of hydrogels in a culture dish using reverberant optical coherence elastography.

Estimating the elasticity of hydrogel phantoms in a cell culture plane is important for understanding the cell behavior in response to various types of mechanical stimuli. Hence, a noncontact tool for measuring the elastic properties of hydrogel phantoms in such three-dimensional cell cultures is required. A well-known method to determine the mechanical properties of hydrogels is the transient wave method. However, due to the multiple reflections of waves from the boundaries, a bigger cell culture plane or multiple directional filters may be required. In this study, we utilized reverberant shear wave elastography, which is based on the autocorrelation principle, to evaluate the shear wave speed in hydrogel samples within a culture dish. Numerical simulations were performed first to confirm the validity of the reverberant elastography method. Subsequently, we used this method to measure the wave speeds in hydrogel phantoms with different concentrations. Shear rheology tests were also performed, and their results were found to be in good agreement with the measured shear wave speeds. The proposed method could be useful for measuring the elasticity of tissues in tissue engineering applications in an inexpensive and noncontact manner.

Recurrence of Local Kyphosis After Percutaneous Kyphoplasty: The Neglected Injury of the Disc-Endplate Complex.

Background: Recurrent of local kyphosis after percutaneous kyphoplasty (PKP) is rarely reported and discussed. Literatures reported that re-kyphosis is usually a consequence of refractures of augmented or adjacent vertebra. However, whether re-kyphosis should be considered as a complication of refractures and has an impact on clinical efficacy of PKP during follow-up time is unknown. The purpose of this study is to evaluate the related risk factors and clinical significance of the recurrent of local kyphosis in osteoporotic vertebral fracture (OVF) patients without refractures. Patients and Methods: A total of 143 patients who underwent single-level PKP were recruited and assigned into the re-kyphosis group and non-re-kyphosis group. Clinical and radiographic data were collected and compared between the two groups. Then, multivariate logistic regression analyses were conducted to identify the related risk factors. Results: During follow-up, 16 of the 143 patients presented postoperative re-kyphosis. The average local kyphosis angle increased from 11.81±8.60° postoperatively to 25.13±8.91° at the final follow-up which showed a statistically significant difference (p<0.05). Both groups had significant improvements in postoperative visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores compared to their preoperative values (p<0.05). However, in the re-kyphosis group at final follow-up, the VAS and ODI scores showed worsening compared to the postoperative scores. Logistic regression analysis showed that disc-endplate complex injury (OR=17.46, p=0.003); local kyphosis angle correction (OR=1.84, p<0.001); and vertebral height restoration (OR=1.15, p=0.003) were risk factors for re-kyphosis. Conclusion: Re-kyphosis is not rare in patients with osteoporotic vertebral fracture and tends to have an inferior prognosis following PKP surgery. Patients with disc-endplate complex injury and more correction of vertebral height and kyphosis angle are at a higher risk for re-kyphosis after PKP surgery than others.

A Device for Isolation of Selected Single Adherent Cells.

In recent years, extensive research has been focused on the field of single cell analysis. The isolation of single cells is the first step in this type of research. However, the techniques used for direct isolation and acquisition of single adherent cells are limited. Here, we present a method of obtaining selected single adherent cells using a separation device. Compared with other single cell isolation methods, this method has the advantages of simple operation, low cost, minimal cell damage, and preservation of cell morphology. Our methodology is, therefore, suitable for the collection of selected single adherent cells.

Regenerating and repairing degenerative intervertebral discs by regulating the micro/nano environment of degenerative bony endplates based on low-tension mechanics.

BACKGROUND: Conservative treatment is the recommended first-line treatment for degenerative disc diseases. Traction therapy has historically been one of the most common clinical methods to address this, but the clinical effect remains controversial. METHODS: Forty-two six-month-old male Sprague-Dawley rats were randomly divided into six groups: the model group (Group A, four coccyx vertebrae (Co7-Co10) were fixed with customized external fixators, and the vertebral disc degeneration model was constructed by axial compression of the target segment Co8 - Co9 for 4 weeks), the experimental control group (Group B, after successful modeling, the external fixation device was removed and self-rehabilitation was performed) and four intervention groups (Groups C to F): Groups C and E: Co8 - Co9 vertebrae compressed for 4 weeks followed by two or 4 weeks of high tension traction (HTT), respectively, and Groups D and F: vertebrae compressed for 4 weeks followed by two or 4 weeks of low-tension traction (LTT), respectively. Imaging tests (X-ray and MRI) were performed to assess disc height and T2 signal intensity at each time point. After the experiment, the animals were euthanized, and the caudal vertebrae were collected for analysis of intervertebral disc histopathology, proteoglycan content, and micronanostructure of the annulus fibrosus, nucleus pulposus and bony endplate. RESULTS: Signs of tissue regeneration were apparent in all four intervention groups. After two to 4 weeks of intervention (HTT and LTT), the morphology of pores in the bony endplate, their number, and diameter had recovered significantly compared with those in Group A. The LTT group was superior to the HTT group, and the 4w in situ group was significantly superior to the 2w group. Meanwhile, the histological scores of discs, the mean fibril diameter and modulus of annulus fibrosus were significantly improved compared with the control groups, and the LTT group was superior to HTT group. CONCLUSIONS: Low-tension traction better promotes active reconstruction of bony endplates and improves the elastic modulus and micro/nanostructure of the disc. Thus, it further promotes the regeneration and repair of intervertebral discs.

Identification of Prognostic lncRNA Related to the Immune Microenvironment of Soft Tissue Sarcoma.

BACKGROUND: Soft tissue sarcoma is a malignant tumor with high degree of malignancy and poor prognosis, originating from mesenchymal tissue. Long noncoding RNAs (lncRNAs) are involved in various biological and pathological processes in the body. They perform preprocessing, splicing, transport, degradation, and translation of mRNA to achieve posttranscriptional level regulation, resulting in the occurrence, invasion, and metastasis of tumors. Therefore, they are highly relevant with regard to early diagnoses and as prognostic indicators. OBJECTIVE: The objective of the present study was to identify immune microenvironment-related lncRNAs that can be used to predict soft tissue sarcomas. METHODS: Clinical data and follow-up data were obtained from the cBioPortal database, and RNA sequencing data used for the model structure can be accessed from The Cancer Genome Atlas (TCGA) database. LncRNAs were screened by differential expression analysis and coexpression analysis. The Cox regression model and Kaplan-Meier analysis were used to study the association between lncRNAs and soft tissue sarcoma prognosis in the immune microenvironment. Unsupervised cluster analysis was then completed to discover the impact of screening lncRNAs on disease. We constructed an mRNA-lncRNA network by Cytoscape software. Finally, qRT-PCR was used to verify the difference in the expression of the lncRNAs in normal cells and sarcoma cells. RESULTS: Unsupervised cluster analysis revealed that the 210 lncRNAs screened showed strong correlation with the tumor immune microenvironment. Two signatures containing seven and five lncRNAs related to the tumor microenvironment were constructed and used to predict overall survival (OS) and disease-free survival (DFS). The Kaplan-Meier (K-M) survival curve showed that the prognoses of patients in the high-risk and low-risk groups differed significantly, and the prognosis associated with the low-risk group was better than that associated with the high-risk group. Two nomograms with predictive capabilities were established. qRT-PCR results showed that the expression of AC108134.3 and AL031717.1 was significantly different in normal and sarcoma cells. CONCLUSION: In summary, the experimental results showed that lncrnA associated with immune microenvironment was related to tumor, which may provide a new idea for immunotherapy of STS.

Stiffness of the extracellular matrix affects apoptosis of nucleus pulposus cells by regulating the cytoskeleton and activating the TRPV2 channel protein.

It is known that nucleus pulposus cells (NPs) play an important role in intervertebral disc degeneration (IVDD), and a previous study indicated that the stiffness of NP tissue changes during the degeneration process. However, the mechanism underlying the cellular response to ECM stiffness is still unclear. To analyze the effects of extracellular matrix (ECM) with different degrees of stiffness on NPs, we prepared polyacrylamide (PA) gels with different elastic moduli, and cells grown under different stiffness conditions were obtained and analyzed. The results showed that the spreading morphology of NPs changed significantly under increased ECM elastic modulus conditions and that TRPV2 and the PI3K / AKT signaling pathway were activated by stiffer ECM. At the same time, mitochondria released cytochrome c (Cyt c) and activated caspase proteins to promote the apoptosis of NPs. After TRPV2 was specifically knocked out, the activation of the PI3K / AKT signaling pathway decreased, and the release of Cyt c and NP apoptosis were reduced. These results indicate that TRPV2 is closely linked to the detection of extracellular mechanical signals, and that conversion of mechanical and biological signals plays an important role in regulating the biological behavior of cells. This study offers a new perspective on the cellular and biochemical events underlying IVDD which could result in novel treatments.

Assessment of viscoelasticity of ex vivo bovine cartilage using Rayleigh wave method in the near-source and far-field region.

Cartilage viscoelasticity changes as cartilage degenerates. Hence, a cartilage viscoelasticity measurement could be an alternative to traditional imaging methods for osteoarthritis diagnosis. In a previous study, we confirmed the feasibility of viscoelasticity measurement in ex vivo bovine cartilage using the Lamb wave method. However, the wave speed-frequency curve of Lamb wave is totally nonlinear and the cartilage thickness could significantly affect the Lamb wave speed, making wave speed measurements and viscoelasticity inversion difficult. The objective of this study was to measure the cartilage viscoelasticity using the Rayleigh wave method (RWM). Rayleigh wave speed in the ex vivo bovine cartilage was measured, and exists only in the near-source and far-field region. The estimated cartilage elasticity was 0.66 ± 0.05 and 0.59 ± 0.07 MPa for samples 1 and 2, respectively; the estimated cartilage viscosity was 24.2 ± 0.7 and 27.1 ± 1.8 Pa·s for samples 1 and 2, respectively. These results were found to be highly reproducible, validating the feasibility of viscoelasticity measurement in ex vivo cartilage using the RWM. Current method of cartilage viscoelasticity measurement might be translated into in vivo application.

Nano-elastic modulus of tendon measured directly in living mice.

The nano-biomechanical environment of the extracellular matrix is critical for cells to sense and respond to mechanical loading. However, to date, this important characteristic remains poorly understood in living tissue structures. This study reports the experimental measurement of the in vivo nano-elastic modulus of the tendon in a mouse tail model. The experiment was performed on the tail tendon of an 8-week-old C57BL/6 live mouse. Mechanical loading on tail tendons was regulated by changing both voltage and frequency of alternating current stimulation on the erector spinae. The nano-elastic modulus of the tail tendon was measured by atomic force microscope. The nano-elastic modulus showed significant variation (2.19-35.70 MPa) between different locations and up to 39% decrease under muscle contraction, suggesting a complicated biomechanical environment in which cells dwell. In addition, the nano-elastic modulus of the tail tendon measured in live mice was significantly lower than that measured in vitro, suggesting a disagreement of tissue mechanical properties in vivo and in vitro. This information is important for the designs of new extracellular biomaterial that can better mimic the biological environment, and improve clinical outcomes of musculoskeletal tissue degenerations and associated disorders.

Low energy extracorporeal shock wave therapy combined with low tension traction can better reshape the microenvironment in degenerated intervertebral disc regeneration and repair.

BACKGROUND: Low-tension traction is more effective than high-tension traction in restoring the height and rehydration of a degenerated disc and to some extent the bony endplate. This might better reshape the microenvironment for disc regeneration and repair. However, the repair of the combination of endplate sclerosis, osteophyte formation, and even collapse leading to partial or nearly complete occlusion of the nutrient channel is greatly limited. PURPOSE: To evaluate the effectiveness of low-intensity extracorporeal shock wave therapy (ESWT) combined with low tension traction for regeneration and repair of moderately and severely degenerated discs; to explore the possible mechanism of action. STUDY DESIGN: Animal study of a rat model of degenerated discs. METHODS: A total of thirty-five 6-month old male Sprague-Dawley rats were randomly assigned to one of five groups (n=7, each group). In Group A (model group), caudal vertebrae were immobilized using a custom-made external device to fix four caudal vertebrae (Co7-Co10) whereas Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration. In Group B (experimental control group), as in Group A, disc degeneration was successfully induced after which the fixed device was removed for 8 weeks of self-recovery. The remaining three groups of rats represented the intervention Groups (C-E): after successful generation of disc degeneration in Group C (com - 4w/tra - 4w) and Group D (com - 4w/ESWT), as described for group A, low-tension traction (in-situ traction) or low-energy ESWT was administered for 4 weeks (ESWT parameters: intensity: 0.15 Mpa; frequency: 1 Hz; impact: 1,000 each time; once/week, 4 times in total); Group E (com - 4w/tra - 4w/ESWT): disc degeneration as described for group A, low-tension traction combined with low-energy ESWT was conducted (ESWT parameters as Group D). After experimentation, caudal vertebrae were harvested and disc height, T2 signal intensity, disc morphology, total glycosaminoglycan (GAG) content, gene expression, structure of the Co8-Co9 bony endplates and elastic moduli of the discs were measured. RESULTS: After continuous low-tension traction, low energy ESWT intervention or combined intervention, the degenerated discs effectively recovered their height and became rehydrated. However, the response in Group D was weaker than in the other intervention groups in terms of restoration of intervertebral disc (IVD) height, whereas Group E was superior in disc rehydration. Tissue regeneration was evident in Groups C to E using different interventions. No apparent tissue regeneration was observed in the experimental control group (Group B). The histological scores of the three intervention groups (Groups C-E) were lower than those of Groups A or B (p<.0001), and the scores of Groups C and E were significantly lower than those of Group D (p<.05), but not Group C versus Group E (p>.05). Compared with the intervention groups (Groups C-E), total GAG content of the nucleus pulposus (NP) in Group B did not increase significantly (p>.05). There was also no significant difference in the total GAG content between Groups A and B (p>.05). Of the three intervention groups, the recovery of NP GAG content was greatest in Group E. The expression of collagen I and II, and aggrecan in the annulus fibrosus (AF) was up-regulated (p<.05), whereas the expression of MMP-3, MMP-13, and ADAMTS-4 was down-regulated (p<.05). Of the groups, Group E displayed the greatest degree of regulation. The trend in regulation of gene expression in the NP was essentially consistent with that of the AF, of which Group E was the greatest. In the intervention groups (Groups C-E), compared with Group A, the pore structure of the bony endplate displayed clear changes. The number of pores in the endplate in Groups C to E was significantly higher than in Group A (p<.0001), among which Group C versus Group D (p=.9724), and Group C versus Group E (p=.0116). There was no significant difference between Groups A and B (p=.5261). In addition, the pore diameter also increased, the trend essentially the same as that of pore density. There was no significant difference between the three intervention groups (p=.7213). It is worth noting that, compared with Groups A and B, peripheral pore density and size in Groups D and E of the three intervention groups recovered significantly. The elastic modulus and diameter of collagen fibers in the AF and NP varied with the type of intervention. Low tension traction combined with ESWT resulted in the greatest impact on the diameter and modulus of collagen fibers. CONCLUSIONS: Low energy ESWT combined with low tension traction provided a more stable intervertebral environment for the regeneration and repair of moderate and severe degenerative discs. Low energy ESWT promoted the regeneration of disc matrix by reducing MMP-3, MMP-13, and ADAMTS-4 resulting in inhibition of collagen degradation. Although axial traction promoted the recovery of height and rehydration of the IVD, combined with low energy ESWT, the micro-nano structure of the bony endplate underwent positive reconstruction, tension in the annulus of the AF and nuclear stress of the NP declined, and the biomechanical microenvironment required for IVD regeneration and repair was reshaped.

Microstructure and mechanical properties of subchondral bone are negatively regulated by tramadol in osteoarthritis in mice.

OBJECTIVES: In the treatment of osteoarthritis (OA), tramadol, a common weak opioid, has become popular due to its effectiveness in inhibition of pain. In the present study, we aimed to explore the effect of tramadol on subchondral bone, especially changes in the microstructure and mechanical properties. METHODS: A mouse model of OA was established in the present study by destabilization of the medial meniscus (DMM). A vehicle or drug was administered for 4 weeks. Specimens were harvested and analyzed radiologically and histologically using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), atomic force microscopy (AFM) and histological staining to evaluate the knee joints of mice undergoing different forms of intervention. RESULTS: In the early stages of OA induced by DMM, the subchondral bone volume fraction in the OA group was significantly higher than in the sham+vehicle (sham+veh) group, while the volume in the treatment groups was lower than in the DMM+vehicle (DMM+veh) and sham+veh groups. In addition, the elastic moduli in the treatment groups clearly decreased compared with the DMM+veh and sham+veh groups. Observations of the subchondral bone surface by SEM indicated serious destruction, principally manifesting as a decrease in lacunae and more numerous and scattered cracks. Histological staining demonstrated that there was no difference in the degeneration of either the articular cartilage or synovial cells whether tramadol was used or not. CONCLUSION: Although tramadol is effective in inhibiting pain in early OA, it negatively regulates the microstructure and mechanical properties of subchondral bone in joints.

Mechanical on-off gates for regulation of drug release in cutaneous or musculoskeletal tissue repairs.

Drug release synchronized with tissue motion is attractive to cutaneous or musculoskeletal tissue injury repair. Here, we have developed a method of regulating drug release by mechanical on-off gates for potential treatment of repeated injury in these tissues. The mechanical gates consisted of a multilayer structure: A brittle outmost layer adhered to an elastic middle layer, which wrapped an inmost drug carrier to form the composite multilayer structure. When it was stretched, cracks appeared as mechanical gates due to mechanical performance difference between the outmost layer and the middle layer, leading to the drug release. When the external force disappeared, it recovered to stop the drug release. The controlled drug release would therefore be achieved by changing the status (opening or closure) of mechanical gates through applying this on-off mechanical stretching. A prototype based on the composite multilayer structure of adhesive coating and electrospinning technique realized the controlled release of drug and effectively repaired the incision. More types of composite multilayer structures for mechanical drug release were expected to meet curing requirement in cutaneous or musculoskeletal tissues.

Structure and mechanical properties of high-weight-bearing and low-weight-bearing areas of hip cartilage at the micro- and nano-levels.

BACKGROUND: Articular cartilage has a high-weight-bearing area and a low-weight-bearing area, the macroscopic elastic moduli of the two regions are different. Chondrocytes are affected by the applied force at the microscopic level. Currently, the modulus of the two areas at the micro and nano levels is unknown, and studies on the relationship between macro-, micro- and nano-scale elastic moduli are limited. Such information may be important for further understanding of cartilage mechanics. Moreover, the surface morphology, proteoglycan content, and micro and nano structure of the two areas, which influences the mechanical properties of cartilage should be discussed. METHODS: Safranin-O/Fast Green staining was used to evaluate the surface morphology and semi-quantify proteoglycan content of porcine femoral head cartilage between the two weight-bearing areas. The unconfined compression test was used to determine the macro elastic modulus. Atomic force microscope was used to measure the micro and nano compressive elastic modulus as well as the nano structure. Scanning electron microscope was employed to evaluate the micro structure. RESULTS: No significant differences in the fibrillation index were observed between two areas (P = 0.5512). The Safranin-O index of the high-weight-bearing area was significantly higher than that of the low-weight-bearing area (P = 0.0387). The compressive elastic modulus of the high-weight-bearing area at the macro and micro level was significantly higher than that of the low-weight-bearing area (P = 0.0411 for macro-scale, and P = 0.0001 for micro-scale), while no statistically significant differences were observed in the elastic modulus of collagen fibrils at the nano level (P = 0.8544). The density of the collagen fibers was significantly lower in the high-weight-bearing area (P = 0.0177). No significant differences were observed in the structure and diameter of the collagen fibers between the two areas (P = 0.7361). CONCLUSIONS: A higher proteoglycan content correlated with a higher compressive elastic modulus of the high-weight-bearing area at the micro level than that of the low-weight-bearing area, which was consistent with the trend observed from the macroscopic compressive elastic modulus. The weight-bearing level was not associated with the elastic modulus of individual collagen fibers and the diameter at the nano level. The micro structure of cartilage may influence the macro- and micro-scale elastic modulus.

Early degeneration of the meniscus revealed by microbiomechanical alteration in a rabbit anterior cruciate ligament transection model.

BACKGROUND: The microbiomechanical properties of the meniscus influence the cell response to the surrounding biomechanical environment â€‹and are beneficial to understand meniscus repairing and healing. To date, however, this information remains ambiguous. This study aims to characterise the microbiomechanical properties of the meniscus after degeneration in a rabbit anterior cruciate ligament transection (ACLT) model and to analyse the corresponding histology at the macroscale and chemical composition. METHODS: Twenty New Zealand white rabbits were used. Menisci were collected from the knee joints 4 and 8 weeks after the ACLT and from those of the corresponding control groups. The central portions of both medial and lateral menisci were investigated using atomic force microscopy, histological study, and an energy-dispersive spectrometer. The evaluation was conducted regionally within the inner, middle, and outer sites from the top layer (facing the femoral surface) to the bottom layer (facing the tibial surface) in both the lateral and medial menisci to obtain the site-dependent properties. RESULTS: At 4 weeks after surgery, the dynamic elastic modulus at the microlevel increased significantly at both the top and bottom layers compared with the intact meniscus (P â€‹= â€‹0.021). At 8 weeks after surgery, the stiffening occurred in all regions (P â€‹= â€‹0.030). The medial meniscus showed greater change than the lateral meniscus. All these microbiomechanical alterations occurred before the histological findings at the macroscale. CONCLUSION: The microbiomechanical properties in the meniscus changed significantly after ACLT and were site dependent. Their alterations occurred before the histological changes of degeneration were observed. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The results of our study indicated that degeneration promoted meniscus stiffening. Thus, they provide a better understanding of the disease process affecting the meniscus. Our results might be beneficial to understand how mechanical forces distribute throughout the healthy and pathologic joint. They indicate the possibility of early diagnosis using a minimally invasive arthroscopic tool, as well as they might guide treatment to the healthy and pathologic meniscus and joint.

Stable mechanical environments created by a low-tension traction device is beneficial for the regeneration and repair of degenerated intervertebral discs.

BACKGROUND: By blocking the cascade of reactions leading to intervertebral disc degeneration through immobilization-traction, a delay in intervertebral disc degeneration and its regeneration, to some extent, has been observed. However, the precise balance of regulation of the microenvironment of intervertebral disc biomechanics and coordination of the complex spatiotemporal reconstruction of the extracellular matrix have not yet been solved, and clinical results are far from successful. PURPOSE: In the present study, a mechanical degeneration model was constructed to evaluate the possibility and effectiveness of disc regeneration or repair through low-tension traction of degenerated discs so as to provide basic biomechanical information for clinical optimization of the traction device and to establish traction parameters for prevention and treatment of disc degeneration. STUDY DESIGN: A macro-, micro-, and nano-level structural analysis of degenerative discs of rat tail before and after controlled traction. METHODS: Six-month-old male Sprague-Dawley rats were randomly divided into seven groups: Group A: control group (instrumented with Kirschner [K]-wires only); Group B: Model group (caudal vertebrae immobilized using a custom-made external device to fix four caudal vertebrae [Co7-Co10], while Co8-Co9 vertebrae underwent 4 weeks of compression to induce disc degeneration); Group C: experimental control group (devices removed after the 4 week compression described in Group B, and recovered by themselves for 4 weeks). The remaining four groups represented intervention groups (Groups D and F: Co8-Co9 vertebrae compressed for 4 weeks followed by 2 or 4 weeks of in situ traction, respectively; Groups E and G: vertebrae compressed for 4 weeks followed by 2 or 4 weeks of excessive traction, respectively). X-ray and magnetic resonance imaging were performed at each time point to measure disc height and T2 signal intensity. At the end of the experiment, the animals were euthanized and tail vertebrae harvested for analysis of intervertebral disc histopathology, proteoglycan content, elastic modulus of fibers of the annulus fibrosus (AF) and nucleus pulposus (NP), and microstructure of the bony end plate. RESULTS: After 2 to 4 weeks of continuous traction (in situ and excessive traction), the Co8-Co9 intervertebral disc space of rats in Groups D to G increased significantly compared with Groups B and C (p < .05). In addition, signs of tissue regeneration were apparent in all four intervention groups (D-G). In addition, histologic scores of the intervention groups (D-G) were significantly lower than those in the model and experimental control groups (Groups B and C, respectively), although no significant difference was found between those four groups. Compared with the model group (Group B), total proteoglycan content of the NP in the intervention groups (D-G) increased significantly (p < .05). After 2 to 4 weeks of intervention (in situ and excessive traction), the morphology of pores in the bony end plate, their number, and the diameter had recovered significantly compared with those in Group B. The in situ traction group was superior to the excessive traction group, and 4 weeks in situ group significantly superior to the 2 weeks group. In all intervention groups, in both the inner and outer AF, mean fibril diameter decreased significantly (p < .05), although they remained larger in the excessive traction group than that in the in situ traction group. Consistent with trend in collagen fiber diameter, the outer AF was stiffer than the inner, and the modulus of the AF in each intervention group not significantly different from that of the control group (Group A) except Group C. However, within the NP, the variation in trend in diameter and modulus of collagen fibers was essentially inconsistent with that of the AF. CONCLUSIONS: Degenerated discs exhibit greater reconstruction after low tension traction. It is clear that the intervertebral disc mechanical microenvironment depends to a greater extent on low-tension traction than high-tension traction.

Nano and micro biomechanical analyses of the nucleus pulposus after in situ immobilization in rats.

Immobilization can lead to intervertebral disc degeneration. The biomechanical characteristics of such discs have not so far been investigated at the micro- or nanoscale, the level at which cells sense and respond to the surrounding environment. This study aimed to characterize changes in the elastic modulus of the collagen fibrils in the nucleus pulposus at the nanoscale and correlate this with micro-biomechanical properties of the nucleus pulposus after immobilization, in addition to observation of tissue histology and its gene expressions. An immobilization system was used on the rat tail with an external fixation device. The elastic modulus was measured using both nano and micro probes for atomic force microscopy after 4 and 8 weeks of immobilization. Histology of the tissue was observed following hematoxylin and eosin staining. Gene expression in the annulus fibrosus tissue was quantified using real-time reverse transcription-polymerase chain reaction. The elastic modulus of the collagen fibrils in the nucleus pulposus at the nanoscale increased from 74.07 ± 17.06 MPa in the control to 90.06 ± 25.51 MPa after 8 weeks (P = 0.007), and from 33.51 ± 9.33 kPa to 43.18 ± 12.08 kPa at the microscale (P = 0.002). After immobilization for 8 weeks, a greater number of cells were observed by histology to be aggregated within the nucleus pulposus. Collagen II (P = 0.007) and aggrecan (P = 0.003) gene expression were downregulated whereas collagen I (P = 0.002), MMP-3 (P < 0.001), MMP-13 (P < 0.001) and ADAMTs-4 (P < 0.001) were upregulated. Immobilization not only influenced individual collagen fibrils at the nanoscale, but also altered the micro-biomechanics and cell response in the nucleus pulposus. These results suggest that significant changes occur in intervertebral discs at both scales after immobilization, a situation about which clinicians should be aware when immobilization has to be used clinically.

Sensory nerves protect from the progression of early stage osteoarthritis in mice.

PURPOSE: Osteoarthritis (OA) is a chronic degenerative joint disease. Sensory nerves play an important role in bone metabolism and in the progression of inflammation. This study explored the effects of sensory nerve on OA progression at early stage in mice. MATERIALS AND METHODS: OA was induced via destabilization of the medial meniscus (DMM) in C57BL/6 mice. Sensory denervation was induced by subcutaneous injection of capsaicin (90 mg/kg) one week prior to DMM. One week after capsaicin injection, sensory denervation in the tibia was confirmed by immunofluorescent staining. Four weeks after DMM, micro-CT scans, histological analysis, and RT-PCR tests were performed to evaluate OA progression. RESULTS: Subcutaneous injection of capsaicin successfully induced sensory denervation in tibia. The Osteoarthritis Research Society International (OARSI) score and synovitis score of the capsaicin+DMM group were significantly higher than the score of the vehicle+DMM group. The BV/TV of the tibial subchondral bone in the capsaicin+DMM group was significantly lower than in the vehicle+DMM group. In addition, the level of expression of inflammatory factors in the capsaicin+DMM group was significantly higher than in the vehicle+DMM group. CONCLUSIONS: Capsaicin-induced sensory denervation accelerated OA progression at early stage in mice. To put it another way, sensory nerve protects from OA progression at early stage in mice.

Tendoscopic versus open release for de Quervain's disease: earlier recovery with 7.21 year follow-up.

PURPOSE: To compare the time return to work and long-term results of tendoscopic versus open technique for de Quervain's disease. METHODS: From 2005 to 2013, either tendoscopic or open decompression was performed on 56 consecutive patients (56 wrists) with symptomatic de Quervain's disease despite a minimum of 3 months non-operative treatment. Of the 50 patients who met the inclusion criteria, 41 patients were followed-up for a mean of 7.21 years postoperatively. Among these 41 wrists, 20 underwent tendoscopic release (group A), and 21 underwent open release (group B). The clinical evaluations were performed preoperatively, 1 month postoperatively and at last follow-up visit, using visual analog scale (VAS); the Disabilities of the Arm, Shoulder and Hand (DASH) Outcome score; and the Finkelstein's test. The Patient and Observer Scar Assessment Scale (POSAS) was used as an esthetic evaluation tool of the scar at last follow-up. RESULTS: No significant baseline differences were found between two groups. The average time return to work in group A was less than in group B (P < 0.05), The mean VAS and DASH scores improved significantly in both groups at 1 month and last follow-up visit (P < 0.001). At 1 month, the scores in group A were significantly better than in group B (P < 0.05 and P < 0.001, respectively). There was no difference between groups at last follow-up. In addition, the improvement of the mean DASH score was significantly greater in group A than in group B (34.74 ± 10.99 in group A and 23.58 ± 12.01 in group B, P < 0.01) at 1 month. For POSAS scale, both the OSAS and PSAS scores were significantly better in group A. One patient in group A had cephalic vein injury and 3 patients in group B was involved with radial sensory nerve injury. All patients showed negative on Finkelstein's test at last follow-up. CONCLUSIONS: The results of this study suggest that tendoscopic technique for de Quervain's disease could provide earlier symptom relief and earlier recovery with fewer complications and more desirable scar, as well as equivalent successful long-term outcome, when compared with traditional open release technique.