Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 113
Filtrar
1.
J Biomech ; 116: 110252, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33485145

RESUMO

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.

2.
J Biomech ; 116: 110248, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33485146

RESUMO

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.

3.
Biosci Rep ; 40(9)2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32803252

RESUMO

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.

4.
Spine J ; 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32800896

RESUMO

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 end plate. This might better reshape the microenvironment for disc regeneration and repair. However, the repair of the combination of end plate 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 end plates 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 end plate displayed clear changes. The number of pores in the end plate 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 end plate 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.

5.
BMC Musculoskelet Disord ; 21(1): 425, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32616028

RESUMO

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.

6.
Mater Sci Eng C Mater Biol Appl ; 115: 111048, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32600683

RESUMO

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.

7.
Spine J ; 20(9): 1503-1516, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32305426

RESUMO

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.

8.
J Orthop Translat ; 21: 146-152, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32309140

RESUMO

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.

9.
Micron ; 130: 102824, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31927410

RESUMO

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.


Assuntos
Módulo de Elasticidade , Expressão Gênica , Imobilização , Núcleo Pulposo/citologia , Animais , Anel Fibroso/fisiologia , Colágeno/fisiologia , Modelos Animais de Doenças , Matriz Extracelular , Masculino , Microscopia de Força Atômica , Núcleo Pulposo/fisiologia , Núcleo Pulposo/ultraestrutura , Ratos , Ratos Sprague-Dawley , Cauda
10.
Connect Tissue Res ; 61(5): 445-455, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31274342

RESUMO

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.

12.
J Orthop Surg Res ; 14(1): 357, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718690

RESUMO

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.


Assuntos
Doença de De Quervain/cirurgia , Descompressão Cirúrgica/métodos , Adulto , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
J Neurosci ; 39(46): 9107-9118, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31597725

RESUMO

Although several genes have been identified to promote axon regeneration in the CNS, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using female mouse sensory axon and optic nerve regeneration as model systems, we reveal an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provide evidence that TERT and p53 act downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells is sufficient to promote sensory axon and optic never regeneration, respectively. The study reveals a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration.SIGNIFICANCE STATEMENT Despite significant progress during the past decade, our understanding of the molecular mechanisms by which mammalian CNS axon regeneration is regulated is still fragmented. By using sensory axon and optic nerve regeneration as model systems, the study revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. The results also delineated a c-Myc-TERT-p53 pathway in controlling axon growth. Last, our results demonstrated that p53 alone was sufficient to promote sensory axon and optic nerve regeneration in vivo Collectively, the study not only revealed a new mechanisms underlying mammalian axon regeneration, but also expanded the pool of potential targets that can be manipulated to enhance CNS axon regeneration.


Assuntos
Axônios/metabolismo , Gânglios Espinais/metabolismo , Regeneração Nervosa , Nervo Óptico/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Telomerase/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Células Cultivadas , Feminino , Camundongos Endogâmicos C57BL
14.
J Orthop Translat ; 17: 121-132, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31194022

RESUMO

Objective: This work focuses on tackling the inadequate bone/implant interface strength of acrylic bone cements, which is a formidable problem diminishing their clinical performance, especially in percutaneous kyphoplasty surgery. Methods: A new strategy of incorporating magnesium particles into clinically used poly(methylmethacrylate) (PMMA) bone cement to prepare a surface-degradable bone cement (SdBC) is proposed and validated both in vitro and in vivo. Results: This surface degradation characteristic enables osseointegrative, angiogenic and antiinfective properties. SdBC showed fast surface degradation and formed porous surfaces as designed, while the desirable high compressive strengths (≥70 MPa) of the cement were preserved. Besides, the SdBC with proper Mg content promoted osteoblast adhesion, spreading, proliferation and endothelial cell angiogenesis capacity compared with PMMA. Also, SdBC demonstrated clear inhibitory effect on Staphylococcus aureus and Escherichia coli. In vivo evaluation on SdBC by the rat femur defect model showed that the bone/implant interface strength was significantly enhanced in SdBC (push-out force of 11.8 ± 1.5 N for SdBC vs 7.0 ± 2.3N for PMMA), suggesting significantly improved osseointegration and bone growth induced by the surface degradation of the cement. The injectability, setting times and compressive strengths of SdBC with proper content of Mg particles (2.8 wt% and 5.4 wt%) were comparable with those of the clinical acrylic bone cement, while the heat release during polymerization was reduced (maximum temperature 78 ± 1 °C for PMMA vs 73.3 ± 1.5 °C for SdBC). Conclusions: This work validates a new concept of designing bioactive bone/implant interface in PMMA bone cement. And this surface-degradable bone cement possesses great potential for minimally invasive orthopaedic surgeries such as percutaneous kyphoplasty. The translational potential of this article: This work reports PMMA/Mg surface-degradable acrylic bone cements that possess enhanced osseointegrative, angiogenic and antiinfective properties that are lacking in the clinically used acrylic bone cements. This new kind of bone cements could improve the treatment outcome of many orthopaedic surgeries such as percutaneous kyphoplasty and arthroplasty.

15.
Math Biosci Eng ; 16(4): 2959-2972, 2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-31137245

RESUMO

The use of mouse models as a tool to study ankle sprain requires a basic understanding of the similarities and differences between human and mouse ankle joint anatomy. However, few studies have been conducted that address the merits and drawbacks of these differences in the functioning of joints. Twenty hindfoot specimens were obtained from 10 male C57BL/6J mice and scanned using micro-CT. The foot and ankle skeletal structures were reconstructed in three dimensions. Morphological parameters were then measured using a plane projection method and normalized data were compared with those of human ankles. There was no significant difference in the malleolar width, maximal tibial thickness, tibial arc length, trochlea tali arc length or trochlea tali width of the mouse specimens compared with the human model. However, a groove was observed on the talar dome in the mouse specimens which was not observed in humans, the talar dome being more symmetric. The mouse ankle was to a large extent able to mimic the mechanism of a human ankle and so a mouse model could be appropriate for expanding our understanding of ankle biomechanics in general. However, the structural differences in the talar dome in the mouse and human should not be ignored. Although there are some differences in the mouse and human ankle that cannot be ignored, compared to other animals, the human ankle is more similar to that of the mouse.


Assuntos
Traumatismos do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/anatomia & histologia , Articulação do Tornozelo/diagnóstico por imagem , Animais , Traumatismos do Tornozelo/patologia , Fenômenos Biomecânicos , Modelos Animais de Doenças , Membro Posterior/anatomia & histologia , Membro Posterior/diagnóstico por imagem , Membro Posterior/lesões , Humanos , Masculino , Conceitos Matemáticos , Camundongos , Camundongos Endogâmicos C57BL , Modelos Anatômicos , Especificidade da Espécie , Tálus/anatomia & histologia , Tálus/diagnóstico por imagem , Tálus/lesões , Articulações Tarsianas/anatomia & histologia , Articulações Tarsianas/diagnóstico por imagem , Articulações Tarsianas/lesões , Microtomografia por Raio-X
16.
Spine J ; 19(7): 1242-1253, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30710732

RESUMO

BACKGROUND CONTEXT: Pfirrmann grading can be used to assess intervertebral disc degeneration (IVDD). There is growing evidence that IVDD is not simply a structural disorder but also involves changes to the substructural characteristics of the disc. Whether Pfirrmann grade can accurately represent these micro-nano environmental changes remains unclear. PURPOSE: We aimed to assess the micro-nano structural characteristics of the degenerative disc to provide more specific biomechanical information than the Pfirrmann score. STUDY DESIGN: A micro- and nano-level structural analysis of degenerative discs of rat tails. METHODS: In this study, 12-week-old adult male Sprague-Dawley rats were divided randomly into five groups: control (no intervention to the intervertebral disc of the tail) and four intervention groups that all had caudal vertebrae immobilized using a custom-made external device to fix four caudal vertebrae (Co7-Co10) but with variable subsequent compression of Co8 and Co9 for 2, 4, 6, or 8 weeks. Magnetic resonance imaging detection of rat coccygeal vertebrae was conducted at each time node of the experiment, and the T2 signal intensity and disc space were evaluated. Animals were euthanized and the caudal vertebrae were harvested for further analysis. Histopathology, glycosaminoglycan (GAG) content, histologic score, end plate structure, and elastic modulus of the intervertebral discs were evaluated. RESULTS: IVDD was observed at an earlier Pfirrmann grade (Pfirrmann II) under the microscope. With an increase in Pfirrmann grade to III-V, the pore structure of the bony end plate changed significantly and the number of pores decreased gradually. Furthermore, the total GAG content of the nucleus pulposus decreased from an average of 640.33 µg GAG/ng DNA in Pfirrmann grade I to 271.33 µg GAG/ng DNA in Pfirrmann grade V (p < .0001). At the early stage of clinical degeneration of intervertebral discs (Pfirrmann grades II and III), there were significant changes in mechanical properties of the outer annulus fibrosus compared with the inner layer (p < .05). Further, the fibril diameters exhibited significant changes compared with the control group (p < .05). CONCLUSIONS: Our study found that the Pfirrmann grading system combined with intervertebral disc micro-nano structural changes more comprehensively reflected the extent of disc degeneration. These data may help improve our understanding of the pathogenesis and process of clinical disc degeneration.


Assuntos
Anel Fibroso/ultraestrutura , Degeneração do Disco Intervertebral/patologia , Núcleo Pulposo/ultraestrutura , Animais , Anel Fibroso/diagnóstico por imagem , Glicosaminoglicanos/metabolismo , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Núcleo Pulposo/diagnóstico por imagem , Núcleo Pulposo/metabolismo , Ratos , Ratos Sprague-Dawley
17.
J Orthop Res ; 37(1): 232-238, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30370678

RESUMO

Annulus fibrosus is critical to bear loads and resist fluid flow in the intervertebral disc. However, the detailed biomechanical mechanism of annulus fibrosus under abnormal loading is still ambiguous, especially at the micro and nano scales. This study aims to characterize the alterations of modulus at the nano scale of individual collagen fibrils in annulus fibrosus after in-situ immobilization, and the corresponding micro-biomechanics of annulus fibrosus. An immobilization model was used on the rat tail with an external fixation device. The elastic modulus of annulus fibrosus at both the nano- and micro-scale was examined using atomic force microscopy after fixation for 4 and 8 weeks, respectively. The fibrils in inner layer showed an alteration in elastic modulus from 91.38 ± 20.19 MPa in the intact annulus fibrosus to 110.64 ± 15.58 MPa (p < 0.001) at the nano scale after immobilization for 8 weeks, while the corresponding modulus at the micro scale also underwent a change from 0.33 ± 0.04 MPa to 0.47 ± 0.04 MPa (p < 0.001). The fibril disorder after immobilization was observed by hematoxylin/eosin staining. The gene expression of annulus fibrosus was also measured by real-time reverse transcription-polymerase chain reaction, which showed the upregulation of collagen II (p = 0.003) after immobilization. The results indicated that the immobilization not only influenced the individual fibril at the nanoscale, but also the micro-biomechanical property of annulus fibrosus which is critical to define the cell response to surrounding biomechanical environment. These alterations may also lead to the change in the mechanical property of the whole disc and the load-bearing function. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-7, 2018.


Assuntos
Anel Fibroso/fisiologia , Colágenos Fibrilares/fisiologia , Imobilização/efeitos adversos , Degeneração do Disco Intervertebral/etiologia , Animais , Fenômenos Biomecânicos , Masculino , Microscopia de Força Atômica , Distribuição Aleatória , Ratos Sprague-Dawley
18.
Spine J ; 19(5): 920-930, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30399448

RESUMO

BACKGROUND CONTEXT: Previous studies have shown the potential for intervertebral disc tissue regeneration is very limited. While in vivo and in vitro studies have shown that traction can restore disc height and internal pressure, in many clinical studies it was shown that axial mechanical traction for the treatment of low back pain is ineffective. PURPOSE: The aim of this study was to identify how the disc could be distracted, how to define the state of traction, and to further examine the feasibility of regenerating or restoring the degenerative disc by means of traction. STUDY DESIGN: A macro- and microlevel structural analysis of degenerative discs of rat tail before and after controlled immobilization-traction. METHODS: In this study, 49 6-month-old male Sprague-Dawley rats were randomly assigned to one of seven groups. Group A was the sham control group in which caudal vertebrae were instrumented with K-wires only. In Group B (model group), caudal vertebrae were immobilized using a custom-made external device to fix four caudal vertebrae (Co7-Co10) and Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration. In Group C, vertebrae Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration, followed by removal of the external apparatus. Rats in the other four groups (Groups D-G), Co8-Co9 underwent 4 weeks of compression to induce moderate disc degeneration followed by 2 weeks, 4 weeks, 6 weeks, and 8 weeks of distraction, respectively. Caudal vertebrae were harvested and disc height, T2 signal intensity of the discs, disc morphology, total glycosaminoglycan content of the nucleus pulposus and the structure of the Co8-Co9 end plate were evaluated. RESULTS: After 4 weeks of compression, the intervertebral height and T2 signal intensity of Co8-Co9 vertebrae of rats in Groups B to G were significantly reduced compared with Group A (sham group, all p<.0001). Histological scores of rats in Group B averaged 10.14 and the total glycosaminoglycan (GAG) of nucleus pulposus averaged 238.21µg GAG/ng DNA. The bony end plate structure showed significant changes in comparison with the control Group. After 2 weeks to 8 weeks of traction, the disc space and T2 signal intensity of Co8-Co9 vertebrae in Group E were significantly recovered compared to that of rats in Group B (p<.0001), and the intervertebral height of the Co8-Co9 in Group D, Group F, and Group G when compared with Group B (p<.0001). Meanwhile, the T2 signal intensity of Co8-Co9 in Group D, F, and G when compared with Group B (p<.001). Histological scores dropped from an average of 10.14 in Group B to 5.57 in Group E, and 5.86 in Group F (all p<.0001). Furthermore, the total GAG content of the nucleus pulposus increased from an average of 238.21µg GAG/ng DNA in Group B to 601.02µg GAG/ng DNA in Group E (p<.0001). The number of pores of end plates in rats in Groups D and E both were significantly increased when compared to that of rats in Group B (Groups D vs Groups B, p<.05; Groups E vs Groups B, p<.0001). CONCLUSIONS: A mechanical degenerative model was successfully established by using a custom-made device. We demonstrated that disc degeneration is a cascade of biochemical, mechanical, and structural changes mediated by cells in an abnormal mechanical environment. Not all levels of disc degeneration can be regenerated or repaired. Regeneration or recovery of disc degeneration requires specific conditions. Based on the immobilization-traction mode, the cascade cycle of disc degeneration is interrupted. Traction of 2 to 6 weeks is a sensitive period for regeneration of the degenerative disc. Moreover, the duration and extent of the traction loading must be moderately controllable, and beyond the limits that can lead to significant degeneration. These data may help improve our understanding of the pathogenesis of clinical disc degeneration and how to optimize the use of traction devices for possible regeneration.


Assuntos
Degeneração do Disco Intervertebral/terapia , Regeneração , Tração/métodos , Animais , Glicosaminoglicanos/metabolismo , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Disco Intervertebral/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley
19.
Biomed Res Int ; 2018: 4210353, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30519575

RESUMO

The pathogenesis of posttraumatic osteoarthritis (PTOA) remains unrevealed. We speculate that cartilage crack caused by joint trauma will induce local abnormal tensile stress, leading to change in extracellular matrix (ECM) expression of chondrocytes, cartilage degeneration, and initiation of osteoarthritis. Finite element model was used to examine whether the local tensile stress could be produced around the crack. Cell experiments were conducted to test the effect of tensile strain on chondrocyte ECM expression. Animal tests in rabbits were carried out to examine the change around the cartilage crack. The results indicated that the local tensile stress was generated around the crack and varied with the crack angles. The maximum principal tensile stress was 0.59 MPa around the 45° crack, and no tensile stress was found at 90°. 10% tensile strain could significantly promote type I collagen mRNA expression and inhibit type II collagen and aggrecan (the proteoglycan core protein) mRNA expression. Type I collagen was detected around the 45° crack region in the cartilage with no change in type II collagen and proteoglycan. We conclude that the local tensile stress produced around the cartilage crack can cause the change in cartilage matrix expression which might lead to cartilage degeneration and initiation of osteoarthritis. This study provides biomechanical-based insight into the pathogenesis of PTOA and potentially new intervention in prevention and treatment of PTOA.


Assuntos
Colágeno Tipo I/genética , Matriz Extracelular/genética , Osteoartrite/genética , Ferimentos e Lesões/genética , Animais , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Condrócitos/metabolismo , Condrócitos/patologia , Expressão Gênica/genética , Humanos , Articulações/fisiopatologia , Osteoartrite/etiologia , Osteoartrite/fisiopatologia , Coelhos , Estresse Mecânico , Ferimentos e Lesões/complicações , Ferimentos e Lesões/fisiopatologia
20.
Stem Cells Int ; 2018: 2613821, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30510582

RESUMO

Tendinopathy is prevalent in athletic and many occupational populations; nevertheless, the pathogenesis of tendinopathy remains unclear. Tendon-derived stem cells (TDSCs) were regarded as the key culprit for the development of tendinopathy. However, it is uncertain how TDSCs differentiate into adipocytes, chondrocytes, or osteocytes in the degenerative microenvironment of tendinopathy. So in this study, the regulating effects of the degenerative tendon microenvironment on differentiation of TDSCs were investigated. TDSCs were isolated from rat Achilles tendons and were grown on normal and degenerative (prepared by stress-deprived culture) decellularized tendon slices (DTSs). Immunofluorescence staining, H&E staining, real-time PCR, and Western blot were used to delineate the morphology, proliferation, and differentiation of TDSCs in the degenerative microenvironment. It was found that TDSCs were much more spread on the degenerative DTSs than those on normal DTSs. The tenocyte-related markers, COL1 and TNMD, were highly expressed on normal DTSs than the degenerative DTSs. The expression of chondrogenic and osteogenic markers, COL2, SOX9, Runx2, and ALP, was higher on the degenerative DTSs compared with TDSCs on normal DTSs. Furthermore, phosphorylated FAK and ERK1/2 were reduced on degenerative DTSs. In conclusion, this study found that the degenerative tendon microenvironment induced TDSCs to differentiate into chondrogenic and osteogenic lineages. It could be attributed to the cell morphology changes and reduced FAK and ERK1/2 activation in the degenerative microenvironment of tendinopathy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA