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1.
Bone ; 135: 115314, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32156663

RESUMO

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

2.
J Mech Behav Biomed Mater ; 104: 103646, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32174404

RESUMO

STUDY DESIGN: Cadaveric biomechanical with imaging analysis. OBJECTIVE: This study aims to compare the fixation failure between pedicel screws (PS) and cortical screws (CS), thus to investigate their failure mechanisms under vertical migration. SUMMARY OF BACKGROUND DATA: Due to their minimal invasive nature, CS are gaining popularity. However, contradictions exist in the literature regarding whether CS may have superior fixation failure resistance compared to PS under vertical migration. METHODS: Human vertebral specimens were examined under Dual-energy X-ray. For each specimen, PS were inserted on the left and CS on the right with rods secured. Vertical force-displacement tests were applied to rods. MicroCT images were taken pre and post-MTS® for microstructural analysis. RESULTS: The average T-scores of the specimens were -4±0.25. Three phases of force-displacement behaviour featuring different PS and CS failure-resistance were discovered. For phase I, the force required to migrate PS tended to be slightly higher than CS. However, during phase II, a fixation instability occurred for PS and the CS fixation strength was superior. For phase III under large displacement, CS did not require increased force to displace, whereas PS re-stabilised and revealed improved displacement resistance. Both force analysis and microstructural analysis indicated that PS migrated along the direction of the vertical loading, whereas CS had a force component in the longitudinal axis of the screw. CONCLUSIONS: Different failure mechanisms underlay PS and CS under large vertical displacement. PS fail with trabecular bone compaction possibly altering the initial material property surround the screw. CS fail with screw cut-out due to the force component along the screw axis.

3.
Biomed Pharmacother ; 126: 109733, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32113051

RESUMO

According to the Chinese medicine, magnoflorine exerted significant anti-inflammatory effects and potentially promoted synthesis of proteoglycans in chondrocytes to reverse the progression of rheumatoid arthritis. However, the latent beneficial effect of magnoflorine for the treatment of traumatic osteoarthritis (OA) is still unknown. Therefore, we aim to demonstrate the efficacy of magnoflorine combined with HA-gel in attenuating cartilage degeneration in anterior cruciate ligament transection (ACLT) induced OA rat model. We found that the histological results showed the elevated cartilage matrix, chondrogenic signals and chondroprogenitor cells in HA-gel + magnoflorine treatment. HA-gel + magnoflorine treatment resulted in a decreased modified Mankin's score, and a higher volume ratio of hyaline cartilage (HC)/calcified cartilage (CC) and HC/Sum (whole cartilage), compared to ACLT and HA-gel groups. Furthermore, both the volume ratios of HC/Sum and HC/CC were negatively correlated with modified Mankin's scores. Finally, HA-gel + magnoflorine could significantly increase the BV/TV, Tb.Th, and decrease the Tb.Pf, Po(tot), Conn.Dn and Tb.Sp. In vitro, 50 µg/ml magnoflorine treatment could significantly increase the viability, S-phase, migration rate and chondrogenesis of chondroprogenitor cells. There were significant downregulations of MAPK/NF-κB signaling, and upregulations of chondrogenic signals in 50 µg/ml magnoflorine treatment. There were significant downregulations of proinflammatory cytokines and upregulation of IL-10 in HA-gel + magnoflorine treated group. Therefore, our study elucidated a protective effect of HA-gel + magnoflorine on attenuating cartilage degradation and maintaining SCB stabilization in ACLT induced OA.

4.
J Mech Behav Biomed Mater ; 103: 103546, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31786511

RESUMO

PURPOSE: Osteoporosis is a critical global health issue. However, the biomechanical properties of osteoporotic trabecular bone have not been well understood due to its hierarchically complex structure mingled with accumulated microcracks. Previous studies indicated the mechanical behaviors of trabecular bone may differ with varying amounts of deformation. Therefore, this study aims to further reveal the relationship between the measured mechanical properties of osteoporotic trabecular bone and various amounts of deformation volume during micro-indentation. METHODS: Two trabecular specimens were dissected transversally and frontally from an osteoporotic lumbar vertebral (L5) cadaver and embedded into Methyl methacrylate. On each specimen, two orthogonal cuts were performed to make a right-angle, followed by five parallel slicing. On each slice, the region of interest was gridded into 16 (4 × 4) sub-regions with the size equal to the microscope field. Within each sub-region, indentations were made on a single trabecula with five different indentation depths (3, 4, 5, 6, 7 µm) to induce different deformation volume. Both the indentation hardness and modulus were computed from the indenting curve for each measurement. The results of the five slices are pooled together to represent the longitudinal and circumferential mechanical characteristics, respectively. Linear regression was performed to investigate the relationship between the measured mechanical properties and various deformation volumes. RESULTS: A total of 1055 indents were made. After eliminating outliers, 840 indents were left for data analysis with 490 indents from transversal slices and 350 indents from frontal slices. Both the hardness and modulus decreased with the increasement of indentation depths. The hardness decreased by slopes of -0.65 (R2 = 0.72, p = 0.044) and -0.869 (R2 = 0.95, p = 0.003) longitudinally and circumferentially while the modulus decreased by slopes of -0.39 (R2 = 0.82, p = 0.02) and -0.348 (R2 = 0.94, p = 0.004) longitudinally and circumferentially. CONCLUSIONS: Mechanical properties of trabecular bone measured by micro-indentation can alter with the variation of deformation volume, which reflects the nonlinear behavior of vertebra from the material perspective.

5.
J Mater Chem B ; 8(4): 636-647, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31829384

RESUMO

Due to the structural similarity to the extracellular matrix of human tissue and the ultra-high surface area-to-volume ratio, three dimensional electrospun fibrous structures have been increasingly used as tissue engineering scaffolds. Given that successful bone regeneration requires both good osteogenesis and vascularization, producing scaffolds that have both osteogenic and angiogenic potential is highly desirable. In this investigation, tricomponent fibrous scaffolds simultaneously incorporated with recombinant human vein endothelial growth factor (rhVEGF), recombinant human bone morphogenetic protein-2 (rhBMP-2) and bioactive calcium phosphate (Ca-P) nanoparticles are produced through a novel multi-source multi-power electrospinning method, and sequential growth factor release with a quick rhVEGF release and a steady rhBMP-2 release is achieved. The enhanced human umbilical vein endothelial cell (HUVEC) migration and tube formation, and up-regulated human bone marrow derived mesenchymal stem cell (hBMSC) osteogenic differentiation and mineralization demonstrate that tricomponent scaffolds have balanced angiogenic-osteogenic properties in vitro. 8 weeks after the scaffold implantation into the cranial defects of mice, obvious new bone regeneration and newly formed capillaries are observed in tricomponent scaffolds, suggesting that the tricomponent scaffolds enhance osteogenesis in vivo with required vascularization, which shows the great potential of the tricomponent scaffolds in bone tissue regeneration.

6.
Macromol Biosci ; 19(6): e1900020, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31066995

RESUMO

Side-effects from allograft, limited bone stock, and site morbidity from autograft are the major challenges to traditional bone defect treatments. With the advance of tissue engineering, hydrogel injection therapy is introduced as an alternative treatment. Therapeutic drugs and growth factors can be carried by hydrogels and delivered to patients. Abaloparatide, as an analog of human recombinant parathyroid hormone protein (PTHrp) and an alternative to teriparatide, has been considered as a drug for treating postmenopausal osteoporosis since 2017. Since only limited cases of receiving abaloparatide with polymeric scaffolds have been reported, the effects of abaloparatide on pre-osteoblast MC3T3-E1 are investigated in this study. It is found that in vitro abaloparatide treatment can promote pre-osteoblast MC3T3-E1 cells' viability, differentiation, and mineralization significantly. For the drug delivery system, 3D porous structure of the methacrylated gelatin (GelMA) hydrogel is found effective for prolonging the release of abaloparatide (more than 10 days). Therefore, injectable photo-crosslinked GelMA hydrogel is used in this study to prolong the release of abaloparatide and to promote healing of defected bones in rats. Overall, data collected in this study show no contradiction and imply that Abaloparatide-loaded GelMA hydrogel is effective in stimulating bone regeneration.


Assuntos
Doenças Ósseas/tratamento farmacológico , Regeneração Óssea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Animais , Doenças Ósseas/patologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Gelatina/química , Gelatina/farmacologia , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Metacrilatos/química , Metacrilatos/farmacologia , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Proteína Relacionada ao Hormônio Paratireóideo/química , Proteína Relacionada ao Hormônio Paratireóideo/genética , Teriparatida/farmacologia
7.
ACS Appl Mater Interfaces ; 11(9): 9415-9424, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30698946

RESUMO

Synthetic biodegradable polymeric scaffolds with uniformly interconnected pore structure, appropriate mechanical properties, excellent biocompatibility, and even enhanced osteogenesis ability are urgently required for in situ bone regeneration. In this study, for the first time, a series of biodegradable piperazine (PP)-based polyurethane-urea (P-PUU) scaffolds with a gradient of PP contents were developed by air-driven extrusion 3D printing technology. The P-PUU ink of 60 wt % concentration was demonstrated to have appropriate viscosity for scaffold fabrication. The 3D-printed P-PUU scaffolds exhibited an interconnected porous structure of about 450 µm in macropore size and about 75% in porosity. By regulating the contents of PP in P-PUU scaffolds, their mechanical properties could be moderated, and P-PUU1.4 scaffolds with the highest PP contents exhibited the highest compressive modulus (155.9 ± 5.7 MPa) and strength (14.8 ± 1.1 MPa). Moreover, both in vitro and in vivo biological results suggested that the 3D-printed P-PUU scaffolds possessed excellent biocompatibility and osteoconductivity to facilitate new bone formation. The small molecular PP itself was confirmed for the first time to regulate osteogenesis of osteoblasts in a dose-dependent manner and the optimum concentration for osteoconductivity was about ∼0.5 mM, which suggests that PP molecules, together with the mechanical behavior, nitrogen-contents, and hydrophilicity of P-PUUs, play an important role in enhancing the osteoconductive ability of P-PUU scaffolds. Therefore, the 3D-printed P-PUU scaffolds, with suitable interconnected pore structure, appropriate mechanical properties, and intrinsically osteoconductive ability, should provide a promising alternative for bone regeneration.


Assuntos
Materiais Biocompatíveis/química , Piperazina/química , Poliuretanos/química , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Doenças Ósseas/terapia , Doenças Ósseas/veterinária , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Força Compressiva , Camundongos , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Porosidade , Impressão Tridimensional , Ratos , Engenharia Tecidual
8.
Histol Histopathol ; 34(3): 275-286, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30234227

RESUMO

Various histological staining methods have been explored to detect the joint lesions in osteoarthritis (OA), but these histological stains cannot comprehensively present the comparatively complex structures of articular cartilage in knee OA. In addition, no integrated histological staining method can be used to evaluate efficiently both the subzone region and matrix composition in cartilage containing tissues. Therefore, in this study, a novel multichromatic staining method termed TTF staining, using Toluidine Blue (T), Tartrazine (T) and Fast Green (F) sequential combined staining for histological analysis, has been exploited to characterize the changes of matrix components and contents in cartilage during OA and in the bone development. This specific TTF staining profile can be used to differentiate the major compartments of knee joint region, including the synovium, meniscus, multiple subzones of cartilage and subchondral bone. An anterior cruciate ligament transection induced OA model in rat has been established to profoundly present the alterations of glycosaminoglycans in cartilage degeneration by TTF staining profile. The changes of TTF staining profile in the chondrification and ossification centers of the postnatal rat knee joint indicate the developmental features of cartilage matrix during the growth of bone. In summary, we have developed an effective histological staining method that enables us to identify the subzones of cartilage in detail and to define the matrix features of bone development. Therefore, finally using this new TTF staining method may help us to exploit a histopathological grading system to assess cartilage lesions in clinical disease.


Assuntos
Desenvolvimento Ósseo , Cartilagem , Osteoartrite/patologia , Coloração e Rotulagem/métodos , Animais , Cartilagem/patologia , Corantes , Ratos , Ratos Sprague-Dawley , Corantes de Rosanilina , Tartrazina , Cloreto de Tolônio
9.
Bone ; 116: 266-278, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30149068

RESUMO

OBJECTIVE: To investigate efficacy of Chinese medicine magnoflorine combined with hyaluronic acid (HA)-gel in promoting subchondral bone (SCB) regeneration and attenuating cartilage degeneration in early osteoarthritis (OA). METHODS: MC3T3-E1 under magnoflorine treatment was assayed by XTT to determine cell viability. Cell proliferation was reflected through cell cycle. Osteoblast mineralization was stained by Alizarin Red. Standardized bone canal of 1 mm in diameter and 4 mm in depth was made on tibial medial plateau of 4-month-old Dunkin-Hartley spontaneous knee OA guinea pigs. Guinea pigs (n = 5/group) were treated once intra-bone canal injection of 2 µl HA-gel, 2 µl HA-gel+50 ng magnoflorine and null (Defect) respectively, except sham group. The left hind limbs were harvested for µCT scan and histopathological staining 2-month post-surgery. RESULTS: 25 µg/ml magnoflorine treatment significantly increased cell viability, S-phase and mineralization of MC3T3-E1 cells. In vivo, HA-gel + magnoflorine treatment significantly altered SCB microstructure; changes included increase in bone volume fraction (BV/TV), trabecular number (Tb.N), connectivity density (Conn.Dn), and decrease in degree of anisotropy (DA), which implied trabecular bone regeneration. Treatment also resulted in a decrease in modified Mankin's scores, and an increase in volume ratio of hyaline cartilage (HC)/calcified cartilage (CC) and fractal dimension (FD, roughness indicator of osteochondral conjunction), compared to Defect and HA groups. Furthermore, FD was positively associated with volume ratio of HC/CC and negatively associated with modified Mankin's scores. Finally, histological results showed that due to a faster regeneration of SCB with the HA-gel + magnoflorine treatment, the reduction of cartilage matrix and the decreased expression of chondrogenic signals were attenuated. CONCLUSION: Our study elucidated the potential benefits of HA-gel + magnoflorine in promoting SCB regeneration and revealed a protective effect of stimulating recovery of the SCB integrity on attenuating cartilage degradation to prevent OA progression.


Assuntos
Aporfinas/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Cartilagem Articular/patologia , Géis/uso terapêutico , Ácido Hialurônico/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Animais , Aporfinas/farmacologia , Remodelação Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Cartilagem Articular/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Feminino , Géis/farmacologia , Cobaias , Ácido Hialurônico/farmacologia , Osteoartrite do Joelho/fisiopatologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Tíbia/diagnóstico por imagem , Tíbia/patologia , Tíbia/fisiopatologia , Microtomografia por Raio-X
10.
Adv Sci (Weinh) ; 5(3): 1700550, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29593958

RESUMO

An osteoblast-laden nanocomposite hydrogel construct, based on polyethylene glycol diacrylate (PEGDA)/laponite XLG nanoclay ([Mg5.34Li0.66Si8O20(OH)4]Na0.66, clay)/hyaluronic acid sodium salt (HA) bio-inks, is developed by a two-channel 3D bioprinting method. The novel biodegradable bio-ink A, comprised of a poly(ethylene glycol) (PEG)-clay nanocomposite crosslinked hydrogel, is used to facilitate 3D-bioprinting and enables the efficient delivery of oxygen and nutrients to growing cells. HA with encapsulated primary rat osteoblasts (ROBs) is applied as bio-ink B with a view to improving cell viability, distribution uniformity, and deposition efficiency. The cell-laden PEG-clay constructs not only encapsulated osteoblasts with more than 95% viability in the short term but also exhibited excellent osteogenic ability in the long term, due to the release of bioactive ions (magnesium ions, Mg2+ and silicon ions, Si4+), which induces the suitable microenvironment to promote the differentiation of the loaded exogenous ROBs, both in vitro and in vivo. This 3D-bioprinting method holds much promise for bone tissue regeneration in terms of cell engraftment, survival, and ultimately long-term function.

11.
J Biomed Nanotechnol ; 14(4): 662-674, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31352940

RESUMO

In this work, a biodegradable and biocompatible nanocomposite hydrogel was successfully prepared on basis of nanoclay and polyethylene-glycol diacrylates (PEGDA). The physical interspersing between nanoclay particles and PEG chains combined with the chemical crosslinking within the PEG networks endowed the obtained nanocomposite hydrogels with enhanced mechanical properties in comparison with pure PEG hydrogels. Simultaneously, the incorporation of nanoclay to the PEGDA/nanoclay (PEGDA-Clay) nanocomposite hydrogel not only improved the adsorption and spreading ability of cells on the hydrogels, but also effectively facilitated the in vitro osteogenic differentiation of primary rat osteoblasts due to the sustainable release of magnesium ions (Mg2+) and silicon ions (Si4+) from the PEGDA-Clay nanocomposite hydrogel. In addition, the implantation of the PEGDA-Clay nanocomposite hydrogels in the tibia defects of Sprague-Dawley rat could promoted the new bone formation efficiently, further suggesting the excellent osteogenic ability of PEGDA-Clay nanocomposite hydrogel. We expect that this kind of biocompatible nanocomposite hydrogels with attractive mechanical properties and a variety of bioactive osteogenic ions will offer a new possibility for bone tissue regeneration.


Assuntos
Nanocompostos , Osteogênese , Animais , Hidrogéis , Polietilenoglicóis , Polietilenos , Ratos , Ratos Sprague-Dawley
12.
J Mater Chem B ; 6(41): 6615-6621, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-32254870

RESUMO

Magnesium (Mg) alloys, having a unique combination of strength and degradation, are being explored for various craniofacial and orthopedic applications. Nevertheless, the underlying mechanism of Mg2+ to stimulate bone formation needs further investigation. In this in vitro study, the degradation behavior of pure Mg and the effect of Mg2+ on the activity of osteoblasts were elucidated. From the corrosion test, it was determined that the degradation of pure Mg was able to create an alkaline microenvironment. It was further determined that Mg2+ promoted the proliferation and differentiation of osteoblasts. By western blotting analysis, it was noted that Mg2+ increased the phosphorylation of ERK (enhanced the c-fos level) and induced GSK3ß phosphorylation (enhanced the ß-catenin levels). These results demonstrated that the degradation of Mg was able to promote the proliferation and differentiation of osteoblasts, which may be related to the newly created alkaline microenvironment and the osteogenesis potential of released Mg2+ through the MAPK/ERK signaling pathway.

13.
J Biomed Mater Res A ; 105(8): 2199-2209, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28380671

RESUMO

Electrospun scaffolds incorporated with both calcium phosphates (Ca-P) and bone morphogenetic protein-2 (BMP-2) have been used for bone tissue regeneration. However, in most cases BMP-2 and Ca-P were simply mixed and loaded in a monolithic structure, risking low BMP-2 loading level, reduced BMP-2 biological activity, uncontrolled BMP-2 release and inhomogeneous Ca-P distribution. In this investigation, novel bicomponent scaffolds having evenly distributed rhBMP-2-containing fibers and Ca-P nanoparticle-containing fibers were made using an established dual-source dual-power electrospinning technique with the assistance of emulsion electrospinning and blend electrospinning. The release behavior of rhBMP-2 and Ca2+ ions could be separately tuned and the released rhBMP-2 retained a 68% level for biological activity. MC3T3-E1 cells showed high viability and normal morphology on scaffolds. Compared to monocomponent scaffolds, enhanced cell proliferation, alkaline phosphatase activity, cell mineralization, and gene expression of osteogenic markers were achieved for bicomponent scaffolds due to the synergistic effect of rhBMP-2 and Ca-P nanoparticles. Bicomponent scaffolds with a double mass elicited further enhanced cell adhesion, spreading, proliferation, and osteogenic differentiation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2199-2209, 2017.


Assuntos
Proteína Morfogenética Óssea 2/administração & dosagem , Fosfatos de Cálcio/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/administração & dosagem , Tecidos Suporte/química , Fator de Crescimento Transformador beta/administração & dosagem , Animais , Proteína Morfogenética Óssea 2/farmacologia , Fosfatos de Cálcio/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Nanofibras/química , Nanofibras/ultraestrutura , Osteogênese/efeitos dos fármacos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Engenharia Tecidual/métodos , Fator de Crescimento Transformador beta/farmacologia
14.
BMC Musculoskelet Disord ; 15: 319, 2014 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-25262001

RESUMO

BACKGROUND: The precise etiology of knee osteoarthritis (KOA) pain remains highly controversial and there is no known effective treatment. Due to the known and suggested effects of neuropeptide Y (NPY) on pain, we have sought to investigate the relationship between the concentration of NPY in synovial fluid of knee, pain of KOA, and structural severity of KOA. METHODS: One hundred KOA patients and twenty healthy participants (control group) were recruited. The pain and the radiographic grade of KOA were assessed separately by Hideo Watanabe's pain score and Tomihisa Koshino's scoring system. Synovial fluid of knee from all participants was collected with arthrocentesis. Radioimmunoassay was used to examine the concentration of NPY in synovial fluid of knee. RESULTS: Concentrations of NPY in synovial fluid were significantly higher in KOA patients (124.7 ± 33.4 pg/mL) compared with controls (64.8 ± 26.3 pg/mL) (p = 0.0297). According to Hideo Watanabe's pain score, 100 KOA patients were divided into 5 subgroups: no pain (n = 12), mild pain (n = 25), moderate pain (n = 37), strong pain (n = 19) and severe pain (n = 7). Within the KOA group, significantly higher concentrations of NPY were found in each subgroup as pain intensified (no pain 81.4 ± 11.7 pg/mL, mild pain 99.1 ± 23.2 pg/mL, moderate pain 119.9 ± 31.5 pg/mL, strong pain 171.2 ± 37.3 pg/mL and severe pain 197.3 ± 41.9 pg/mL). Meanwhile, according to Tomihisa Koshino's scoring system, 100 KOA patients were divided into 3 subgroups: early stage (n = 30), middle stage (n = 53), advanced stage (n = 17). Concentrations of NPY in middle and advanced stage groups of KOA patients were significant higher than early stage group of KOA patients (early stage 96.4 ± 27.1 pg/mL, middle stage 153.3 ± 16.9 pg/mL, advanced stage 149.5 ± 36.7 pg/mL) (p = 0.0163, p = 0.0352). Concentrations of NPY in advanced stage group of KOA patients has no significant difference compare with middle stage group of KOA patients (p = 0. 2175). CONCLUSIONS: This study demonstrated the presence and variation of concentrations of NPY in the KOA joint fluid, suggesting a role for NPY as a putative regulator of pain transmission and perception in KOA pain.


Assuntos
Neuropeptídeo Y/metabolismo , Osteoartrite do Joelho/metabolismo , Medição da Dor/métodos , Dor/metabolismo , Líquido Sinovial/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico , Dor/diagnóstico
15.
Int Orthop ; 38(5): 973-81, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24566992

RESUMO

PURPOSE: The tibial drill-guide angle in anterior cruciate ligament (ACL) reconstruction influences the tunnel placement and graft-tunnel force, and is potentially associated with post-operative tunnel widening. This study aimed to examine the effect of the drill-guide angle on the stress redistribution at the tibial tunnel aperture after anatomic single-bundle ACL reconstruction. METHODS: A validated finite element model of human knee joint was used. The tibial tunnel with drill-guide angle ranging from 30° to 75° was investigated. The post-operative stress redistribution in tibia under the compressive, valgus, rotational and complex loadings was analysed. RESULTS: Compressive loading played a leading role on the stress redistribution at intra-articular tibial tunnel aperture. After ACL reconstruction, stress concentration occurred in the anterior and posterior regions of tunnel aperture while stress reduction occurred in the lateral and posteromedial regions under the compressive loading. Stress redistribution was partially alleviated by using the drill-guide angle ranging from 55° to 65°. CONCLUSIONS: The present study quantified the effect of bone tunnel drill-guide angle on the post-operative stress redistribution. This phenomenon potentially contributed to tunnel widening. A tunnel drill-guide angle ranging from 55° to 65° was proposed based on the biomechanical rationale. It could serve as a helpful surgical guide for ACL reconstruction.


Assuntos
Reconstrução do Ligamento Cruzado Anterior/métodos , Tíbia/cirurgia , Adulto , Fenômenos Biomecânicos , Humanos , Masculino , Estresse Mecânico
16.
Mater Sci Eng C Mater Biol Appl ; 33(8): 5100-4, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24094231

RESUMO

Strontium (Sr) has become more attractive for orthopaedic applications as they can simultaneously stimulate bone formation and prevent bone loss. A Sr-containing bioactive bone cement (Sr-BC) has been designed to fix osteoporotic bone fracture. Sr is a trace element, so the safety of containing Sr is concerned when Sr-BC is implanted in human body. The preclinical assessment of biocompatibility of Sr-BC was conducted according to ISO 10993 standards. MTT assay showed that this bioactive bone cement was non-toxic to mouse fibroblasts, and it met the basic requirement for the orthopaedic implant. The three independent genetic toxicity studies including Ames, chromosome aberration and bone marrow micronucleus assays demonstrated absence of genotoxic components in Sr-BC, which reassured the safety concerns of this novel bone cement. The muscle implantation results in present study were also encouraging. The acute inflammation around the cement was observed at 1 week post-implantation; however, no significant difference was observed between control and Sr-BC groups. These responses may be attributed to the presence of the foreign body, but the tissue healed after 12 weeks implantation. In summary, the above preclinical results provide additional assurance for the safety of this implant. Sr-BC can be used as a potential alternative to the traditional bone cement.


Assuntos
Cimentos para Ossos/química , Estrôncio/química , Animais , Cimentos para Ossos/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Aberrações Cromossômicas , Cricetinae , Fibroblastos/citologia , Fibroblastos/metabolismo , Teste de Materiais , Camundongos , Músculo Esquelético/fisiologia , Próteses e Implantes , Coelhos
17.
Nat Med ; 19(6): 704-12, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23685840

RESUMO

Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for the condition because of limited understanding of its pathogenesis. We show that transforming growth factor ß1 (TGF-ß1) is activated in subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) mouse model of osteoarthritis. TGF-ß1 concentrations are also high in subchondral bone from humans with osteoarthritis. High concentrations of TGF-ß1 induced formation of nestin-positive mesenchymal stem cell (MSC) clusters, leading to formation of marrow osteoid islets accompanied by high levels of angiogenesis. We found that transgenic expression of active TGF-ß1 in osteoblastic cells induced osteoarthritis, whereas inhibition of TGF-ß activity in subchondral bone attenuated the degeneration of articular cartilage. In particular, knockout of the TGF-ß type II receptor (TßRII) in nestin-positive MSCs led to less development of osteoarthritis relative to wild-type mice after ACLT. Thus, high concentrations of active TGF-ß1 in subchondral bone seem to initiate the pathological changes of osteoarthritis, and inhibition of this process could be a potential therapeutic approach to treating this disease.


Assuntos
Osso e Ossos/metabolismo , Células-Tronco Mesenquimais/fisiologia , Osteoartrite/terapia , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Animais , Cartilagem/patologia , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Ratos , Ratos Endogâmicos Lew , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/análise , Fator de Crescimento Transformador beta/fisiologia
18.
Ann Biomed Eng ; 40(7): 1554-67, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22302321

RESUMO

Bone tunnel enlargement is a common effect associated with knee laxity after anterior cruciate ligament(ACL) reconstruction. Nevertheless, its exact pathomechanism remains controversial. One of the possible reasons could be bone remodeling due to tunnel creation, which changes the stress environment in the joint. The present study aims to characterize the deteriorated stress distribution on the articular surface, which is due to tunnel creation after single-bundle or double-bundle ACL reconstruction. The stress distributions in the knee following ACL reconstruction under the compression, rotation, and valgus torques were calculated using a validated three-dimensional finite element(FE) model. The results indicate that, (a) under compression,von Mises stress is decreased at lateral and posteromedial regions of single/anteromedial (AM) tunnel, whereas it is increased at anterior region of single/AM tunnel in tibial subchondral bone; (b) the concentration of tensile stress is transferred from the articular surface to the location of graft fixation, and tensile stress in subchondral plate is decreased after ACL reconstruction; (c) severe stress concentration occurs between AM and posterolateral tunnels following the double-bundle reconstruction, which may contribute to the tunnel communication after surgery. In summary, the present study affirms that the deterioration of stress distribution occurs near the articular surface, which may cause the collapse of the tunnel wall, and lead to tunnel enlargement.The present study provides an insight into the effect of tunnel creation on articular stress deterioration after single-bundle or double-bundle ACL reconstruction. These findings provide knowledge on the effect of tunnel enlargement after ACL reconstruction in the long term.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior/fisiopatologia , Modelos Biológicos , Estresse Fisiológico , Adulto , Ligamento Cruzado Anterior/diagnóstico por imagem , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior , Força Compressiva , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Radiografia , Tíbia/diagnóstico por imagem , Tíbia/fisiopatologia
19.
J Spinal Disord Tech ; 24(6): E49-56, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21685804

RESUMO

STUDY DESIGN: An in vitro biomechanical cadaver study. OBJECTIVES: To evaluate the pull-out strength after 5000 cyclic loading among 4 revision techniques for the loosened iliac screw using corticocancellous bone, longer screw, traditional cement augmentation, and boring cement augmentation. SUMMARY OF BACKGROUND DATA: Iliac screw loosening is still a clinical problem for lumbo-iliac fusion. Although many revision techniques using corticocancellous bone, larger screw, and polymethylmethacrylate (PMMA) augmentation were applied in repairing pedicle screw loosening, their biomechanical effects on the loosened iliac screw remain undetermined. METHODS: Eight fresh human cadaver pelvises with the bone mineral density values ranging from 0.83 to 0.97 g/cm were adopted in this study. After testing the primary screw of 7.5 mm diameter and 70 mm length, 4 revision techniques were sequentially established and tested on the same pelvis as follows: corticocancellous bone, longer screw with 100 mm length, traditional PMMA augmentation, and boring PMMA augmentation. The difference of the boring technique from traditional PMMA augmentation is that PMMA was injected into the screw tract through 3 boring holes of outer cortical shell without removing the screw. On an MTS machine, after 5000 cyclic compressive loading of -200∼-500 N to the screw head, axial maximum pull-out strengths of the 5 screws were measured and analyzed. RESULTS: The pull-out strengths of the primary screw and 4 revised screws with corticocancellous bone, longer screw and traditional and boring PMMA augmentation were 1167 N, 361 N, 854 N, 1954 N, and 1820 N, respectively. Although longer screw method obtained significantly higher pull-out strength than corticocancellous bone (P<0.05), the revised screws using these 2 techniques exhibited notably lower pull-out strength than the primary screw and 2 PMMA-augmented screws (P<0.05). Either traditional or boring PMMA screw showed obviously higher pull-out strength than the primary screw (P<0.05); however, no significant difference of pull-out strength was detected between the 2 PMMA screws (P>0.05). CONCLUSIONS: Wadding corticocancellous bone and increasing screw length failed to provide sufficient anchoring strength for a loosened iliac screw; however, both traditional and boring PMMA-augmented techniques could effectively increase the fixation strength. On the basis of the viewpoint of minimal invasion, the boring PMMA augmentation may serve as a suitable salvage technique for iliac screw loosening.


Assuntos
Cimentos para Ossos , Parafusos Ósseos , Ílio/cirurgia , Vértebras Lombares/cirurgia , Falha de Prótese , Idoso , Fenômenos Biomecânicos , Feminino , Humanos , Fixadores Internos , Masculino , Pessoa de Meia-Idade , Reoperação
20.
Clin Biomech (Bristol, Avon) ; 26(6): 556-61, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21345556

RESUMO

BACKGROUND: Iliac screw loosening has been a clinical problem in the lumbo-pelvic reconstruction. Although iliac screws are commonly inserted into either upper or lower iliac column, the biomechanical effects of the two fixations and their revision techniques with bone cement remain undetermined. The purpose of this study was to compare the anchoring strengths of the upper and lower iliac screws with and without cement augmentation. METHODS: 5 pairs of formalin fixed cadaveric ilia with the bone mineral density values ranged from 0.82 to 0.97 g/cm(2) were adopted in this study. Using screws with 70-mm length and 7.5-mm diameter, 2 conventional iliac screw fixations and their revision techniques with cement augmentation were sequentially established and tested on the same ilium as follows: upper screw, upper cement screw, lower screw, and lower cement screw. Following 2000 cyclic compressive loading of -300 N to -100 N to the screw on a material testing machine, the maximum pull-out strengths were measured and analyzed. FINDINGS: The average pull-out strengths of upper, upper cement, lower, and lower cement screws were 964 N, 1462 N, 1537 N, and 1964 N, respectively. The lower screw showed significantly higher pull-out strength than the upper one (P=0.008). The cement augmentation notably increased the pull-out strengths of both upper and lower screws. The positive correlation between pull-out strength and bone mineral density value was obtained for the 4 fixations. INTERPRETATION: The lower iliac screw technique should be the preferred choice in lumbo-pelvic stabilization surgery; cement augmentation may serve as a useful salvage technique for iliac screw loosening; preoperative evaluation of bone quality is crucial for predicting fixation strength of iliac screw.


Assuntos
Cimentos para Ossos/química , Parafusos Ósseos , Idoso , Fenômenos Biomecânicos , Densidade Óssea , Feminino , Humanos , Ílio/química , Masculino , Pessoa de Meia-Idade , Ossos Pélvicos/patologia , Pelve/patologia , Estresse Mecânico
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