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1.
Orthop Traumatol Surg Res ; 108(4): 103273, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35331920

RESUMO

INTRODUCTION: Pelvic internal fixation has become a popular method for treatment of unstable pelvic ring injuries. Although successful, one complication is femoral nerve palsy from compression of the connecting rod. In light of this complication, this study was designed to evaluate sagittal inclinations of the rod and the feasibility of using a rod with a constant curvature. HYPOTHESIS: It is hypothesized that that there is a connection between the sagittal inclination of the rod and the rod to bone distance, as well as single rod can be contoured with a constant curvature to be used in the majority of all patients. METHODS: Three dimensional models of pelvis CTs from a single level 1 trauma center were created and imported into a program where software superimposed a pre-contoured rod in the sagittal planes upon the pelvic slices. The sagittal inclination was deemed acceptable is no interference occurred between the area of compression risk and the rod. For each pelvis and considered sagittal rod inclination, the rod radius of curvature (ROC), minimal rod to bone distance (RTB) and transverse inclinations (φL and φR) were measured at which the pedicle screws should be inserted to follow the direction of the smallest RTB. RESULTS: The sagittal inclinations feasible for all subjects were between 15° to 30°. In this sagittal range, the average RTB varied in values ranging from 4.0±0.9mm to 25.4±11.4mm (p<0.01). Only 46% of subjects allowed a rod with constant curvature. DISCUSSION AND CONCLUSION: Our study found that a rod to bone distance of 15mm was not safe for all models. As well, many subject models did not allow placement of pre-contoured rod. Patient specific templating of pelvic subcutaneous internal fixation is strictly needed to limit complications. LEVEL OF EVIDENCE: VII; Basic Science.


Assuntos
Fraturas Ósseas , Parafusos Pediculares , Ossos Pélvicos , Traumatismos dos Nervos Periféricos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Humanos , Ossos Pélvicos/lesões , Ossos Pélvicos/cirurgia , Pelve
2.
J Funct Morphol Kinesiol ; 6(3)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34564190

RESUMO

Screw stripping during bone fixation is a common occurrence during operations that results in decreased holding capacity and bone healing. We aimed to evaluate the rescue of the stripped screw site using screws of different dimensions. Five screw configurations were tested on cadaveric specimens for pull-out strength (POS). The configurations included a control screw tightened without stripping, a configuration voluntarily stripped and left in place, and three more configurations in which the stripped screws were replaced by a different screw with either increased overall length, diameter, or thread length. Each configuration was tested five times, with each screw tested once. The POS of the control screw, measured to be 153.6 ± 27 N, was higher than the POS measured after stripping and leaving the screw in place (57.1 ± 18 N, p = 0.001). The replacement of the stripped screw resulted in a POS of 158.4 ± 64 N for the screw of larger diameter, while the screws of the same diameter but increased length or those with extended thread length yielded POS values of 138.4 ± 42 and 185.7 ± 48 N, respectively. Screw stripping is a frequent intraoperative complication that, according to our findings, cannot be addressed by leaving the screw in place. The holding capacity of a stripped screw implanted in cancellous bone can successfully be restored with a different screw of either larger diameter, longer length, or extended thread length.

3.
JSES Int ; 5(3): 549-553, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34136869

RESUMO

BACKGROUND: The ulnar collateral ligament (UCL) complex of the elbow plays a primary role in valgus and posteromedial stability of the elbow. The anterior oblique ligament (AOL) of the UCL is believed to provide the majority of resistance to external forces on the medial elbow. The transverse ligament (TL) of the UCL is generally thought to have minimal contribution to the elbow's overall stability. However, recent studies have suggested a more significant role for the TL. The primary aim of this study was to identify the TL's contribution to the stability of the elbow joint in determining the joint stiffness and neutral zone variation in internal rotation. METHODS: Twelve cadaveric elbows, set at a 90° flexion angle, were tested by applying an internal rotational force on the humerus to generate a medial opening torque at the level of the elbow. The specimens were preconditioned with 10 cycles of humeral internal rotation with sinusoidal torque ranging from 0 to 5 Nm. Elbow stiffness measures and joint neutral zone were first evaluated in its integrity during a final ramp loading. The test was subsequently repeated after cutting the TL at 33%, 66%, and 100% followed by the AOL in the same fashion. RESULTS: The native UCL complex joint stiffness to internal rotation measured 1.52 ± 0.51 Nm/°. The first observable change occurred with 33% sectioning of the AOL, with further sectioning of the AOL minimizing the joint stiffness to 1.26 ± 0.32 Nm/° (P = .004). A 33% resection of the TL found an initial neutral zone variation of 0.376 ± 0.23° that increased to 0.771 ± 0.41° (P < .01) at full resection. These values were marginal when compared with the full resection of the AOL for which we have found 3.69 ± 1.65° (P < .01). CONCLUSION: The TL had no contribution to internal rotation elbow joint stiffness at a flexion angle of 90°. However, sequential sectioning of the TL was found to significantly increase the joint neutral zone when compared with the native cadaveric elbow at a flexion angle of 90°. This provides evidence toward the TL having some form of contribution to the elbow's overall stability.

4.
World J Orthop ; 12(5): 254-269, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34055584

RESUMO

Isolated distal fibula fractures represent the majority of ankle fractures. These fractures are often the result of a low-energy trauma with external rotation and supination mechanism. Diagnosis is based on clinical signs and radiographic exam. Stress X-rays have a role in detecting associated mortise instability. Management depends on fracture type, displacement and associated ankle instability. For simple, minimally displaced fractures without ankle instability, conservative treatment leads to excellent results. Conservative treatment must also be considered in overaged unhealthy patients, even in unstable fractures. Surgical treatment is indicated when fracture or ankle instability are present, with several techniques described. Outcome is excellent in most cases. Complications regarding wound healing are frequent, especially with plate fixation, whereas other complications are uncommon.

5.
JAMA Surg ; 156(5): e207259, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33760010

RESUMO

Importance: Despite the widespread use of systemic antibiotics to prevent infections in surgically treated patients with fracture, high rates of surgical site infection persist. Objective: To examine the effect of intrawound vancomycin powder in reducing deep surgical site infections. Design, Setting, and Participants: This open-label randomized clinical trial enrolled adult patients with an operatively treated tibial plateau or pilon fracture who met the criteria for a high risk of infection from January 1, 2015, through June 30, 2017, with 12 months of follow-up (final follow-up assessments completed in April 2018) at 36 US trauma centers. Interventions: A standard infection prevention protocol with (n = 481) or without (n = 499) 1000 mg of intrawound vancomycin powder. Main Outcomes and Measures: The primary outcome was a deep surgical site infection within 182 days of definitive fracture fixation. A post hoc comparison assessed the treatment effect on gram-positive and gram-negative-only infections. Other secondary outcomes included superficial surgical site infection, nonunion, and wound dehiscence. Results: The analysis included 980 patients (mean [SD] age, 45.7 [13.7] years; 617 [63.0%] male) with 91% of the expected person-time of follow-up for the primary outcome. Within 182 days, deep surgical site infection was observed in 29 of 481 patients in the treatment group and 46 of 499 patients in the control group. The time-to-event estimated probability of deep infection by 182 days was 6.4% in the treatment group and 9.8% in the control group (risk difference, -3.4%; 95% CI, -6.9% to 0.1%; P = .06). A post hoc analysis of the effect of treatment on gram-positive (risk difference, -3.7%; 95% CI, -6.7% to -0.8%; P = .02) and gram-negative-only (risk difference, 0.3%; 95% CI, -1.6% to 2.1%; P = .78) infections found that the effect of vancomycin powder was a result of its reduction in gram-positive infections. Conclusions and Relevance: Among patients with operatively treated tibial articular fractures at a high risk of infection, intrawound vancomycin powder at the time of definitive fracture fixation reduced the risk of a gram-positive deep surgical site infection, consistent with the activity of vancomycin. Trial Registration: ClinicalTrials.gov Identifier: NCT02227446.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Negativas/prevenção & controle , Infecções por Bactérias Gram-Positivas/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle , Fraturas da Tíbia/cirurgia , Vancomicina/uso terapêutico , Adulto , Antibacterianos/administração & dosagem , Método Duplo-Cego , Feminino , Fixação Interna de Fraturas/efeitos adversos , Fraturas não Consolidadas/etiologia , Humanos , Fraturas Intra-Articulares/cirurgia , Masculino , Pessoa de Meia-Idade , Pós , Probabilidade , Estudos Prospectivos , Deiscência da Ferida Operatória/etiologia , Infecção da Ferida Cirúrgica/etiologia , Fatores de Tempo , Vancomicina/administração & dosagem
7.
Emerg Radiol ; 28(3): 581-588, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33449260

RESUMO

PURPOSE: To evaluate the safety and image quality of extremity MR examinations performed with two MR conditional external fixators located in the MR bore. MATERIALS AND METHODS: Single-center retrospective study of a prospectively maintained imaging dataset that evaluated MR examinations of extremities in patients managed with external fixations instrumentation and imaged on a single 1.5T MR scanner. The fixation device was one of two MR-conditional instrumentation systems: DuPuy Synthes (aluminum, stainless steel, carbonium and Kevlar) or Dolphix temporary fixation system (PEEK-CA30). Safety events were recorded by the performing MR radiologic technologist. A study musculoskeletal radiologist assessed all sequences to evaluate for image quality, signal- and contrast-to-noise ratios (SNR/CNR), and injury patterns/findings. RESULTS: In the 13 men and 9 women with a mean age of 42 years (range 18 to 72 years), most patients (19/22 patients; 86%) were involved with trauma resulting in extremity injury requiring external fixation. MR examinations included 19 knee, 2 ankle, and 1 elbow examinations. There were no adverse safety events, heating that caused patient discomfort, fixation dislodgement/perturbment, or early termination of MR examinations. All examinations were of diagnostic quality. Fat-suppressed proton density sequences had significantly higher SNR and CNR compared to STIR (p = 0.01 to 0.04). The lower SNR of STIR and increased quality of fat-suppressed proton density during the study period led to the STIR sequence being dropped in standard MR protocol. CONCLUSION: MR of the extremity using the two study MR conditional external fixators within the MR bore is safe and feasible.


Assuntos
Fixadores Externos , Imageamento por Ressonância Magnética , Adolescente , Adulto , Idoso , Extremidades , Feminino , Fixação de Fratura , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
8.
J Funct Morphol Kinesiol ; 7(1)2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-35076530

RESUMO

Performing MR investigation on patients instrumented with external fixators is still controversial. The aim of this study is to evaluate the quality of MR imaging of the knee structures in the presence of bridging external fixators. Different cadaveric lower limbs were instrumented with the MR-conditional external fixators Hofmann III (Stryker, Kalamazoo, MI, USA), Large external Fixator (DePuy Synthes, Raynham, MA, USA), XtraFix (Zymmer, Warsaw, IN, USA) and a newer implant of Ketron Peek CA30 and ERGAL 7075 pins, Dolphix®, (Citieffe, Bologna, Italy). The specimens were MR scanned before and after the instrumentation. The images were subjectively judged by a pool of blinded radiologists and then quantitatively evaluated calculating signal intensity, signal to noise and contrast to noise in the five regions of interest. The area of distortion due to the presence of metallic pins was calculated. All the images were considered equally useful for diagnosis with no differences between devices (p > 0.05). Only few differences in the quantification of images have been detected between groups while the presence of metallic components was the main limit of the procedure. The mean length of the radius of the area of distortion of the pins were 53.17 ± 8.19 mm, 45.07 ± 4.33 mm, 17 ± 5.4 mm and 37.12 ± 10.17 mm per pins provided by Zimmer, Synthes, Citieffe and Stryker, respectively (p = 0.041). The implant of Ketron Peek CA30 and ERGAL 7075 pins showed the smallest distortion area.

9.
Eur J Orthop Surg Traumatol ; 30(7): 1163-1170, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32358714

RESUMO

INTRODUCTION: Pelvic external fixation using anterosuperior pins provides a quick method of stabilization without necessitating fluoroscopic guidance. Various locations, depths, and inclinations have been cited for external fixator pins; however, the existing literature lacks clear indications for the angular difference between pins. Thus, we aimed to determine the greatest degree of sagittal pin spanning angulation (SPSA) between two iliac crest pins and how intraosseous depth (ID) affects these angulations. MATERIALS AND METHODS: A newly developed computer algorithm produced cross sections of 3D pelvic reconstructions in the sagittal plane in 5° increments. Computer-generated pins with IDs of 60, 75, and 90 mm were positioned in 5° increments transversely. Pins were assessed for cortical containment to define values for SPSA and transverse pin spanning angulation (TPSA). RESULTS: A bimodal distribution revealed varying degrees of insertion frequency and SPSA, cranially and caudally. The caudal distribution exhibited greater cortical containment with larger values for SPSA and TPSA. The highest insertion frequency (85.7%) and largest SPSA (155°) were observed for the 60-mm ID. Increasing ID resulted in further bony penetration and smaller values for SPSA and TPSA. CONCLUSIONS: Expanding the degree of SPSA between inserted pins in anterosuperior pelvic external fixation can be challenging due to the thinning of the iliac wing, which affords a narrow corridor for intraosseous pin containment. An ID of 60 mm allows larger degrees of SPSA while maintaining higher rates of cortical pin containment when compared to pins with greater IDs.


Assuntos
Fixadores Externos , Ossos Pélvicos , Pinos Ortopédicos , Fixação de Fratura , Humanos , Ílio/diagnóstico por imagem , Ílio/cirurgia , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/cirurgia
10.
Orthop Traumatol Surg Res ; 106(7): 1405-1412, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32245692

RESUMO

INTRODUCTION: Temporary external fixation has been widely utilized in the stabilization of plateau fractures while waiting for an optimization of the soft tissue conditions before subsequent permanent internal fixation. Simultaneously, MRI is beneficial in the assessment of concomitant damage to ligaments and menisci so that these injuries could be promptly identified, and surgical planning executed at the time of definitive fixation of the bony injury. Increasing numbers of side-bars and pins have been previously suggested to increase frame rigidity, but at the same time, several studies have indicated the presence of MRI artifacts which may obscure key anatomical structures, even when MRI-compatible fixation devices are used. This study aims to identify, among six potential configurations, the construct that maximizes stability while most minimizing the number of MRI artifacts generated among different configurations commonly used. HYPOTHESIS: There is one or more configurations among the others that maximize stability while preserving a clinically acceptable level of MRI quality. MATERIAL AND METHODS: Six constructs were recreated on cadaveric specimens and identified by the disposition of the bars: H, Anterior, Flash, Hashtag, Rhomboid, and Diamond. Stage one evaluated the amount of artifact produced during MRI on instrumented cadaveric legs, as well as the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) at five specific regions of interest. Stage two assessed the amount of compressional and torsional stiffness of the configurations on bone surrogate models. RESULTS: Image artifacts were not detected within the knee joint for all considered constructs. In terms of SNR The H, Anterior, Hashtag, and Diamond configurations were not significantly different from their control (p>0.366) while the others were significantly different (p<0.03). The values of CNR found for the H and Hashtag configurations were not significantly different from their controls (p>0.07) while the remaining configurations were significantly different (p<0.03). In compression, the H and Diamond configurations had similar stiffness (p=0.468) of 35.78N/mm and 31.44N/mm, respectively, and were stiffer than the other configurations. In torsion, the constructs have shown different stiffness (p<0.001) with a minimum value of 0.66 Nm/deg for the Rhomboid configuration, which was significantly less stiff than the Anterior configuration (1.20 Nm/deg [p<0.001]). There was no difference between the Diamond and H configurations (p=0.177) or between them and the Hashtag configuration (p=0.215). DISCUSSION: An external fixator construct directly bridging the femur and tibia without interconnections is the most stable and produces MRI scans without image artifacts that would interfere with diagnostic quality. LEVEL OF EVIDENCE: V, basic science study, diagnostic imaging and mechanical testing.


Assuntos
Fixação de Fratura , Fraturas da Tíbia , Fenômenos Biomecânicos , Pinos Ortopédicos , Fixadores Externos , Humanos , Imageamento por Ressonância Magnética , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia
11.
Clin Biomech (Bristol, Avon) ; 72: 130-135, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31864036

RESUMO

BACKGROUND: Pull-out strength is a critical parameter to judge screw fixation in orthopaedic implants. However, the insertion torque is the main feeling in the hand of a surgeon relating to the strength of synthesis. The correlation between pull-out strength and torque is not completely understood. This creates uncertainty about the key-question: Should the torque be considered a valid parameter to judge the quality of fixation? METHODS: Using the ASTM F543 as reference, three screws differing only in pitch (1.5, 2.1, 2.8 mm pitches) were tested in three foam-block densities (10, 15, and 20 pcf). The correlation was investigated by assessing the role of density and screw geometry. FINDINGS: Torque was related to pull-out strength in all configurations (R = 0.979, P = 0.000). No difference in pull-out strength was found when screws were tightened to a range of 71.6%, SD = 7.6, of torque to fail (P > 0.05). Torque and pull-out strength were stratified according to density that influenced the two parameters up to 524% (P < 0.000). Pitch determined pull-out strength up to 33% (P < 0.000) while the 2.1 mm screw pitch showed the highest pull-out strength and torque in all configurations. INTERPRETATION: Insertion torque was demonstrated to be a valid parameter to judge the quality of bone under fixation and therefore, the strength of the synthesis. Surgeons should not tighten the screws to values approaching torque to fail to obtain the highest pull-out strength. Density was the main factor influencing pull-out strength and torque. Pitch is another parameter deciding screw holding capacity.


Assuntos
Densidade Óssea , Parafusos Ósseos , Torque , Fenômenos Biomecânicos , Humanos
12.
J Orthop Res ; 37(8): 1790-1797, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31042305

RESUMO

In pelvic fractures, dysfunction of the pelvic ring is often stabilized with supra-acetabular pin insertion. In existing literature, there are heterogeneous indications on proper pins selection and inclinations. Therefore, this study aimed to quantify the narrowing of safe pin corridors in the transverse and sagittal planes with increments of intraosseous screw depths. A computer algorithm created cross-sections over three-dimensional pelvic reconstructions at sagittal inclinations from 45° cranial to 45° caudal in 5° increments. Templates of screw depths spanning 60-120 mm in 15 mm increments were disposed in the transverse plane from 45° medial to 45° lateral. Each intraosseous screw depth and transverse angle were evaluated for intraosseous containment to evaluate ranges narrowing with increasing screw depths. The 60-mm depth resulted in the largest sagittal range (60.9° ± 6.9°) and transverse range (27.5° ± 4.1°) at 30° caudal. Increasing depths by 15 mm resulted in ranges being significantly different from one another (p < 0.01). The sagittal plane of 20° cranial had the highest frequency of insertion for all depths, while transverse ranges were narrowed (p < 0.01). Bisecting angles were similar for sagittal planes 20° cranial to 30° caudal with an average of 27.9° ± 1.2° (p ≥ 0.115). In conclusion, while 60 mm depths can be inserted with the highest discretion, 15 mm increments in depth significantly reduce safe ranges. Screws depths above 90 mm have low frequencies of insertion, should be inserted more cranially and must be considered prone to breaching. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1790-1797, 2019.


Assuntos
Parafusos Ósseos , Fixação Interna de Fraturas/instrumentação , Fraturas Ósseas/cirurgia , Ossos Pélvicos/lesões , Adulto , Fraturas Ósseas/diagnóstico por imagem , Humanos , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/cirurgia , Estudos Retrospectivos
13.
Exp Mol Med ; 50(9): 1-10, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30242147

RESUMO

Placenta-derived mesenchymal stromal cells (PMSCs) provide a promising cell source for tissue regeneration. However, rapid induction of PMSC chondrogenic differentiation during therapeutic transplantation remains extremely challenging. Here we undertook a study to determine if Notch inhibition by soluble Jagged1 (JAG1) peptides could be utilized to accelerate PMSC-induced cartilage regeneration in a mouse post-traumatic osteoarthritis (PTOA) model. Our results showed that treatment of PMSCs with soluble JAG1 significantly enhanced chondrogenesis in culture as shown by increased alcian blue staining and decreased Notch target Hes1 expression when compared to those in lgG-treated control cells. Importantly, significantly enhanced cartilage formation and decreased joint inflammation were observed when JAG1-treated PMSCs were injected into mouse PTOA knee joints. Finally, in vivo cell tracing showed that more JAG1-treated PMSCs remained in knee joint tissues and that JAG1-treated PMSCs exhibited greater PMSC chondrogenic differentiation than lgG-treated control PMSCs at 4 weeks after injection. These data indicate that transient Notch inhibition by soluble JAG1 could be used to enhance PMSC survival and chondrogenic differentiation, thereby increasing the therapeutic potential of PMSCs for cartilage regeneration.


Assuntos
Cartilagem/patologia , Proteína Jagged-1/metabolismo , Células-Tronco Mesenquimais/metabolismo , Cicatrização , Adipogenia , Animais , Apoptose , Sobrevivência Celular , Células Cultivadas , Condrogênese , Feminino , Humanos , Inflamação/patologia , Articulação do Joelho/patologia , Ligantes , Camundongos , Osteoartrite/patologia , Osteogênese , Placenta/citologia , Gravidez
14.
J Cell Physiol ; 233(10): 6921-6928, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29693255

RESUMO

Notch activator Jagged1 (JAG1) plays a critical role in the regulation of osteoblast differentiation and bone metabolism. In this study, JAG1-induced osteoblast proliferation, differentiation, and mineralization has been analyzed in primary osteoblasts for up to 7 days. Alkaline phosphatase and Alizarin red staining showed an enhanced osteoblast maturation and mineralization in JAG1 treated cells, as well as higher mRNA levels of late osteoblast differentiation markers. In contrast, Notch inhibitor DAPT and deletion of Runx2 totally blocked JAG1 effects on osteoblast mineralization. Flow cytometry data further showed a significantly higher cell proliferation in early stages of culture at day 3, and lower levels of osteoblast apoptosis in late stages of culture at day 7. More importantly, activation of anti-apoptotic factor BCL-2 was enhanced, while pro-apoptotic factor Caspase3 was reduced in JAG1 treated osteoblasts. Therefore, we conclude that cell mineralization is enhanced via anti-apoptotic actions of Notch signaling within the osteoblast cells.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proteína Jagged-1/farmacologia , Osteoblastos/citologia , Osteogênese/efeitos dos fármacos , Receptores Notch/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Osteoblastos/metabolismo , Ratos , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Sci Rep ; 7(1): 7982, 2017 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-28801687

RESUMO

To determine whether cell sheets generated with long-term passaged (P10) aging human mesenchymal stromal cells (MSCs) could be used for bone tissue regeneration as tissue engineered periosteum in a femoral allograft mouse model similar to fresh passaged (P3) young MSCs. At 3 weeks after transplantation of MSC sheets, results showed more bony callus formed between allograft and host bone ends in both young P3 MSC and aged P10 MSC sheet-wrapped groups when compared to allograft alone. At 6 weeks, while both MSC sheet-wrapped allografts showed more bony callus formation when compared to allograft alone groups, the bony callus size in aged P10 MSC sheet groups was significantly less than young P3 MSC sheet groups. Biomechanical testing confirmed that P3 MSC sheet-grafted femurs had the highest biomechanical strength in the three groups. Histology sections showed that the area of the chondriod callus in the aged P10 MSC sheet groups was significantly larger than in P3 MSC sheet groups. Finally, a significant increase of chondro-osteoclast activity was observed in the P3 MSC sheet-grafted femur. Our data demonstrates that extensive long-term culture-induced MSC aging impaired their osteogenic ability and subsequent bony callus formation, and could be used to induce cartilaginous callus formation.


Assuntos
Regeneração Óssea , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Idoso , Animais , Células Cultivadas , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Osteogênese , Transplante Homólogo/métodos
16.
Sci Rep ; 7(1): 7002, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28765584

RESUMO

Oleanolic acid (OA), a pentacyclic triterpenoid, has been shown to modulate multiple signaling pathways in a variety of cell linages. But the mechanisms underlying OA-mediated mesenchymal stromal cell (MSC) osteogenic differentiation are not known. In this study, we examined effects of OA on cell viability, osteogenic differentiation in MSCs, and the involvement of Notch and BMP signaling. OA induced bone marrow derived MSC differentiation towards osteoprogenitor cells and inhibited Notch signaling in a dose dependent manner. Constitutive activation of Notch signaling fully blocked OA induced MSC osteogenic differentiation. The expression level of early osteogenic marker genes, ALP, Runx2, and type I collagen, which play a critical role in MSC to osteoblast transition and servers as a downstream target of BMP signaling, was significantly induced by OA. Furthermore, BMP2 mediated MSC osteogenic differentiation was significantly enhance by OA treatment, indicating a synergistic effect between BMP2 and OA. Our results suggest that OA is a promising bioactive agent for bone tissue regeneration, and inhibition of Notch signaling is required for its osteogenic effects on MSCs.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Ácido Oleanólico/metabolismo , Osteogênese/efeitos dos fármacos , Receptores Notch/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Perfilação da Expressão Gênica , Humanos
17.
Cell Death Dis ; 8(2): e2595, 2017 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-28151468

RESUMO

Our previous studies have confirmed the therapeutic effects of mesenchymal stem cell (MSC) monolayer sheet transplantation on allograft repair. A limiting factor in their application is the loss of MSC multi-potency as a result of high density sheet culture-induced senescence. In the study reported in this article, we tested whether Notch activation could be used to prevent or delay sheet culture-induced cell aging. Our results showed that, during in vitro long-term (5-day) cell sheet culture, MSCs progressively lose their progenitor characteristics. In contrast, Notch activation by Jagged1 in MSC sheet culture showed reduced cellular senescence and cell cycle arrest compared with control MSCs without Notch activation. Importantly, knockdown of Notch target gene Hes1 totally blocked the inhibition effect of Jagged1 on cellular senescence. Finally, the in vivo allograft transplantation data showed a significant enhanced callus formation and biomechanical properties in Notch activation cultured long-term sheet groups when compared with long-term cultured sheet without Notch activation. Our results suggest that Notch activation by Jagged1 could be used to overcome the stem cell aging caused by high density sheet culture, thereby increasing the therapeutic potential of MSC sheets for tissue regeneration.


Assuntos
Senescência Celular/fisiologia , Células-Tronco Mesenquimais/metabolismo , Osteogênese/fisiologia , Receptores Notch/metabolismo , Animais , Pontos de Checagem do Ciclo Celular/fisiologia , Células Cultivadas , Humanos , Proteína Jagged-1/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Regeneração/fisiologia , Fatores de Transcrição HES-1/metabolismo
18.
Sci Rep ; 6: 25594, 2016 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-27146698

RESUMO

Cell cycle regulation is critical for chondrocyte differentiation and hypertrophy. Recently we identified the Notch signaling pathway as an important regulator of chondrocyte proliferation and differentiation during mouse cartilage development. To investigate the underlying mechanisms, we assessed the role for Notch signaling regulation of the cell cycle during chondrocyte differentiation. Real-time RT-PCR data showed that over-expression of the Notch Intracellular Domain (NICD) significantly induced the expression of p57, a cell cycle inhibitor, in chondrocytes. Flow cytometric analyses further confirmed that over-expression of NICD in chondrocytes enhances the G0/G1 cell cycle transition and cell cycle arrest. In contrast, treatment of chondrocytes with the Notch inhibitor, DAPT, decreased both endogenous and BMP2-induced SMAD 1/5/8 phosphorylation and knockdown of SMAD 1/5/8 impaired NICD-induced chondrocyte differentiation and p57 expression. Co-immunoprecipitation using p-SMAD 1/5/8 and NICD antibodies further showed a strong interaction of these proteins during chondrocyte maturation. Finally, RT-PCR and Western blot results revealed a significant reduction in the expression of the SMAD-related phosphatase, PPM1A, following NICD over-expression. Taken together, our results demonstrate that Notch signaling induces cell cycle arrest and thereby initiates chondrocyte hypertrophy via BMP/SMAD-mediated up-regulation of p57.


Assuntos
Proteína Morfogenética Óssea 2/genética , Pontos de Checagem do Ciclo Celular/genética , Condrócitos/metabolismo , Receptores Notch/genética , Animais , Proteína Morfogenética Óssea 2/metabolismo , Diferenciação Celular/genética , Crescimento Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Condrócitos/patologia , Inibidor de Quinase Dependente de Ciclina p57/genética , Inibidor de Quinase Dependente de Ciclina p57/metabolismo , Regulação da Expressão Gênica , Camundongos , Fosforilação , Interferência de RNA , Receptores Notch/metabolismo , Transdução de Sinais/genética , Proteínas Smad Reguladas por Receptor/genética , Proteínas Smad Reguladas por Receptor/metabolismo
19.
Rev. bras. ortop ; 47(2): 169-172, mar.-abr. 2012. ilus, tab
Artigo em Português | LILACS | ID: lil-643093

RESUMO

OBJETIVO: A haste intramedular (HIM) é o padrão ouro no tratamento das fraturas diafisárias da tíbia. Uma das complicações frequentes é a dor no joelho após o procedimento. MÉTODOS: Vias alternativas, como a suprapatelar para a introdução da haste como opção para evitar a dor no joelho no período pós-operatório tardio, têm sido estudadas. A questão é se nesta nova via ocorre alguma lesão às estruturas intra-articulares do joelho. RESULTADOS: Este estudo analisa a via suprapatelar e o risco para as estruturas adjacentes através da sua reprodução em 10 joelhos de cinco cadáveres. CONCLUSÃO: Foi visto facilidade para a localização do ponto de entrada por esta via, lesando apenas a gordura de Hoffa. Em três dos nossos casos houve lesão da superfície condral, sendo um obstáculo de difícil transposição e indicando necessidade de fabricação de material específico para minimizar a lesão das estruturas intra-articulares por essa via.


OBJECTIVE: Intramedullary nails are the gold standard for treating tibial shaft fractures. Knee pain is a frequent complication after the procedure. Alternative routes such as the suprapatellar approach for nail insertion are seen as an option for avoiding late postoperative knee pain. The question is whether this approach might give rise to any injury to intra-articular structures of the knee. METHODS: This study analyzed the suprapatellar approach and the risk to adjacent structures by reproducing it in 10 knees of five cadavers. RESULTS: This approach was seen to make it easy to locate the entry point, with lesions only occurring in the Hoffa fat. In three of our cases, there were lesions of the chondral surface, which is an obstacle that is difficult to overcome. CONCLUSION: There is a need to develop specific material to minimize injury to intra-articular structures when using this route.


Assuntos
Humanos , Cadáver , Fixação Intramedular de Fraturas , Procedimentos Ortopédicos , Fraturas da Tíbia
20.
Rev Bras Ortop ; 47(2): 169-72, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-27042617

RESUMO

OBJECTIVE: Intramedullary nails are the gold standard for treating tibial shaft fractures. Knee pain is a frequent complication after the procedure. Alternative routes such as the suprapatellar approach for nail insertion are seen as an option for avoiding late postoperative knee pain. The question is whether this approach might give rise to any injury to intra-articular structures of the knee. METHODS: This study analyzed the suprapatellar approach and the risk to adjacent structures by reproducing it in 10 knees of five cadavers. RESULTS: This approach was seen to make it easy to locate the entry point, with lesions only occurring in the Hoffa fat. In three of our cases, there were lesions of the chondral surface, which is an obstacle that is difficult to overcome. CONCLUSION: There is a need to develop specific material to minimize injury to intra-articular structures when using this route.

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