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Secreted protein acidic and rich in cysteine (SPARC) is the most abundant glycoprotein in bone and is thought to play a critical role in bone remodeling and homeostasis. However, the effect of SPARC in relation to gender and exercise on bone quality is not well understood. The purpose of this study was to quantify differences in the structural and biomechanical properties between calvarial and femoral bone from male and female wild-type (WT) and SPARC null (SPARC(-/-)) mice as well as the ability of exercise to rescue bone health. Male and female WT and transgenic SPARC(-/-) mice were given either a fixed or rotating running wheel for exercise. Bone structural, biomechanical, and morphological parameters were quantified using micro computed tomography, push out testing for the calvaria, three-point flexural testing for the femurs, histological and immunofluorescent staining. Similar reductions in structural and biomechanical strength were observed in both male and female SPARC(-/-) calvaria, most of which were not significantly affected by exercise. In femurs, SPARC(-/-) had a significant effect on structural parameters in both sexes, but was more pronounced in females with some properties being rescued with running. Interestingly, the effect of SPARC(-/-) on bone mineral density was only detected in female SPARC(-/-) mice, not males, and was subsequently rescued with exercise. This study emphasizes the differences between sexes in WT and SPARC(-/-) mice in regard to structural parameters and biomechanical properties. Research into gender differences can help inform and personalize treatment options to more accurately meet patient needs.
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INTRODUCTION: Reconstruction nails are commonly used to treat proximal femur fractures, with cephalic screw placement for femoral neck "prophylaxis" becoming standard practice. These implants are traditionally introduced through piriformis fossa (PF) or greater trochanter (GT) entry portals. A third "central collinear" (CC) portal has been proposed that allows entry along the femoral anatomic axis and central placement of cephalic screws. The present study aimed to quantify and compare the CC portal femoral neck strength with the two traditional (PF and GT) entry portals. MATERIALS AND METHODS: Eighteen cadaveric femur specimens (nine matched pairs) were divided into three groups using a balanced incomplete block design to control for variations in age and sex: (1) GT, (2) CC, and (3) PF entry points. Specimens and implants were cut to a standard length and instrumented with straight or valgus bend nails of appropriate laterality and two cephalic screws. Specimens were mounted on a custom jig replicating load distribution along the mechanical axis. A 100 N compressive preload was applied to the femoral head, followed by loading to failure at a rate of 10 mm/s until fracture, indicated by 30 % drop in axial force. RESULTS: THE THREE ENTRY POINTS DID NOT DIFFER IN LOAD-TO-FAILURE: GT (6378.7 ± 1494.9 N), P (6912.4 ± 4924.1 N) and CC (7044.2 ± 2911.4 N) (P = 0.948) or maximum displacement, stiffness, and toughness. Most PF specimens failed at the basicervical neck, whereas most GT specimens failed at the subcapital neck; these differences were not significant. CC specimens failed evenly split between subcapital and basicervical. CONCLUSION: There were no significant difference in femoral neck load-to-failure after placement of a reconstruction nail through a CC entry portal when compared to both GT and PF entry. Clinically, this suggests the CC entry portal is a viable option when clinical considerations warrant its use.
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Pinos Ortopédicos , Parafusos Ósseos , Cadáver , Fraturas do Colo Femoral , Fixação Intramedular de Fraturas , Humanos , Fraturas do Colo Femoral/cirurgia , Fraturas do Colo Femoral/fisiopatologia , Fenômenos Biomecânicos , Masculino , Feminino , Fixação Intramedular de Fraturas/métodos , Fixação Intramedular de Fraturas/instrumentação , Idoso , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Suporte de Carga/fisiologiaRESUMO
Background: Medial ulnar collateral ligament (mUCL) injury can cause significant pain and alter throwing mechanics. Common autograft options for mUCL reconstruction (UCLR) include the palmaris longus (PL) and hamstring tendons. Allograft use may reduce donor site morbidity and decrease function related to PL autografts. Purpose: To compare varus stability and load to failure between a novel allograft for UCLR-knee medial collateral ligament (kMCL)-and a PL autograft in human donor elbow specimens. Study Design: Controlled laboratory study. Methods: A total of 24 fresh-frozen human elbows were dissected to expose the mUCL. Medial elbow stability was tested with the mUCL intact (native), deficient, and reconstructed utilizing the humeral single-docking technique with either a (1) kMCL allograft (n = 12) or (2) a PL autograft (n = 12). A 3-N·m valgus torque was applied to the elbow, and valgus rotation of the ulna was recorded via motion tracking cameras. The elbow was cycled through a full range of motion 5 times. After kinematic testing, specimens were loaded to failure at 70° of elbow flexion, and failure modes were recorded. Results: The mUCL-deficient elbows demonstrated significantly greater valgus rotation compared with the intact and reconstructed elbows at every flexion angle tested (10°-120°) (P <.001). Both kMCL- and PL-reconstructed elbows exhibited significantly higher mean valgus rotation compared with the intact state between 10° and 40° of flexion (P < .01). There were no significant differences in valgus rotation at any flexion angle between the kMCL and PL graft groups. When loaded to failure, elbows reconstructed with both kMCL and PL grafts failed at similar torque values (18.6 ± 4 and 18.1 ± 3.4 N·m, respectively; P = .765). Conclusion: Fresh-frozen and aseptically processed kMCL allografts demonstrated similar kinematic and failure properties to PL tendon autografts in UCL-reconstructed elbows, although neither graft fully restored kinematics between 10° and 40°. Clinical Relevance: Prepared kMCL ligament allografts may provide a viable graft material when reconstructing elbow ligaments while avoiding the potential complications related to PL autografts- including donor site morbidity.
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Background: Osteoadsorptive fluorogenic sentinel 3 (OFS-3) is a recently described compound that contains a bone-targeting bisphosphonate (BP) and cathepsin K (Ctsk)-triggered fluorescence signal. A prior study in a murine Achilles repair model demonstrated its effectiveness at targeting the site of tendon-to-bone repair, but the intrinsic effect of this novel bisphosphonate chaperone on tendon-to-bone healing has not been previously explored. We hypothesized that application of this bisphosphonate-fluorophore cargo conjugate would not affect the biomechanical properties or histologic appearance of tendon-bone repairs. Materials and Methods: Right hindlimb Achilles tendon-to-bone repair was performed on 12-week old male mice. Animals were divided into 2 groups of 18 each: 1) Achilles repair with OFS-3 applied directly to the repair site prior to closure, and 2) Achilles repair with saline applied prior to closure. Repaired hindlimbs from 12 animals per group were harvested at 6 weeks for biomechanical analysis with a custom 3D-printed jig. At 4 and 6 weeks, repaired hindlimbs from the remaining animals were assessed histologically using H&E, immunohistochemistry (IHC) staining for the presence of Ctsk, and second harmonic generation (SHG) imaging to evaluate collagen fibers. Results: At 6 weeks, there was no significant difference in failure load, stiffness, toughness, or displacement to failure between repaired hindlimbs that received OFS-3 versus saline. There was no difference in tissue healing on H&E or Ctsk staining on immunohistochemistry between animals that received OFS-3 versus saline. Finally, second harmonic generation imaging demonstrated no difference in collagen fiber parameters between the two groups. Conclusion: OFS-3 did not significantly affect the biomechanical properties or histologic appearance of murine Achilles tendon-to-bone repairs. This study demonstrates that OFS-3 can target the site of tendon-to-bone repair without causing intrinsic negative effects on healing. Further development of this drug delivery platform to target growth factors to the site of tendon-bone repair is warranted.
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BACKGROUND: Even with the best conservative care, patients with Charcot neuroarthropathy (CN) of the foot and ankle often ulcerate, increasing their risk of infection, amputation, and death. Surgical fixation has been associated with risk of recurrent ulceration, potentially due to poor bone quality prone to recurrent deformity and ulceration. We propose midfoot beam reconstruction with PMMA augmentation as a novel means of improving fixation. METHODS: A protocol was developed to create characteristic CN midfoot fragmentation both visually and fluoroscopically in each of 12 matched-pair cadaveric feet. Afterward, the pairs were divided into 2 groups: (1) midfoot beam fusion surgery alone, and (2) midfoot beam fusion surgery augmented with PMMA. A solid 7.0-mm beam was placed into the medial column and a solid 5.5-mm beam was placed across the lateral column. In the PMMA group, 8 to 10 mL of PMMA was inserted into the medial column. The hindfoot of each specimen was potted and the metatarsal heads were cyclically loaded for 1800 cycles, followed by load to failure while load and displacement were continually recorded. RESULTS: One specimen in the beam alone group failed before reaching the 1800th cycle and was not included in the failure analysis. The midfoot beam only group demonstrated greater mean displacement during cycle testing compared with the PMMA group, P < .05. The maximum force (N), stiffness (N/mm), and toughness (Nmm) were all significantly greater in the group augmented with PMMA, P < .05. CONCLUSION: In a CN cadaveric model, PMMA augmentation significantly decreased gapping during cyclic loading and nearly doubled the load to failure compared with midfoot beams alone. CLINICAL RELEVANCE: The results of this biomechanical study demonstrate that augmentation of midfoot beams with PMMA increases the strength and stiffness of the fusion construct. This increased mechanical toughness may help reduce the risk of nonunion and infection in patients with neuropathic midfoot collapse.
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Artropatia Neurogênica , Cadáver , Polimetil Metacrilato , Humanos , Artropatia Neurogênica/cirurgia , Artropatia Neurogênica/fisiopatologia , Fenômenos Biomecânicos , Cimentos Ósseos , Artrodese/métodos , IdosoRESUMO
In regenerative medicine, experimental animal models are commonly used to study potential effects of human cells as therapeutic candidates. Although some studies describe certain cells, such as mesenchymal stromal cells (MSC) or human primary cells, as hypoimmunogenic and therefore unable to trigger strong inflammatory host responses, other studies report antibody formation and immune rejection following xenotransplantation. Accordingly, the goal of our study was to test the cellular retention and survival of human-induced pluripotent stem cell (iPSCs)-derived MSCs (iMSCs) and primary nucleus pulposus cells (NPCs) following their xenotransplantation into immune-privileged knee joints (14 days) and intervertebral discs (IVD; 7 days) of immunocompromised Nude and immunocompetent Sprague Dawley (SD) rats. At the end of both experiments, we could demonstrate that both rat types revealed comparably low levels of systemic IL-6 and IgM inflammation markers, as assessed via ELISA. Furthermore, the number of recovered cells was with no significant difference between both rat types. Conclusively, our results show that xenogeneic injection of human iMSC and NPC into immunoprivileged knee and IVD sites did not lead to an elevated inflammatory response in immunocompetent rats when compared to immunocompromised rats. Hence, immunocompetent rats represent suitable animals for xenotransplantation studies targeting immunoprivileged sites.
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Ulnar collateral ligament reconstruction (UCLR) is frequently performed among injured overhead-throwing athletes. One of the most common graft choices when performing a UCLR is the ipsilateral palmaris longus tendon (PL). The purpose of this study was to investigate the material properties of aseptically processed cadaveric knee collateral ligaments (kMCL) as a potential graft source for UCLR and compare them to the gold standard PL autograft. Each PL and kMCL cadaveric sample was subjected to cyclic preconditioning, stress relaxation, and load-to-failure testing, and the mechanical properties were recorded. PL samples exhibited a greater average decrease in stress compared to the kMCL samples during the stress-relaxation test (p < 0.0001). PL samples also demonstrated a greater average Young's modulus in the linear region of the stress-strain curve compared to the kMCL samples (p < 0.01). The average yield strain and maximum strain of kMCL samples were significantly greater than the PL, p = 0.03 and 0.02, respectively. Both graft materials had comparable maximum toughness and demonstrated a similar ability to deform plastically without rupture. The clinical significance of our result is that prepared knee medial collateral ligament allografts may provide a viable graft material for use in the reconstruction of elbow ligaments.
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Articulação do Cotovelo , Ligamento Colateral Médio do Joelho , Reconstrução do Ligamento Colateral Ulnar , Humanos , Cotovelo/cirurgia , Músculo Esquelético/cirurgia , Fenômenos Biomecânicos , CadáverRESUMO
Tendons and ligaments have a poor innate healing capacity, yet account for 50% of musculoskeletal injuries in the United States. Full structure and function restoration postinjury remains an unmet clinical need. This study aimed to assess the application of novel three dimensional (3D) printed scaffolds and induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) overexpressing the transcription factor Scleraxis (SCX, iMSCSCX+ ) as a new strategy for tendon defect repair. The polycaprolactone (PCL) scaffolds were fabricated by extrusion through a patterned nozzle or conventional round nozzle. Scaffolds were seeded with iMSCSCX+ and outcomes were assessed in vitro via gene expression analysis and immunofluorescence. In vivo, rat Achilles tendon defects were repaired with iMSCSCX+ -seeded microgrooved scaffolds, microgrooved scaffolds only, or suture only and assessed via gait, gene expression, biomechanical testing, histology, and immunofluorescence. iMSCSCX+ -seeded on microgrooved scaffolds showed upregulation of tendon markers and increased organization and linearity of cells compared to non-patterned scaffolds in vitro. In vivo gait analysis showed improvement in the Scaffold + iMSCSCX+ -treated group compared to the controls. Tensile testing of the tendons demonstrated improved biomechanical properties of the Scaffold + iMSCSCX+ group compared with the controls. Histology and immunofluorescence demonstrated more regular tissue formation in the Scaffold + iMSCSCX+ group. This study demonstrates the potential of 3D-printed scaffolds with cell-instructive surface topography seeded with iMSCSCX+ as an approach to tendon defect repair. Further studies of cell-scaffold constructs can potentially revolutionize tendon reconstruction by advancing the application of 3D printing-based technologies toward patient-specific therapies that improve healing and functional outcomes at both the cellular and tissue level.
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Tendão do Calcâneo , Células-Tronco Pluripotentes Induzidas , Ratos , Animais , Tenócitos , Cicatrização , Impressão Tridimensional , Alicerces Teciduais/química , Engenharia Tecidual/métodos , RegeneraçãoRESUMO
PURPOSE: To measure and compare the torque to failure and stiffness of the capsular repair construct consisting of four-suture simple stitches to a two-figure of eight stitches repair construct in external rotation following an interportal capsulotomy. METHODS: Six pairs of fresh-frozen cadaveric hemipelves were divided into two capsular repair groups. All hips underwent a 40-mm interportal capsulotomy from the 12 o'clock position to the 3 o'clock position. Capsular closure was performed using either the two stitches in a figure of eight or with four simple stitches. Afterward, each hemipelvis was securely fixed to the frame of a mechanical testing system with the hip in 10° of extension and externally rotated to failure. Significance was set at P < .05. RESULTS: The average failure torque was 86.2 ± 18.9 N·m and 81.5 ± 8.9 N·m (P = .57) for the two stitches in a figure of eight and the four simple stitches, respectively. Failure stiffness was also not statistically different between groups and both capsular closure techniques failed at similar degrees of rotation (P = .65). CONCLUSION: Hip capsular repair using either the four simple stitch or two-figure of eight configurations following interportal capsulotomy demonstrated comparable failure torques and similar stiffness in a cadaveric model. CLINICAL RELEVANCE: Adequate and comprehensive capsular management in hip arthroscopy is critical. Capsular repair following capsulotomy in femoroacetabular impingement surgery has been associated with higher patient-reported outcomes when compared to capsulotomy without repair. Therefore, determining which capsular closure construct provides the higher failure torque is important.
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Impacto Femoroacetabular , Articulação do Quadril , Humanos , Articulação do Quadril/cirurgia , Torque , Cadáver , Impacto Femoroacetabular/cirurgia , Artroscopia/métodosRESUMO
BACKGROUND: Questions remain about whether circumferential labral reconstruction (CLR) using an iliotibial band (ITB) allograft can effectively restore the labral suction seal of the hip. HYPOTHESES: (1) CLR with an ITB allograft >6.5 mm would restore distractive stability force to that of the intact labrum. (2) CLR with an ITB allograft >6.5 mm would achieve significantly superior distractive stability force compared with CLR with an ITB allograft <6.5 mm. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 6 fresh-frozen pelves with attached femurs (n = 12 matched hemipelves) from male donors were procured and dissected free of all soft tissue, including the hip capsule but preserving the native labrum, transverse acetabular ligament, and ligamentum teres. Potted hemipelves were placed in a saline bath and securely fixed to the frame of a hydraulic testing system. A 500-N compressive load was applied, followed by femoral distraction at a rate of 5.0 mm/s until the suction seal ruptured. Force and femoral displacement were continually recorded. Force versus displacement curves were plotted, the maximum force was recorded, and the amount of femoral distraction to rupture the suction seal was determined. After intact testing, the labrum was excised, and specimens were retested using the same protocol. CLR was subsequently performed twice in a randomized fashion using (1) an ITB allograft with a width >6.5 mm (7.5-9.0 mm) and (2) an ITB allograft with a width <6.5 mm (4.5-6.0 mm). Specimens were retested after each CLR procedure. Force (in Newtons) and femoral distraction (in millimeters) required to rupture the suction seal were measured and compared between the 4 testing states (intact, deficient, CLR <6.5 mm, and CLR >6.5 mm) using repeated-measures analysis of variance. RESULTS: On average, intact specimens required 148.4 ± 33.1 N of force to rupture the hip suction seal, which significantly decreased to 44.3 N in the deficient state (P < .001). CLR with ITB allografts <6.5 mm did not improve the maximum force (63 ± 62 N) from the deficient state (P = .42) and remained significantly lower than the intact state (P < .01). CLR with ITB allografts >6.5 mm recorded significantly greater force to rupture the suction seal (135.8 ± 44.6 N) compared with both the deficient and CLR <6.5 mm states (P < .01), with a mean force comparable with the intact labrum (P = .59). The amount of femoral distraction to rupture the suction seal demonstrated similar findings. CONCLUSION: In a cadaveric model, CLR using ITB allografts >6.5 mm restored the distractive force and distance to the suction seal rupture to values comparable with hips with an intact labrum. CLR using ITB allografts >6.5 mm outperformed CLR with ITB allografts <6.5 mm, demonstrated by a significantly higher force to rupture the suction seal and increased distraction before the rupture. CLINICAL RELEVANCE: The results of this cadaveric investigation suggest that using wider labral allografts during CLR will provide the distractive force required to rupture the suction seal and immediate postoperative stability of the hip, although further studies are required to determine if these results translate to improved clinical outcomes.