vendex and Disease-Models--Animal

Metal-on-metal bearings have wear rates that are 20 to 100 times lower than metal-on-conventional polyethylene. The amount of wear generally is the same order of magnitude for the head and the cup. There is an initial run-in period of higher wear followed by lower, steady-state wear. Wear rate is a function of the interplay of material(s), macrogeometry, microgeometry, and the resultant type and amount of lubrication. The wear resistance and clinical performance of a metal-on-metal bearing are more sensitive to macrogeometry and lubrication than a metal-on-polyethylene bearing. Metal wear particles are nanometers in linear dimension. They are much smaller and more numerous than the submicron polyethylene wear particles, but the volume of periprosthetic inflammatory tissue is less. Osteolysis seems to be relatively rare. Little is known about the systemic distribution of metal particles and ions. The significance of systemic distribution also is not known. The levels of serum and urine Co and Cr ions are elevated in patients with metal-on-metal bearings, but the long-term, steady-state levels are not much higher than those from corrosion of modular femoral components. Because of the elevated levels of Co and Cr ions, there is a greater risk of delayed type hypersensitivity. There also is concern about the potential for malignant degeneration secondary to prolonged exposure to these elements. The available data are insufficient to address this concern. Rigorous long-term studies are needed. It will take decades of close clinical observation to determine if the benefits of metal-on-metal bearings outweigh the associated risks.

Topics: Animals; Arthroplasty, Replacement, Hip; Disease Models, Animal; Foreign-Body Reaction; Friction; Hip Prosthesis; Humans; Metals; Neoplasms; Prosthesis Design; Risk Factors; Stress, Mechanical; Synovial Fluid; Torque

A key event in the etiology of volumetric muscle loss (VML) injury is the bulk loss of structural cues provided by the underlying extracellular matrix (ECM). To re-establish the lost cues, there is broad consensus within the literature supporting the utilization of implantable scaffolding. However, while scaffold based regenerative medicine strategies have shown potential, there remains a significant amount of outcome variability observed across the field. We suggest that an overlooked source of outcome variability is differences in scaffolding architecture. The goal of this study was to test the hypothesis that implant alignment has a significant impact on genotypic and phenotypic outcomes following the repair of VML injuries. Using a rat VML model, outcomes across three autograft implant treatment groups (aligned implants, 45° misaligned, and 90° misaligned) and two recovery time points (2 weeks and 12 weeks) were examined (n = 6-8/group). At 2 weeks post-repair there were no significant differences in muscle mass and torque recovery between the treatment groups, however we did observe a significant upregulation of MyoD (2.5 fold increase) and Pax7 (2 fold increase) gene expression as well as the presence of immature myofibers at the implant site for those animals repaired with aligned autografts. By 12 weeks post-repair, functional and structural differences between the treatment groups could be detected. Aligned autografts had significantly greater mass and torque recovery (77 ± 10% of normal) when compared to 45° and 90° misaligned autografts (64 ± 10% and 61 ± 11%, respectively). Examination of tissue structure revealed extensive fibrosis and a significant increase in non-contractile tissue area fraction for only those animals treated using misaligned autografts. When taken together, the results suggest that implant graft orientation has a significant impact on in-vivo outcomes and indicate that the effect of graft alignment on muscle phenotype may be mediated through genotypic changes to myogenesis and fibrosis at the site of injury and repair. STATEMENT OF SIGNIFICANCE: A key event in the etiology of volumetric muscle loss injury is the bulk loss of architectural cues provided by the underlying extracellular matrix. To re-establish the lost cues, there is broad consensus within the literature supporting the utilization of implantable scaffolding. Yet, although native muscle is a highly organized tissue with network and cellular alignment in the di

Topics: Animals; Disease Models, Animal; Gene Expression Regulation; Muscle, Skeletal; Organ Size; Rats, Inbred F344; Regeneration; Tibia; Tissue Scaffolds; Torque

Electrophysiological measurements are used in longitudinal clinical studies to provide insight into the progression of amyotrophic lateral sclerosis (ALS) and the relationship between muscle weakness and motor unit (MU) degeneration. Here, we used a similar longitudinal approach in the Cu/Zn superoxide dismutase (SOD1[G93A]) mouse model of ALS.. In vivo muscle contractility and MU connectivity assays were assessed longitudinally in SOD1(G93A) and wild type mice from postnatal days 35 to 119.. In SOD1(G93A) males, muscle contractility was reduced by day 35 and preceded MU loss. Muscle contractility and motor unit reduction were delayed in SOD1(G93A) females compared with males, but, just as with males, muscle contractility reduction preceded MU loss.. The longitudinal contractility and connectivity paradigm employed here provides additional insight into the SOD1(G93A) mouse model and suggests that loss of muscle contractility is an early finding that may precede loss of MUs and motor neuron death. Muscle Nerve 59:254-262, 2019.

Topics: Action Potentials; Age Factors; Amyotrophic Lateral Sclerosis; Animals; Disease Models, Animal; Disease Progression; Female; Longitudinal Studies; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motor Neurons; Muscle Contraction; Muscle, Skeletal; Muscular Diseases; Neuromuscular Junction; Superoxide Dismutase; Torque

This work was to investigate potential roles of HMGB1-mediated ERK pathway in the healing process of bone fracture. Rat tibial fracture models were established and divided into control (rats with normal saline), HMGB1 (rats with HMGB1), and HMGB1+ PD98059 groups (rats with HMGB1 and 1 mg/kg of ERK1/2 inhibitor PD98059) with 30 rats per each. The healing of rats' fracture was observed by X-ray films, the morphological changes of bone fractures by HE staining, the callus formation by micro-CT and biomechanical test, and the expression of osteogenesis-related genes, HMGB1 and ERK-related proteins by qRT-PCR and Western blot. Rats in the HMGB1 group was increased in X-ray scores, peak torque, torsional stiffness, and the bone volume fraction (bone volume/total volume, BV/TV); meanwhile, those rats presented elevations in osteogenesis-related genes and HMGB1 expressions, as well as p-ERK/ERK ratio. However, rats in the HMGB1+ PD98059 group was significantly reduced in X-ray score, peak torque, torsional stiffness, and BV/TV, as well as the expression of osteogenesis-related genes and the ratio of p-ERK/ERK, as compared to those from HMGB1 group. HMGB1 could promote the expressions of osteogenesis-related genes and accelerate the healing process of fracture via activation of the ERK signaling pathway.

Topics: Animals; Biomechanical Phenomena; Disease Models, Animal; Enzyme Activation; Fracture Healing; Gene Expression Regulation; HMGB1 Protein; Male; MAP Kinase Signaling System; Osteogenesis; Rats, Sprague-Dawley; Tibial Fractures; Torque; X-Ray Microtomography; X-Rays

Successful strategies to halt or reverse sarcopenia require a basic understanding of the factors that cause muscle loss with age. Acute periods of muscle loss in older individuals have an incomplete recovery of muscle mass and strength, thus accelerating sarcopenic progression. The purpose of the current study was to further understand the mechanisms underlying the failure of old animals to completely recover muscle mass and function after a period of hindlimb unloading.. Hindlimb unloading was used to induce muscle atrophy in Fischer 344-Brown Norway (F344BN F1) rats at 24, 28, and 30 months of age. Rats were hindlimb unloaded for 14 days and then reloaded at 24 months (Reloaded 24), 28 months (Reloaded 28), and 24 and 28 months (Reloaded 24/28) of age. Isometric torque was determined at 24 months of age (24 months), at 28 months of age (28 months), immediately after 14 days of reloading, and at 30 months of age (30 months). During control or reloaded conditions, rats were labelled with deuterium oxide (D. After 14 days of reloading, in vivo isometric torque returned to baseline in Reloaded 24, but not Reloaded 28 and Reloaded 24/28. Despite the failure of Reloaded 28 and Reloaded 24/28 to regain peak force, all groups were equally depressed in peak force generation at 30 months. Increased age did not decrease muscle protein synthesis rates, and in fact, increased resting rates of protein synthesis were measured in the myofibrillar fraction (Fractional synthesis rate (FSR): %/day) of the plantaris (24 months: 2.53 ± 0.17; 30 months: 3.29 ± 0.17), and in the myofibrillar (24 months: 2.29 ± 0.07; 30 months: 3.34 ± 0.11), collagen (24 months: 1.11 ± 0.07; 30 months: 1.55 ± 0.14), and mitochondrial (24 months: 2.38 ± 0.16; 30 months: 3.20 ± 0.10) fractions of the tibialis anterior (TA). All muscles increased myofibrillar protein synthesis (%/day) in Reloaded 24 (soleus: 3.36 ± 0.11, 5.23 ± 0.19; plantaris: 2.53 ± 0.17, 3.66 ± 0.07; TA: 2.29 ± 0.14, 3.15 ± 0.12); however, in Reloaded 28, only the soleus had myofibrillar protein synthesis rates (%/day) >28 months (28 months: 3.80 ± 0.10; Reloaded 28: 4.86 ± 0.19). Across the muscles, rates of protein synthesis were correlated with RNA synthesis (all muscles combined, R. These data add to the growing body of literature that indicate that changes with age, including following disuse atrophy, differ by muscle. In addition, our findings lead to additional questions of the underlying mechanisms by which some muscles are maintained with age while others are not.

Topics: Aging; Animals; Disease Models, Animal; Hindlimb Suspension; Male; Muscle Fibers, Skeletal; Muscle Proteins; Muscular Disorders, Atrophic; Organ Size; Protein Biosynthesis; Rats; Rats, Inbred F344; Torque

Patients with hereditary peripheral neuropathies exhibit characteristic deformities of the hands and feet and have difficulty ambulating. To examine to what extent neuropathic animals recapitulate these deficits, we studied trembler J (TrJ) mice, which model early-onset demyelinating neuropathy.. A cohort of 4-month-old female wild type and neuropathic mice were evaluated for locomotor measurements, neuromuscular function, and skeletal muscle proteolysis and morphometry.. Utilizing the DigiGait imaging system, we identified pronounced alterations in forepaw and hindpaw angles and a decrease in hindpaw area on the treadmill in neuropathic rodents. Torque production by the tibialis anterior (TA) muscle was significantly weakened and was paralleled by a decrease in myofiber cross-sectional area and an increase in muscle tissue proteolysis.. Our findings in TrJ mice reflect the phenotypic presentation of the human neuropathy in which patients exhibit weakness of the TA muscle resulting in foot drop and locomotor abnormalities. Muscle Nerve 57: 664-671, 2018.

Topics: Animals; Charcot-Marie-Tooth Disease; Disease Models, Animal; Female; Gait Analysis; Hereditary Sensory and Motor Neuropathy; Locomotion; Mice; Muscle, Skeletal; Myelin Proteins; Peripheral Nervous System Diseases; Phenotype; Torque

Heightened local inflammation due to muscle trauma or disease is associated with impaired bone regeneration.. We hypothesized that FK506, an FDA approved immunomodulatory compound with neurotrophic and osteogenic effects, will rescue the early phase of fracture healing which is impaired by concomitant muscle trauma in male (~4 months old) Lewis rats. FK506 (1 mg/kg; i.p.) or saline was administered systemically for 14 days after an endogenously healing tibia osteotomy was created and fixed with an intermedullary pin, and the overlying tibialis anterior (TA) muscle was either left uninjured or incurred volumetric muscle loss injury (6 mm full thickness biopsy from middle third of the muscle).. The salient observations of this study were that 1) concomitant TA muscle trauma impaired recovery of tibia mechanical properties 28 days post-injury, 2) FK506 administration rescued the recovery of tibia mechanical properties in the presence of concomitant TA muscle trauma but did not augment mechanical recovery of an isolated osteotomy (no muscle trauma), 3) T lymphocytes and macrophage presence within the traumatized musculature were heightened by trauma and attenuated by FK506 3 days post-injury, and 4) T lymphocyte but not macrophage presence within the fracture callus were attenuated by FK506 at 14 days post-injury. FK506 did not improve TA muscle isometric torque production CONCLUSION: Collectively, these findings support the administration of FK506 to ameliorate healing of fractures with severe muscle trauma comorbidity. The results suggest one potential mechanism of action is a reduction in local T lymphocytes within the injured musculoskeletal tissue, though other mechanisms to include direct osteogenic effects of FK506 require further investigation.

Topics: Adaptive Immunity; Animals; Biopsy; Bone Nails; Bone Regeneration; Bony Callus; Disease Models, Animal; Fracture Fixation, Intramedullary; Fracture Healing; Humans; Immunity, Innate; Immunosuppressive Agents; Macrophages; Male; Muscle, Skeletal; Muscular Diseases; Osteotomy; Rats; Rats, Inbred Lew; Soft Tissue Injuries; T-Lymphocytes; Tacrolimus; Tibial Fractures; Torque

Topics: Adaptation, Physiological; Adenylate Kinase; Animals; Diaphragm; Disease Models, Animal; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Muscle Contraction; Muscle Strength; Muscle Weakness; Muscle, Skeletal; Muscular Dystrophy, Animal; Muscular Dystrophy, Duchenne; Physical Conditioning, Animal; Torque; Up-Regulation

We evaluated sciatic nerve impairment after eccentric contractions (ECs) in rat triceps surae.. Wistar rats were randomly assigned to different joint angular velocity: 180°/s (FAST), 30°/s (SLOW), or nontreated control (CNT). FAST and SLOW groups were subjected to multiple (1-4) bouts of 20 (5 reps, 4 sets) ECs. Nerve conduction velocity (NCV) and isometric tetanic ankle torque were measured 24 h after each ECs bout. We also assessed nerve morphology.. After 4 ECs bouts, NCVs and isometric torque in the FAST group were significantly lower than those in the CNT (NCV: 42%, torque: 66%; P < 0.05). After 4 bouts, average nerve diameter was significantly smaller in the FAST group [2.39 ± 0.20 μm vs. 2.69 ± 0.20 μm (CNT) and 2.93 ± 0.24 μm (SLOW); P < 0.05] than that in other two groups.. Chronic ECs with high angular velocity induce serious nerve damage. Muscle Nerve 54: 936-942, 2016.

Topics: Analysis of Variance; Animals; Ankle; Body Weight; Disease Models, Animal; Isometric Contraction; Male; Microscopy, Electron; Muscle, Skeletal; Myelin Sheath; Nerve Fibers; Neural Conduction; Organ Size; Rats; Rats, Wistar; Reaction Time; Sciatic Neuropathy; Torque

Eccentric contractions may cause immediate and long-term reductions in muscle strength that can be recovered through increased protein synthesis rates. The purpose of this study was to determine whether the mechanistic target-of-rapamycin complex 1 (mTORC1), a vital controller of protein synthesis rates, is required for return of muscle strength after injury.. Isometric muscle strength was assessed before, immediately after, and then 3, 7, and 14 days after a single bout of 150 eccentric contractions in mice that received daily injections of saline or rapamycin.. The bout of eccentric contractions increased the phosphorylation of mTORC1 (1.8-fold) and p70s6k1 (13.8-fold), mTORC1's downstream effector, 3 days post-injury. Rapamycin blocked mTORC1 and p70s6k1 phosphorylation and attenuated recovery of muscle strength (∼20%) at 7 and 14 days.. mTORC1 signaling is instrumental in the return of muscle strength after a single bout of eccentric contractions in mice. Muscle Nerve 54: 914-924, 2016.

Topics: Animals; Disease Models, Animal; Electric Stimulation; Female; Immunosuppressive Agents; Mice; Mice, Inbred C57BL; Muscle Contraction; Muscle, Skeletal; Muscular Diseases; Recovery of Function; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Sirolimus; Time Factors; TOR Serine-Threonine Kinases; Torque

In vivo evaluation of scoliosis treatment using a novel approach in which two posterior implants are implanted: XSLAT (eXtendable implant correcting Scoliosis in LAT bending) and XSTOR (eXtendable implant correcting Scoliosis in TORsion). The highly flexible and extendable implants use only small, but continuous lateral forces (XSLAT) and torques (XSTOR), thereby allowing growth and preventing fusion.. Since (idiopathic) scoliosis does not occur spontaneously in animals, the device was used to induce a spinal deformity rather than correct it. Six of each implants were tested for their ability to induce scoliotic deformations in 12 growing pigs. Each implant spanned six segments and was attached to three vertebrae using sliding anchors. Radiological and histological assessments were done throughout the 8-week study.. In all animals, the intended deformation was accomplished. Average Cobb angles were 19° for XSLAT and 6° for XSTOR. Average apical spinal torsion was 0° for XSLAT and 9° for XSTOR. All instrumented segments remained mobile and showed 20 % growth. Moderate degeneration of the facet joints was observed and some debris was found in the surrounding tissue.. The approach accomplished the intended spinal deformation while allowing growth and preventing fusion.

Topics: Analysis of Variance; Animals; Disease Models, Animal; Female; Orthopedic Procedures; Prostheses and Implants; Radiography; Scoliosis; Swine; Thoracic Vertebrae; Torque

Studies have shown that titanium implants can be challenging to explant due to the material's excellent biocompatibility and resulting osseointegration. Clinically, titanium alloy nail interlocking screws may require removal to dynamize a construct or revise the nail due to nonunion, infection, pain, or periprosthetic fracture. This study was designed to determine what variables influence the removal torque for titanium alloy interlocking screws. An intramedullary nail with four interlocking screws was used to stabilize a 1-cm segmental femoral defect in a canine model for 16 weeks. The animals were observed to be active following a several-day recovery after surgery. In six animals, the femora and implanted nail/screws were first tested to failure in torsion to simulate periprosthetic fracture of an implant after which the screws were then removed. In four additional animals, the screws were removed without mechanical testing. Both intraoperative insertional and extraction torques were recorded for all screws. Mechanical testing to failure broke 10/24 screws. On average, the intact screws required 70% of the insertional torque during removal while broken screws only required 16% of the insertional torque (p < 0.001). In addition, intact screws closer to the fracture required 2.8 times more removal torque than the outboard distal screw (p < 0.005). On average, the angle of rotation to peak torque was ∼80°. The peak axial load did not significantly correlate with the torque required to remove the screws. On average, the removal torque was lower than at the time of insertion, and less torque was required to remove broken screws and screws remote to the fracture. However, broken screws will require additional time to retrieve the remaining screw fragment. This study suggests that broken screws and screws in prematurely active patients will require less torque to remove.

Topics: Alloys; Animals; Biomechanical Phenomena; Bone Nails; Bone Screws; Device Removal; Disease Models, Animal; Dogs; Equipment Failure; Femoral Fractures; Fracture Fixation, Intramedullary; Humans; Osseointegration; Titanium; Torque

Secondary dystroglycanopathies are a subset of muscular dystrophy caused by abnormal glycosylation of α-dystroglycan (αDG). Loss of αDG functional glycosylation prevents it from binding to laminin and other extracellular matrix receptors, causing muscular dystrophy. Mutations in a number of genes, including FKTN (fukutin), disrupt αDG glycosylation.. We analyzed conditional Fktn knockout (Fktn KO) muscle for levels of mTOR signaling pathway proteins by Western blot. Two cohorts of Myf5-cre/Fktn KO mice were treated with the mammalian target of rapamycin (mTOR) inhibitor rapamycin (RAPA) for 4 weeks and evaluated for changes in functional and histopathological features.. Muscle from 17- to 25-week-old fukutin-deficient mice has activated mTOR signaling. However, in tamoxifen-inducible Fktn KO mice, factors related to Akt/mTOR signaling were unchanged before the onset of dystrophic pathology, suggesting that Akt/mTOR signaling pathway abnormalities occur after the onset of disease pathology and are not causative in early dystroglycanopathy development. To determine any pharmacological benefit of targeting mTOR signaling, we administered RAPA daily for 4 weeks to Myf5/Fktn KO mice to inhibit mTORC1. RAPA treatment reduced fibrosis, inflammation, activity-induced damage, and central nucleation, and increased muscle fiber size in Myf5/Fktn KO mice compared to controls. RAPA-treated KO mice also produced significantly higher torque at the conclusion of dosing.. These findings validate a misregulation of mTOR signaling in dystrophic dystroglycanopathy skeletal muscle and suggest that such signaling molecules may be relevant targets to delay and/or reduce disease burden in dystrophic patients.

Topics: Animals; Biomechanical Phenomena; Disease Models, Animal; Down-Regulation; Dystroglycans; Electric Stimulation; Female; Genetic Predisposition to Disease; Glycosylation; Male; Mice, Knockout; Muscle Contraction; Muscle Strength; Muscle, Skeletal; Muscular Dystrophy, Animal; Myogenic Regulatory Factor 5; Phenotype; Protein Kinase Inhibitors; Protein Processing, Post-Translational; Proteins; Proto-Oncogene Proteins c-akt; Signal Transduction; Sirolimus; Time Factors; TOR Serine-Threonine Kinases; Torque; Transferases

In our study, we examined postural stability during head turns for two rhesus monkeys: one animal study contrasted normal and mild bilateral vestibular ablation and a second animal study contrasted severe bilateral vestibular ablation with and without prosthetic stimulation. The monkeys freely stood, unrestrained on a balance platform and made voluntary head turns between visual targets. To quantify each animals' posture, motions of the head and trunk, as well as torque about the body's center of mass, were measured. In the mildly ablated animal, we observed less foretrunk sway in comparison with the normal state. When the canal prosthesis provided electric stimulation to the severely ablated animal, it showed a decrease in trunk sway during head turns. Because the rhesus monkey with severe bilateral vestibular loss exhibited a decrease in trunk sway when receiving vestibular prosthetic stimulation, we propose that the prosthetic electrical stimulation partially restored head velocity information. Our results provide an indication that a semicircular canal prosthesis may be an effective way to improve postural stability in patients with severe peripheral vestibular dysfunction.

Topics: Aminoglycosides; Animals; Catheter Ablation; Disease Models, Animal; Electric Stimulation; Female; Head Movements; Macaca mulatta; Neural Prostheses; Postural Balance; Posture; Prostheses and Implants; Reflex, Vestibulo-Ocular; Torque; Vestibular Diseases

In this investigation we aimed to determine whether: (1) physical activity protects rat skeletal muscle from ischemia/reperfusion (I/R) injury; and (2) continued activity after I/R improves the rate of healing.. Rats were divided into sedentary or active (voluntary wheel running) groups. Active rats ran for 4 weeks before I/R or 4 weeks before plus 4 weeks after I/R.. Activity before I/R resulted in 73.2% less muscle damage (Evans blue dye inclusion). Sedentary and active rats had a similar decline in neural-evoked (∼ 99%) and directly stimulated (∼ 70%) in vivo muscle torque, and a similar reduction in junctophilin 1. Active rats produced 19% and 15% greater neural-evoked torque compared with sedentary rats at 14 and 28 days postinjury, respectively, although the rate of recovery appeared similar.. Activity protects against long-term muscle damage, but not short-term neural injury or excitation-contraction uncoupling. Continued activity neither accelerates nor hinders the rate of functional recovery.

Topics: Animals; Body Weight; Disease Models, Animal; Ischemia; Isometric Contraction; Male; Muscle Fibers, Skeletal; Muscular Diseases; Physical Conditioning, Animal; Rats; Rats, Inbred Lew; Regeneration; Reperfusion Injury; Running; Statistics, Nonparametric; Torque

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting secondary to repeated muscle damage and inadequate repair. Elevations in intracellular free Ca²⁺ have been implicated in disease progression, and sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase 1 (SERCA1) overexpression has been shown to ameliorate the dystrophic phenotype in mdx mice. The purpose of this study was to assess the effects of SERCA1 overexpression in the more severe mdx/Utr(-/-) mouse model of DMD. Mice overexpressing SERCA1 were crossed with mdx/Utr ± mice to generate mdx/Utr(-/-)/+SERCA1 mice and compared with wild-type (WT), WT/+SERCA1, mdx/+SERCA1, and genotype controls. Mice were assessed at ∼12 wk of age for changes in Ca²⁺ handling, muscle mass, quadriceps torque, markers of muscle damage, and response to repeated eccentric contractions. SERCA1-overexpressing mice had a two- to threefold increase in maximal sarcoplasmic reticulum Ca²⁺-ATPase activity compared with WT which was associated with normalization in body mass for both mdx/+SERCA1 and mdx/Utr(-/-)/+SERCA1. Torque deficit in the quadriceps after eccentric injury was 2.7-fold greater in mdx/Utr(-/-) vs. WT mice, but only 1.5-fold greater in mdx/Utr(-/-)/+SERCA1 vs. WT mice, an attenuation of 44%. Markers of muscle damage (% centrally nucleated fibers, necrotic area, and serum creatine kinase levels) were higher in both mdx and mdx/Utr(-/-) vs. WT, and all were attenuated by overexpression of SERCA1. These data indicate that SERCA1 overexpression ameliorates functional impairments and cellular markers of damage in a more severe mouse model of DMD. These findings support targeting intracellular Ca²⁺ control as a therapeutic approach for DMD.

Topics: Animals; Biomarkers; Biomechanical Phenomena; Calcium Signaling; Creatine Kinase, MM Form; Disease Models, Animal; Genotype; Hypertrophy; Mice, Inbred mdx; Mice, Transgenic; Muscle Contraction; Muscle Strength; Muscular Dystrophy, Duchenne; Necrosis; Organ Size; Phenotype; Quadriceps Muscle; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Severity of Illness Index; Torque; Up-Regulation; Utrophin

To develop and validate a translatable and reproducible rodent critical-sized defect (CSD) model and to determine the optimal dose of recombinant human bone morphogenetic protein (BMP)-7 required to consistently heal the CSD in the new model.. Rats with 6-mm CSDs stabilized with a commercial radiolucent plate and screws with angular stability were randomly assigned to 4 treatment groups with varied doses of recombinant human BMP-7 (25, 50, 75, and 100 μg) on absorbable collagen sponge and a single control group (absorbable collagen sponge alone). Bone formation was evaluated by radiographs, micro-computed tomography, histology, and biomechanics.. All the rats treated with 100 μg of BMP-7 with CSDs were united by 4 weeks and all 75- and 50-μg-group rats united by 6 weeks. None of the animals in the 25-μg BMP-7 group or the control group were healed at the time of killing. Bone volume, bone mineral density, the ratio of bone volume to total volume, stiffness, and ultimate load to failure were maximal in the 50-μg group. Total callus volume progressively increased with increasing BMP dose. Histologic analysis demonstrated increased callus width with increasing BMP-7 doses above 50 μg, but the bone seemed structurally abnormal.. There was a 100% union rate in the 50-, 75-, and 100-μg BMP-7-treated groups. None of the control or 25-μg-dose rats united. The biomechanical data demonstrated that 50 μg of BMP-7 produced the highest mechanical strength in the bone regenerate. These data also suggest that administration of BMP-7 above 50 μg does not improve bone regeneration and actually seems to produce lower quality bone with diminished biomechanical properties.

Topics: Animals; Bone Morphogenetic Protein 7; Bone Regeneration; Combined Modality Therapy; Disease Models, Animal; Dose-Response Relationship, Drug; Femoral Fractures; Fracture Fixation, Internal; Male; Rats; Rats, Inbred F344; Tensile Strength; Torque; Treatment Outcome; Weight-Bearing

Conventional nails are being used for an expanding range of fractures from simple to more complex. Angle stable designs are a relatively new innovation; however, it is unknown if they will improve healing for complex fractures.. When comparing traditional and angle stable nails to treat complex open canine femur fractures, the current study addressed the following questions: do the two constructs differ in (1) radiographic evidence of bone union across the cortices; (2) stability as determined by toggle (torsional motion with little accompanying torque) and angular deformation; (3) biomechanical properties, including stiffness in bending, axial compression, and torsional loading, and construct failure properties in torsion; and (4) degree of bone tissue mineralization?. Ten hounds with a 1-cm femoral defect and periosteal stripping were treated with a reamed titanium angle stable or nonangle stable nail after the creation of a long soft tissue wound. Before the study, the animals were randomly assigned to receive one of the nails and to be evaluated with biomechanical testing or histology. After euthanasia at 16 weeks, all operative femora were assessed radiographically. Histological or biomechanical evaluation was conducted of the operative bones with nails left in situ compared with the nonoperative contralateral femora.. Radiographic and gross inspection demonstrated hypertrophic nonunion in all 10 animals treated with the nonangle stable nail, whereas six of 10 animals treated with the angle stable nail bridged at least one cortex (p = 0.023). The angle stable nail construct demonstrated no toggle in nine of 10 animals, whereas all control femora exhibited toggle. The angle stable nail demonstrated less angular deformation and toggle (p ≤ 0.005) and increased compressive stiffness (p = 0.001) compared with the conventional nonangle stable nail. Histology demonstrated more nonmineralized tissue in the limbs treated with the conventional nail (p = 0.005).. Angle stable nails that eliminate toggle lead to enhanced yet incomplete fracture healing in a complex canine fracture model.. Care should be taken in tailoring the nail design features to the characteristics of the fracture and the patient.

Topics: Animals; Biomechanical Phenomena; Bone Nails; Disease Models, Animal; Dogs; Femoral Fractures; Femur; Fracture Fixation, Internal; Fracture Healing; Male; Prosthesis Design; Radiography; Stress, Mechanical; Time Factors; Titanium; Torque; Weight-Bearing

The frank loss of a large volume of skeletal muscle (i.e., volumetric muscle loss [VML]) can lead to functional debilitation and presents a significant problem to civilian and military medicine. Current clinical treatment for VML involves the use of free muscle flaps and physical rehabilitation; however, neither are effective in promoting regeneration of skeletal muscle to replace the tissue that was lost. Toward this end, skeletal muscle tissue engineering therapies have recently shown great promise in offering an unprecedented treatment option for VML. In the current study, we further extend our recent progress (Machingal et al., 2011, Tissue Eng; Corona et al., 2012, Tissue Eng) in the development of tissue engineered muscle repair (TEMR) constructs (i.e., muscle-derived cells [MDCs] seeded on a bladder acellular matrix (BAM) preconditioned with uniaxial mechanical strain) for the treatment of VML. TEMR constructs were implanted into a VML defect in a tibialis anterior (TA) muscle of Lewis rats and observed up to 12 weeks postinjury. The salient findings of the study were (1) TEMR constructs exhibited a highly variable capacity to restore in vivo function of injured TA muscles, wherein TEMR-positive responders (n=6) promoted an ≈61% improvement, but negative responders (n=7) resulted in no improvement compared to nonrepaired controls, (2) TEMR-positive and -negative responders exhibited differential immune responses that may underlie these variant responses, (3) BAM scaffolds (n=7) without cells promoted an ≈26% functional improvement compared to uninjured muscles, (4) TEMR-positive responders promoted muscle fiber regeneration within the initial defect area, while BAM scaffolds did so only sparingly. These findings indicate that TEMR constructs can improve the in vivo functional capacity of the injured musculature at least, in part, by promoting generation of functional skeletal muscle fibers. In short, the degree of functional recovery observed following TEMR implantation (BAM+MDCs) was 2.3×-fold greater than that observed following implantation of BAM alone. As such, this finding further underscores the potential benefits of including a cellular component in the tissue engineering strategy for VML injury.

Topics: Animals; Disease Models, Animal; Extracellular Matrix; Inflammation; Male; Muscle, Skeletal; Prosthesis Implantation; Rats; Rats, Inbred Lew; Recovery of Function; Regeneration; Sus scrofa; Tissue Engineering; Tissue Scaffolds; Torque; Urinary Bladder; Wound Healing

The overexpression of tumor necrosis factor (TNF)-α leads to systemic as well as local loss of bone and cartilage and is also an important regulator during fracture healing. In this study, we investigate how TNF-α inhibition using a targeted monoclonal antibody affects fracture healing in a TNF-α driven animal model of human rheumatoid arthritis (RA) and elucidate the question whether enduring the anti TNF-α therapy after trauma is beneficial or not.. A standardized femur fracture was applied to wild type and human TNF-α transgenic mice (hTNFtg mice), which develop an RA-like chronic polyarthritis. hTNFtg animals were treated with anti-TNF antibody (Infliximab) during the fracture repair. Untreated animals served as controls. Fracture healing was evaluated after 14 and 28 days of treatment by clinical assessment, biomechanical testing and histomorphometry.. High levels of TNF-α influence fracture healing negatively, lead to reduced cartilage and more soft tissue in the callus as well as decreased biomechanical bone stability. Blocking TNF-α in hTNFtg mice lead to similar biomechanical and histomorphometrical properties as in wild type.. High levels of TNF-α during chronic inflammation have a negative impact on fracture healing. Our data suggest that TNF-α inhibition by an anti-TNF antibody does not interfere with fracture healing.

Topics: Animals; Antibodies, Monoclonal; Arthritis; Arthritis, Rheumatoid; Bone Nails; Bony Callus; Disease Models, Animal; Female; Femoral Fractures; Fracture Fixation, Internal; Fracture Healing; Humans; Inflammation; Infliximab; Mice; Mice, Transgenic; Stress, Mechanical; Torque; Tumor Necrosis Factor-alpha; Weight-Bearing

The aim of this study was to evaluate histologically and biomechanically the peri-implant bone healing around implants placed with high torque after a follow-up of 8 and 12 weeks. A total of 12 implants were placed in the lower edge of the mandible of 2 sheep. In each sheep, 3 implants were placed with a low torque (<25 N · cm, LT group) as a control, and 3 implants were placed with a high insertion torque (maximum torque, HT group). The sheep were killed after 8 and 12 weeks of healing, and the implants were examined for removal torque, resonance frequency analysis, and histologic analysis.The mean insertion torque in the LT group was 24 N · cm, whereas it was 105.6 N · cm in HT. All the implants osseointegrated and histologic analysis showed similar aspects of the peri-implant bone tissue for both groups and both healing times. Mean removal torque values for LT implants were 159.5 and 131.5 N · cm after 8 and 12 weeks, respectively, whereas those for the HT were 140 and 120 N · cm at 8 and 12 weeks, respectively. Implant stability quotient values were 26.6 and 76 for the LT group and 74 and 76 for the HT group at 8 and 12 weeks, respectively.It could be concluded that high implant insertion torque does not induce adverse reaction in cortical bone and does not lead to implant failure.

Topics: Animals; Biomechanical Phenomena; Dental Implantation, Endosseous; Dental Implants; Disease Models, Animal; Female; Mandible; Osseointegration; Sheep; Torque; Vibration; Wound Healing

Joint contractures are a common complication of many neurologic conditions, and stretching often is advocated to prevent and treat these contractures. However, the magnitude and duration of the stretching done in practice usually are guided by subjective clinical impressions.. Using an established T8 spinal cord injury rat model of knee contracture, we sought to determine what combination of static or intermittent stretching, varied by magnitude (high or low) and duration (long or short), leads to the best (1) improvement in the limitation in ROM; (2) restoration of the muscular and articular factors leading to contractures; and (3) prevention and treatment of contracture-associated histologic alterations of joint capsule and articular cartilage.. Using a rat animal model, the spinal cord was transected completely at the level of T8. The rats were randomly assigned to seven treatment groups (n = 4 per group), which were composed of static or intermittent stretching in combination with different amounts of applied torque magnitude and duration. We assessed the effect of stretching by measuring the ROM and evaluating the histologic alteration of the capsule and cartilage.. Contractures improved in all treated groups except for the low-torque and short-duration static stretching conditions. High-torque stretching was effective against shortening of the synovial membrane and adhesions in the posterosuperior regions. Collagen Type II and VEGF in the cartilage were increased by stretching.. High-torque and long-duration static stretching led to greater restoration of ROM than the other torque and duration treatment groups. Stretching was more effective in improving articular components of contractures compared with the muscular components. Stretching in this rat model prevented shortening and adhesion of the joint capsule, and affected biochemical composition, but did not change morphologic features of the cartilage.. This animal study tends to support the ideas that static stretching can influence joint ROM and histologic qualities of joint tissues, and that the way stretching is performed influences its efficacy. However, further studies are warranted to determine if our findings are clinically applicable.

Topics: Animals; Biomechanical Phenomena; Cartilage, Articular; Collagen Type II; Contracture; Disease Models, Animal; Joint Capsule; Knee Joint; Male; Muscle Stretching Exercises; Range of Motion, Articular; Rats; Rats, Wistar; Spinal Cord Injuries; Time Factors; Torque; Vascular Endothelial Growth Factor A

Understanding the biological mechanisms of why certain fractures are at risk for delayed healing or nonunion requires translational animal models that take advantage of transgenic and other genetic manipulation technologies. Reliable murine nonunion models can be an important tool to understand the biology of nonunion. In this study, we report the results of a recently established model for creating critical defects that lead to atrophic nonunions based on a unique fracture fixation technique.. Subcritical (0.6 mm long) and critical (1.6 mm long) defects were created in femurs of 10-week-old double transgenic (Col1/Col2) mice and stabilized using a custom-designed plate and four screws. Four groups were used: normal, sham, subcritical, and critical. Histology (n = 3 for each group) was analyzed at 2 and 5 weeks, and micro-computed tomography (μCT) and torsional biomechanics (n = 12 for each group) were analyzed at 5 weeks.. Subcritical defects showed healing at 2 weeks and were completely healed by 5 weeks, with biomechanical properties not significantly different from normal controls. However, critical defects showed no healing by histology or μCT. These nonunion fractures also displayed no torsional stiffness or strength in 10 of 12 cases.. Our murine fracture model creates reproducible and reliable nonunions and can serve as an ideal platform for studying molecular pathways to contrast healing versus nonhealing events and for evaluating innovative therapeutic approaches to promote healing of a challenging osseous injury.

Topics: Animals; Biomechanical Phenomena; Bone Plates; Bone Screws; Disease Models, Animal; Femoral Fractures; Fracture Healing; Fractures, Ununited; Internal Fixators; Male; Mice; Random Allocation; Torque; X-Ray Microtomography

To evaluate bone healing around dental implants with established osseointegration in experimental diabetes mellitus (DM) and insulin therapy by histomorphometric and removal torque analysis in a rat model.. A total of 80 male Wistar rats received a titanium implant in the tibiae proximal methaphysis. After a healing period of 60 days, the rats were divided into four groups of 20 animals each: a 2-month control group, sacrificed at time (group A), a diabetic group (group D), an insulin group (group I), and a 4-month control group (group C), subdivided half for removal torque and half for histomorphometric analysis. In the D and I groups the DM was induced by a single injection of 40 mg/kg body weight streptozotocin (STZ). Two days after DM induction, group I received subcutaneous doses of insulin twice a day, during 2 months. Groups C and D received only saline. Two months after induction of DM, the animals of groups D, C and I were sacrificed. The plasmatic levels of glucose (GPL) were monitored throughout the experiment. Evaluation of the percentages of bone-to-implant contact and bone area within the limits of the implant threads was done by histomorphometric and mechanical torque analysis. Data were analyzed by anova at significant level of 5%.. The GPL were within normal range for groups A, C and I and higher for group D. The means and standard deviations (SD) for histomorphometric bone area showed significant difference between group D (69.34 ± 5.00%) and groups C (78.20 ± 4.88%) and I (79.63 ± 4.97%). Related to bone-to-implant contact there were no significant difference between the groups D (60.81 + 6.83%), C (63.37 + 5.88%) and I (66.97 + 4.13%). The means and SD for removal torque showed that group D (12.91 ± 2.51 Ncm) was statistically lower than group I (17.10 ± 3.06 Ncm) and C (16.95 ± 5.39 Ncm).. Diabetes mellitus impaired the bone healing around dental implants with established osseointegration because the results presented a lower percentage of bone area in group D in relation to groups C and I resulting in a lowest torque values for implant removal. Moreover, insulin therapy prevents the occurrence of bone abnormalities found in diabetic animals and osseointegration was not compromised.

Topics: Animals; Blood Glucose; Dental Implants; Dental Materials; Diabetes Mellitus, Experimental; Disease Models, Animal; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Male; Osseointegration; Random Allocation; Rats; Rats, Wistar; Streptozocin; Tibia; Titanium; Torque; Wound Healing

Mutations in the DYSF gene, encoding dysferlin, cause muscular dystrophies in man. We compared 4 dysferlinopathic mouse strains: SJL/J and B10.SJL-Dysf(im)/AwaJ (B10.SJL), and A/J and B6.A-Dysf(prmd)/GeneJ (B6.A/J). The former but not the latter two are overtly myopathic and weaker at 3 months of age. Following repetitive large-strain injury (LSI) caused by lengthening contractions, all except B6.A/J showed ~40% loss in contractile torque. Three days later, torque in SJL/J, B10.SJL and controls, but not A/J, recovered nearly completely. B6.A/J showed ~30% torque loss post-LSI and more variable recovery. Pre-injury, all dysferlinopathic strains had more centrally nucleated fibers (CNFs) and all but A/J showed more inflammation than controls. At D3, all dysferlinopathic strains showed increased necrosis and inflammation, but not more CNFs; controls were unchanged. Dystrophin-null DMD(mdx) mice showed more necrosis and inflammation than all dysferlin-nulls. Torque loss and inflammation on D3 across all strains were linearly related to necrosis. Our results suggest that (1) dysferlin is not required for functional recovery 3 days after LSI; (2) B6.A/J mice recover from LSI erratically; (3) SJL/J and B10.SJL muscles recover rapidly, perhaps due to ongoing myopathy; (4) although they recover function to different levels, all 4 dysferlinopathic strains show increased inflammation and necrosis 3 days after LSI.

Topics: Animals; Disease Models, Animal; Dysferlin; Histocytochemistry; Inflammation; Macrophages; Membrane Proteins; Mice; Mice, Inbred Strains; Mice, Transgenic; Muscle Contraction; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Dystrophies, Limb-Girdle; Necrosis; Torque

Open fractures with severe soft-tissue trauma are predisposed to poor bone healing. The vital coupling between osteo- and angiogenesis is disturbed. Cysteine-rich protein 61 (CYR61) is an angiogenic inducer promoting vascularisation. However, little is known about the effect of CYR61 on the callus regenerate after acute musculoskeletal trauma. Therefore, our aim was to determine whether local administration of CYR61: (1) has an influence on callus formation and remodelling, (2) increases bone volume and (3) partially restores callus stability.. A musculoskeletal trauma was created in 20 rabbits. To simulate fracture-site debridement, the limb was shortened. In the test group, a CYR61-coated collagen matrix was locally applied around the osteotomy. After ten days, gradual distraction was commenced (0.5 mm/12 h) to restore the original length. New bone formation was evaluated histomorphometrically, radiographically and biomechanically.. Osseus consolidation occured in all animals. Average maximum callus diameter was higher in the test group [1.39 mm; standard deviation (SD) = 0.078 vs 1.26 mm (SD = 0.14); p = 0.096]. In addition, bone volume was higher (p = 0.11) in the test group, with a mean value of 49.73 % (SD = 13.68) compared with 37.6 % (SD = 5.91). Torsional strength was significantly higher (p = 0.005) in the test group [105.43 % (SD = 31.68 %) vs. 52.57 % (SD = 24.39)]. Instead, stiffness of the newly reconstructed callus decreased (64.21 % (SD = 11.52) vs. 71.30 % (SD = 32.25) (p = 0.81)).. CYR61 positively influences callus regenerate after acute trauma, not only histologically and radiographically but also biomechanically, most probably by a CYR61-associated pathway.

Topics: Administration, Topical; Animals; Biomechanical Phenomena; Bone and Bones; Bony Callus; Cysteine-Rich Protein 61; Disease Models, Animal; Osteogenesis; Osteotomy; Rabbits; Radiography; Regeneration; Soft Tissue Injuries; Stress, Mechanical; Torque; Wound Healing

Although muscle dysfunction caused by unfamiliar lengthening contraction is one of most important issues in sports medicine, there is little known about the molecular events on regeneration process. The purpose of this study was to investigate the temporal and spatial expression patterns of myogenin, myoD, pax7, and myostatin after acute lengthening contraction (LC)-induced injury in the rat hindlimb.. We employed our originally developed device with LC in rat gastrocnemius muscle (n = 24). Male Wistar rats were anesthetized with isoflurane (aspiration rate, 450 ml/min, concentration, 2.0%). The triceps surae muscle of the right hindlimb was then electrically stimulated with forced isokinetic dorsi-flexion (180°/sec and from 0 to 45°). Tissue contents of myoD, myogenin, pax7, myostatin were measured by western blotting and localizations of myoD and pax7 was measured by immunohistochemistry. After measuring isometric tetanic torque, a single bout of LC was performed in vivo.. The torque was significantly decreased on days 2 and 5 as compared to the pre-treatment value, and recovered by day 7. The content of myoD and pax7 showed significant increases on day 2. Myogenin showed an increase from day 2 to 5. Myostatin on days 5 and 7 were significantly increased. Immunohistochemical analysis showed that myoD-positive/pax7-positive cells increased on day 2, suggesting that activated satellite cells play a role in the destruction and the early recovery phases.. We, thus, conclude that myogenic events associate with torque recovery after LC-induced injury.

Topics: Animals; Ankle Joint; Biomechanical Phenomena; Blotting, Western; Disease Models, Animal; Hindlimb; Immunohistochemistry; Male; Muscle Contraction; Muscle Development; Muscle, Skeletal; MyoD Protein; Myogenin; Myostatin; Paired Box Transcription Factors; Rats; Rats, Wistar; Recovery of Function; Regeneration; Satellite Cells, Skeletal Muscle; Sprains and Strains; Time Factors; Torque

Spasticity is a common disorder following spinal cord injury that can impair function and quality of life. While a number of mechanisms are thought to play a role in spasticity, the role of motoneuron persistent inward currents (PICs) is emerging as pivotal. The presence of PICs can be evidenced by temporal summation or wind-up of reflex responses to brief afferent inputs. In this study, a combined neurophysiological and novel biomechanical approach was used to assess the effects of passive exercise and modafinil administration on hyper-reflexia and spasticity following complete T-10 transection in the rat. Animals were divided into 3 groups (n=8) and provided daily passive cycling exercise, oral modafinil, or no intervention. After 6weeks, animals were tested for wind-up of the stretch reflex (SR) during repeated dorsiflexion stretches of the ankle. H-reflexes were tested in a subset of animals. Both torque and gastrocnemius electromyography showed evidence of SR wind-up in the transection only group that was significantly different from both treatment groups (p<0.05). H-reflex frequency dependent depression was also restored to normal levels in both treatment groups. The results provide support for the use of passive cycling exercise and modafinil in the treatment of spasticity and provide insight into the possible contribution of PICs.

Topics: Analysis of Variance; Animals; Benzhydryl Compounds; Chronic Disease; Disease Models, Animal; Electromyography; Female; H-Reflex; Modafinil; Muscle Spasticity; Muscle, Skeletal; Neuroprotective Agents; Physical Conditioning, Animal; Random Allocation; Rats; Rats, Sprague-Dawley; Reflex, Stretch; Severity of Illness Index; Spinal Cord Injuries; Time Factors; Torque

Current approaches for segmental bone defect reconstruction are restricted to autografts and allografts which possess osteoconductive, osteoinductive and osteogenic properties, but face significant disadvantages. The objective of this study was to compare the regenerative potential of scaffolds with different material composition but similar mechanical properties to autologous bone graft from the iliac crest in an ovine segmental defect model. After 12 weeks, in vivo specimens were analysed by X-ray imaging, torsion testing, micro-computed tomography and histology to assess amount, strength and structure of the newly formed bone. The highest amounts of bone neoformation with highest torsional moment values were observed in the autograft group and the lowest in the medical grade polycaprolactone and tricalcium phosphate composite group. The study results suggest that scaffolds based on aliphatic polyesters and ceramics, which are considered biologically inactive materials, induce only limited new bone formation but could be an equivalent alternative to autologous bone when combined with a biologically active stimulus such as bone morphogenetic proteins.

Topics: Animals; Biomechanical Phenomena; Bone and Bones; Disease Models, Animal; Equipment Failure Analysis; Osseointegration; Osteogenesis; Prostheses and Implants; Radiography; Sheep; Tissue Engineering; Tissue Scaffolds; Torque

This study evaluated the effect of magnesium dietary deficiency on bone metabolism and bone tissue around implants with established osseointegration.. For this, 30 rats received an implant in the right tibial metaphysis. After 60 days for healing of the implants, the animals were divided into groups according to the diet received. Control group (CTL) received a standard diet with adequate magnesium content, while test group (Mg) received the same diet except for a 90% reduction of magnesium. The animals were sacrificed after 90 days for evaluation of calcium, magnesium, osteocalcin and parathyroid hormone (PTH) serum levels and the deoxypyridinoline (DPD) level in the urine. The effect of magnesium deficiency on skeletal bone tissue was evaluated by densitometry of the lumbar vertebrae, while the effect of bone tissue around titanium implants was evaluated by radiographic measurement of cortical bone thickness and bone density. The effect on biomechanical characteristics was verified by implant removal torque testing.. Magnesium dietary deficiency resulted in a decrease of the magnesium serum level and an increase of PTH and DPD levels (P ≤ 0.05). The Mg group also presented a loss of systemic bone mass, decreased cortical bone thickness and lower values of removal torque of the implants (P ≤ 0.01).. The present study concluded that magnesium-deficient diet had a negative influence on bone metabolism as well as on the bone tissue around the implants.

Topics: Absorptiometry, Photon; Animals; Biomechanical Phenomena; Bone Density; Dental Implantation, Endosseous; Dental Implants; Device Removal; Disease Models, Animal; Implants, Experimental; Magnesium Deficiency; Osseointegration; Rats; Statistics, Nonparametric; Tibia; Torque

Muscle strains are one of the most common complaints treated by physicians. A muscle injury is typically diagnosed from the patient history and physical exam alone, however the clinical presentation can vary greatly depending on the extent of injury, the patient's pain tolerance, etc. In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Biological markers, such as serum creatine kinase levels, are typically elevated with muscle injury, but their levels do not always correlate with the loss of force production. This is even true of histological findings from animals, which provide a "direct measure" of damage, but do not account for all the loss of function. Some have argued that the most comprehensive measure of the overall health of the muscle in contractile force. Because muscle injury is a random event that occurs under a variety of biomechanical conditions, it is difficult to study. Here, we describe an in vivo animal model to measure torque and to produce a reliable muscle injury. We also describe our model for measurement of force from an isolated muscle in situ. Furthermore, we describe our small animal MRI procedure.

Topics: Animals; Disease Models, Animal; Mice; Muscle Contraction; Muscles; Rats; Recovery of Function; Torque

This study investigated the effects of ultrasound (US) at different frequencies on fracture healing over a three-week period in a rabbit fibular fracture model. Forty-five adult New Zealand White rabbits were divided into five groups: a control group and four groups treated with US frequencies of 0.5, 1.0, 1.5 and 2.0 MHz (0.5 W/cm(2), 200-μs burst, pulsed 1:4). After anesthesia, transverse osteotomy was performed on the fibula bone. This was followed by intravital staining and fluorescence microscopic examination of new bone formation and biomechanical tests of torsional stiffness at the osteotomy site. Results showed that total new bone formation and torsional stiffness of the fibula were greater in all US-treated groups than in the control group. No significant difference was found between any of the four US-treated groups. The US treatment also enhanced bone growth of the sham-treated contralateral fracture site. These results suggest that US treatment at 0.5, 1.0, 1.5 or 2.0 MHz can enhance fracture healing in a rabbit model. Furthermore, the effects of US on fracture healing at present parameters might not be confined locally.

Topics: Animals; Biomechanical Phenomena; Disease Models, Animal; Fibula; Fracture Healing; Male; Microscopy, Fluorescence; Osteotomy; Rabbits; Random Allocation; Staining and Labeling; Statistics, Nonparametric; Torque; Ultrasonic Therapy

Although glucocorticoids are frequently prescribed for the symptomatic management of inflammatory disorders such as rheumatoid arthritis, extended glucocorticoid exposure is the leading cause of physician-induced osteoporosis and leaves patients at a high risk of fracture. To study the biochemical effects of glucocorticoid exposure and how they might affect biomechanical properties of the bone, Raman spectra were acquired from ex vivo tibiae of glucocorticoid- and placebo-treated wild-type mice and a transgenic mouse model of rheumatoid arthritis. Statistically significant spectral differences were observed due to both treatment regimen and mouse genotype. These differences are attributed to changes in the overall bone mineral composition, as well as the degree of phosphate mineralization in tibial cortical bone. In addition, partial least squares regression was used to generate a Raman-based prediction of each tibia's biomechanical strength as quantified by a torsion test. The Raman-based predictions were as accurate as those produced by microcomputed tomography derived parameters, and more accurate than the clinically-used parameter of bone mineral density. These results suggest that Raman spectroscopy could be a valuable tool for monitoring bone biochemistry in studies of bone diseases such as osteoporosis, including tests of drugs being developed to combat these diseases.

Topics: Analysis of Variance; Animals; Arthritis, Rheumatoid; Biomechanical Phenomena; Disease Models, Animal; Glucocorticoids; Least-Squares Analysis; Mice; Osteoporosis; Prednisolone; Reproducibility of Results; Spectrum Analysis, Raman; Tibia; Torque; X-Ray Microtomography

We studied the response of dysferlin-null and control skeletal muscle to large- and small-strain injuries to the ankle dorsiflexors in mice. We measured contractile torque and counted fibers retaining 10-kDa fluorescein dextran, necrotic fibers, macrophages, and fibers with central nuclei and expressing developmental myosin heavy chain to assess contractile function, membrane resealing, necrosis, inflammation, and myogenesis. We also studied recovery after blunting myogenesis with X-irradiation. We report that dysferlin-null myofibers retain 10-kDa dextran for 3 days after large-strain injury but are lost thereafter, following necrosis and inflammation. Recovery of dysferlin-null muscle requires myogenesis, which delays the return of contractile function compared with controls, which recover from large-strain injury by repairing damaged myofibers without significant inflammation, necrosis, or myogenesis. Recovery of control and dysferlin-null muscles from small-strain injury involved inflammation and necrosis followed by myogenesis, all of which were more pronounced in the dysferlin-null muscles, which recovered more slowly. Both control and dysferlin-null muscles also retained 10-kDa dextran for 3 days after small-strain injury. We conclude that dysferlin-null myofibers can survive contraction-induced injury for at least 3 days but are subsequently eliminated by necrosis and inflammation. Myogenesis to replace lost fibers does not appear to be significantly compromised in dysferlin-null mice.

Topics: Animals; Cumulative Trauma Disorders; Dextrans; Disease Models, Animal; Dysferlin; Fluoresceins; Inflammation; Macrophages; Male; Membrane Proteins; Mice; Mice, Knockout; Muscle Contraction; Muscle Development; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Dystrophies, Limb-Girdle; Necrosis; Recovery of Function; Time Factors; Torque

The objective of this study was to determine the capability of silk fibroin powder as a biomaterial template for the restoration of peri-implant defects when mixed with Choukroun platelet-rich fibrin (PRF) in vivo.. Ten New Zealand white rabbits were used for this study. Using a trephine bur (diameter 7.0 mm), 2 monocortical defects were prepared. Subsequently, 2 dental implants were installed into the tibia (diameter 3.0 mm, length 10.0 mm). In the experimental group, the peri-implant defect was filled with a combination graft of silk fibroin powder and Choukroun PRF. The control was left in an unfilled state. The animals were killed at 8 weeks. Subsequently, a removal torque test and a histomorphometric analysis were done.. The removal torque for the experimental group was 30.34 +/- 5.06 N.cm, whereas it was 21.86 +/- 3.39 N.cm for the control. The difference between the 2 groups was statistically significant (P = .010). Mean new bone formation was 51.93 +/- 27.90% in the experimental group and 11.67 +/- 15.12% in the control (P = .003). Mean bone-to-implant contact was 43.07 +/- 21.96% in the experimental group and 15.37 +/- 23.84% in the control (P = .002).. A peri-implant defect can be successfully repaired by the application of Choukroun PRF and silk fibroin powder.

Topics: Alveolar Bone Loss; Animals; Biocompatible Materials; Biological Dressings; Bombyx; Bone Regeneration; Bone Substitutes; Dental Implantation, Endosseous; Dental Implants; Device Removal; Disease Models, Animal; Drug Combinations; Fibrin; Fibroins; Insect Proteins; Osseointegration; Platelet-Rich Plasma; Rabbits; Silk; Tissue Scaffolds; Torque

Contractures are a major clinical issue for patients with muscular dystrophies. However, it is unknown whether contractures are present in the widely used mdx mouse model of Duchenne muscular dystrophy. Therefore, the objectives of this study were to develop methods to measure muscle contractures in mice, to determine whether plantarflexion contractures are present in mdx mice, and to analyze the composition of the major muscles involved.. Hindlimbs of eight wild type and six mdx mice were assessed every 2 wks during the course of a 12-wk study. Assessments included range of motion and in vivo torques about the ankle. At the end of the study, mice were euthanized, and muscles were analyzed for composition.. The mdx mice had ∼10 degrees less dorsiflexion, increased passive torque moving the ankle into dorsiflexion, and an increased passive-to-active torque ratio relative to wild type mice. Gastrocnemius muscle composition alterations included increased wet mass, decreased protein content, and increased collagen.. The results indicate that mdx mice have plantarflexion contractures similar to those seen in children with Duchenne muscular dystrophy. In future studies, these measures can be used to assess strategies to slow the progression of contractures that occur with muscular dystrophies.

Topics: Animals; Collagen; Disease Models, Animal; Hindlimb; Hydroxyproline; Male; Mice; Mice, Inbred mdx; Muscle Contraction; Muscle Proteins; Muscle, Skeletal; Muscular Dystrophy, Duchenne; Range of Motion, Articular; Torque

Glucocorticoids inhibit bone remodeling and fracture healing. We sought to determine whether osteogenic protein 1 (OP-1) can overcome this inhibition in a closed fracture model in the rat. Time-released prednisolone or placebo pellets were implanted subcutaneously; closed femoral fractures were created 2 weeks later in rats. Fractures received sham, OP-1 and collagen, or collagen-only implants. Femurs were harvested at 3, 10, 21, 28, and 42 days postfracture. Fractures were examined radiographically for amount of hard callus; mechanically for torque and stiffness (also expressed as a percentage of the contralateral intact femur); and histomorphometrically for amount of cartilaginous and noncartilaginous soft callus, hard callus, and total callus. Glucocorticoid administration inhibited fracture healing. The application of a devitalized Type I collagen matrix mitigated the inhibitory effects of prednisolone on fracture healing However, further increases in indices of fracture healing were observed when OP-1 was added to the collagen matrix compared with collagen alone. OP-1 and collagen was more effective than collagen alone.

Topics: Animals; Biomechanical Phenomena; Bone Morphogenetic Protein 7; Bone Remodeling; Bony Callus; Collagen Type I; Disease Models, Animal; Drug Carriers; Drug Implants; Femoral Fractures; Femur; Fracture Healing; Glucocorticoids; Male; Prednisolone; Radiography; Rats; Time Factors; Torque

Neuromuscular electrical stimulation (NMES) can be used to activate paralyzed or paretic muscles to generate functional or therapeutic movements. The goal of this research was to develop a rodent model of NMES-assisted movement therapy after spinal cord injury (SCI) that will enable investigation of mechanisms of NMES-induced plasticity, from the molecular to systems level. Development of the model requires accurate mapping of electrode and muscle stimulation sites, the capability to selectively activate muscles to produce graded contractions of sufficient strength, stable anchoring of the implanted electrode within the muscles and stable performance with functional reliability over several weeks of the therapy window. Custom designed electrodes were implanted chronically in hindlimb muscles of spinal cord transected rats. Mechanical and electrical stability of electrodes and the ability to achieve appropriate muscle recruitment and joint angle excursion were assessed by characterizing the strength duration curves, isometric torque recruitment curves and kinematics of joint angle excursion over 6-8 weeks post implantation. Results indicate that the custom designed electrodes and implantation techniques provided sufficient anchoring and produced stable and reliable recruitment of muscles both in the absence of daily NMES (for 8 weeks) as well as with daily NMES that is initiated 3 weeks post implantation (for 6 weeks). The completed work establishes a rodent model that can be used to investigate mechanisms of neuroplasticity that underlie NMES-based movement therapy after spinal cord injury and to optimize the timing of its delivery.

Topics: Animals; Ankle Joint; Biomechanical Phenomena; Biophysics; Disease Models, Animal; Electric Stimulation; Electrodes, Implanted; Female; Isometric Contraction; Muscle Strength; Muscle, Skeletal; Musculoskeletal Physiological Phenomena; Paraplegia; Rats; Rats, Long-Evans; Spinal Cord Injuries; Time Factors; Torque

This study evaluated healing of equine metatarsal osteotomies and ostectomies in response to percutaneous injection of adenoviral (Ad) bone morphogenetic protein (BMP)-2, Ad-BMP-6, or beta-galactosidase protein vector control (Ad-LacZ) administered 14 days after surgery. Radiographic and quantitative computed tomographic assessment of bone formation indicated greater and earlier mineralized callus in both the osteotomies and ostectomies of the metatarsi injected with Ad-BMP-2 or Ad-BMP-6. Peak torque to failure and torsional stiffness were greater in osteotomies treated with Ad-BMP-2 than Ad-BMP-6, and both Ad-BMP-2- and Ad-BMP-6-treated osteotomies were greater than Ad-LacZ or untreated osteotomies. Gene expression of ostectomy mineralized callus 8 weeks after surgery indicated upregulation of genes related to osteogenesis compared to intact metatarsal bone. Expression of transforming growth factor beta-1, cathepsin H, and gelsolin-like capping protein were greater in Ad-BMP-2- and Ad-BMP-6-treated callus compared to Ad-LacZ-treated or untreated callus. Evidence of tissue biodistribution of adenovirus in distant organs was not identified by quantitative PCR, despite increased serum antiadenoviral vector antibody. This study demonstrated a greater relative potency of Ad-BMP-2 over Ad-BMP-6 in accelerating osteotomy healing when administered in this regimen, although both genes were effective at increasing bone at both osteotomy and ostectomy sites.

Topics: Adenoviridae; Animals; Biomechanical Phenomena; Bone Morphogenetic Protein 2; Bone Morphogenetic Protein 6; Bone Morphogenetic Proteins; Bony Callus; Disease Models, Animal; Fracture Healing; Fractures, Bone; Gene Expression Regulation; Gene Transfer Techniques; Genetic Therapy; Horses; Humans; Lac Operon; Metatarsal Bones; Oligonucleotide Array Sequence Analysis; Osteogenesis; Osteotomy; Tomography, X-Ray Computed; Torque; Torsion, Mechanical; Transforming Growth Factor beta

Prolonged immobilization reduces passive range of motion of joints creating joint contractures. Whether and to what extent these iatrogenic contractures can be reduced is unknown. We raised three questions using an animal model: What degree of contracture remains at the end of a defined remobilization period? Do contractures in sham-operated and immobilized joints differ? What is the contribution of the posterior knee capsule in limiting knee extension? We immobilized one knee of 11 adult male rats in flexion to induce a joint contracture; 10 control animals underwent a sham operation. After 8 weeks, the internal fixation device was removed, and the animals were allowed to resume unrestricted activity for 4 weeks at the end of which the knee range of motion was measured with standardized torques. The mean flexion contracture was higher in the immobilized group (51.9 degrees +/- 2.8 degrees ) than in the sham-operated group (18.9 degrees +/- 2.1 degrees ). Eighty-eight percent of the contractures remained in the immobilized group after dividing skin and muscle, suggesting an important contribution of the posterior knee capsule in limiting knee mobility. Based on our preliminary study the range of motion of rat knees immobilized for 8 weeks remained substantially reduced after a 4-week period of unassisted remobilization.

Topics: Animals; Contracture; Disease Models, Animal; Immobilization; Joint Capsule; Knee Joint; Male; Pilot Projects; Range of Motion, Articular; Rats; Rats, Sprague-Dawley; Recovery of Function; Time Factors; Torque

The purpose of this study was to clarify the relationship between mechanical stress and tissue response of the contracted knee joint in rats and to propose a new design of contracture correction device for clinical use. Wistar rats were operated on to immobilize their knee joints with a procedure causing periarticular bleeding and were kept in flexed position for 40 days. At day 40, the immobilizing wire was removed, and after day 43, the contracted knee joint had been treated with tunable corrective devices secured by an external fixation method to the rear limb. These devices consisted of four types of motor-driving system which provided several different low-load and continuous stretch torques. Measuring the angle of maximum knee extension, its effectiveness was assessed comparing with a lower load and control group of natural recovery course. The device also had a cyclic joint movement within the acquired range of motion and an oval cam mechanism producing a small distraction force to the joint along its long axis. The results showed that an appropriate range of low-load continuous torque was more effective to correct joint contracture. On the basis of the animal experiment, a new computer-controlled, gas-driven contracture correction device was developed for clinical trial. It was concluded that mechanical application in a condition with low and continuous torque is a useful treatment for fixed joint contracture.

Topics: Animals; Contracture; Disease Models, Animal; Equipment Design; Knee Joint; Male; Range of Motion, Articular; Rats; Rats, Wistar; Therapy, Computer-Assisted; Torque; Weight-Bearing

Topics: Animal Welfare; Animals; Contracture; Disease Models, Animal; Rats; Therapy, Computer-Assisted; Torque

Osteoarthritic patients show only a weak association between radiographic signs of joint disease and joint pain and disability. Conversely, muscle weakness is one of the earliest and most common symptoms of patients with osteoarthritis (OA). However, while many experimental models of osteoarthritis include a component of muscular weakness, no model has isolated this factor satisfactorily. Therefore, the purpose of this study was to develop and validate an experimental animal model of muscle weakness for future use in the study of OA. Botulinum Type-A toxin (BTX-A) was uni-laterally injected into the quadriceps musculature of New Zealand white rabbits (3.5 units/kg). Isometric knee extensor torque at a range of knee angles and stimulation frequencies, and quadriceps muscle mass, were quantified for control animals, and at one- and six-months post-repeated injections, in both, the experimental and the contralateral hindlimb. Ground reaction forces were measured in all animals while hopping across two force platforms. Isometric knee extension torque and quadriceps muscle mass was systematically decreased in the experimental hindlimb. Vertical ground reaction forces in the push off phase of hopping were also decreased in the experimental compared to control hindlimbs. We conclude that BTX-A injection into the rabbit musculature creates functional and absolute muscle weakness in a reproducible manner. Therefore, this model may be used to systematically study the possible effects of muscle weakness on joint degeneration, either as an isolated intervention, or in combination with other interventions (anterior cruciate ligament transection, meniscectomy) known to create knee joint degeneration.

Topics: Animals; Botulinum Toxins; Disease Models, Animal; Knee Joint; Muscle Weakness; Muscle, Skeletal; Osteoarthritis; Rabbits; Torque

The spine is routinely subjected to repetitive combined loading, including axial torque. Repetitive flexion-extension motions with low magnitude compressive forces have been shown to be an effective mechanism for causing disc herniations. The addition of axial torque to the efficacy of failure mechanisms, such as disc herniation, need to be quantified. The purpose of this study was to determine the role of static axial torque on the failure mechanics of the intervertebral joint under repetitive combined loading.. Repetitive flexion-extension motions combined with 1472 N of compression were applied to two groups of nine porcine motion segments. Five Nm of axial torque was applied to one group. Load-displacement behaviour was quantified, and planar radiography was used to document tracking of the nucleus pulposus and to identify fractures.. The occurrence of facet fractures was found to be higher (P=0.028) in the axial torque group (7/9), compared to the no axial torque group (2/9). More hysteresis energy was lost up to 3000 cycles of loading in the axial torque group (P<0.014). The flexion-extension cycle stiffness was not different between the two groups until 4000 cycles of loading, after which the axial torque group stiffness increased (P=0.016). The percentage of specimens that herniated after 3000 cycles of loading was significantly larger (P=0.049) for the axial torque group (71%) compared to the no axial torque group (29%).. Small magnitudes of static axial torque alter the failure mechanics of the intervertebral disc and vertebrae in combined loading situations. Axial torque appears to accelerate the susceptibility for injury to the intervertebral joint complex. This suggests tasks involving axial torque with other types of loading, apart from axial twist motion, should be monitored to assess exposure and injury risk.

Topics: Animals; Biomechanical Phenomena; Cervical Vertebrae; Disease Models, Animal; Elasticity; Fractures, Cartilage; Hernia; In Vitro Techniques; Intervertebral Disc Displacement; Range of Motion, Articular; Spinal Fractures; Stress, Mechanical; Swine; Torque; Weight-Bearing

Abnormalities of the intervertebral discs have been found in a high frequency among young elite athletes. Several studies have also reported that the adolescent spine, especially the vertebral growth zones, is vulnerable to trauma. However, there is incomplete knowledge regarding the injury mechanism of the growing spine. In this study, the injury patterns of the adolescent porcine spine with disc degeneration were examined.. Twenty-four male pigs were used. A degenerative disc was created by drilling a hole through the cranial endplate of a lumbar vertebra into the disc. Two months later the animals were sacrificed and the degenerative functional spinal units (segments) were harvested. The segments were divided into three groups and exposed to axial compression, flexion compression or extension compression to failure. The load and angle at failure were measured for each group. The segments were examined with magnetic resonance imaging and plain radiography before and after the loading and finally examined macroscopically and histologically.. The degenerated segments required considerably more compressive load to failure than non-degenerated segments. Creating a flexion injury required significantly more load than an extension injury. Fractures and/or separations of the endplates from the vertebral bodies were seen at the margins of the endplates and in the growth zone. Only severe separations and fractures could be seen on plain radiography and magnetic resonance imaging.. The weakest part of the adolescent porcine lumbar spine with experimentally-induced degeneration, when loaded in axial compression, flexion compression or extension compression, was the growth zone, and, to a lesser extent, the endplate. Degenerated discs seem to withstand higher mechanical loads than non-degenerated discs, probably due to altered stress distribution.

Topics: Aging; Animals; Biomechanical Phenomena; Cervical Vertebrae; Compressive Strength; Disease Models, Animal; Elasticity; Fractures, Cartilage; In Vitro Techniques; Intervertebral Disc Displacement; Male; Range of Motion, Articular; Spinal Fractures; Stress, Mechanical; Swine; Torque; Weight-Bearing

Neuromuscular electrical stimulation (NMES) could simulate physiological muscle functions known to be associated with the normal bone healing process. The object of the present study was to evaluate the effect of NMES on fracture healing, using an animal model. Thirty rabbits received unilateral, transverse, mid-tibial, 3-mm gapped osteotomies that were stabilized with double-bar external fixators. The femoral vein was ligated to induce venous stasis. From the fourth post-operative day, the study group was treated with 1 h daily of NMES for four weeks, while the control group was treated without NMES. For NMES, two surface electrodes were used: one above the patellar tendon and another around the lateral thigh. Callus area and mineral content at the osteotomy gap were measured, biweekly, using computerized tomographic examinations. Biomechanical properties of healing were evaluated with a torsion test, eight weeks after the index operation. Osteotomies treated with NMES exhibited 31% (p=0.01) higher mineral content and 27% (p=0.009) larger callus area than control osteotomies at eight weeks. The maximum torque, torsional stiffness, angular displacement at maximum torque, and energy required to failure of specimens in the study group were 62% (p=0.006), 29% (p=0.03), 34.6% (p=0.008), and 124% (p<0.0001) higher, respectively, than those in the control group at eight weeks. The results of the present study demonstrated that the use of NMES can enhance callus development and mineralization, with the consequent improvement in biomechanical properties of the healing bone.

Topics: Animals; Bone Density; Bony Callus; Disease Models, Animal; Electric Stimulation Therapy; Female; Fracture Healing; Fractures, Bone; Osteogenesis; Osteotomy; Rabbits; Radiography; Stress, Mechanical; Tibia; Time Factors; Torque; Torsion Abnormality

We investigated the effects of low-intensity pulsed ultrasound (LIPUS; 30 mW/cm2 spatial and temporal average) on the timing of LIPUS treatment in distraction osteogenesis. Lengthening of the right tibia was performed in 75 male Japanese white rabbits using unilateral fixators (waiting period, 7 days; distraction rate, 1.5 mm/day; distraction period, 7 days). Rabbits were divided into four groups according to the timing of the LIPUS treatment. Control group had no stimulation. Waiting group was treated with a daily 20-min session of LIPUS during a 7-day latency period. Lengthening group was treated during the lengthening period. Maturation group was treated for the first 7 days after completion of distraction. We evaluated the distraction site by radiography and histology every week for 4 weeks. Bone mineral density (BMD) and mechanical strength were tested and microfocus X-ray computed tomography was performed on specimens 2 weeks after completion of distraction. The lengthening group had greater BMD and mechanical strength than the other groups, bone regeneration was enhanced more in the maturation group than in the control or waiting groups. Histologically, endochondral bone formation in the lengthening and the maturation groups occurred earlier than in the control or waiting groups. These results suggest the LIPUS effect is mediated via endochondral pathways. We concluded that LIPUS stimulates bone formation in distraction osteogenesis and is most effective during the lengthening phase.

Topics: Absorptiometry, Photon; Animals; Bone Density; Bony Callus; Disease Models, Animal; Elasticity; Imaging, Three-Dimensional; Male; Osteogenesis, Distraction; Osteotomy; Rabbits; Stress, Mechanical; Tibia; Time Factors; Tomography, X-Ray Computed; Torque; Ultrasonic Therapy; Ultrasonography

This study tested the hypothesis that interfragmentary axial movement of transverse diaphyseal osteotomies would result in improved fracture healing compared to interfragmentary shear movement. Ten skeletally mature merino sheep underwent a middiaphyseal osteotomy of the right tibia, stabilized by external fixation with an interfragmentary gap of 3 mm. A custom made external fixator allowed either pure axial (n=5) or pure shear movement (n=5) of 1.5 mm amplitude during locomotion by the animals. The movement of the osteotomy gap was monitored weekly in two sheep by an extensometer temporarily attached to the fixator. After 8 weeks the sheep were killed, and healing of the osteotomies was evaluated by radiography, biomechanical testing, and undecalcified histology. Shear movement considerably delayed the healing of diaphyseal osteotomies. Bridging of the osteotomy fragments occurred in all osteotomies in the axial group (100%), while in the shear group only three osteotomies (60%) were partially bridged. Peripheral callus formation in the shear group was reduced by 36% compared to the axial group (p<0.05). In the axial group bone formation was considerably larger at the peripheral callus and in between the osteotomy gaps but not in the intramedullary area. The larger peripheral callus and excess in bone tissue at the level of the gap resulted in a more than three times larger mechanical rigidity for the axial than for the shear group (p<0.05). In summary, fixation that allows excessive shear movement significantly delayed the healing of diaphyseal osteotomies compared to healing under axial movement of the same magnitude.

Topics: Animals; Bony Callus; Compressive Strength; Disease Models, Animal; External Fixators; Female; Fracture Fixation; Fracture Healing; Radiography; Shear Strength; Sheep; Tibia; Tibial Fractures; Torque

The purpose of this study was to determine whether both neutrophils and macrophages infiltrate the hematoma site of stretch-injured rabbit tibialis anterior muscle. The Mab.198 antibody was used to detect CD11b(+) neutrophils or macrophages. Neutrophils were identified specifically by using the RPN3/57 antibody. The RAM11 antibody was used to detect macrophages. The histological characteristics of the hematoma site, torn fibers or inflammatory cells, were present primarily at 4 and 24 h, but not at 48 and 72 h after injury. A difference in the Mab.198(+) cellular concentration was detected over time between uninjured and injured muscles (P = 0.03). The injured-uninjured difference in the RPN3/57(+) or RAM11(+) cellular concentrations approached significance (P = 0.07) or else was deemed insignificant (P = 0.13), respectively. Therefore, neutrophils may predominate over RAM11(+) macrophages in stretch-injured muscle. These findings may influence the antiinflammatory strategies used to treat stretch injuries.

Topics: Animals; Antigens, Differentiation; Biomarkers; Cell Count; Disease Models, Animal; Disease Progression; Hematoma; Immunohistochemistry; Macrophage-1 Antigen; Macrophages; Muscle, Skeletal; Neutrophil Infiltration; Neutrophils; Rabbits; Sprains and Strains; Stress, Mechanical; Torque

The effects of a pulsed electromagnetic field (PEMF) on late bone healing phases using an osteotomy gap model in the canine mid-tibia were investigated. A transverse mid-diaphyseal tibial osteotomy with a 2-mm gap was performed unilaterally in 12 adult mixed-breed dogs and stabilized with external fixation. Animals in the variable group (n = 6) were treated with PEMF for 1 h daily starting 4 weeks after surgery for a total of 8 weeks, whereas no stimulation signal was generated in the control group (n = 6). Functional load-bearing and radiographic assessments were conducted time-sequentially until euthanasia 12 weeks after surgery. Torsional tests and an analysis of undecalcified histology were performed on the retrieved mid-tibial diaphysis containing the osteotomy site. In the PEMF group, load-bearing of the operated limb recovered earlier when compared to the control group (p < 0.05). Load-bearing in the PEMF group at 8 weeks was greater than in the control group (p < 0.02). The periosteal callus area increased following surgery at 6 weeks (p < 0.05) and thereafter (p < 0.01) in the PEMF group, while a significant increase was observed at 8 and 10 weeks after surgery (p < 0.05) in the control group. Both the normalized maximum torque and torsional stiffness of the PEMF group were significantly greater than those of the control group (p < 0.04 and p < 0.007, respectively). Histomorphometric analyses revealed greater new-bone formation (p < 0.05) in the osteotomy gap tissue and increased mineral apposition rate (p < 0.04) and decreased porosity in the cortex adjacent to the osteotomy line (p < 0.02) in the PEMF group. PEMF stimulation of 1 h per day for 8 weeks provided faster recovery of load-bearing, a significant increase in new bone formation, and a higher mechanical strength of the healing mid-tibial osteotomy. This study revealed enhancing effects of PEMF on callus formation and maturation in the late-phase of bone healing.

Topics: Animals; Disease Models, Animal; Dogs; Electric Stimulation Therapy; Electromagnetic Fields; Fracture Healing; Male; Osteotomy; Radiography; Stress, Mechanical; Tibia; Time Factors; Torque; Treatment Outcome; Weight-Bearing

Several clinical series, analyzing fracture healing in patients with diabetes mellitus (DM). demonstrated significant incidence of delayed union, non-union, and pseudarthrosis. In this study, analysis was performed to evaluate the effects of blood glucose (BG) control on fracture healing in the DM BB Wistar rat, a rat strain that represents a close homology to Type I DM in man. Our study showed decreased cell proliferation at the fracture site as well as decreased mechanical stiffness and bony content in the poorly controlled DM rats. To determine the effect of BG control, DM rats were treated with insulin sufficient to maintain physiologic BG levels throughout the course of the study. Values of cellular proliferation, biomechanical properties and callus bone content in tightly controlled DM animals were not significantly different from values of non-DM control values. This study suggests that insulin treatment with resultant improved BG control will ameliorate the impaired early and late parameters of DM fracture healing.

Topics: Animals; Biomechanical Phenomena; Blood Glucose; Bromodeoxyuridine; Cell Division; Diabetes Mellitus, Type 1; Disease Models, Animal; Femoral Fractures; Fracture Healing; Hypoglycemic Agents; Insulin; Male; Microscopy, Acoustic; Rats; Rats, Inbred BB; Rats, Wistar; Torque

To evaluate whether coating AO/ASIF screws with osteoconductive materials can improve bone-screw fixation.. Ninety-six AO/ASIF 4.5-millimeter cortical screws were divided into four paired groups and implanted in the femurs and tibiae of six sheep: Group A = standard stainless steel screws; Group B = stainless steel screws coated with highly crystalline hydroxyapatite; Group C = stainless steel screws coated with low crystalline hydroxyapatite; Group D = titanium screws coated with titanium. The screws were implanted according to the standard AO technique to an insertion torque of 2,000 Newton-millimeters. Sheep were killed at one, three, and twelve months after surgery.. Extraction torque was measured on six screws from each group selected at random at time of each euthanization. Morphologic analysis of the bone-screw interface was performed on the remaining screws.. At each euthanization the extraction torque of Group A was lower than that of the other groups (p < 0.0001). At three and twelve months the extraction torque of Group B was higher than that of Group D (p = 0.002). Morphologic results showed extensive bone-screw gap in Group A. Optimal osteointegration was observed in Groups B and C. Osteointegration of Group D was higher than that of Group A and lower than that of Groups B and C.. It was demonstrated that AO/ASIF screws coated with osteoconductive materials achieve optimal fixation strength, even in the early phase. This fixation strength was significantly higher than that of the standard screws.

Topics: Animals; Biomechanical Phenomena; Bone Screws; Coated Materials, Biocompatible; Disease Models, Animal; Durapatite; Female; Femoral Fractures; Fracture Fixation; Fracture Healing; Random Allocation; Sheep; Tensile Strength; Tibial Fractures; Titanium; Torque

Pathologic fractures from a reduction in bone mass and strength are a debilitating complication affecting the quality of life of individuals with metastatic lesions. There are a number of existing animal models for studying the effects of bone metastases experimentally, but these models are unsuitable for measuring structural changes in metastatic bone. Our goal was to present an in vivo model for directly investigating the densitometric and structural consequences of tumor-induced osteolysis in long bones. One femur from female Sprague Dawley rats was implanted with Walker Carcinosarcoma 256 malignant breast cancer cells or with a Sham implant. After 28 days, the animals were killed, and both femora of each animal evaluated using histomorphometry, densitometry, and mechanical testing. Compared to Sham-operated controls, we found an 11% decrease in bone mineral content, a 9% decrease in bone mineral density using dual energy X-ray absorptiometry, and a 16% decrease in bone density using peripheral quantitative computed tomography in the group with tumor cell implants. In addition, failure torque was decreased by 35% compared to the contralateral controls and by 41% compared to the Sham-operated controls. Torsional stiffness in the tumor cell-implanted femora was decreased by 35% compared to contralateral controls and by 39% compared to Sham-operated controls. Bone density was only weakly to moderately associated with bone strength in our model. By creating reproducible localized tumor-induced osteolytic lesions in a long bone, this model provides the most direct evaluation of the structural consequences of bone metastases. In the future, this model may provide a method for determining the effects of new therapeutic approaches on the preservation of bone mass and bone strength in the presence of metastatic bone disease.

Topics: Absorptiometry, Photon; Animals; Biomechanical Phenomena; Bone Density; Breast Neoplasms; Disease Models, Animal; Elasticity; Female; Femoral Neoplasms; Osteolysis; Rats; Rats, Sprague-Dawley; Tensile Strength; Tomography, X-Ray Computed; Torque

Xenograft is considered an alternative material for bone transplantation, but its bone healing capacity is inferior compared to that of autografts and allografts. Here, we tested whether bone morphogenetic protein (BMP) addition enhances the suitability of demineralized xenogeneic bovine bone for bone grafting in dogs, and whether xenogeneic bone is a suitable carrier material for BMPs. The capacity of demineralized bovine bone implants, with and without native partially purified bovine BMP, to heal a 2-cm ulnar defect was determined in six dogs over a follow-up time of 20 weeks. No instances of bone union were seen, but there was slightly more bone formation in the xenografts with BMP, though the difference was not statistically significant. The ulnas treated with an implant with BMP were also mechanically stronger, but the difference was not significant. Computed tomography scans showed no differences in the implant area in bone density, bone mineral content, or bone cross-sectional area. It is concluded that native, partially purified BMP does not sufficiently improve the suitability of bovine demineralized xenografts as a bone substitute material for dog. Demineralized xenogeneic bone does not seem to be a feasible carrier material for BMP.

Topics: Animals; Bone Morphogenetic Proteins; Bone Plates; Bone Regeneration; Bone Screws; Bone Transplantation; Cattle; Disease Models, Animal; Dogs; Drug Carriers; Drug Evaluation, Preclinical; Feasibility Studies; Female; Male; Osteotomy; Tensile Strength; Torque; Transplantation, Heterologous; Ulna

Pin tract infection is a common complication of external fixation. An antiinfective external fixator pin might help to reduce the incidence of pin tract infection and improve pin fixation.. Stainless steel and titanium external fixator pins, with and without a lipid stabilized hydroxyapatite/chlorhexidine coating, were evaluated in a goat model. Two pins contaminated with an identifiable Staphylococcus aureus strain were inserted into each tibia of 12 goats. The pin sites were examined daily. On day 14, the animals were killed, and the pin tips cultured. Insertion and extraction torques were measured.. Infection developed in 100% of uncoated pins, whereas coated pins demonstrated 4.2% infected, 12.5% colonized, and the remainder, 83.3%, had no growth (p < 0.01). Pin coating decreased the percent loss of fixation torque over uncoated pins (p = 0.04).. These results demonstrate that the lipid stabilized hydroxyapatite/chlorhexidine coating was successful in decreasing infection and improving fixation of external fixator pins.

Topics: Animals; Anti-Infective Agents, Local; Bone Nails; Chi-Square Distribution; Chlorhexidine; Coated Materials, Biocompatible; Device Removal; Disease Models, Animal; Durapatite; External Fixators; Fracture Fixation; Goats; Male; Stainless Steel; Staphylococcal Infections; Statistics, Nonparametric; Tibial Fractures; Titanium; Torque

During multimicroelectrode stimulation within the cat L6 spinal cord, the number of electrodes activated, their separation distance, and the stimulus interleave time all influenced isometric knee joint extension torque. The torque evoked by stimulation with a three electrode combination could be enhanced or suppressed when compared with that evoked by single or paired electrode stimulation. A similar difference was noted when comparing two electrode combination versus single electrode stimulation. Relative fatigue was not improved significantly by interleaving the stimuli from two or three microelectrodes. Compared with the extension torque response evoked by noninterleaved stimulation, torque evoked by interleaved stimulation with the two microelectrode combination was decreased when the electrode distance was 2.0 mm or less and increased when the electrode distance was 3.0 mm. Designing an optimal stimulation strategy for multimicroelectrode spinal cord stimulation will be challenging and complex if a suppression effect among these electrodes is to be avoided. To reduce muscle fatigue, an asynchronous, interleaved strategy of stimulation may be required.

Topics: Animals; Cats; Disease Models, Animal; Electric Stimulation Therapy; Electromyography; Knee Joint; Lumbar Vertebrae; Male; Microelectrodes; Muscle Contraction; Muscle Fatigue; Random Allocation; Range of Motion, Articular; Reaction Time; Sacrum; Spinal Cord; Spinal Cord Injuries; Time Factors; Torque

Animal models for joint diseases are necessary for in vivo studies. Joint contractures are characterized by lack of the normal range of motion of a joint most often due to increased soft tissue stiffness. Biological and biochemical data have been obtained but biomechanical data on small animals are rare. An instrument was developed to measure rat knee angular displacement at various soft tissue loads in normal and pathological circumstances. This article describes the instrument and reports its reproducibility and accuracy. The reproducibility and accuracy of this instrument was found to be acceptable thereby validating its use for research purposes with adult rat knees.

Topics: Animals; Anthropometry; Bias; Contracture; Disease Models, Animal; Equipment Design; Knee Joint; Range of Motion, Articular; Rats; Reproducibility of Results; Torque; Weight-Bearing

Three-month-old male rats were subjected 3 times weekly for 1 h to eccentric exercise of one triceps surae muscle (30 stimulations/min) under general anesthesia in order to induce Achilles tendon disorder corresponding to paratenonitis and tendinosis in man. Net muscle work during the sessions ranged between 0.67 and 4.37 mJ (mean 1.72, SD 0.77). After 9 and 13 sessions, respectively, 2 rats started to show gait alterations during the functional test which was performed 2-3 times weekly. These rats were killed after additional sessions which showed a worsening of the limp. The other trained rats and controls did not limp and were killed after 7-11 weeks. Histologic evaluation of the Achilles tendons from the exercised limb showed in the majority of the cases hypervascularization, increased number of nerve filaments and increased immunoreactivity for substance P and calcitonin gene-related peptide. The tendons from the nonstimulated limb looked normal. The distribution of collagen types I and II appeared normal in the tendon and its insertion to the calcaneus. Inflammation of the epi- and paratenon could be provoked in the rat, but tendon changes corresponding to chronic tendinosis did not develop within 11 weeks with the used training regime. The clinical relevance of this model for chronic tendon disease needs to be evaluated further.

Topics: Achilles Tendon; Animals; Biomechanical Phenomena; Calcitonin Gene-Related Peptide; Chronic Disease; Collagen; Cumulative Trauma Disorders; Disease Models, Animal; Gait; Hindlimb; Hip Joint; Male; Peripheral Nerves; Physical Conditioning, Animal; Pilot Projects; Rats; Rats, Sprague-Dawley; Substance P; Torque

We investigated whether -intermittent hyperbaric oxygen (HBO) therapy can mitigate the adverse effects of cigarette smoking on the bone healing of tibial lengthening by using a previously validated rabbit model.. Eighteen male rabbits were randomly divided into three groups of six animals each. Group 1 (smoking plus HBO) went through intermittent cigarette smoke inhalation and hyperbaric oxygen therapy, group 2 (control) did not go through intermittent cigarette smoke inhalation or hyperbaric oxygen therapy and group 3 (smoking) went through intermittent cigarette smoke inhalation. Each animal's right tibia was lengthened 5 mm by using an uniplanar lengthening device. Bone mineral density (BMD) study was performed for all the animals at 1 day before operation and 3, 4, 5, and 6 weeks after operation. All of the animals were killed at 6 weeks postoperatively for biomechanical testing.. By using the preoperative BMD as an internal control, we found that the BMD of group 1 (smoking plus HBO)and group 2 (control) was superior to that of group 3 (smoking). The mean %BMD at 3, 4, 5, and 6 weeks were 58.6%, 66.6%, 73.7%, and 83.8%, respectively, in group 1, whereas the mean %BMD were 52.0%, 64.3%, 70.1%, and 76.2%, respectively, in group 2, and the mean %BMD were 46.2%, 54.0%, 64.9%, and 69.4%, respectively, in group 3 (two-tailed t test, p > 0.05, p > 0.05, p > 0.05, and p < 0.05 at 3, 4, 5, and 6 week respectively between group 1 and group 2, p < 0.01,p < 0.01,p < 0.01, and p < 0.01 at 3, 4, 5, and 6 week, respectively, between group 1 and group 3 and p < 0.05, p < 0.05, p < 0.05, and p < 0.05 at 3, 4, 5, and 6 week respectively between group 2 and group 3). By using the contralateral nonoperated tibia as an internal control, we found that the torsional strength of group 1 (smoking plus HBO) and group 2 (control) was superior to that of group 3 (smoking). The mean percentage of maximum torque was 80.9% in group 1 (smoking plus HBO) and was 78.0% in group 2 (control), whereas the mean percentage of maximum torque was 59.6 % in group 3 (smoking) (two-tailed t test, p < 0.05 between groups land 3 and between groups 2 and 3, whereas p > 0.05 between groups 1 and 2).. This study suggests that smoke inhalation delays the bone healing in tibial lengthening; however, HBO mitigates the delayed healing effect of smoke inhalation and, thus, helps the smoking animal in achieving an expeditious bone healing in tibial lengthening.

Topics: Absorptiometry, Photon; Animals; Bone Density; Bone Lengthening; Disease Models, Animal; Fracture Healing; Hyperbaric Oxygenation; Male; Rabbits; Radionuclide Imaging; Random Allocation; Smoking; Tensile Strength; Tibia; Time Factors; Torque

Pathologic fractures may occur with minimal trauma after spinal cord injury (SCI) because of osteoporosis. Rats were evaluated to determine whether they could be used as an SCI animal model. Male Sprague-Dawley rats underwent spinal cord transection at the ninth thoracic vertebrae. Control rats underwent a sham procedure. Mechanical testing of the humeral shaft, femoral shaft, tibial shaft, femoral neck, distal femur, and proximal tibia was performed separately at 0, 8, and 24 weeks after surgery. At 24 weeks, significant differences between SCI and control rats were found in maximum torque needed to produce failure in the femoral shaft (63 percent of control, p < 0.05) and tibial shaft (63 percent, p < 0.01), and in compressive load to produce failure in cross-sectional specimens of the distal femur (51 percent, p < 0.05) and proximal tibia (50 percent, p < 0.01). No differences were found in the maximum torque needed to produce failure of the humeral shaft (106 percent, p = 0.77) between SCI and control rats. Reductions in relative bone strength in SCI rats at 24 weeks were similar in magnitude to bone mineral density changes reported in humans with chronic paraplegia. Thus, Sprague-Dawley rats appear to be good animal models in which to evaluate changes in bone strength following SCI.

Topics: Animals; Bone Density; Disease Models, Animal; Male; Paraplegia; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries; Stress, Mechanical; Torque; Torsion Abnormality

A sheep study was performed to compare the in vivo performance of bone plates of 316L stainless steel and a new titanium alloy, titanium + 13% niobium + 13% zirconium (Ti-13Nb-13Zr), which had been subjected to a diffusion hardening treatment to produce a blue, wear resistant surface. Bone plates and screws of stainless steel and diffusion hardened Ti-13Nb-13Zr were implanted in adult sheep, in one group (with unosteotomized femurs) for 16 weeks, and in the other (with osteotomized femurs) for 8 weeks. At harvest, the diffusion hardened Ti-13Nb-13Zr devices had superior fixation strength, with greater screw torque out strength and fewer loose screws. In the osteotomized animals, the femurs with diffusion hardened Ti-13Nb-13Zr plates had higher torsional strength after removal of the implants; however, the difference was not statistically significant. In the unosteotomized animals, the torsional strength of the femurs was identical for both materials. There was a slightly reduced incidence of infection (bacterial adhesion) for the sheep with diffusion hardened Ti-13Nb-13Zr implants. In a parallel in vitro study, the magnetic resonance imaging compatibility of Ti-13Nb-13Zr was significantly superior to that of stainless steel. This indicates that diffusion hardened Ti-13Nb-13Zr may be an attractive alternative material for osteosynthesis.

Topics: Alloys; Animals; Bacterial Adhesion; Bone Plates; Bone Screws; Chemical Phenomena; Chemistry, Physical; Color; Diffusion; Disease Models, Animal; Equipment Contamination; Femur; Fracture Fixation, Internal; Granuloma, Foreign-Body; Incidence; Magnetic Resonance Imaging; Magnetics; Materials Testing; Microscopy, Electron, Scanning; Osteotomy; Sheep; Stainless Steel; Stress, Mechanical; Surface Properties; Surgical Wound Infection; Titanium; Torque

This investigation compared the variation of the biomechanical properties of canine and porcine craniofacial bones in homotypical (same site in opposite sides of an animal) and heterotypical (same site in different animals) sites. Biomechanical analysis is a reliable method to assess bone healing, because fracture repair correlates closely with the changes in biomechanical properties. Paired bone fragments were harvested in nine dogs and nine minipigs from each side of the skull from three different sites-the frontal bone, the supraorbital rim, and the zygomatic arch- and submitted to torque to failure. Maximum torque, stiffness, and toughness were recorded and comparative analysis performed. A normal range of variation between paired craniofacial bones in two useful animal models is provided. The results showed that the variability between homotypic left and right sides was not significant, whereas the variability between heterotypic sites in separate animals was. Maximum torque was the most reliable of the three parameters considered, because the data fell over a much narrower range. We conclude that the use of the contralateral side is a valid control in experimental procedures that may alter the biomechanical properties of one side.

Topics: Analysis of Variance; Animals; Biomechanical Phenomena; Disease Models, Animal; Dogs; Facial Bones; Female; Skull; Statistics, Nonparametric; Stress, Mechanical; Swine; Swine, Miniature; Torque