Joint Immobilization Research Articles

Remodeling of the skeletal muscle and postsynaptic component after short-term joint immobilization and aquatic training.

Joint immobilization is commonly used as a conservative treatment for osteoarticular and musculotendinous traumas. However, joint immobilization might elicit degenerative effects on the neuromuscular system and muscle atrophy. For this reason, the choice of strategies that mitigate these effects is essential in the post-immobilization period. Therefore, this study aimed to investigate the impact of aquatic training on the morphology of muscle fibers and motor endplates of the gastrocnemius muscle in the post-immobilization period. Male Wistar rats (90days old) were divided into groups: Sedentary: no procedure; Immobilization: joint immobilization protocol (10days); Immobilization/non-training: joint immobilization protocol (10days) followed by four weeks without exercise intervention; Immobilization/training: joint immobilization protocol (10days) and post-immobilization aquatic training (4weeks). After the procedures, we quantified the cross-sectional area (CSA), volume and numerical density of different myofibers types, and total and stained area and perimeter of the motor endplate. We demonstrate the following main results: (a) short-term joint immobilization resulted in myofibers atrophy; however, we verified a small change in the postsynaptic component; (b) the period of inactivity after immobilization caused severe changes in the motor endplate (lower stained area, stained perimeter, total area, and total perimeter) and maintenance of muscle atrophy due to immobilization; (c) the prescription of post-immobilization exercise proved to be effective in restoring muscle morphology and inducing plasticity in the motor endplate. We conclude that short-term joint immobilization (10days) results in atrophy type I and II myofibers, in addition to a decline in the total perimeter of the motor endplate. Besides, the post-immobilization period appears to be decisive in muscle and postsynaptic remodeling. Thus, aquatic training is effective in stimulating adjustments associated with muscle hypertrophy and plasticity of the motor endplate during the post-immobilization period.

Reversibility of marrow adipose accumulation and reduction of trabecular bone in the epiphysis of the proximal tibia

Mechanical stimuli play an important role in the homeostasis of trabecular bone and marrow adipose tissue, particularly for the weight-bearing skeleton. Prolonged immobilization and disuse have been shown to reduce trabecular bone content and increase marrow adipose tissue in the bones of lower limb joints such as the knee. However, details on the temporal response of this relationship to prolonged immobilization and its reversibility is limited. Forty rats had one knee immobilized at 45° of flexion for 2, 4, 8, or 16 weeks and subsequently remobilized for 0 or 8 weeks. The contralateral knees were used as controls. Histomorphometric measures of trabecular bone and marrow adipose tissue (MAT) areas were conducted in the epiphysis of the proximal tibia. Knee immobilization for 4, 8, and 16 weeks significantly reduced trabecular bone area by -0.125, -0.139, and -0.161 mm2/mm2, respectively, with corresponding 95 % CIs of [-0.012, -0.239], [-0.006, -0.273], and [-0.101, -0.221]. MAT area significantly increased at 2 and 16 weeks by +0.008 and +0.027 mm2/mm2, respectively, with 95 % CIs of [0.014, 0.002] and [0.039, 0.016]. Remobilization for 8 weeks restored trabecular bone area compared to the contralateral knee and the magnitude of change was significantly greater for 8 and 16 weeks of immobilization with effect sizes of 1.69 and 1.86, respectively. The difference in MAT area between immobilized and contralateral knees were eliminated with remobilization. These results characterize the temporal response of trabecular bone and MAT in the epiphysis of the proximal tibia to joint immobilization and remobilization.

Joint immobilization: effects on bone tissue of obese and malnourished animals.

Introduction: The immobilization induces an unbalanced bone metabolism, followed by rapid bone loss and consequent loss of the mechanical function of the bone. In general, the obesity and protein malnutrition conditions affect a large number of people worldwide, and both morbidities have specific characteristics that may cause deleterious effects on bone tissues of patients by different mechanisms. Objective: the present study aimed to verify experimentally if the joint immobilization protocol causes bone tissue atrophy in obese and undernourished animals. Method: 20 adult male mice (C57/BL6) were used, divided into four groups (N=5): Control Group (CG), Immobilized Control Group (ICG), Immobilized Obese Group (IOG) and Immobilized Malnourished Group (IMG). The histomorphometric analysis of the tibia quantified the number of osteocytes, cortical thickness and diameter of the medullary canal. Results: The study involving the tibia of the animals showed statistical differences in variables analysis. All immobilized groups showed lower amount of osteocytes in the evaluated tissue and increase in diameter of the spinal canal when compared to the CG. The cortical thickness was reduced in ICG and IMG groups when compared to the CG. Conclusion: The used joint immobilization protocol caused bone atrophy in the studied animals. The association between obesity, malnutrition and joint immobilization conditions cause increase in bone tissue atrophy.

The effect of orthoses on the kinematics of the trapeziometacarpal, scaphotrapeziotrapezoidal, and radioscaphoid joints.

The in vivo effect of four different types of thumb and thumb-wrist orthoses on the three-dimensional kinematics of the trapeziometacarpal (TMC), scaphotrapeziotrapezoidal (STT) and radioscaphoid joints was quantified using computed tomography (CT). Eighteen healthy female volunteers were recruited. The dominant hand of each subject was scanned in four thumb and wrist positions, each in three conditions: without orthosis, with a thumb orthosis (Push Ortho and immediate fitting, IMF) and with a thumb-wrist orthosis (Ligaflex Manu and IMF). CT images were analyzed and rotations relative to the more proximal bone were expressed in a joint-specific coordinate system. Without orthosis, the largest STT rotations were observed during radioulnar deviation of the wrist and the STT range of motion (ROM) was significantly lower during wrist flexion-extension. All tested orthoses caused a significant reduction of the ROM at each joint compared to free motion. Significant differences in movement reduction were observed between prefabricated and IMF orthoses.The IMF thumb-wrist outperformed the Ligaflex Manu in terms of immobilization of the radioscaphoid joint. In addition, the IMF thumb orthosis immobilized the TMC joint significantly better during thumb abduction and adduction than the Push Ortho. We found that different types of thumb and thumb-wrist orthotics are effective in reducing joint mobility. While this reduction tends to be higher using IMF compared to prefabricated orthoses, this effect is only significant for the radioscaphoid and TMC joint. The finding that thumb movements do not induce large STT rotations suggests that the thumb does not need to be immobilized in case of isolated STT osteoarthritis.

Approaches to antithrombotic modification of vascular implants

Vascular implants in contact with blood must have high thrombotic resistance. However, in some cases, their implantation is associated with thrombosis and subsequent impaired patency of the blood vessel. Most often, this problem affects implants intended for reconstruction of small diameter vessels, which is associated with hemodynamic features in this part of the bloodstream. These include blood vessel prostheses, tissue-engineered vascular grafts, and endovascular stents. The features of the implant material are of great importance when choosing a method for its modification in order to improve biocompatibility and thromboresistance. The review analyzes current experience in using various methods of immobilizing drugs to the surface of vascular prostheses and endovascular stents made from stable and biodegradable polymers. The prospects of creating thromboresistant vascular grafts and stents by joint immobilization on the surface of the polymer material of drugs with antithrombogenic activity and biologically active molecules that regulate the reaction to a foreign body and implant remodeling were evaluated. Numerous studies in the review demonstrating a wide range of ways to modify blood vessel prostheses, tissue-engineered vascular grafts, and endovascular stents with antithrombotic drugs to increase their thrombosis resistance. The main approaches of antithrombotic modification include conjugation of drugs and biologically active molecules on the implant surface. At the same time, new technologies are aimed not only at inhibiting the process of thrombus formation, but also at reducing the intensity of the inflammation process and stimulating the reparation of vascular tissue.

Abstract 40: Post-Traumatic Limb Immobilization Alters Mesenchymal Stem Cell Fate

Purpose: Traumatic heterotopic ossification (HO) is a debilitating condition where aberrant bone is formed outside the skeleton due to a fate switch of tissue resident mesenchymal/progenitor cells (MSCs). HO can occur after extremity trauma, burns, and extremity surgeries including amputations and joint replacements. No effective preventive strategies exist as the underlying mechanisms have not been elucidated. Though HO forms at sites of mechanical stress, the role of joint mobilization during extremity trauma, healing, and HO formation has not been clearly defined. We hypothesize that movement is central to HO formation via mechanotransductive signaling, and can provide a basis for improving post-trauma guidelines to prevent HO. Methods: HO was induced in mice via a dorsal partial thickness burn with concomitant Achilles tenotomy (B/T). Single cell RNA (scRNA) sequencing was performed prior to injury and on 3, 7, and 21 days post-B/T tissue using 10X genomics and downstream analysis with Seurat R package. scRNA sequencing was performed on immobilized mice 7 days post B/T and compared to that of mobile mice at the same time point. Scores were generated for each cell based on correlations with either osteogenic or adipogenic gene signatures in MSCs from mobile or immobilized mice. B/T was performed in mice of 4 groups (n=3/group): forced run, exercised passive range of motion (ROM), ambulated normally (mobile), or immobilized, and hindlimb bone volume was assessed at 9 weeks post-B/T by MicroCT (uCT). Immunofluorescent (IF) labeling for PDGFRα and pFAK, TAZ, or Perilipin-1 was done on 1 week cross sections and quantified (n=3/group). Results: Single cell clustering showed there are 15 unique clusters, 3 of which are MSC populations with increased expression of mechanotransductive markers such as Ptk2 (FAK), Yap1 (YAP) and Wwtr1 (TAZ). Joint immobilization of the ankle completely inhibited HO formation, therefore, the comparison of mobile and immobile mice was explored. Histology of immobilized mice demonstrated there is decreased mechanotransductive signaling (pFAK and nuclear TAZ) compared to mobile group. Interestingly, we noted increased adipocytes in the immobilized group at 1 week. Comparing scRNA sequencing revealed that MSCs (clusters 2, 3, and 14) from immobile mice correlated with an adipogenic signature compared to mobile MSCs that favored osteogenesis. This finding suggests a cell fate shift towards adipogenesis with joint immobilization. Conclusion: Hindlimb immobilization plays a significant role altering mechanotransductive pathways which we demonstrate results in an shift in MSC differentiation programming from endochondral ossification to adipogenesis. Immobilization protocols should be considered in patients at high HO risk.

Risk of Deep Vein Thrombosis After Acute Achilles Tendon Rupture: A Secondary Analysis of a Randomized Controlled Trial Comparing Early Controlled Motion of the Ankle Versus Immobilization

Background:Immobilization of the ankle joint has been suggested as a key element in the pathogenesis leading to deep vein thrombosis (DVT).Purpose:To investigate whether early controlled ankle motion (ECM) could reduce the incidence of DVT compared with immobilization (IM) in the treatment of acute Achilles tendon rupture.Study Design:Randomized controlled trial; Level of evidence, 2.Methods:Patients aged 18 to 70 years were eligible for inclusion, and treatment was nonoperative. The ECM group performed movements of the ankle 5 times a day from weeks 3 to 8 after rupture. The control group was immobilized for 8 weeks. The outcome measure was DVT diagnosed with color Doppler ultrasound for above- and below-knee DVT at 2 and 8 weeks. The Achilles tendon Total Rupture Score, the heel-rise work test, and the Copenhagen Achilles ultrasonographic Length Measurement were performed at 4-, 6-, and 12-month follow-up.Results:A total of 189 patients were assessed for eligibility from February 2014 to December 2016. Of these, 130 were randomized: 68 patients were allocated to the ECM group and 62 to the IM group. All patients participated in follow-up at 8 weeks assessing for DVT. In total, 62 (47.7%) patients were diagnosed with DVT: 33 of 68 (48.5%) in the ECM group and 28 of 61 (46.8%) in the IM group (P = .84). DVT did not affect treatment outcomes at 4, 6, and 12 months. D-dimer had low sensitivity (71%) for detecting DVT.Conclusion:We found that 1 in 2 patients presented with DVT in nonoperative treatment of acute Achilles tendon rupture. The ECM protocol revealed no benefit versus IM in reducing the incidence of DVT. DVT did not influence functional and patient-reported outcomes the first year after rupture. D-dimer seems an inappropriate test for detection of DVT in patients with acute Achilles tendon rupture.Registration:NCT02015364 (ClinicalTrials.gov identifier).

Lesser Metatarsophalangeal Instability: Diagnosis and Conservative Management of a Common Cause of Metatarsalgia.

Lesser metatarsophalangeal (MTP) instability is a common condition that can become debilitating and require surgery. An extensive literature review was performed through MEDLINE and Google Scholar for publications relating to the etiology, diagnosis, and treatment of lesser MTP instability using the keywords metatarsophalangeal instability, athlete, forefoot pain, and metatarsalgia from database inception to 2019. Clinical review. Level 4. Lesser MTP instability is a common condition, especially in the active and aging populations. It is frequently misdiagnosed, causing delays in treatment that allow for progressive pain and deformity, which prevents an active lifestyle. Fortunately, MTP instability can be diagnosed easily with the drawer test. Magnetic resonance imaging is helpful when still in doubt. Conservative treatment entails joint immobilization and gradual return to play with taping and offloading metatarsal pads. Lesser MTP instability is a common diagnosis. Its early detection and conservative treatment can help the patient regain their previous level of activity and avoid surgery.

Three-week joint immobilization increases anterior-posterior laxity without alterations in mechanical properties of the anterior cruciate ligament in the rat knee

BackgroundAlthough knee immobilization may deteriorate the mechanical parameters of the anterior cruciate ligament, such as stiffness and failure strength, it is unknown whether it induces laxity in the whole joint. We examined the effects of immobilization on anterior-posterior joint laxity and mechanical properties of the anterior cruciate ligament, as well as histological and gene expression profiles of the joint capsule in rat knee joints. MethodsUnilateral rat knees were immobilized using an external fixator. Non-immobilized contralateral knees were used as controls. After 3 weeks, anterior-posterior laxity in the whole joint (i.e., a complex of bones, ligaments, and capsule) and stiffness and failure strength in the anterior cruciate ligament were examined using a universal testing machine. Moreover, the knee joint capsule was histologically analyzed, and the expression levels of genes related to collagen turnover in the posterior joint capsule were examined. FindingsJoint immobilization slightly but significantly increased anterior-posterior laxity compared with the contralateral side. Unexpectedly, the stiffness and failure strength of the anterior cruciate ligament were not altered by immobilization. There was no correlation found between anterior cruciate ligament stiffness and anterior-posterior joint laxity. In the posterior joint capsule, thinning of the collagen fiber bundles accompanied by a decrease in COL3A1 gene expression was observed after immobilization. InterpretationThese results suggest that 3 weeks of joint immobilization alters the biomechanical integrity in the knee joint without altering the mechanical properties of the anterior cruciate ligament. Changes in the joint capsule may contribute to the immobilization-induced increase in anterior-posterior laxity.

Preventive Effects of Dulaglutide on Disuse Muscle Atrophy Through Inhibition of Inflammation and Apoptosis by Induction of Hsp72 Expression.

Pathological conditions such as joint immobilization, long-time bed rest, or inactivity may result in disuse-induced muscle wasting and dysfunction. To investigate the effect of dulaglutide, a long-acting glucagon-like peptide-1 receptor agonist, on disuse muscle atrophy, disuse condition was induced by spiral wire immobilization in C57BL/6 mice and the mice were treated with dulaglutide. Dulaglutide treatment effectively improved muscle function and increased muscle mass compared with vehicle treatment. Dulaglutide inhibited the decrease of muscle fiber size and the expression of atrophic factors such as myostatin, atrogin-1/MAFbx, and muscle RING-finger protein-1 in immobilized mice. In addition, dulaglutide inhibited nuclear factor kappa B activation, leading to a decrease in the mRNA levels of proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in muscle of immobilized mice. Dulaglutide suppressed the expression of apoptotic markers such as caspase-3, cleaved poly-ADP ribose polymerase, and Bax under immobilization condition and increased the expression of heat shock protein 72 (Hsp72), which is related to the amelioration of inflammation and apoptosis during disuse time. Further study showed that dulaglutide could induce Hsp72 expression via the regulation of 5′-AMP-activated protein kinase signaling. Our data suggest that dulaglutide could exert beneficial effects against disuse-induced muscle atrophy.

Intra-articular injection of mitomycin C prevents progression of immobilization-induced arthrogenic contracture in the remobilized rat knee.

This study tested whether cell cycle inhibitor mitomycin C (MMC) prevents arthrogenic contracture progression during remobilization by inhibiting fibroblast proliferation and fibrosis in the joint capsule. Rat knees were immobilized in a flexed position to generate flexion contracture. After three weeks, the fixation device was removed and rat knees were allowed to freely move for one week. Immediately after and three days after fixator removal, rats received intra-articular injections of MMC or saline. The passive extension range of motion (ROM) was measured before and after myotomy of the knee flexors to distinguish myogenic and arthrogenic contractures. In addition, both cellularity and fibrosis in the posterior joint capsule were assessed histologically. Joint immobilization significantly decreased ROMs both before and after myotomy compared with untreated controls. In saline-injected knees, remobilization increased ROM before myotomy, but further decreased that after myotomy compared with that of knees immediately after three weeks of immobilization. Histological analysis revealed that hypercellularity, mainly due to fibroblast proliferation, and fibrosis characterized by increases in collagen density and joint capsule thickness occurred after remobilization in saline-injected knees. Conversely, MMC injections were able to prevent the remobilization-enhanced reduction of ROM after myotomy by inhibiting both hypercellularity and joint capsule fibrosis. Our results suggest that joint capsule fibrosis accompanied by fibroblast proliferation is a potential cause of arthrogenic contracture progression during remobilization, and that inhibiting fibroblast proliferation may constitute an effective remedy.

Knee joint function and walking biomechanics in patients in acute phase anterior cruciate ligament tear.

The purpose of the study was to investigate the biomechanics of walking and of the knee joint in the acute phase of ACL injury. We examined 18 patients with acute ACL injuries and 20 healthy adults as controls. The biomechanics of the knee joint and of walking was assessed by 5 inertial sensors fixed with special cuffs to the lower back, the lower third of the thigh, and the lower third of the shank of the right and left legs. The movements and temporal characteristics were recorded while the subject was walking 10 m at a comfortable pace. Based on the results of examination, the patients were divided into two groups: with severe function impairment (6 patients) and with moderate function impairment (12 patients). It was found that in the first days post-trauma, not only the knee function was reduced, but the function of the entire lower limb as well. This led to a functional asymmetry. The kinematics of movements in the joints changed in accordance with slower walking. The walking became not only slower, but it was also associated with a decreased impact load in the weight acceptance phase. At later dates, the functional impairments were less pronounced. The total range of flexion motion did not exceed 20 degrees in the first group and 55 degrees in the second one. The injured joint developed functional immobilization within the first days post-injury. This was a guarding response by additional muscle strain to prevent unusual and limit physiological movements in the knee joint. The movements in the knee joint while walking were of small amplitude, rocking, and occurred only under load. The amplitude of the main flexion in the swing phase was reduced. The stage of an ACL injury should be assessed not only based on the time post-trauma, but also taking account of the functional parameter-the knee range of flexion while walking. According to our findings, the only factor that had influenced the functional condition of the KJ was the duration of joint immobilization after trauma.

Declines in skeletal muscle quality vs. size following two weeks of knee joint immobilization.

BackgroundDisuse of a muscle group, which occurs during bedrest, spaceflight, and limb immobilization, results in atrophy. It is unclear, however, if the magnitude of decline in skeletal muscle quality is similar to that for muscle size. The purpose of this study was to examine the effects of two weeks of knee joint immobilization on vastus lateralis and rectus femoris echo intensity and cross-sectional area.MethodsThirteen females (mean ± SD age = 21 ± 2 years) underwent two weeks of left knee joint immobilization via ambulating on crutches and use of a brace. B-mode ultrasonography was utilized to obtain transverse plane images of the immobilized and control vastus lateralis and rectus femoris at pretest and following immobilization. Effect size statistics and two-way repeated measures analyses of variance were used to interpret the data.ResultsNo meaningful changes were demonstrated for the control limb and the rectus femoris of the immobilized limb. Analyses showed a large increase in vastus lateralis echo intensity (i.e., decreased muscle quality) for the immobilized limb (p = .006, Cohen’s d = .918). For vastus lateralis cross-sectional area, no time × limb interaction was observed (p = .103), but the effect size was moderate (d = .570). There was a significant association between the increase in vastus lateralis echo intensity and the decrease in cross-sectional area (r = − .649, p = .016).ConclusionIn female participants, two weeks of knee joint immobilization resulted in greater deterioration of muscle quality than muscle size. Echo intensity appears to be an attractive clinical tool for monitoring muscle quality during disuse.

Nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME) attenuates remobilization-induced joint inflammation

Shortly after joint remobilization, inflammation is induced in the joint and aggravates joint contracture via subsequent fibrosis. However, the mechanisms involved in remobilization-induced inflammation are not yet fully understood. We hypothesized that joint immobilization followed by remobilization induces hypoxia/reoxygenation, initiating inflammatory reactions through nitric oxide (NO) production via NO synthase 2 (NOS2). This study aimed to investigate whether: 1) administration of the NOS inhibitor L-NG-nitroarginine methyl ester (l-NAME) can attenuate remobilization-induced joint inflammation; and 2) hypoxia/reoxygenation is induced by joint immobilization and followed by remobilization. Unilateral knee joints of rats were immobilized using external fixators for three weeks. After removal of the fixation device, knees were allowed to move freely for one day (remobilization) with or without l-NAME administration. Without l-NAME administration, inflammatory reactions including joint swelling and inflammatory cell infiltration, edema, and upregulation of inflammatory mediator genes in the joint capsule were detected following upregulation of the NOS2 gene after remobilization. These remobilization-induced inflammatory reactions were partially attenuated by administration of l-NAME. Therefore, NOS2/NO elevation has potential as a novel treatment for remobilization-induced joint inflammation. Gene expression of the hypoxia marker hypoxia inducible factor-1α was upregulated after one day of remobilization, rather than after immobilization. These results suggest that upregulation of NOS2 by remobilization might be not due to hypoxia/reoxygenation.

The common comorbidities leading to poor clinical outcomes after the surgical treatment of ankle fracture-dislocations.

The ankle fracture-dislocations are a significant traumatic incident for the bone and the soft tissue surrounding the ankle. Bone stabilization, joint immobilization, anatomic reduction and intervention for soft tissue protection should be performed as early as possible. The present study aims to determine the frequency of major comorbidities that can be seen after surgery in patients with ankle fracture-dislocations and the relationship between the trauma mechanism and clinical status with these comorbidities. Thirty-eight patients (25 males, 13 females) who underwent surgery with ankle fracture-dislocations between May 2014 and February 2017 were evaluated retrospectively in this study. All patients were evaluated clinically and radiologically at least 24 months postoperatively. Arthrosis, synostosis, presence of the chondral lesion and AOFAS scores were detected for all patients. Mean AOFAS score was lower in open ankle fracture-dislocations than in closed dislocations (p=0.044). An accompanying osteochondral lesion (OCL) and increased patient age were found to be strongly associated with the development of arthrosis (p=0.005 and p=0.017; respectively). Four of 29 patients who received primer definitive surgery and four of nine patients who received step-by-step surgery had poorly calculated AOFAS scores (p=0.071). There was no significant relationship between dislocation direction and AOFAS scores (p=0.087). Clinical and functional results were found to be worse in patients with open ankle fractures, the rate of arthrosis increased with age, and the use of syndesmosis screw had a positive but not a statistically significant effect on clinical and functional outcomes.

Chondroprotective Effects of Combination Therapy of Acupotomy and Human Adipose Mesenchymal Stem Cells in Knee Osteoarthritis Rabbits via the GSK3β-Cyclin D1-CDK4/CDK6 Signaling Pathway.

Adipose-derived stem cells (ASCs) are highly chondrogenic and can be used to treat knee osteoarthritis (KOA) by alleviating cartilage defects. Acupotomy, a biomechanical therapy guided by traditional Chinese medicine theory, alleviates cartilage degradation and is widely used in the clinic to treat KOA by correcting abnormal mechanics. However, whether combining acupotomy with ASCs will reverse cartilage degeneration by promoting chondrocyte proliferation in KOA rabbits is unknown. The present study aimed to investigate the effects of combination therapy of acupotomy and ASCs on chondrocyte proliferation and to determine the underlying mechanism in rabbits with KOA induced by knee joint immobilization for 6 weeks. After KOA modeling, five groups of rabbits (acupotomy, ASCs, acupotomy + ASCs, model and control groups) received the indicated intervention for 4 weeks. The combination therapy significantly restored the KOA-induced decrease in passive range of motion (PROM) in the knee joint and reduced the elevated serum level of cartilage oligomeric matrix protein (COMP), a marker for cartilage degeneration. Furthermore, magnetic resonance imaging (MRI) and scanning electron microscopy (SEM) images showed that the combination therapy inhibited cartilage injury. The combination therapy also significantly blocked increases in the mRNA and protein expression of glycogen synthase kinase-3β (GSK3β) and decreases in the mRNA and protein expression of cyclin D1/CDK4 and cyclin D1/CDK6 in cartilage. These findings indicated that the combination therapy mitigated knee joint immobility, promoted chondrocyte proliferation and alleviated cartilage degeneration in KOA rabbits, and these effects may be mediated by specifically regulating the GSK3β-cyclin D1-CDK4/CDK6 pathway.

Evaluation of nociception induced by whole-body vibration remobilization in Wistar rats

ABSTRACT BACKGROUND AND OBJECTIVES: The vibrating platform can attenuate the deleterious effects of immobilization related to muscle atrophy. However, there is still a gap regarding the effect of this modality on hyperalgesia related to immobilization. The objective of this study was to analyze the effect of remobilization with whole-body vibration on the nociception of Wistar rats. METHODS: Sixteen rats were randomly distributed into two groups: the FRG group - immobilization and free remobilization and the VPRG - immobilization and remobilization with the vibrating platform. For remobilization with the vibrating platform, the frequency of 60Hz for 10 minutes, five days a week for two weeks was used. The nociception was evaluated on the right paw by a digital analgesiometer, before and at the end of the immobilization, and after two weeks of remobilization. RESULTS: There were differences between evaluations but not between groups, indicating that immobilization reduced the nociceptive threshold and free remobilization, and the remobilization associated with vibration improved the nociceptive threshold compared to the post-immobilization moment. However, they were not able to return to the initial parameters. CONCLUSION: Joint immobilization reduced the nociceptive threshold; however, two weeks of whole-body vibration remobilization were not able to revert the threshold in the immobilized groups.

Sustainable release of vancomycin from micro-arc oxidised 3D-printed porous Ti6Al4V for treating methicillin-resistant Staphylococcus aureus bone infection and enhancing osteogenesis in a rabbit tibia osteomyelitis model.

Elimination of infection and enhancement of osteogenesis by orthopaedic implants are two critical factors in the treatment of complex bone infections. A prolonged and expensive procedure requiring two surgical steps and a 6-8-week period of joint immobilisation is utilised as a primary treatment for revision arthroplasty of an infected prosthesis, greatly affecting long-term patient care for the ageing population. Here, we evaluated the effects of vancomycin-loaded in micro-arc oxidised (MAO) three-dimensional (3D) printed porous Ti6Al4V scaffolds on osteogenesis. This system showed a high loading capacity and sustained vancomycin release kinetics, as demonstrated using high-performance liquid chromatography. In vivo, 0.1 mL of 108 colony forming units (CFU) methicillin-resistant Staphylococcus aureus was injected into the tibias of rabbits to induce severe osteomyelitis. Physical, haematological, radiographic, microbiological, and histopathological analyses were performed to evaluate the effects of treatment. Rabbits with vancomycin-loaded in MAO scaffolds showed the inhibition of bone infection and enhancement of osteogenesis, resulting in better outcomes than in the other groups. Overall, these findings demonstrated the potential of this 3D printed porous Ti6Al4V, with good osteogenesis and sustained vancomycin release properties, for application in the treatment of complex bone infections.

A rat model of arthrofibrosis developed after anterior cruciate ligament reconstruction without rigid joint immobilization

ABSTRACT Purpose: Complications including arthrofibrosis have been reported after anterior cruciate ligament reconstruction (ACLR) even under accelerated rehabilitation. To overcome this, we developed an animal model of ACLR-induced arthrofibrosis without immobilization. Materials and Methods: Thirteen male Wistar rats were divided into ACL transection (ACLT) and ACLR groups. Surgery was performed in the right knees and untreated left knees were used as controls. After surgery, rats could move freely without joint immobilization. Results: One week after surgery, flexion contracture represented by passive ROM reduction was 49 ± 5° and 21 ± 6° in ACLR and ACLT groups, respectively. Thereafter, flexion contractures were gradually reduced to 21 ± 8° and 12 ± 6° after 12 weeks, respectively. Fibrosis, which is characterized by significant upregulation of fibrosis-related genes, thickening, and adhesion in the posterior joint capsule, was observed in the ACLR group after 12 weeks of surgery. Nociceptive behavior and joint swelling were more apparent in the ACLR group than in the ACLT group, especially after 1 week of surgery. Discussions: We developed a rat model of ACLR-induced joint contracture due to arthrofibrosis without rigid immobilization. Joint contracture was also observed in the ACLT group, but to a considerably milder degree than in the ACLR group. Thus, signs of inflammation as a result of reconstruction surgery, rather than ACL transection, play an important role in the formation of joint contracture after ACLR. Our animal model is suited to examine the mechanisms and efficacy of therapeutic strategies for arthrofibrosis following ACLR treated without rigid joint immobilization.

Disuse histological changes of an unloading environment on joint components in rat knee joints

To clarify the effects of mechanical unloading on joint components, including the articular cartilage by knee compartments, synovial membrane, and the infrapatellar fat pad (IFP), using a hindlimb suspension rat model. Twenty-five male rats were divided into the three following experimental groups: the baseline, control (CON), and hindlimb unloading (HU) groups. Rats in the HU group were subjected to periods of hindlimb unloading by tail suspension. The joint components were evaluated by histopathological and histomorphometric analyses. The unloading condition caused articular cartilage thinning and decreased matrix staining. The tendency of these histological changes in articular cartilage was similar between the knee compartments. In general, the unloading environment resulted in no critical histological changes to the synovial membrane and IFP. At 4 weeks, thickening of the synovial membrane and synovial-like tissue invasion were observed in the HU group, but there was no significant change in inflammation. There was no obvious histological change to the IFP caused by unloading. The unloading environment caused disuse histological changes in the articular cartilage; however, the tendency of the changes was similar between compartments. Furthermore, the unloading condition caused no critical histological changes to the synovial membrane or IFP. Clinically, the unloading environment without joint immobilization over a short period may not have caused critical histological changes to the joint components.