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Background: Biomechanical measurement tools have been developed and widely used to precisely quantify knee anterior-posterior laxity after anterior cruciate ligament (ACL) injury. However, validated objective device to document knee rotational laxity, though being developed by different researchers, are not yet widely used in the daily clinical practice. A new biomechanical device was developed to quantify knee internal and external rotations. Methods: The reliability of the new biomechanical device which measures knee rotations were tested. Different torques (1-10Nm) were applied by the device to internally and externally rotate human cadaveric knees, which were held in a flexion angle of 30°. The rotations were measured by the device in degrees. There were two independent testers, and each tester carried out three trials. Intra-rater and inter-rater reliability were quantified in terms of intraclass correlation (ICC) coefficient among trials and between testers. The device was verified by the comparison with a computer assisted navigation system. ICC was measured. Mean, standard deviation and 95% confident interval of the difference as well as the root mean square difference were calculated. The correlations were deemed to be reliable if the ICC was above 0.75. Results: The intra-rater and inter-rater reliability achieved high correlation for both internal and external rotation, ranged from 0.959 to 0.992. ICC between the proposed meter and the navigation system for both internal and external rotation was 0.78. The mean differences were 2.3° and 2.5° for internal and external rotation respectively. Conclusions: A new knee rotational laxity meter was proposed in this study. Its reliability was verified by showing high correlation among trials. It also showed good correlation to a gold standard of measurement. It might be used to document knee rotational laxity for various purposes, especially after ACL injury, after further validation of the device in human subjects. Keywords: Tibial rotation, Knee stability, Measurement, Laxity

Purpose: Graft remodeling in anterior cruciate ligament reconstruction (ACLR) demonstrates three distinct phases: necrosis, proliferation and ligamentization. Biological enhancement involves modulating these processes, but the cellular activities related to extracellular matrix remodeling have not been investigated. We hypothesized that changes in matrix metalloproteinases (MMPs) 1 and 13 expression are involved in the transition of proliferation phase to ligamentization phase of graft remodeling. Materials and methods: Thirty-three rats underwent ACLR. Tendon grafts were harvested at week 1 (necrosis), 2 (proliferation), or 12 (ligamentization) post-operation for histological examination (n = 3), or for isolation of graft-derived cells (n = 8) for flow cytometry, proliferation assay, cell invasion assay, measurement of gene expression related to matrix remodeling (Col1A1, Col3A1, MMP1, tissue inhibitor of marix metalloproteinase 1 (TIMP1), and MMP13) and total MMP activities. Results: Increased cellularity in tendon graft was contributed by active cell proliferation and migration at week 2 post-operation, while decreased cellularity were paralleled by increased apoptosis at week 12. All genes measured (Col1A1, Col3A1, MMP1, TIMP1, and MMP13) increased significantly in week 2 cells compared to week 1 cells. MMP1 expression subsided at week 12, while MMP13 expression kept increasing till 12 weeks post-operation. Total MMP activities was 3-fold higher in cultured graft-derived cells from week 2 as compared to cells from week 12. Two distinct processes of graft remodeling were identified, characterized by increased MMP1 expression with cell proliferation and increased MMP13 expression with cell apoptosis. Conclusions: Unfavorable matrix remodeling during the proliferation phase is found with increased MMP1, while remodeling leading to ligamentization is associated with increased MMP13 expression.

The 2008 Sichuan Earthquake resulted in many amputees, yet due to the rare incidence, few studies have explored the rehabilitation outcomes and quality of life of bilateral lower limb amputees after major natural disasters.To evaluate rehabilitation outcomes of 17 young and adult bilateral lower limb amputees under the StandTall rehabilitation programme and to identify factors associated with successful functional recovery of bilateral amputees after large-scale disasters.Cross-sectional study.Mobility (amputee mobility predictor), prosthesis use (Houghton Scale) and health-related quality of life (Trinity Amputation and Prosthesis Experience Scale, Short Form 12) were evaluated through questionnaires and performance-based assessments. Means of scores were compared using T-tests.Subjects with bilateral through-knee or transtibial amputations had less activity restriction ( p 0.01) and higher mobility ( p = 0.03). Subjects using prostheses more than 50% waking time had better general adjustment ( p = 0.02) and less functional restriction ( p = 0.01). Exercise and education were associated with higher mobility ( p = 0.06) and mental quality of life, respectively ( p = 0.09).Amputation level and knee joint salvage, prosthesis use, exercise and education were associated with better rehabilitation outcomes including ambulation, adjustment and quality of life in bilateral lower limb amputees from the 2008 Sichuan Earthquake.The study examined a unique group of traumatic bilateral lower limb amputees who were young and healthy before having traumatic amputations from a single episode of natural disaster. The factors associated with better functional recovery after the earthquake were investigated and may support future development of post-disaster rehabilitation strategies for bilateral lower limb amputees.

Tendinopathy includes cases with chronic tendon pain and spontaneous tendon ruptures, which is putatively resulted from failed tendon healing. Overuse is a major risk factor of tendinopathy, which can impose mechanical and oxidative stress to tendons. Previous studies investigated the influences of mechanical stress, but the direct impact of oxidative stress on tendon healing remains unclear. We hypothesized that imposed oxidative stress can impair tendon healing and lead to tendinopathic changes. Thirty-nine rats were operated for patellar tendon window injury. From weeks 3-5 post-operation, the rats received three weekly subcutaneous injections of saline, 50 or 500 μM H2 O2 (n = 13) over patellar tendon. Gait analysis for pain assessment and 3D ultrasound imaging for detection of tendinopathic changes were performed at pre-injury and 6-week post-operation. At week 6, knee specimens were harvested for histology or tensile mechanical test. Elastic modulus of the healing patellar tendons was significantly lower in 50 μM but not 500 μM H2 O2 group, while ultimate mechanical stress was not significantly different across groups. Similarly, only the 50 μM H2 O2 group exhibited pain-associated gait asymmetry. Significant tendon swelling with increased tendon volume was observed in the 50 μM H2 O2 group. There were hypoechogenic changes in the tendon wound, but there was no significant difference in percentage vascularity. H2 O2 impaired tendon healing and elicited tendinopathic changes, with respect to pain and structural abnormalities. Oxidative stress plays a role in the failed tendon healing of tendinopathies, and H2 O2 -induced failed tendon healing may serve as a good animal model to study tendinopathy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3268-3274, 2018.

Tendon disorders, which are commonly presented in the clinical setting, disrupt the patients’ normal work and life routines, and they damage the careers of athletes. However, there is still no effective treatment for tendon disorders. In the field of tissue engineering, the potential of the therapeutic application of exogenous stem cells to treat tendon pathology has been demonstrated to be promising. With the development of stem cell biology and chemical biology, strategies that use inductive tenogenic factors to program stem cell fate in situ are the most easily and readily translatable to clinical applications. In this review, we focus on bioactive molecules that can potentially induce tenogenesis in adult stem cells, and we summarize the various differentiation factors found in comparative studies. Moreover, we discuss the molecular regulatory mechanisms of tenogenesis, and we examine the various challenges in developing standardized protocols for achieving efficient and reproducible tenogenesis. Finally, we discuss and predict future directions for tendon regeneration.

SUMMARYIn this paper, we introduce a lower extremity exoskeleton CUHK-EXO that is developed to help paraplegic patients, who have lost the motor and sensory functions of their lower limbs to perform basic daily life motions. Since the sit-to-stand and stand-to-sit (STS) motion is the first step for paraplegic patients toward walking, analysis of the exoskeleton's applicability to the STS motion assistance is performed. First, the human-exoskeleton system (HES) is modeled as a five-link model during the STS motion, and the center of pressure (COP) on the ground and center of gravity of the whole system are calculated. Then, a description of the CUHK-EXO hardware design is presented, including the mechatronics design and actuator selection. The COP position is an important factor indicating system balance and wearer's comfort. Based on the COP position, a trajectory online modification algorithm (TOMA) is proposed for CUHK-EXO to counteract disturbances, stabilize system balance, and improve the wearer's comfort in the STS motion. The results of STS motion tests conducted with a paraplegic patient demonstrate that CUHK-EXO can provide a normal reference pattern and proper assistive torque to support the patient's STS motion. In addition, a pilot study is conducted with a healthy subject to verify the effectiveness of the proposed TOMA under external disturbances before future clinical trials. The testing results verify that CUHK-EXO can counteract disturbances, and help the wearer perform the STS motion safely and comfortably.

Continuous blood pressure is measured from various extracranial body sites, with difference in amplitude and phase with intracranial blood pressure. Consequent influences on the accuracy of Windkessel model need further investigation. Between blood pressure and intracranial flow rate, a model with non-linear flow resistance (R-DT) was proposed and compared with the 3-element Windkessel (RCR) model. From the measured blood flow velocity in middle cerebral artery, the blood pressure was estimated by R-DT and RCR models respectively. The parameters in the models were optimized by genetic algorithm. The accuracies of R-DT and RCR models were compared based on their estimation errors to the measured blood pressure. The capacitance element in RCR model indicated limited ability to take the time shift into account. Compared with RCR model, R-DT model had less error (averaged relative error: 5.19% and 2.49% for RCR and RDT models). The non-linear flow resistance was applicable in simulating cerebral arteries.

Platelet concentrates (PC) generally refers to a group of products that are prepared from autologous blood intended to enhance healing activities. PC therapy is now very popular in treating musculoskeletal injuries; however, inconsistent clinical results urge the need to understand the working mechanism of PC. It is generally believed that the platelet-derived bioactive factors are the active constituents, and their bioavailability in the vicinity of the lesion sites determines the treatment efficacies. Therefore, the composition, localisation, and duration of the action of PC would be key determinants. In this review, we discuss how different preparations and delivery methods of PC would affect the treatment outcomes with respect to clinical evidence about PC therapy for osteoarthritis, tendinopathies, rotator cuff tears, anterior cruciate ligament injuries, and bone fractures. This review can be used as a quick guide for the use of PC therapy and provide insights for the further optimisation of the therapy in the near future.

Summary Background/objective Oxidative stress plays an important role in osteoarthritis (OA), causing inflammation and matrix degradation in joints. Previous studies have shown that antioxidants such as quercetin and vitamin C are potential candidates for treating OA. We aimed to determine whether a formulation of quercetin and vitamin C, together with an iron chelator, could retard OA progression in a post-traumatic OA rat model. Methods Twelve rats received anterior cruciate ligament transection for OA induction. At 20 weeks postoperation, weekly intra-articular injection of 50 μL of either saline or a formulation of quercetin dehydrate, sodium-L-ascorbate, and deferoxamine mesylate was given consecutively for 4 weeks ( n = 5). Gait analysis was performed at pretreatment, and at 1 week and 5 weeks post-treatment. Microcomputed tomography scanning and histological scoring were performed at 5 weeks post-treatment. Results Gait analysis showed that intra-articular injections of antioxidant formulation did not improve pain-associated Limb Idleness Index over time ( p = 0.449, Friedman test). However, at 5 weeks post-treatment, the treatment group exhibited a significantly lower Limb Idleness Index than the control group ( p = 0.047, Mann–Whitney U test). At 5 weeks post-treatment, microcomputed tomography analysis revealed that there was no difference in any parameter between the treatment and control groups ( p > 0.05, Student t test). Severe OA histopathological changes were found in both groups. The Osteoarthritis Research Society International scores of the treatment and control groups were 20 (range, 20–26) and 20 (range, 9–26), respectively ( p = 0.382, Mann–Whitney U test). Conclusion Intra-articular injection of an antioxidant formulation containing quercetin, vitamin C, and deferoxamine did not retard OA progression in advanced-stage OA. Future studies should aim to determine whether giving antioxidants in early OA, with prolonged drug retention, would be effective in retarding OA progression.

Tendon healing is slow and usually results in inferior fibrotic tissue formation. Recently, application of tendon derived stem cells (TDSCs) improved tendon healing in animal studies. In a chicken model, local injection of antioxidants reduced tendon adhesion after tendon injury. An in vitro study demonstrated that supplementation of H2O2reduced tenogenic marker expression in TDSCs. These findings suggested that the possibility of TDSCs is involved in tendon healing and the cellular activities of TDSCs might be affected by oxidative stress of the local environment. After tendon injury, oxidative stress is increased. Redox modulation might affect healing outcomes via affecting cellular activities in TDSCs. To study the effect of oxidative stress on TDSCs, the cellular activities of rat/human TDSCs were measured under different dosages of vitamin C or H2O2in this study. Lower dose of vitamin C increased cell proliferation, viability and migration; H2O2affected colony formation and suppressed cell migration, cell viability, apoptosis, and proliferation. Consistent with previous studies, oxidative stresses (H2O2) affect both recruitment and survival of TDSCs, while the antioxidant vitamin C may exert beneficial effects at low doses. In conclusion, redox modulation affected cellular activities of TDSCs and might be a potential strategy for tendon healing treatment.

Tendon injures are common orthopedic conditions, but tendon development and the pathogenesis of tendon injures, such as tendinopathy, remain largely unknown and have limited the development of clinical therapy. Studies on tenogenic differentiation at the molecular level may help in developing novel therapeutic strategies. As novel regulators, long noncoding RNAs (lncRNAs) have been found to have widespread biological functions, and emerging evidence demonstrates that lncRNAs may play important regulatory roles in cell differentiation and tissue regeneration. In this study, we found that lncRNA H19 stimulated tenogenesis of human tendon-derived stem cells. Stable overexpression of H19 significantly accelerated TGF-β1-induced tenogenic differentiation in vitro and accelerated tendon healing in a mouse tendon defect model. H19 directly targeted miR-29b-3p, which is considered to be a negative regulator of tenogenesis. Furthermore, miR-29b-3p directly suppressed the expression of TGF-β1 and type I collagen, thereby forming a novel regulatory feedback loop between H19 and TGF-β1 to mediate tenogenic differentiation. Our study demonstrated that H19 promotes tenogenic differentiation both in vitro and in vivo by targeting miR-29b-3p and activating TGF-β1 signaling. Regulation of the TGF-β1/H19/miR-29b-3p regulatory loop may be a new strategy for treating tendon injury.-Lu, Y.-F., Liu, Y., Fu, W.-M., Xu, J., Wang, B., Sun, Y.-X., Wu, T.-Y., Xu, L.-L, Chan, K.-M., Zhang, J.-F., Li, G. Long noncoding RNA H19 accelerates tenogenic differentiation and promotes tendon healing through targeting miR-29b-3p and activating TGF-β1 signaling.

Purpose To examine the different motion tasks and the protocols used to objectively quantify dynamic stability in terms of knee kinematics at different stages of anterior cruciate ligament reconstruction (ACLR) recovery. Methods A systematic search was done using OVID in Embase, Cochrane Central Register of Controlled Trials, Medline, PsychINFO, and AMED. A combination of the following keywords and their variations were used: anterior cruciate ligament, motion tasks (e.g., jump, hop, gait), and stability. The inclusion criteria were as follows: (1) ACLR subjects were recruited, (2) at least 1 motion task was performed and kinematics data were recorded, and (3) uninjured subjects or the contralateral uninjured limbs were included as a control group. Exclusion criteria were as follows: (1) non-English language publications, (2) retrospective studies and review articles, (3) animal studies, and (4) cadaveric studies. Results The search returned 2,195 studies, and 56 were included in this review according to the criteria. A total of 1,086 ACLR subjects were included. Pivoting, landing, walking, running, stair negotiation, and squats were assessed using optoelectronic motion capture, electrogoniometry, or video-radiography. Conclusions The appropriate selection of motion tasks is an integral factor in dynamic stability testing as it evokes different kinematic outcomes in relation to the different stages of ACLR recovery. Stair negotiation and landing tasks are best performed during the early stages of recovery, and landing and pivoting are recommended 6 months after ACLR surgery. Level of Evidence Level II, systematic review of Level I and II studies.

Background/objective Anterior cruciate ligament (ACL) rupture results in knee instability, and patients are often unable to return to their previous level of activity. Current assessments rely on passive laxity tests, which do not correlate with function. Dynamic stability may be a better indicator for return to sport. However, equipment for measuring dynamic stability is ill suited for clinical use. The purpose of this study is to evaluate knee kinematics in ACL-deficient patients with a single-legged hop task using a portable motion analysis system. We hypothesize that the assessment task is able to differentiate ACL-deficient knees from healthy knees. Methods Ten ACL-deficient patients and 10 healthy controls were recruited. Participants were instructed to perform a single-legged hop, while kinematics was measured using a portable motion capture system (Opti-Knee; Shanghai Innomotion Inc., Shanghai, China). Kinematic changes after initial contact were examined. Repeatability of the results was examined by calculating the coefficient of variations of the pooled standard deviation of the tibiofemoral displacements. Side-to-side differences were calculated and compared between the two groups. Results One patient could not perform the task. Intraindividual variability was small after initial contact; the coefficient of variation in this region was 13–26%. ACL-deficient knees demonstrated lower flexion range of motion (p = 0.008) and increased internal/external rotation range of motion after landing (p = 0.038), while no significant differences were detected in the healthy group. Only the side-to-side difference in flexion was significantly different between the two groups (p = 0.002). Conclusion The altered knee kinematics in ACL-deficient patients can be revealed by a portable motion capture system, which may enable the clinical application of kinematic assessment in the evaluation of ACL deficiency.

Background The purpose of this study was to investigate the power and endurance characteristics of Hong Kong professional football players. Training recommendations can be deduced based on the comparison between Hong Kong and international football players. Methods Eighty-eight Hong Kong professional football players (height, 177.2 ± 6.4 cm; weight, 70.6 ± 7.6 kg; age, 25.6 ± 5.0 years) in the first division league participated in a battery of tests, which included: (1) height, (2) weight, (3) countermovement jump, (4) 30-m sprinting, and (5) Yo-Yo Intermittent Recovery Test Level 2. Results Compared with the test results of the first division players in other countries as reported in the literature (Norway, France, and Scandinavian countries), Hong Kong players were shorter in height (0.1–2.1%), lighter in weight (5.5–8.3%), fair in vertical jump height (−4.8–17%), slower in acceleration (4.2–5.1%) and maximum speed (3–14.2%), and had poorer aerobic and anaerobic endurance (22.9%). Conclusion The present study suggests that Hong Kong football players (or players with similar physique and ability) need to improve their power and endurance.

There are currently no studies that determine the total burden that tendinopathy places on patients and society. A systematic search was conducted to understand the impact of tendinopathy. It demonstrated that the current prevalence is underestimated, particularly in active populations, such as athletes and workers. Search results demonstrate that due to the high prevalence, impact on patients' daily lives and the economic impact due to work-loss, treatments are significantly higher than currently observed. A well-accepted definition by medical professionals and the public will improve documentation and increase awareness, in order to better tackle the disease burden.

Patients suffering from neurological and orthopedic diseases or injuries usually have mobility impairment problems, and they require customized rehabilitation training to recover. In recent years, robotic assistive devices have been widely studied for gait rehabilitation. In this paper, methods to determine user-adaptive assistance of assistive knee braces (AKBs) in gait rehabilitation are investigated. A fuzzy expert system, which takes a patient’s physical condition and gait analysis results as inputs, is proposed to configure suitable levels of different assistive functions of the AKB. During gait rehabilitation, the AKB generates a reference knee trajectory according to the patient’s individual gait pattern, and the interaction force is controlled through a hybrid impedance controller considering the individual assistive function configuration. The proposed methods are verified through clinical pilot studies of a patient with lower limb weakness. Experimental results show that AKB with the proposed control strategies can provide effective assistance to improve the patient’s gait performance during gait rehabilitation.

Objective Quercetin (Que), a bioflavonoid, is both anti-inflammatory and antioxidative. Que has been used as an oral supplement for osteoarthritis (OA) with inconsistent findings because of its low bioavailability. We encapsulated Que in a mPEG-polypeptide thermogel to prolong its bioactivity. The efficacy of this formulation was evaluated in a posttraumatic OA rat model. Design Methoxy-poly(ethylene glycol)-l-poly(alanine) (mPEG-PA) polymer was synthesized and characterized in terms of cytotoxicity and release kinetics in vitro. At 12 weeks old, Sprague-Dawley rats underwent anterior cruciate ligament transection (ACLT). At 24 weeks post-operation, rats received either an intra-articular (IA) injection of saline, hydrogel, or hydrogel with Que (50 or 500 μg). Gait analysis was performed at pre-ACLT, pre-treatment, and at 4, 8, and 12 weeks post-treatment. At 12 weeks post-treatment, knee joints were collected for histopathological evaluation. Results In vitro studies showed that chondrocytes were viable after 72 hours of incubation with mPEG-PA, and the release of Que could be sustained for >28 days. Among all OA rats, the limb idleness index (LII) were significantly increased at 24 weeks post-ACLT. Rats that received hydrogel with Que (50 μg) showed the most reduction in LII at both 4 and 8 weeks post-treatment. The Osteoarthritis Research Society International score of rats received hydrogel with Que (50 μg) was significantly lower than the control group. All rats suffered from low-grade synovitis (Krenn score: 2-4). Conclusion This study suggests that a sustained delivery of Que (50 μg) could provide symptom relief and also delay the progression of OA in the knee.