Introduction and Objective. Clinically, it is considered that spastic muscles of patients with cerebral palsy (CP) are shortened, and produce higher force in shorter muscle lengths. Yet, direct quantification of spastic muscles’ forces is rare. Remarkably, previous intraoperative tests in which muscle forces are measured directly as a function of joint angle showed for spastic gracilis (GRA) that its passive forces are low, and only a small percentage of its maximum active force is measured in flexed knee positions. However, the relationship of force characteristics of spastic GRA with its muscle-tendon unit length (l. MTU. ) is unknown. Combining intraoperative experiments with participants’ musculoskeletal models developed based on their gait analyses, we aimed to test if spastic GRA muscle (1) operates at short l. MTU. compared to that of typically developing (TD) children, and exerts higher (2) passive and (3) active forces at shorter lengths, within gait-relevant l. MTU. range. Materials and Methods. Ten limbs of seven children with CP (GMFCS-II) were tested. Pre-surgery, gait analyses were conducted. Intraoperatively, isometric spastic GRA distal forces were measured in ten hip-knee joint angle combinations, in two conditions: (i) passive state and (ii) maximal activation of the GRA exclusively. In OpenSim, gait_2392 model was used for each limb to calculate l. MTU. 's per each hip and knee angle combination and the gait-relevant l. MTU. range, and to analyze gait relevant spastic muscle force - l. MTU. data. l. MTU. values were normalized for the participants’ thigh lengths. Two-way ANOVA was used to compare the patients’ l. MTU. to those of the seven age-matched TD children to test the first hypothesis. In order to test the second and the third hypotheses, Spearman's rank correlation coefficient (ρ) was calculated to seek a correlation between the muscle's operational length (represented by mean l. MTU. within gait cycle) and muscular force characteristics (the percent force at shortest l. MTU. of peak force, either in passive or in active conditions) within gait-relevant l. MTU. range. Results. ANOVA showed that l. MTU. 's of spastic GRA are shorter (on average by 15.4%) compared to those of TD. At the shortest gait-relevant l. MTU. , the GRA passive force was 84.6 (13.7)% of the peak passive force; and the active force was 55.8 (33.9)% of the peak active force. Passive state forces show an increase at longer lengths, whereas active state force characteristics vary in a patient-specific way. Spearman's rank correlation indicated weak correlations between muscle's operational length and muscular force characteristics (ρ= −0.30 P= 0.40, and ρ= −0.27 P= 0.45, for passive and active states, respectively). Therefore, only the first hypothesis was confirmed. Conclusions. Novel muscle force - l. MTU. data for spastic GRA were obtained using intraoperative data and modelling combined. The modelling showed in concert with the clinical considerations that spastic GRA may be a shortened muscle. However, because the model does not distinguish the muscle-belly and tendon lengths, it cannot isolate shorter muscle belly length and how this compares to the data of TD children remains unknown. Moreover, the absence of a strong correlation between shorter operational muscle length and higher force production either in passive or in active conditions highlights the influence of other factors (e.g., muscle structural proteins, and muscle mechanical characteristics including intermuscular interactions etc.) on the pathology rather than ascribing it solely to the length of a spastic muscle itself

Background. Spastic muscles of patients with cerebral palsy (CP) are considered structurally as shortened muscles, that produce high force in short muscle lengths. Yet, previous intraoperative studies in which muscles’ forces are measured directly as a function of joint angle showed consistently that spastic knee flexor muscles produce a low percentage of their maximum force in flexed knee positions. They also showed effects of epimuscular myofascial force transmission (EMFT): simultaneous activation of different muscles elevated target muscle's force. However, quantification of spastic muscle's force - muscle-tendon unit length (l. MTU. ) data during gait is lacking. Aim. Combining intraoperative experiments with participants’ musculoskeletal models developed based on their gait analyses, we aimed to test the following hypotheses: activated spastic semitendinosus (ST) muscle (1) operates at short l. MTU. 's during gait, forces are (2) low at short l. MTU. 's and (3) increase by co-activating other muscles. Methods. Ten limbs of seven children with CP (GMFCS-II) were tested. Pre-surgery, gait analyses were conducted. Intraoperatively, isometric spastic ST distal forces were measured in ten hip-knee joint angle combinations, in two conditions: (i) activation of the ST individually and (ii) simultaneously with the gracilis, biceps femoris, and rectus femoris muscles endorsing EMFT. In OpenSim, gait_2392 model was used for each limb to (a) calculate l. MTU. per each hip and knee angle combination and the gait relevant l. MTU. range, and (b) analyze gait relevant spastic muscle force - l. MTU. data. Two-way ANOVA was used to compare the patients’ l. MTU. to those of the seven age-matched typically developing (TD) children. l. MTU. values were normalized for the participants’ thigh length. (a) was used to test hypothesis (1) and (b) to test hypotheses (2) and (3): in condition (i), the percent of peak force exerted at the shortest l. MTU. calculated per limb was used as a metric for (2). In condition (ii), mean percent change in muscle force calculated within gait-relevant l. MTU. range was used as a metric for (3). Results. Modeling showed that l. MTU. of spastic ST during gait is shorter on average by 14.1% compared to TD. The ST active force at the shortest gait-relevant l. MTU. was 68.6 (20.6)% (39.9–99.2%) of the peak force. Simultaneous activation of other muscles caused substantial increases in force (minimally by 11.1%, up to several folds, with an exception for one limb). Therefore, only the first and third hypotheses were confirmed. Conclusion. The modeling showed in concert with the clinical considerations that spastic ST may be a shortened muscle that produces high force in short muscle lengths. However, this contrasts intraoperative data, which shows only low forces in flexed knee positions. Note that, the model does not distinguish the muscle-belly and tendon lengths. Therefore, it cannot isolate shorter muscle length and how this compares to the data of TD children remains unknown. Yet, the effects of co-activation of other muscles shown intraoperatively to cause an increase of the spastic ST's force are observed also in muscle force - l. MTU. data characterizing gait. Therefore, if indeed spastic ST produces high forces in short muscle-belly lengths alone, elevated forces due to co-activation of other muscles may be considered as a contributor to the patients’ pathological gait. Otherwise, such EMFT effect may be the main determinant of the pathological condition

The inability to replace human muscle in surgical practice is a significant challenge. An artificial muscle controlled by the nervous system is considered a potential solution for this. We defined it as neuromuscular prosthesis. Muscle loss and dysfunction related to musculoskeletal oncological impairments, neuromuscular diseases, trauma or spinal cord injuries can be treated through artificial muscle implantation. At present, the use of dielectric elastomer actuators working as capacitors appears a promising option. Acrylic or silicone elastomers with carbon nanotubes functioning as the electrode achieve mechanical performances similar to human muscle in vitro. However, mechanical, electrical, and biological issues have prevented clinical application to date. In this study, materials and mechatronic solutions are presented which can tackle current clinical problems associated with implanting an artificial muscle controlled by the nervous system. Progress depends on the improvement of the actuation properties of the elastomer, seamless or wireless integration between the nervous system and the artificial muscle, and on reducing the foreign body response. It is believed that by combining the mechanical, electrical, and biological solutions proposed here, an artificial neuromuscular prosthesis may be a reality in surgical practice in the near future

Summary Statement. Paraspinal muscle contain higher proportion of slow-twich fibers. The fixation of the rat tail induced transition of muscle fiber types in the paravertebral muscles characterised by the decrease in the proportion of the slow type myosin heavy chain. Introduction. Lumbar degenerative kyphosis often accompanies back pain, easy fatigability, fatty degeneration and atrophy of back muscles. There are two types of skeletal muscle fibers according to oxidative activities: slow-twich (Type 1) and fast-twitch (Type 2) fibers. Type 2 fibers were subdivided into three types: Type 2A, 2B and 2D/X. Each fiber type primarily expresses a specific isoform of myosin heavy chain (MHC). It has been known that back muscles contain higher proportion of MHC type 1. However, the impact of kyphosis on the proportion of fiber types in the paravertebral muscles has not been fully understood. The aim of this study is to analyze the transition of muscle fiber types after kyophotic or straight fixation using a rat tail model. Methods. A rat tail was fixed in straight or kyphotic position (straight or kyphosis group) by a custom-made external fixator and wires. A group of animals which underwent only pierced wounds in their tails served as control. The gene expression profiles of isoforms of MHCs in dorsal coccygeal muscles were analyzed by quantitative RT-PCR. The fiber types of muscles were assessed using SDS-PAGE. Band densities of silver-stained gel were quantified. Results. At first, the gene expression profiles of MHCs and protein expression in the dorsal coccygeal muscles were compared with tibilis anterior and gastrocunemius muscles. Higher proportion of MHC type 1 gene and protein expression were confirmed in the dorsal coccygeal muscles than tibialis anterior and gastrocuneimus muscles. MHC type 2B protein expression was not detected in dorsal coccygeal muscles. Next, coccygeal muscles after straight or kyphotic fixation were analyzed and compared with control. Gene expression of MHC type 1 was decreased at 7 and 28 days after fixation in straight and kyphosis group. The significant difference was seen at 28 days in kyphosis group. The band densities of MHC protein type 1 and 2A plus 2D/X were decreased in both straight and kyophosis groups at 28 days after fixation while sample volume was adjusted by wet wight of dissected coccygeal muscles. The mean proportion of MHC protein type 1 separated by SDS-PAGE were decreased in straight and kyphosis group. The difference was significant in straight group. Discussion. Our results demonstrated that the fixation of the rat tail induced transition of muscle fiber types in the paravertebral muscles characterized by the decrease in the proportion of the MHC type 1. Back muscles are required to contract continuously to keep posture. Slow-twitch fibers in back muscle contribute for continuous contraction. Slow-twitch fibers utilise energy efficiently by oxidative process while fast-twitch fibers mainly consume glucose through glycolysis producing lactate acid. Not only decreased amount of MHC but also decreased proportion of MHC type 1 might be the reason of easy fatigability in lumbar degenerative kyphosis. The limitations of this study is the difference between human paravertebral and rat coccygeal muscles and short duration of observation

Introduction. Intra-articular injury has been described as primary cause of pain in hip dysplasia. At this point it is unknown whether external muscle-tendon related pain coexists with intra-articular pathology. The primary aim was to identify muscle-tendon related pain in 100 dysplasia patients. The secondary aim was to test if muscle-tendon related pain is linearly associated to self-reported hip disability and muscle strength in patient with hip dysplasia. Materials and methods. One hundred patients (17 men) with a mean age of 29 years (SD 9) were included. Clinical entity approach was carried out to identify muscle-tendon related pain. Muscle strength was assessed with a handheld dynamometer and self-reported hip disability was recorded with the Copenhagen Hip and Groin Outcome Score (HAGOS). Results. Iliopsoas- and abductor-related pain were most prevalent with prevalences of 56% (CI 46; 66) and 42% (CI 32; 52), respectively. Adductor-, hamstrings- and rectus abdominis-related pain were less common. There was a significant inverse linear association between muscle-tendon related pain and self-reported hip disability ranging from −3.35 to −7.51 points in the adjusted analysis (p<0.05). Likewise an inverse linear association between muscle-tendon related pain and muscle strength was found ranging from −0.11 Nm/kg to −0.12 Nm/kg in the adjusted analysis (p<0.05). Conclusion. Muscle-tendon related pain seem to exist in about half of patients with hip dysplasia with a high prevalence of muscle-tendon related pain in the iliopsoas and the hip abductors and affects patients” self-reported hip disability and muscle strength negatively

The nervous system is known to be involved in inflammation and repair. We aimed to determine the effect of physical activity on the healing of a muscle injury and to examine the pattern of innervation. Using a drop-ball technique, a contusion was produced in the gastrocnemius in 20 rats. In ten the limb was immobilised in a plaster cast and the remaining ten had mobilisation on a running wheel. The muscle and the corresponding dorsal-root ganglia were studied by histological and immunohistochemical methods. In the mobilisation group, there was a significant reduction in lymphocytes (p = 0.016), macrophages (p = 0.008) and myotubules (p = 0.008) between three and 21 days. The formation of myotubules and the density of nerve fibres was significantly higher (both p = 0.016) compared with those in the immobilisation group at three days, while the density of CGRP-positive fibres was significantly lower (p = 0.016) after 21 days. Mobilisation after contusional injury to the muscle resulted in early and increased formation of myotubules, early nerve regeneration and progressive reduction in inflammation, suggesting that it promoted a better healing response

Falls in adults are a major problem and can lead to injuries and death. In order to better understand falls and successful recoveries, identifying kinematics, kinetics, and muscle forces during recovery from loss of balance is crucial. To obtain reactive gait patterns, participants must be subjected to unexpected perturbations such as trips and slips. Previous researchers have reported kinetics recovery data following stumbling; however, the muscle force recovery patterns remain unknown. To better target exercises to reduce the risk of falls, we must first understand which muscles, their magnitude, and their coordination patterns, play a role in a successful recovery from a trip and a slip. Additionally, knowing the successful patterns of lower limb function can help with the diagnosis of faulty movements. A total of 20 healthy adults in their twenties with similar athletic backgrounds were perturbed on a split-belt treadmill using Computer-Assisted Rehabilitation Environment (Motkforce Link) at a preset speed of 1.1m/s. Two kinds of perturbations were administered: slip and trip. Slips were simulated by accelerating one belt, whereas trips were simulated by decelerating one belt. Both perturbations had similar intensity and only differed in the direction. Computational modeling was used to obtain lower-limb function during the compensatory step. SPM paired t-test was used to compare differences in recovery strategies between slip and trip through magnitude and patterns of joints. There were no significant differences in joint angles post tripping vs post-slipping. Results of net joint moments showed that compensating for the loss of balance due to tripping required a higher ankle plantarflexion moment than slipping (at 22-52%; 1.2± 0.3vs0.4±0.2, p<0.001). Additionally, larger gluteus maximus (at 40-50%;8.7±3.8vs2.7±1.1N/kg, p=0.001), gluteus medius (at23~33%; 22.6±5.7vs6.8±3.6N/kg, p<0.001) were generated than post-slipping, respectively. These findings suggested that greater GMAX and GMED forces are required post-trip recovery than slip. Future analysis of trip recovery showed the importance of ankle joint in recovering from forward and backward fall. These results can be used as references in remote diagnosis of joint and muscle weakness and assessment of the risk of falls with the use of accelerometers

Abstract. Objectives. Acute compartment syndrome (ACS) is a progressive form of muscle ischaemia that is a surgical emergency and can have detrimental outcomes for patients if not treated optimally. The current problem is that there is no clear diagnostic threshold for ACS or guidance as to when fasciotomies should be performed. A new diagnostic method(s) is necessary to provide real-time information about the extent of muscle ischaemia in ACS. Given that lactic acid is produced by cells through anaerobic respiration, it may be possible to measure H+ ion concentration and to use this as a measure of ischaemia within muscle. Although we are familiar with the key biochemical metabolites involved in ischaemia; and the use of viability dyes in cell culture to distinguish between living or dead cells is well recognised; research has not been undertaken to correlate the biochemical and histological findings of ischaemia in skeletal muscle biopsies. Our primary aim was to investigate the potential for viability dyes to be used on live skeletal muscle biopsies (explants). Our secondary aim was to correlate the intramuscular pH readings with muscle biopsy viability. Methods. Nine euthanised Wistar rats were used. A pH catheter was inserted into one exposed gluteus medius muscles to record real-time pH levels and muscle biopsies were taken from the contralateral gluteus medius at the start of experiment and subsequently at every 0.1 of pH unit drop. Prior to muscle biopsy, the surface of the gluteus medius was painted with a layer of 50µmol/l Brilliant blue FCF solution to facilitate biopsy orientation. A 4mm punch biopsy tool was used to take biopsies. Each muscle biopsy was placed in a base mould filled with 4% ultra-low melting point agarose. The agarose embedded tissue block was sectioned to generate 400 micron thick tissue slices with a vibratome. The tissue slices were then placed in the staining solution with Hoechst 33342, Ethidium homodimer-1 and Calcein am. The tissue slices were imaged with Zeiss LSM880 confocal microscope's Z stack function. A dead muscle control was created by adding TritonX-100 to other tissue slices. For quantitative analyses, the images were analysed in Image J using the selection tool. This permitted individual cells to be identified and the mean grey value of each channel to be defined. Using the dead control, we were able to identify the threshold value for living cells using the Calcein AM channel. Results. Viability dyes, used primarily for cell cultures, can be used with skeletal muscle explants. Our study also showed that despite a significant reduction in tissue pH concentration over time, that almost 100% of muscle cells were still viable at pH 6.0, suggesting that skeletal muscle cells are robust to hypoxic insult in the absence of reperfusion. Conclusions. Viability dyes can be used on skeletal muscle biopsies. Further research investigating the likely associations between direct measured pH using a pH catheter, the concentrations of key cellular metabolic markers, and muscle tissue histology using vitality dyes in response to ischaemia, rather than hypoxia, is warranted. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Abstract. Background. Progressive muscle ischaemia results in reduced aerobic respiration and increased anaerobic respiration, as cells attempt to survive in a hypoxic environment. Acute compartment syndrome (ACS) is a progressive form of muscle ischaemia that is a surgical emergency resulting in the production of Lactic acid by cells through anaerobic respiration. Our previous research has shown that it is possible to measure H+ ions concentration (pH) as a measure of progressive muscle ischaemia (in vivo) and hypoxia (in vitro). Our aim was to correlate intramuscular pH readings and cell viability techniques with the intramuscular concentration of key metabolic biomarkers [adenosine triphosphate (ATP), Phosphocreatine (PCr), lactate and pyruvate], to assess overall cell health in a hypoxic tissue model. Methods. Nine euthanised Wistar rats were used in a non-circulatory model. A pH catheter was used to measure real-time pH levels from one of the exposed gluteus medius muscles, while muscle biopsies were taken from the contralateral gluteus medius at the start of the experiment and subsequently at every 0.1 of a pH unit decline. The metabolic biomarkers were extracted from the snap frozen muscle biopsies and analyzed with standard fluorimetric method. Another set of biopsies were stained with Hoechst 33342, Ethidium homodimer-1 and Calcein am and imaged with a Zeiss LSM880 confocal microscope. Results. Our study shows that the direct pH electrode readings decrease with time and took an average of 69 minutes to drop to a pH of 6.0. The concentrations of ATP, pyruvate and PCr declined over time, and the concentration of lactate increased over time. At pH 6.0, both ATP and PCr concentrations had decreased by 20% and pyruvate has decreased by 50%, whereas lactate had increased 6-fold. The majority of cells were still viable at a pH of 6.0, suggesting that skeletal muscle cells are remarkably robust to hypoxic insult, although this was a hypoxic model where reperfusion was not possible. Conclusions. Our research suggests that histologically, skeletal muscle cells are remarkably robust to hypoxic insult despite the reduction in the total adenine nucleotide pool, but this may not reflect the full extent of cell injury and quite possibly irreversible injury. The timely restoration of blood flow in theory should halt the hypoxic insult, but late reperfusion results in cellular dysfunction and cell death due to localised free radical formation. Further research investigating the effects of reperfusion in vivo are warranted, as this may identify an optimal time for using pharmacological agents to limit reperfusion injury, around the time of fasciotomy to treat acute compartment syndrome. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Sarcopenia is an age-related geriatric syndrome which is associated with subsequent disability and morbidity. Currently there is no promising therapy approved for the treatment of sarcopenia. The receptor activator of nuclear factor NF-κB ligand (RANKL) and its receptor (RANK) are expressed in bone and skeletal muscle. Activation of the NF-κB pathway mainly inhibits myogenic differentiation, which leads to skeletal muscle dysfunction and loss. LYVE1 and CD206 positive macrophage has been reported to be associated with progressive impairment of skeletal muscle function with aging. The study aims to investigate the effects of an anti-RANKL treatment on sarcopenic skeletal muscle and explore the related mechanisms on muscle inflammation and the polarization status of macrophages. Sarcopenic senescence-accelerated mouse P8 (SAMP8) mice at month 8 were treated intraperitoneally with 5mg/kg anti-RANKL (IK22/5) or isotype control (2A3; Bio X Cell) antibody every 4 weeks and harvested at month 10. Senescence accelerated mouse resistant-1 (SAMR1) were collected at month 10 as the age-matched non-sarcopenic group. Ex-vivo functional assessment, grip strength and immunostaining of C/EBPa, CD206, F4/80, LYVE1 and PAX7 were performed. Data analysis was done with one-way ANOVA, and the significant level was set at p≤0.05. At month 10, tetanic force/specific tetanic force, twitch force/specific twitch force in anti-RANKL group were significantly higher than control group (all p<0.01). The mice in the anti-RANKL treatment group also showed significantly higher grip strength than Con group (p<0.001). The SAMP8 mice at month 10 expressed significantly more C/EBPa, CD206 and LYVE1 positive area than in SAMR1, while anti-RANKL treatment significantly decreased C/EBPa, CD206 and LYVE1 positive area. The anti-RANKL treatment protected against skeletal muscle dysfunctions through suppressing muscle inflammation and modulating M2 macrophages, which may represent a novel therapeutic approach for sarcopenia. Acknowledgment: Collaborative Research Fund (CRF, Ref: C4032-21GF)

Aim. To assess the relationship between mRNA expression of genetic markers of inflammation (tumour necrosis factor-alpha (TNFα)) and interleukin-6 (IL-6) in the vastus lateralis (VL) of the operated leg, and the strength of the operated leg quadriceps, in patients following THR. Methods. Following ethical approval, 10 patients were recruited prospectively. Distal VL (5cm proximal to lateral supra-patellar pouch) biopsies were obtained intraoperatively and at 6 weeks post-operatively, with maximal voluntary contraction of the operated leg quadriceps (MVCOLQ) in Newtons(N), assessed preoperatively and at 6 weeks post-op. mRNA expression in the biopsies was assessed using the reverse transcriptase polymerase chain reaction (RT-PCR). Relationships were assessed using Spearman's correlation coefficient (data not normally distributed). Results. mRNA RQ (comparison of 6 week VL samples to intraoperative samples) was (mean (SD)) 6.23(12.85) for TNFα and 17.10(47.46) for IL-6. Preoperatively mean MVCOLQ was 188.90(76.84) N and at 6 weeks it was 217.00(53.91) N. There was no significant relationship between TNFα or IL-6 RQ and absolute MVCOLQ at 6 weeks. A trend to significance was noted between TNFα and the improvement (%) in MVCOLQ at 6 weeks (R = −0.552, p=0.098) with no such relationship observed for IL-6 (R = 0.127, p=0.726). Conclusions. In patients with hip osteoarthritis, reduced strength (MVCOLQ) appears to be mediated by muscle inflammation. The trend to correlation that exists for improvement in MVCOLQ with TNFα indicates that muscle inflammation may be one of the causes of pain in patients with severe osteoarthritis

The HIPGEN study funded under EU Horizon 2020 (Grant 7792939) has the aim to investigate the potential of the first regenerative cell therapy for the improvement of recovery after muscle injury in hip fracture patients. For this aim we intramuscularly injected placental derived mesenchymal stromal cells during hip fracture arthroplasty. Despite not having reached the primary endpoint, which was the Short Physical Performance Battery, we could observe an increase in abductor muscle strength and a faster return to balance looking at symmetry in insole measurements during follow up

To investigate changes in quadriceps and hamstrings muscle groups during sustained isokinetic knee flexion and extension. 125 paediatric participants (45 males and 80 females, mean age 14.2 years) were divided into two groups: participants with a confirmed ACL tear (ACLi, n = 64), and puberty- and activity-level matched control participants with no prior history of knee injuries (CON, n = 61). Participants completed a series of 44 repetitions of isokinetic knee flexion and extension at 90 deg/ sec using a Biodex dynamometer (Biodex Medical Systems Inc, Shirley, New York). Surface EMG sensors (Delsys Incorporated, Natick, MA) simultaneously recorded the quadriceps and hamstring activations. Muscle function was assessed as the change in quadriceps activation and extension torque were calculated using the percent difference between the mean of the first five trials, and the mean of the last five trials. ACLi participants had significantly higher percent change in quadriceps activation for both healthy and injured legs, in comparison to CON dominant leg. As such, the healthy leg of the ACLi participants is activating significantly more than their health matched controls, while also demonstrating reduced muscular endurance (less torque in later repetitions). Therefore, we conclude that the non-injured limb of the ACLi participant is not performing as a healthy limb. Since return to activity clearance following ACLi implies return to sport against age- and activity matched opponents, clearing young athletes based on the non-injured contralateral limb may put them at greater risk of reinjury

Objectives. Regenerative medicine is an emerging field aimed at the repair and regeneration of various tissues. To this end, cytokines (CKs), growth factors (GFs), and stem/progenitor cells have been applied in this field. However, obtaining and preparing these candidates requires invasive, costly, and time-consuming procedures. We hypothesised that skeletal muscle could be a favorable candidate tissue for the concept of a point-of-care approach. The purpose of this study was to characterize and confirm the biological potential of skeletal muscle supernatant for use in regenerative medicine. Methods. Semitendinosus muscle was used after harvesting tendon from patients who underwent anterior cruciate ligament reconstructions. A total of 500 milligrams of stripped muscle was minced and mixed with 1 mL of saline. The collected supernatant was analysed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The biological effects of the supernatant on cell proliferation, osteogenesis, and angiogenesis in vitro were evaluated using human mesenchymal stem cells (hMSCs) and human umbilical cord vein endothelial cells (HUVECs). Results. The supernatant contained several GFs/CKs, with especially high levels of basic fibroblast growth factor, and CD34+ cells as the stem/progenitor cell fraction. With regard to biological potential, we confirmed that cell proliferation, osteoinduction, and angiogenesis in hMSCs and HUVECs were enhanced by the supernatant. Conclusions. The current study demonstrates the potential of a new point-of-care strategy for regenerative medicine using skeletal muscle supernatant. This attractive approach and readily-available material could be a promising option for tissue repair/regeneration in the clinical setting. Cite this article: M. Yoshikawa, T. Nakasa, M. Ishikawa, N. Adachi, M. Ochi. Evaluation of autologous skeletal muscle-derived factors for regenerative medicine applications. Bone Joint Res 2017;6:277–283. DOI: 10.1302/2046-3758.65.BJR-2016-0187.R1

Cam-type femoroacetabular impingement (FAI) is a common cause for athletic hip injury and early hip osteoarthritis. Although corrective cam FAI surgery can improve patient reported outcome measures (PROMs), it is not clear how surgery affects muscle forces and hip joint loading. Surgery for FAI may redistribute muscle forces and contact forces at the hip joint during routine activities. The purpose of this study was to examine the muscle contributions and hip contact forces during gait in patients prior and after two years of undergoing surgery for cam FAI. Kinematics and kinetics were recorded in 11 patients with symptomatic cam FAI as they completed a gait task. Muscle and hip contact forces during the stance phase were estimated using musculoskeletal modelling and static optimization in OpenSim. All patients reported improvements in PROMs. Post-operatively, patients showed reduced forces in the long head of the biceps femoris at ipsilateral foot-strike and in the rectus femoris at the contralateral foot-strike. The reduced muscle forces decreased sagittal hip moment but did not change hip contact forces. This was the first study to evaluate hip muscle and contact forces in FAI patients post-operatively. Although hip contact forces are not altered following surgery, muscle forces are decreased even after two years. These findings can provide guidance in optimizing recovery protocols after FAI surgery to improve hip flexor and extensor muscle forces

Objectives. The aim of this study was to systematically review the literature on measurement of muscle strength in patients with femoroacetabular impingement (FAI) and other pathologies and to suggest guidelines to standardise protocols for future research in the field. Methods. The Cochrane and PubMed libraries were searched for any publications using the terms ‘hip’, ‘muscle’, ‘strength’, and ‘measurement’ in the ‘Title, Abstract, Keywords’ field. A further search was performed using the terms ‘femoroacetabular’ or ‘impingement’. The search was limited to recent literature only. Results. A total of 29 articles were reviewed to obtain information on a number of variables. These comprised the type of device used for measurement, rater standardisation, the type of movements tested, body positioning and comparative studies of muscle strength in FAI versus normal controls. The studies found that hip muscle strength is lower in patients with FAI; this is also true for the asymptomatic hip in patients with FAI. Conclusions. Current literature on this subject is limited and examines multiple variables. Our recommendations for achieving reproducible results include stabilising the patient, measuring isometric movements and maximising standardisation by using a single tester and familiarising the participants with the protocol. Further work must be done to demonstrate the reliability of any new testing method. Cite this article: E. Mayne, A. Memarzadeh, P. Raut, A. Arora, V. Khanduja. Measuring hip muscle strength in patients with femoroacetabular impingement and other hip pathologies: A systematic review. Bone Joint Res 2017;6:66–72. DOI: 10.1302/2046-3758.61.BJR-2016-0081

Objectives. We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. Materials and Methods. We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy. Results. C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (. sd. ) 0.8) and BMP-7 (50.6 ng/mg, . sd. 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage. Conclusion. Extra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation. Cite this article: D. B. Raina, A. Gupta, M. M. Petersen, W. Hettwer, M. McNally, M. Tägil, M-H. Zheng, A. Kumar, L. Lidgren. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial. Bone Joint Res 2016;5:500–511. DOI: 10.1302/2046-3758.510.BJR-2016-0133.R1

Last decade, a shift towards operative treatment of midshaft clavicle fractures has been observed [T. Huttunen et al., Injury, 2013]. Current fracture fixation plates are however suboptimal, leading to reoperation rates up to 53% [J. G. Wijdicks et al., Arch. Orthop. Trauma Surg, 2012]. Plate irritation, potentially caused by a bad geometric fit and plate prominence, has been found to be the most important factor for reoperation [B. D. Ashman et a.l, Injury, 2014]. Therefore, thin plate implants that do not interfere with muscle attachment sites (MAS) would be beneficial in reducing plate irritation. However, little is known about the clavicle MAS variation. The goal of this study was therefore to assess their variability by morphing the MAS to an average clavicle. 14 Cadaveric clavicles were dissected by a medical doctor (MH), laser scanned (Nikon, LC60dx) and a photogrammetry was created with Agisoft photoscan (Agisoft, Russia). Subsequently a CT-scan of these bones was acquired and segmented in Mimics (Materialise, Belgium). The segmented bone was aligned with the laser scan and MAS were indicated in 3-matic (Materialise, Belgium). Next, a statistical shape model (SSM) of the 14 segmented clavicles was created. The average clavicle from the SSM was then registered to all original clavicle meshes. This registration assures correspondences between source and target mesh. Hence, MAS of individual muscles of all 14 bones were indicated on the average clavicle. Mean area is 602 mm. 2. ± 137 mm. 2. for the deltoid muscle, 1022 mm. 2. ±207 mm. 2. for the trapezius muscle, and 683 mm. 2. ± 132 mm. 2. for the pectoralis major muscle. The sternocleidomastoid muscle has a mean area of 513 mm. 2. ± 190 mm. 2. and the subclavius muscle had the smallest mean area of 451 mm. 2. ± 162 mm. 2. Visualization of all MAS on the average clavicle resulted in 72% coverage of the surface, visualizing only each muscle's largest MAS led to 52% coverage. The large differences in MAS surface areas, as shown by the standard deviation, already indicate their variability. Difference between coverage by all MAS and only the largest, shows that MAS location varies strongly as well. Therefore, design of generic plates that do not interfere with individual MAS is challenging. Hence, patient-specific clavicle fracture fixation plates should be considered to minimally interfere with MAS

Objectives. Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics. Methods. Chronic supraspinatus tears were induced in adult rats, and repaired 28 days later. Rats received 0 mg/kg, 3 mg/kg, or 10 mg/kg GSK1120360A daily. Collagen content, contractility, fibre type distribution and size, the expression of genes involved in fibrosis, lipid accumulation, atrophy and inflammation, and the mechanical properties of the enthesis were then assessed two weeks following surgical repair. Results. At two weeks following repair, treatment groups showed increased muscle mass but there was a 15% decrease in force production in the 10 mg/kg group from controls, and no difference between the 0 mg/kg and the 3 mg/kg groups. There was a decrease in the expression of several gene transcripts related to matrix accumulation and fibrosis, and a 50% decrease in collagen content in both treated groups compared with controls. Additionally, the expression of inflammatory genes was reduced in the treated groups compared with controls. Finally, PHD inhibition improved the maximum stress and displacement to failure in repaired tendons. Conclusions. GSK1120360A resulted in improved enthesis mechanics with variable effects on muscle function. PHD inhibition may be beneficial for connective tissue injuries in which muscle atrophy has not occurred. Cite this article: J. P. Gumucio, M. D. Flood, A. Bedi, H. F. Kramer, A. J. Russell, C. L. Mendias. Inhibition of prolyl 4-hydroxylase decreases muscle fibrosis following chronic rotator cuff tear. Bone Joint Res 2017;6:57–65. DOI: 10.1302/2046-3758.61.BJR-2016-0232.R1

After total hip replacement, force generating capacity of gluteal muscles is an impotant parameter on joint contact forces and primary fixation of total hip replacement. Femoral offset is an option to optimize muscle moment arms, especially main abductor Gluteus Medius and Minimus. To investigate relationship with weak gluteal muscles (Gluteus Medius and Minimus) and increased femoral offset, we build a musculoskeletal model. Creating of three-dimensional femur geometry and scaling of the musculoskeletal model according to the subject were performed with computed tomography data. Obtained gait kinematic and kinetic data were applied and to mimic gluteal muscle weakness, the force generating capacities of Gluteus Medius and Minimus reduced (%20-%80). Analysis were done for both anatomical and +10mm offset. Then, muscle and joint reaction forces obtained from musculoskeletal analysis transfered to CT based finite element model to evaluate changes in maximum principle stresses on femur. According to the results of the musculoskeletal analysis, the weakness of the gluteal muscles caused an increase in the activation of Gluteus Maximus, Rectus Femoris and Tensor Fasciae Latae. Effects of +10 mm femoral offset on total abductor muscle activity increased with reduced muscle strength. As a result of the finite element analysis, no significant difference was observed for maximum principle stresses on femur with varying muscle activites. The results of these analyses are important to understand weakness of gluteal muscles and for planning hip surgery