Mechanical failure of spine posterior fixation in the lumbar region Is suspected to occur more frequently when the sagittal balance is not properly restored. While failures at the proximal extremity have been studied in the literature, the lumbar distal junctional pathology has received less attention. The aim of this work was to investigate if the spinopelvic parameters, which characterize the sagittal balance, could predict the mechanical failure of the posterior fixation in the distal lumbar region. All the spine surgeries performed in 2017-2019 at Rizzoli Institute were retrospectively analysed to extract all cases of lumbar distal junctional pathology. All the revision surgeries performed due to the pedicle screws pull-out, or the breakage of rods or screws, or the vertebral fracture, or the degenerative disc disease, in the distal extremity, were included in the junctional (JUNCT) group. A total of 83 cases were identified as JUNCT group. All the 241 fixation surgeries which to date have not failed were included in the control (CONTROL) group. Clinical data were extracted from both groups, and the main spinopelvic parameters were assessed from sagittal standing preoperative (pre-op) and postoperative (post-op) radiographs with the software Surgimap (Nemaris). In particular, pelvic incidence (PI), sagittal vertical axis (SVA), pelvic tilt (PT), T1 pelvic angle (TPA), sacral slope (SS) and lumbar lordosis (LL) have been measured. In JUNCT, the main failure cause was the screws pull-out (45%). Spine fixation with 7 or more levels were the most common in JUNCT (52%) in contrast to CONTROL (14%). In CONTROL, PT, TPA, SS and PI-LL were inside the recommended ranges of good sagittal balance. For these parameters, statistically significant differences were observed between pre-op and post-op (p<0.0001, p=0.01, p<0.0001, p=0.004, respectively, Wilcoxon test). In JUNCT, the spinopelvic parameters were out of the ranges of the good sagittal balance and the worsening of the balance was confirmed by the increase in PT, TPA, SVA, PI-LL and by the decrease of LL (p=0.002, p=0.003, p<0.0001, p=0.001, p=0.001, respectively, paired t-test) before the revision surgery. TPA (p=0.003, Kolmogorov-Smirnov test) and SS (p=0.03, unpaired t-test) differed significantly in pre-op between JUNCT and CONTROL. In post-op, PI-LL was significantly different between JUNCT and CONTROL (p=0.04, unpaired t-test). The regression model of PT vs PI was significantly different between JUNCT and CONTROL in pre-op (p=0.01, Z-test). These results showed that failure is most common in long fused segments, likely due to long lever arms leading to implant failure. If the sagittal balance is not properly restored, after the surgery the balance is expected to worsen, eventually leading to failure: this effect was confirmed by the worsening of all the spinopelvic parameters before the revision surgery in JUNCT. Conversely, a good sagittal balance seems to avoid a revision surgery, as it is visible is CONTROL. The mismatch PI-LL after the fixation seems to confirm a good sagittal balance and predict a good correction. The linear regression of PT vs PI suggests that the spine deformity and pelvic conformation could be a predictor for the failure after a fixation

Medical and allied health staff are beginning to incorporate the Nintendo Wii-Fit into musculoskeletal rehabilitation protocols. One potential application is the assessment of standing balance following Orthopaedic lower limb surgery. The Wii Balance Board (WBB) has been shown to be a valid equivalent to a laboratory grade force platform for the assessment of standing balance. Our objective was to investigate the validity and reliability of the balance tests included with the Wii-Fit software. Initially, a single subject performed multiple repeats of a standing balance test. The data was collected simultaneously from a commercial force platform using its integrated software that measured centre of pressure and from the WBB using the Wii-Fit software that generated a percentage score. The data from each was compared and analyzed, applying the equations of known, validated standing balance measurements. Then, thirty subjects free of lower limb pathology performed a series of standing balance tests combining single leg and double leg stance with their eyes open and then closed. Data was collected from one set of trials on the WBB using the Wii-Fit software and another using bespoke centre of pressure software on a laptop computer. The tests were then repeated on a second occasion within 2 weeks. The algorithm used by the Wii-Fit software to generate the ‘Stillness’ standing balance score was calculated with a predictive value (R squared) of 0.94. This correlated well to a known, valid measure of standing balance. Test-retest reliability was examined for the data from both pieces of software. Both demonstrated good-to-excellent test-retest reliability within ‘software’. The laptop data was transformed using the algorithm and the between ‘software’ reliability was calculated as good-to-excellent. The Wii-Fit software collects standing balance data from the WBB at a fraction of the cost of laboratory grade systems. The score generated by the Wii-Fit software is reliable and valid as an overall assessment of standing balance. Although its application would be limited for detailed assessment of balance disorders, it could still provide surgeons with an affordable, clinic based balance-screening tool. This could form part of an assessment protocol following lower limb surgery

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

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

Adult Spine Deformity (ASD) is a degenerative condition of the adult spine leading to altered spine curvatures and mechanical balance. Computational approaches, like Finite Element (FE) Models have been proposed to explore the etiology or the treatment of ASD, through biomechanical simulations. However, while the personalization of the models is a cornerstone, personalized FE models are cumbersome to generate. To cover this need, we share a virtual cohort of 16807 thoracolumbar spine FE models with different spine morphologies, presented in an online user-interface platform (SpineView). To generate these models, EOS images are used, and 3D surface spine models are reconstructed. Then, a Statistical Shape Model (SSM), is built, to further adapt a FE structured mesh template for both the bone and the soft tissues of the spine, through mesh morphing. Eventually, the SSM deformation fields allow the personalization of the mean structured FE model, leading to generate FE meshes of thoracolumbar spines with different morphologies. Models can be selectively viewed and downloaded through SpineView, according to personalized user requests of specific morphologies characterized by the geometrical parameters: Pelvic Incidence; Pelvic Tilt; Sacral Slope; Lumbar Lordosis; Global Tilt; Cobb Angle; and GAP score. Data quality is assessed using visual aids, correlation analyses, heatmaps, network graphs, Anova and t-tests, and kernel density plots to compare spinopelvic parameter distributions and identify similarities and differences. Mesh quality and ranges of motion have been assessed to evaluate the quality of the FE models. This functional repository is unique to generate virtual patient cohorts in ASD. Acknowledgements: European Commission (MSCA-TN-ETN-2020-Disc4All-955735, ERC-2021-CoG-O-Health-101044828)

Poor tendon repair is an unsolved issue in clinical practice, due to complex tendon structure. Tendon stem/progenitor cells (TSPCs) play key roles in homeostasis, regeneration, and inflammation regulation in acute tendon injuries, and rely on TGF-β signaling for recruitment into degenerative tendons. In this study, we aimed to develop an in vitro model for tenogenesis adopting a dynamic culture of a fibrin 3D scaffold, bioengineered with human TSPCs collected from both healthy and tendinopathic surgery explants (Review Board prot./SCCE n.151, 29 October 2020). 3D culture was maintained for 21 days under perfusion provided by a custom-made bioreactor, in a medium supplemented with hTGF-β1 at 20 ng/mL. The data collected suggested that the 3D in vitro model well supported survival of both pathological and healthy cells, and that hTGF-β signaling, coupled to a dynamic environment, promoted differentiation events. However, pathological hTSPCs showed a different expression pattern of tendon-related genes throughout the culture and an impaired balance of pro-inflammatory and anti-inflammatory cytokines, compared to healthy hTSPCs, as indicated by qRT-PCT and immunofluorescence analyses. Additionally, the expression of both tenogenic and cytokine genes in hTSPCs was influenced by hTGF-β1, indicating that the environment assembled was suitable for studying tendon stem cells differentiation. The study offers insights into the use of 3D cultures of hTSPCs as an in vitro model for investigating their behavior during tenogenic events and opens perspectives for following the potential impact on resident stem cells during regeneration and healing events

Chronic inflammatory events have been associated to almost every chronic disease, including cardiovascular-, neurodegenerative- and autoimmune- diseases, cancer, and host-implant rejection. Given the toll of chronic inflammation in healthcare and socioeconomical costs developing strategies to resolve and control chronic states of inflammation remain a priority for the significant benefit of patients. Macrophages (Mφ) hold a central role both in the initiation and resolution of inflammatory events, assuming different functional profiles. The outstanding features of Mφ counting with the easy access to tissues, and the extended networking make Mφ excellent candidates for precision therapy. Moreover, sophisticated macrophage-oriented systems could offer innovative immune-regulatory alternatives to effectively regulate chronic environments that traditional pharmacological agents cannot provide. We propose magnetically assisted systems for balancing Mφ functions at the injury site. This platform combines polymers, inflammatory miRNA antagonists and magnetically responsive nanoparticles to stimulate Mφ functions towards pro-regenerative phenotypes. Strategies with magnetically assisted systems include contactless presentation of immune-modulatory molecules, cell internalization of regulatory agents for functional programming via magnetofection, and multiple payload delivery and release. Overall, Mφ-oriented systems stimulated pro-regenerative functions of Mφ supporting magnetically assisted theranostic nanoplatforms for precision therapies, envisioning safer and more effective control over the distribution of sensitive nanotherapeutics for the treatments of chronical inflammatory conditions. Acknowledgements: ERC CoG MagTendon No.772817; FCT Doctoral Grant SFRD/BD/144816/2019, and TERM. RES Hub (Norte-01-0145-FEDER-022190)

Introduction. Recent studies suggested that the progression of osteoarthritis (OA), a chronic degenerative joint disease, may be affected by the autonomic nervous system (ANS). Under healthy conditions, the sympathetic (SNS) and parasympathetic (PNS) branches of the ANS are well coordinated to maintain homeostasis. However, pathological conditions are frequently associated with a disturbance of this fine-tuned balance. Therefore, we analyzed whether an autonomic dysfunction occurs in OA patients. Method. 225 participants with early- or late-stage knee OA as well as 40 healthy age-matched probands were included in this study. Autonomic activity was investigated by analyzing heart rate variability (HRV), which decreases under chronic sympathetic overactivity. Time- and frequency-domain HRV indices SDRR, RMSSD, pRR50 and LF were examined. Linear regression analysis was performed to adjust for clinical characteristics, such as age, sex, BMI, or medication. Moreover, perceived chronic stress (PSQ) and pain (WOMAC) were assessed via questionnaires. In addition, the serum stress hormones cortisol, DHEA-S and IL-6 were analyzed via ELISA. Result. SDRR, RMSSD, and pRR50 were slightly reduced in the early stage of OA and showed significant decrease in the later stage of the disease. Also LF decreased significantly with OA progression. HRV was significantly influenced by the grade of OA, but not other patient characteristics. Moreover, late-stage OA patients demonstrated significantly higher PSQ and WOMAC levels compared to healthy controls. In addition, cortisol/DHEA-S ratio and IL-6 serum concentrations were significantly higher in late-stage than in early-stage OA patients and healthy controls. Conclusion. Reduced HRV, increased cortisol/DHEA-S ratio and PSQ level as well as elevated systemic IL-6 concentration indicated an autonomic shift towards a more pronounced SNS activity due to PNS deficiency in OA patients, particularly in the late-stage of the disease. Therefore, modulation of the ANS, for example by vagus nerve stimulation, might be a potential treatment strategy for of knee OA patients

Purpose. To compare postoperative clinical outcomes between posterior cruciate ligament (PCL) retaining and resecting total knee arthroplasty (TKA) using same cruciate-substituting (CS) inserts, and to elucidate the clinical relevance of the residual PCL in cruciate-retaining TKA, considering intraoperative influence factors, such as the posterior tibial slope, posterior condylar offset, joint gap, joint balance, and joint laxity. Methods. A total of 64 consecutive knees (44 patients) were enrolled in this study and divided into following two groups: 39 knees underwent PCL-retaining TKA group (CR group), and 25 underwent PCL-resecting TKA group (CS group). Preoperative patients’ demographic data and one-year postoperative clinical outcomes including range of motion, the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Japanese Orthopaedic Association (JOA) score, and Forgotten Joint Score-12 (FJS-12) were compared between two groups. Results. Regarding range of motion, the average preoperative ROM was -14.3/120.0 degrees in the CR group and improved to -2.4/118.9 degrees postoperatively. In the CS group, the average preoperative ROM was -7.5/130 degrees and changed to -2.2/122.4 degrees postoperatively. There was no significant difference in the postoperative ROM between the groups (P=0.16). The KOOS (from 47.1 to 69.5 in CR group; from 41.1 to 70.8 in CS group) and JOA scores (from 59.2 to 76.9 in CR group; from 55.6 to 80.8 in CS group) were significantly improved postoperatively in both groups (P < 0.01). However, there was no significance in these postoperative scores between two groups (P = 0.09). There was also no significance in FJS-12 between two groups (70.3 in CR group and 66.9 in CS group; P=0.53). Conclusions. Residual PCL in TKA with a CS insert would not impact one-year postoperative clinical outcomes including KOOS, JOA, and FJS-12

Vacuum orthoses are being applied in the care of patients with foot and lower leg conditions, as ankle fractures or sprains. The lower leg is protected and immobilized, which increases mobility. Due to the design, the orthoses lead to a difference in leg length, i.e. the side with the orthosis becomes longer, which changes the gait kinematics. To prevent or mitigate the unfavourable effects of altered gait kinematics, leg length-evening devices (shoe lifts) are offered that are worn under the shoe on the healthy side. Our aim was to evaluate the effect of such a device on the normality of gait kinematics. Gait analysis was conducted with 63 adult, healthy volunteers having signed an informed consent form that were asked to walk on a treadmill at a speed of 4.5km/h in three different conditions:. barefoot - as reference for establishing the normality score baseline. with a vacuum orthosis (VACOPed, OPED GmbH, Germany) and a sport shoe. with a vacuum orthosis and a shoe lift (EVENup, OPED GmbH, Germany). Data was sampled using the gait analysis system MCU 200 (LaiTronic GmbH, Austria). The positions of the joint markers were exported from the software and evaluated for the joint angles during the gait cycle using custom software (implemented in DIAdem 2017, National Instruments). A normality score using a modification of the Gait Profile Score (GPS) was calculated in every 1%-interval of the gait cycle and evaluated with a Wilcoxon signed rank test. The GPS value was reduced by 0.33° (0.66°) (median and IQR) while wearing the shoe lift. The effect was statistically significant, and very large (W = 1535.00, p < .001; r (rank biserial) = 0.52, 95% CI [0.29, 0.70]). The significant reduction of the GPS value indicates a more normal gait kinematics while using the leg length-evening device on the contralateral shoe. This rather simple and inexpensive device thus might improve patient comfort and balance while using the vacuum orthoses

Worldwide, tendon disorders are one of the main causes of disability that decrease the quality of life of individuals and represent a substantial economic burden on society. Currently, the main therapies used for tendon injuries are not able to restore tendon functionality, and due to tendons' hypovascular and hypocellular nature, they present a reduced healing capacity, which also limits the success of the available therapies. In order to discover new therapies, extracellular vesicles (EVs), key players in cell-cell communication, have been widely explored for tissue engineering and regenerative medicine applications. Thus, the aim of this study is to assess the role of EVs derived from platelets in stem cell tenogenic commitment using a bioengineered tendon in vitro model for potential use as tendon therapeutic agents. Biomimetic platelet-derived EVs were produced by freeze-thaw cycles of platelets and isolation at different centrifugation speed. To recreate the architecture of tendons, a 3D system consisting of electrospun anisotropic nanofiber scaffolds coated with collagen encapsulating human adipose stem cells (hASCs) and different types of platelet-derived EVs, were produced. Then, the influence of the tendon-mimetic constructs and the distinct EVs populations in the hASCs tenogenic differentiation were assessed over culture time. We observed that the hASCs on the nanofibrous tendon scaffolds, show high cytoskeleton anisotropic organization that is characteristic of tenocytes. Moreover, acting as biological cues, platelet-derived EVs boosted hASCs tenogenic commitment, supported by the increased gene expression of tendon-related markers (SCX and TNMD). Additionally, EVs enhanced the deposition of tendon like extracellular matrix (ECM), as evidenced by the increased gene expression of ECM-related markers such as COL1, COL3, DCN, TNC, and MMP-3, which are fundamental for ECM synthesis and degradation balance. Moreover, EVs induced lower collagen matrix contraction on hASCs, which has been related with lower myofibroblast differentiation. Overall, the results revealed that EVs are capable of modulating stem cells' behavior boosting their tenogenic commitment, through the increased expression of healthy tendon cell markers, potentiating ECM deposition and decreasing cell contractility. Therefore, platelet EVs are a promising biochemical tool, worthy to be further explored, as paracrine signaling that might potentiate tendon repair and regeneration

In this study, we aimed to investigate tibiofemoral and allograft loading parameters after OCA transplantation using tibial plateau shell grafts to characterize the clinically relevant biomechanics that may influence joint kinematics and OCA osseointegration after transplantation. The study was designed to test the hypothesis that there are significant changes in joint loading after tibial plateau OCA transplantation that may require unique post-operative rehabilitation regimens in patients to restore balance in the knee joint. Fresh-frozen cadaveric knees (n=6) were thawed and mounted onto a 6 DOF KUKA robot. Specimens were size matched to +2 mm for the medial-to-lateral width of the medial tibial hemiplateaus. Three specimens served as allograft recipient knees and three served as donor knees. Recipient knees were first tested in their native state and then tested with size-matched medial tibial hemiplateau shell grafts (n=3) prepared from the donor knees using custom-cut tab-in-slot and subchondral drilling techniques. Tekscan sensors were placed in the joint spaces to evaluate the loading conditions under 90N biaxial loading at full extension of the knee before and after graft placement. The I-Scan system used in conjunction analyzed the total force, pressure distribution, peak pressure, and center of force within the joint space. Data demonstrated significant difference (p<0.05) in joint space loading after graft implantation compared to controls in both lateral and medial tibial plateaus. The I-Scan pressure mapping system displayed changes in femoral condylar contact points as well. The results demonstrated that joint space loading was significantly different (p<0.05) between all preoperative and postoperative cadaveric specimens. Despite the best efforts to size match grafts, slight differences in the host's joint geometry resulted in shifts of contact areas between the tibial plateau and femoral condyle therefore causing either an increase or decrease in pressure measured by the sensor. This concludes that accuracy in graft size matching is extremely important to restoring close to normal loading across the joint and this can be further ensured through postoperative care customized to the patient after OCA surgery

Our previous research has demonstrated that minor adjustments to in vitro cellular aggregation parameters, i.e. alterations to aggregate size, can influence temporal and spatial mineral depositions within maturing bone cell nodules. What remains unclear, however, is how aggregate size might affect mineralisation within said nodules over long-term in vivo culture. In this study, we used an osteoblast cell line, MLO-A5, and a primary cell culture, mesenchymal stem cells (MSC), to compare small (approximately 80 µm) with large (approximately 220 µm) cellular aggregates for potential bone nodule development after 8 weeks of culturing in a mouse model (n = 4 each group). In total, 30 chambers were implanted into the intra-peritoneal cavity of 20 male, immunocompromised mice (MF1-Nu/Nu, 4 – 5 weeks old). Nine small or three large aggregates were used per chamber. Neoveil mesh was seeded directly with 2 × 10. 3. cells for monolayer control. At 8 weeks, the animals were euthanised and chambers fixed with formalin. Aggregate integrity and extracellular material growth were assessed via light microscopy and the potential mineralisation was assessed via micro-CT. Many large aggregates appeared to disintegrate, whilst the small aggregates maintained their form and produced additional extracellular material with increased sizes. Both MLO-A5 cells and MSC cells saw similar results. Interestingly, however, the MSCs were also seen to produce a significantly higher volume of dense material compared to the MLO-A5 cells from micro-CT analysis. Overall, a critical cell aggregate size appeared to exist balancing optimal tissue growth with oxygen diffusion, and cell source may influence differentiation pathway despite similar experimental parameters. The MSCs, for example, were likely producing bone via the endochondral ossification pathway, whilst the matured bone cells, MLO-A5 cells, were likely producing bone via the intramembranous ossification pathway

Introduction. Knee osteoarthritis often causes malalignment and altering bone load. This malalignment is corrected during total knee arthroplasty surgery, balancing the ligaments. Nonetheless, preoperative gait patterns may influence postoperative prosthesis load and bone support. Thus, the purpose is to investigate the impact of preoperative gait patterns on postoperative femoral and tibial component migration in total knee arthroplasty. Method. In a prospective cohort study, 66 patients with primary knee osteoarthritis undergoing cemented Persona total knee arthroplasty were assessed. Preoperative knee kinematics was analyzed through dynamic radiostereometry and motion capture, categorizing patients into four homogeneous gait patterns. The four subgroups were labeled as the flexion group (n=20), the abduction (valgus) group (n=17), the anterior drawer group (n=10), and the tibial external rotation group (n=19). The femoral and tibial component migration was measured using static radiostereometry taken supine on the postoperative day (baseline) and 3-, 12-, and 24- months after surgery. Migration was evaluated as maximum total point motion. Result. Of the preoperatively defined four subgroups, the abduction group with a valgus-characterized gait pattern exhibited the highest migration for both the femoral (1.64 mm (CI95% 1.25; 2.03)) and tibial (1.21 mm (CI95% 0.89; 1.53)) components at 24-month follow-up. For the femoral components, the abduction group migrated 0.6 mm (CI95% 0.08; 1.12) more than the external rotation group at 24 months. For the tibial components, the abduction group migrated 0.43 mm (CI95% 0.16; 0.70) more than the external rotation group at 3 months. Furthermore, at 12- and 24-months follow-up the abduction group migrated 0.39 mm (95%CI 0.04; 0.73) and 0.45 mm (95%CI 0.01; 0.89) more than the flexion group, respectively. Conclusion. A preoperative valgus-characterized gait pattern seems to increase femoral and tibial component migration until 2 years of follow-up. This suggests that the implant fixation depends on load distributions originating from specific preoperative gait patterns

Extracellular matrix (ECM) mechanical cues guide healing in tendons. Yet, the molecular mechanisms orchestrating the healing processes remain elusive. Appropriate tissue tension is essential for tendon homeostasis and tissue health. By mapping the attainment of tensional homeostasis, we aim to understand how ECM tension regulates healing. We hypothesize that diseased tendon returns to homeostasis only after the cells reach a mechanically gated exit from wound healing. We engineered a 3D mechano-culture system to create tendon-like constructs by embedding patient-derived tendon cells into a collagen I hydrogel. Casting the hydrogel between posts anchored in silicone allowed adjusting the post stiffness. Under this static mechanical stimulation, cells remodel the (unorganized) collagen representing wound healing mechanisms. We quantified tissue-level forces using post deflection measurements. Secreted ECM was visualized by metabolic labelling with non-canonical amino acids, click chemistry and confocal microscopy. We blocked cell-mediated actin-myosin contractility using a ROCK inhibitor (Y27632) to explore the involvement of the Rho/ROCK pathway in tension regulation. Tissue tension forces reached the same homeostatic level at day 21 independent of post compliance (p = 0.9456). While minimal matrix was synthesized in early phases of tissue formation (d3-d5), cell-deposited ECM was present in later stages (d7-d9). More ECM was deposited by tendon constructs cultured on compliant (1Nm) compared to rigid posts (p = 0.0017). Matrix synthesized by constructs cultured on compliant posts was less aligned (greater fiber dispersion, p = 0.0021). ROCK inhibition significantly decreased tissue-level tensional forces (p < 0.0001). Our results indicate that tendon cells balance matrix remodeling and synthesis during tissue repair to reach an intrinsically defined “mechanostat setpoint” guiding tension-mediated exit from wound healing towards homeostasis. We are identifying specific molecular mechanosensors governing tension-regulated healing in tendon and investigate the Rho/ROCK system as their possible downstream pathway

The risk of falls in patients undergoing orthopedic procedures is particularly significant in terms of health and socioeconomic effects. The literature analyzed closely this risk following procedures performed on the lower limb, but the implications following procedures on the upper limb remain to be investigated. Interestingly, it is not clear whether the increased risk of falling in patients undergoing shoulder surgery is due to preexisting risk factors at surgery or postoperative risk factors, such as anesthesiologic effects, opioid medications used for pain control, or brace use. Only one prospective study examined gait and fall risk in patients using a shoulder abduction brace (SAB) after shoulder surgery, revealing that the brace adversely affected gait kinematics with an increase in the risk of falls. The main purpose of the study was to investigate the influence of SAB on gait parameters in patients undergoing shoulder surgery. Patients undergoing elective shoulder surgery (arthroscopic rotator cuff repair, reverse total shoulder arthroplasty, and Latarjet procedure), who used a 15° SAB in the postoperative period, were included. Conversely, patients age > 65 years old, with impaired lower extremity function (e.g., fracture sequelae, dysmorphism, severe osteo-articular pathology), central and peripheral nervous system pathologies, and cardiac/respiratory/vascular insufficiency were excluded. Participants underwent kinematic analysis at four different assessment times: preoperative (T0), 24 hours after surgery (T1), 1 week after surgery (T2), and 1 week after SAB removal (T3). The tests used for kinematic assessment were the Timed Up and Go (TUG) and the 10-meter test (10MWT), both of which examine functional mobility. Agility and balance were assessed by a TUG test (transitions from sitting to standing and vice versa, walking phase, turn-around), while gait (test time, cadence, speed, and pelvic symmetry) was evaluated by the 10MWT. Gait and functional mobility parameters during 10MWT and TUG tests were assessed using the BTS G-Walk sensor (G-Sensor 2). One-way ANOVA for repeated measures was conducted to detect the effects of SAB on gait parameters and functional mobility over time. Statistical analysis was performed with IBM®SPSS statistics software version 23.0 (SPSS Inc., Chicago, IL, USA), with the significant level set at p<0.05. 83% of the participants had surgery on the right upper limb. A main effect of time for the time of execution (duration) (p=0.01, η2=0.148), speed (p<0.01, η2=0.136), cadence (p<0.01, η2=0.129) and propulsion-right (R) (p<0.05, η2=0.105) and left (L) (p<0.01, η2=0.155) in the 10MWT was found. In the 10MWT, the running time at T1 (9.6±1.6s) was found to be significantly longer than at T2 (9.1±1.3s, p<0.05) and at T3 (9.0±1.3s, p=0.02). Cadence at T1 (109.7±10.9steps/min) was significantly lower than at T2 (114.3 ±9.3steps/min, p<0.01) and T3 (114.3±9.3steps/min, p=0.02). Velocity at T1 (1.1±0.31m/s) was significantly lower than at T2 (1.2± 0.21m/s, p<0.05). No difference was found in the pelvis symmetry index. No significant differences were found during the TUG test except for the final rotation phase with T2 value significantly greater than T3 (1.6±0.4s vs 1.4±0.3s, p<0.05). No statistically significant differences were found between T0 and T2 and between T0 and T3 in any of the parameters analyzed. Propulsion-R was significantly higher at T3 than T1 (p<0.01), whereas propulsion-L was significantly lower at T1 than T0 (p<0.05) and significantly higher at T2 and T3 than T1 (p<0.01). Specifically, the final turning phase was significantly higher at T2 than T3 (p<0.01); no significant differences were found for the duration, sit to stand, mid-turning and stand to sit phases. The results demonstrated that the use of the abduction brace affects functional mobility 24 hours after shoulder surgery but no effects were reported at longer term observations

Poor soft tissue balance in total knee arthroplasty (TKA) is one of the most primary causes of dissatisfaction and reduced joint longevity, which are associated with postoperative instability and early implant failure. 1. Therefore, surgical techniques, including mechanical instruments and 3-D guided navigation systems, in TKA aim to achieve optimum soft tissue balancing in the knee to improve postoperative outcome. 2. Patella-in-Place balancing (PIPB) is a novel technique which aims to restore native collateral ligament behaviour by preserving the original state without any release. Moreover, reduction of the joint laxity compensates for the loss of the visco-elastic properties of the cartilage and meniscus. Following its clinical success, we aimed to evaluate the impact of the PIPB technique on collateral ligament strain and laxity behaviour, with the hypothesis that PIPB would restore strains in the collateral ligaments. 3. . Eight fresh-frozen cadaveric legs were obtained (KU Leuven, Belgium, H019 2015-11-04) and CT images were acquired while rigid marker frames were affixed into the femur, and tibia for testing. After carefully removing the soft tissues around the knee joint, while preserving the joint capsule, ligaments, and tendons, digital extensometers (MTS, Minnesota, USA) were attached along the length of the superficial medial collateral ligament (MCL) and lateral collateral ligament (LCL). A handheld digital dynamometer (Mark-10, Copiague, USA) was used to apply an abduction or adduction moment of 10 Nm at fixed knee flexion angles of 0°, 30°, 60° and 90°. A motion capture system (Vicon Motion Systems, UK) was used to record the trajectories of the rigid marker frames while synchronized strain data was collected for MCL/LCL. All motion protocols were applied following TKA was performed using PIPB with a cruciate retaining implant (Stryker Triathlon, MI, USA). Furthermore, tibiofemoral kinematics were calculated. 4. and combined with the strain data. Postoperative tibial varus/valgus stresses and collateral ligament strains were compared to the native condition using the Wilcoxon Signed-Rank Test (p<0.05). Postoperative tibial valgus laxity was lower than the native condition for all flexion angles. Moreover, tibial valgus of TKA was significantly different than the native condition, except for 0° (p=0.32). Although, tibial varus laxity of TKA was lower than the native at all angles, significant difference was only found at 0° (p=0.03) and 90° (p=0.02). No significant differences were observed in postoperative collateral ligament strains, as compared to the native condition, for all flexion angles, except for MCL strain at 30° (p=0.02) and 60° (p=0.01). Results from this experimental study supported our hypotheses, barring MCL strain in mid-flexion, which might be associated with the implant design. Restored collateral ligament strains with reduced joint laxity, demonstrated by the PIPB technique in TKA in vitro, could potentially restore natural joint kinematics, thereby improving patient outcomes. In conclusion, to further prove the success of PIPB, further biomechanical studies are required to evaluate the success rate of PIPB technique in different implant designs

Background. Balance impairment and falling are of the major health problems in elderly individuals. The ability to maintain standing balance influences the risk of falling while performing everyday activities. Postural control is the base of balance that is the result of collaboration of visual, vestibular and somatosensory systems. Single leg stance test is a simple clinical method to evaluate static balance. In this test, the center of body mass is on a small support level and need to make corrective movements to create balance by postural control system. Kinesiotaping and stretching of ankle plantar flexor muscles used in physical therapy are effective in improvement of postural balance. Kinesiotaping is effective in maintaining balance by activates cutaneous receptors and promoting alpha motor neuron stimulation. Moreover, stretching is a common treatment used to prevent muscle shortness and increase the range of motion that improves the balance. Aim. Therefore the aim of current study was to compare the effects of these two methods in elderly women and men on ankle plantar flexor muscles which are effective to maintain postural status. Materials and Methods. In a single blind randomized clinical trial, 20 elderly male and 20 elderly female were assigned into 2 groups of kinesiotaping and stretching. Inhibitory Y shape tape was applied on the gastrocnemius in first group. In the stretching group, the muscle was stretched for 60 seconds by 4 times. The static balance was examined before and after the interventions by using single leg stance test. In this test, the subjects were asked to stand bare foot on dominant limb and cross their arms over chest. A maximum time for this test is 30 seconds. The researcher who was assessing balance was unaware to the intervention group. Results. According to paired t-test, Despite progress in time to stance on one leg after the interventions, the changes were not significant (P>0.05). Although the trend was more pronounced in the stretching group, independent t-test results showed no significant difference between groups (P>0.05). While in any of the treatment groups, there was no difference between men and women (P=0.1 and P=0.7 for kinesiotaping and stretching group, respectively). Conclusion. While the results did not show any significant difference after the intervention, but Increasing of the test time, which means improving the balance of participants, is evident. However, changes in the stretching group were more pronounced. Keyword. Single leg stance test, Elderly, Stretching, kinesiotaping, Plantar flexor muscle

Differences at motor control strategies to provide dynamic balance in various tasks in diabetic polyneuropatic (DPN) patients due to losing the lower extremity somatosensory information were reported in the literature. It has been stated that dynamics of center of mass (CoM) is controlled by center of pressure (CoP) during human upright standing and active daily movements. Indeed analyzing kinematic trajectories of joints unveil motor control strategies stabilizing CoM. Nevertheless, we hypothesized that imbalance disorders/CoM destabilization observed at DPN patients due to lack of tactile information about the base of support cannot be explained only by looking at joint kinematics, rather functional foot usage is proposed to be an important counterpart at controlling CoM. In this study, we included 14 DPN patients, who are diagnosed through clinical examination and electroneuromyography, and age matched 14 healthy subjects (HS) to identify control strategies in functional reach test (FRT). After measuring participants’ foot arch index (FAI) by a custom-made archmeter, they were tested by using a force plate, motion analysis system, surface electromyography and pressure pad, all working in synchronous during FRT. We analyzed data to determine effect of structural and functional foot pathologies due to neuropathy on patient performance and postural control estimating FAI, reach length (FR), FR to height (H) ratio (FR/H; normalized FR with respect to height), displacement of CoM and CoP in anteroposterior direction only, moment arm (MA, defined as the difference between CoP and CoM at the end of FRT), ankle, knee and hip joint angles computed at the sagittal plane for both extremities. Kinematic metrics included initial and final joint angles, defined with respect to start and end of reaching respectively. Further difference in the final and initial joint angles was defined as Δ. FAI was founded significantly lower in DPN patients (DPN: 0.3404; HS: 0.3643, p= <0.05). The patients’ FR, FR/H and absolute MA and displacement of CoM were significantly shorter than the control group (p= <0.05). Displacement of CoP between the two groups were not significant. Further we observed that CoM was lacking CoP in DPN patients (mean MA: +0.88 cm), while leading CoP in HS (mean MA: −1.59 cm) at the end of FRT. All initial angles were similar in two groups, however in DPN patients final right and left hip flexion angle (p=0.016 and p=0.028 respectively) and left ankle plantar flexion angle (p=0.04) were smaller than HS significantly. DPN patients had significantly less (p=0.029) hip flexion (mean at right hip angle, Δ=25.0°) compared to HS (Δ=33.53°) and ankle plantar flexion (DPN mean at right ankle angle, Δ=6.42°, HS mean Δ=9.07°; p=0.05). The results suggest that movement of both hip and ankle joints was limited simultaneously in DPN patients causing lack of CoM with respect to CoP at the end of reaching with significantly lower FAI. These results lead to the fact that cutaneous and joint somatosensory information from foot and ankle along with the structure of foot arch may play an important role in maintaining dynamic balance and performance of environmental context. In further studies, we expect to show that difference at control strategies in DPN patients due to restricted functional foot usage might be a good predictor of how neuropathy evolves to change biomechanical aspects of biped erect posture

Phosphate metabolism is central to the bone formation pathway. Phosphate is shuttled through the cell membrane to the mitochondria, where it is polymerised to form adenosine triphosphate. Once exocytosed the ATP may then be cleaved to form pyro and orthophosphates, the balance of which can determine whether mineralisation occurs or not. We are developing a range of materials at the University of Birmingham that have been formulated so that they can influence this balance, with the potential either to drive or prevent mineralisation from occurring. This talk will describe how we have used this process to develop materials that can be used to stimulate bone formation around an implant or to prevent the formation of pathological bone. It will also talk about the steps that we have taken to move these therapies towards clinical trial