Introduction and Objective

Forced external rotation is hypothesized as the key mechanism of syndesmotic ankle injuries. This complex trauma pattern ruptures the syndesmotic ligaments and induces a three-dimensional deviation from the normal distal tibiofibular joint configuration. However, current diagnostic imaging modalities are impeded by a two-dimensional assessment, without taking into account ligamentous stabilizers. Therefore, our aim is two-fold: (1) to construct an articulated statistical shape model of the normal ankle with inclusion of ligamentous morphometry and (2) to apply this model in the assessment of a clinical cohort of patients with syndesmotic ankle injuries.

One-fourth of all ankle trauma involve injury to the syndesmotic ankle complex, which may lead to syndesmotic instability and/or posttraumatic ankle osteoarthritis in the long term if left untreated. The diagnosis of these injuries still poses a deceitful challenge, as MRI scans lack physiologic weightbearing and plain weightbearing radiographs are subject to beam rotation and lack 3D information. Weightbearing cone-beam CT (WBCT) overcomes these challenges by imaging both ankles during bipedal stance, but ongoingdebate remains whether these should be taken under weightbearing conditions and/or during application of external rotation stress. The aim of this study is study therefore to compare both conditions in the assessment of syndesmotic ankle injuries using WBCT imaging combined with 3D measurement techniques. In this retrospective study, 21 patients with an acute ankle injury were analyzed using a WBCT. Patients with confirmed syndesmotic ligament injury on MRI were included, while fracture associated syndesmotic injuries were excluded. WBCT imaging was performed in weightbearing and combined weightbearing-external rotation. In the latter, the patient was asked to internally rotate the shin until pain (VAS>8/10) or a maximal range of motion was encountered. 3D models were developed from the CT slices, whereafter. The following 3D measurements were calculated using a custom-made Matlab® script; Anterior tibiofibular distance (AFTD), Alpha angle, posterior Tibiofibular distance (PFTD) and Talar rotation (TR) in comparison to the contralateral non-injured ankle. The difference in neutral-stressed Alpha angle and AFTD were significant between patients with a syndesmotic ankle lesion and contralateral control (P=0.046 and P=0.039, respectively). There was no significant difference in neutral-stressed PFTD and TR angle. Combined weightbearing-external rotation during CT scanning revealed an increased AFTD in patients with syndesmotic ligament injuries. Based on this study, application of external rotation during WBCT scans could enhance the diagnostic accuracy of subtle syndesmotic instability

Abstract. Objectives. Tendon and ligament injury poses an increasingly large burden to society. With surgical repair and grafting susceptible to high failure rates, tissue engineering provides novel avenues for treatment. This systematic review explores in vivo evidence whether mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) can facilitate tendon and ligament repair in animal models. Methods. On May 26th 2021, a systematic search was performed on PubMed, Web of Science, Cochrane Library, Embase, using search terms ‘mesenchymal stem cell’ or ‘multipotent stem cell’ AND ‘extracellular vesicles’ or ‘exosomes’ AND ‘tendon’ or ‘ligament’ or ‘connective tissue’. Risk of bias was assessed using SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) tool. Studies administering EVs isolated from human or animal-derived MSCs into in vivo models of tendon/ligament injury were included. In vitro, ex vivo, in silico studies were excluded, and studies without a control group were excluded. Data on isolation and characterisation of MSCs and EVs, and in vivo findings in animal models were extracted. Results. Out of 383 relevant studies, 11 case-control studies were included for data extraction, including a total of 448 animal subjects (range 10–90). Six studies utilised bone marrow-derived MSCs. All studies characterised their MSCs via flow cytometry, which expressed CD44 and CD90, and isolated EVs via ultracentrifugation (average diameter 125nm). Five studies utilised histological scoring systems, all of which reported a lower score with EV treatment, suggesting improved healing ability. Four studies reported increased anti-inflammatory cytokine expression (IL-10, TGF-β1); three studies reported decreased endogenous M1/M2 macrophage ratio with EV treatment. Eight studies reported increased maximum stiffness, breaking load, tensile strength in EV-treated tendons. Conclusion. MSC-EVs are effective therapeutic agents for tendon/ligament pathologies, attenuating the initial inflammatory response, and accelerating tendon matrix regeneration. Future randomised controlled trials are needed to definitely demonstrate MSC-EVs superiority in management of tendon/ligament injury

Chronic lateral ankle instability (CLAI) is treated operatively, whereas acute ligament injury is usually treated nonoperatively. Such treatments have been widely validated. Apoptosis is known to cause ligament degeneration; however, few reports have focused on the possible role of apoptosis in degeneration of ruptured lateral ankle ligaments. The aim of our study is to elucidate the apoptosis that occurs within anterior talofibular ligament (ATFL) to further validate current CLAI treatments by adducing molecular and cellular evidence. Between March 2019 and February 2021, 50 patients were prospectively enrolled in this study. Ruptured ATFL tissues were collected from 21 CLAI patients (group C) and 17 acute ankle fracture patients (group A). Apoptotic cells were counted using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Western blotting for caspases 3, 7, 8, and 9 and cytochrome c, was performed to explore intrinsic and extrinsic apoptotic pathways. Immunohistochemistry was used to detect caspases 3, 7, 8, and 9 and cytochrome c, in ligament vessel endothelial cells. More apoptotic cells were observed in group C than group A in TUNEL assay. Western blotting revealed that the apoptotic activities of group C ligaments were significantly higher than those of group A (all p < 0.001). Immunohistochemistry revealed increased expression of caspases 3, 7, 8, and 9, and cytochrome c, in group C compared to group A. The ATFL apoptotic activities of CLAI patients were significantly higher than those of acute ankle fracture patients, as revealed biochemically and histologically. Our data further validate current CLAI treatments from a molecular and cellular perspective. Efforts should be made to reverse or prevent ATFL apoptosis in CLAI patients

Acute lateral ankle sprain accounts for 85% of sprains. The lateral sprain is associated with other ligament injuries e.g. medial and syndesmosis sprain. Long-term, approximately 20% of acute lateral sprains develop into chronic lateral ankle instability (CLAI) which includes persistent pain, and recurring ankle sprains. This study evaluated the grade of an ankle ligament injury by ultrasonography (US) and compared the findings to the outcome of patient-reported questionnaires. 48 subjects (18–40 years) diagnosed with an ankle sprain attended a clinical and US examination of ankle ligaments within two weeks after the sprain. Evaluation was done by US of acute lateral ligament injuries (ATFL, CFL), syndesmosis injury (AiTFL), and medial injury (dPT, TCt) only in participants with the positive clinical signs of medial injury. Participants were then mailed a questionnaire (PROMQ) every third month for a year. 29 women and 19 men participated with a mean age at 26.50 years. One-year follow-ups need to be analyzed further for final results. Temporary results include data based on the initial 26 patients: Two clinical signs statistically correlated. Multiple logistic regression analysis confirmed the results. Positive palpated tenderness AiTFL predicted with partial ruptured ATFL and reported pain during active plantar flexion of ankle predicted with normal CFL confirmed by the US. Patients with partial rupture of ATFL presented with tenderness at AiTFL point. Patients presenting with intact CFL reported pain during active plantar flexion. Compared to the US findings, the overall examinations were inconclusive in predicting ATFL, CFL, AiTFL, and medial ligament injuries

Applications of weightbearing computed tomography (WBCT) imaging in the foot and ankle have emerged over the past decade. However, the potential diagnostic benefits are scattered across the literature, and a concise overview is currently lacking. Therefore, we aimed to systematically review all reported diagnostic applications per anatomical region in the foot and ankle. A systematic literature search was performed in the electronic databases PubMed, EMBASE, Cochrane Library, and Web of Science. Search terms consisted of “weightbearing/standing CT and ankle, hind-, mid- or forefoot”. English language studies analyzing the diagnostic applications of WBCT were included. Studies were excluded if they simulated weightbearing CT, described normal subjects, included cadaveric samples or samples were case reports. The modified Methodological Index for Non-Randomized Studies (MINORS) was applied for quality assessment. The added value was defined as the review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and registered in the Prospero database (CRD42019106980). A total of 48 studies (prospective N=8, retrospective N=36, cohort study N=1, diagnostic N=2, prognostic comparative study N=1) were found to be eligible for review. The following diagnostic applications were identified per anatomical area in the foot: ankle (osteoarthritis N=5, ligament injury N=6); hindfoot (deformity N=9); midfoot (Lisfranc injury N=2, flatfoot deformity N=13, osteoarthritis N=1); forefoot (hallux valgus N=12). The identified studies contained diagnostic applications that could not be used on plain radiographs. The mean MINORS equaled 10.1 on a total of 16 (range: 8 to 12). Diagnostic applications of weightbearing CT imaging are most frequently studied in hindfoot deformity, but other area's areas are on the rise. Post-processing of images was identified as the main added value compared to WBRX. However, the findings should be interpreted with caution as the average quality score was moderate. Therefore, future prospective studies are warranted to consolidate the role of WBCT in diagnostic and therapeutic algorithms

The primary purpose of this longitudinal study was to examine the impact of physical and mental well-being on a successful return to work after cartilage or ligament knee injury. A secondary purpose was to examine the effectiveness of our program regarding ordering imaging (plain X-rays, US, MRI, CT scan), and the impact that costly investigations made in clinical management. Workers who had sustained a work-related knee injury and were assessed at the lower extremity specialty clinic of our hospital program were followed up until they were discharged. All patients completed the numeric pain rating scale (NPRS), the Lower Extremity Functional Scale (LEFS), and the Hospital Anxiety and Depression Scale (HADS) on the initial assessment and at final follow-up. We included 30 patients, mean age, 50(9), 11(37%) females, 19(63%) males. The most common mechanisms of injury were twisting (13, 45%) and falls (12, 41%). The knee injuries included 10 anterior collateral ligament (ACL), 3 posterior collateral ligament (PCL), 19 medical and lateral ligament injuries, and 22 meniscus injuries with some injuries overlapping. Ten patients (30%) underwent surgery (8 meniscectomy, two ligamentous repairs). Patients showed improvement in pain scores (p<0.0001) and the LEFS scores (p=0.004). Seventeen patients (57%) returned to full-time work and 11 (37%) were not working at the time of discharge with one patient performing part-time work, and one on re-training. Higher levels of pre (p=0.02) and post-treatment (p=0.03) depression and post-treatment anxiety (p=0.02) had a negative impact on a successful return to work. Most clients had proper investigations ordered by their family physicians in the community (24 plain x-rays, 11 US, and 21 MRI). Our team ordered only 6 plain x-rays and 6 new MRI. We found significant improvement in pain and disability in injured workers who received an expedited multidisciplinary care. Anxiety and depression were the most important predictors of poorer recovery and a less successful work status. The judicious use of costly imaging is expected to reduce the overall health care cost of an injury, while providing new important information such as adding a new diagnosis or changing the management

Background. Ankle fractures are often associated with ligamentous injuries of the distal tibiofibular syndesmosis, the deltoid ligament and are predictive of ankle instability, early joint degeneration and long-term ankle dysfunction. Detection of ligamentous injuries and the need for treatment remain subject of ongoing debate. In the classic article of Boden it was made clear that injuries of the syndesmotic ligaments were of no importance in the absence of a deltoid ligament rupture. Even in the presence of a deltoid ligament rupture, the interosseous membrane withstood lateralization of the fibula in fractures up to 4.5mm above the ankle joint. Generally, syndesmotic ligamentous injuries are treated operatively by temporary fixation performed with positioning screws. But do syndesmotic injuries need to be treated operatively at all?. Methods. The purpose of this biomechanical cadaveric study was to investigate the relative movements of the tibia and fibula, under normal physiological conditions and after sequential sectioning of the syndesmotic ligaments. Ten fresh-frozen below-knee human cadaveric specimens were tested under normal physiological loading conditions. Axial loads of 50 Newton (N) and 700N were provided in an intact state and after sequential sectioning of the following ligaments: anterior-inferior tibiofibular (AITFL), posterior-inferior tibiofibular (PITFL), interosseous (IOL), and whole deltoid (DL). In each condition the specimens were tested in neutral position, 10 degrees of dorsiflexion, 30 degrees of plantar flexion, 10 degrees of inversion, 5 degrees of eversion, and externally rotated up to 10Nm torque. Finally, after sectioning of the deltoid ligament, we triangulated Boden's classic findings with modern instruments. We hypothesized that only after sectioning of the deltoid ligament; the lateralization of the talus will push the fibula away from the tibia. Results. During dorsiflexion and external rotation the ankle syndesmosis widened, and the fibula externally rotated after sequential sectioning of the syndesmotic ligaments. After the AITFL was sectioned the fibula starts rotating externally. However, the external rotation of the fibula significantly reduced when the external rotation torque was combined with axial loading up to 700N as compared to the external rotation torque alone. The most relative moments between the tibia and fibula were observed after the deltoid ligament was sectioned. Conclusion. Significant increases in movements of the fibula relative to the tibia occur when an external rotation torque is provided. However, axial pressure seemed to limit external rotation because of the bony congruence of the tibiotalar surface. The AITFL is necessary to prevent the fibula to rotate externally when the foot is rotating externally. The deltoid ligament is the main stabilizer of the ankle mortise

Although multifunctional delivery systems can potentially improve safety and efficacy of therapeutic protein delivery in the biological treatment of injured tissues, ability to track and manipulate protein delivery systems in vivo to ensure localization at the treatment site is still a concern. We hypothesized that incorporating superparamagnetic iron oxide (SPIO) into calcium phosphate (CaP) coated β-tricalcium phosphate (β-TCP) microparticles would allow for Magnetic Resonance Imaging (MRI) based tracking in vivo and SPIO incorporation would not impact the biological activity of proteins delivered with these microparticles. To address the efficacy and limitations in therapeutic protein delivery, a CaP coated microparticle which incorporates superparamagnetic iron oxide (SPIO-CaP-MP) was created and used in a rat knee medial collateral ligament. The system has trifunctional properties: (1) it is trackable using magnetic resonance imaging (MRI), (2) it can be manipulated with a magnetic field, (3) it can release active proteins in the injury site. SPIO-Ca-MPs were formed on β-tricalcium phosphate cores. Using MRI, SPIO-CaP-MPs were visible in T2 weighted sequences as an area of hypointesive signal. SPIO-CaP-MPs could be visualized and remained localized for at least 15 days after injection into the medial collateral ligament. Recombinant human basic fibroblast growth factor delivered with SPIO-CaP-MPs stimulated the proliferation of human dermal fibroblasts. Finally, SPIO-CaP-MPs could be localized to a bar magnet when suspended in solution. Taken together, these results suggest that SPIO-CaPMPs could be useful for protein delivery applications in the treatment of ligament injury that may benefit from externally controlled localization and MRI-based tracking

Being commonly missed in the clinical practice, Lisfranc injuries can lead to arthritis and long-term complications. There are controversial opinions about the contribution of the main stabilizers of the joint. Moreover, the role of the ligament that connects the medial cuneiform (MC) and the third metatarsal (MT3) is not well investigated. The aim of this study was to investigate the influence of different Lisfranc ligament injuries on CT findings under two specified loads. Sixteen fresh-frozen human cadaveric lower limbs were embedded in PMMA at mid-shaft of the tibia and placed in a weight-bearing radiolucent frame for CT scanning. All intact specimens were initially scanned under 7.5 kg and 70 kg loads in neutral foot position. A dorsal approach was then used for sequential ligaments cutting: first – the dorsal and the (Lisfranc) interosseous ligaments; second – the plantar ligament between the MC and MT3; third – the plantar Lisfranc ligament between the MC and the MT2. All feet were rescanned after each cutting step under the two loads. The average distances between MT1 and MT2 in the intact feet under 7.5 kg and 70 kg loads were 0.77 mm and 0.82 mm, whereas between MC and MT2 they were 0.61 mm and 0.80 mm, without any signs of misalignment or dorsal displacement of MT2. A slight increase in the distances MT1-MT2 (0.89 mm; 0.97 mm) and MC-MT2 (0.97 mm; 1.13 mm) was observed after the first disruption of the dorsal and the interosseous ligaments under 7.5 kg and 70 kg loads. A further increase in MT1-MT2 and MC-MT2 distances was registered after the second disruption of the ligament between MC and MT3. The largest distances MT1-MT2 (1.5 mm; 1.95 mm) and MC-MT2 (1.74 mm; 2.35 mm) were measured after the final plantar Lisfranc ligament cut under the two loads. In contrast to the previous two the previous two cuts, misalignment and dorsal displacement of 1.25 mm were seen at this final disrupted stage. The minimal pathological increase in the distances MT1-MT2 and MC-MT2 is an important indicator for ligamentous Lisfranc injury. Dorsal displacement and misalignment of the second metatarsal in the CT scans identify severe ligamentous Lisfranc injury. The plantar Lisfranc ligament between the medial cuneiform and the second metatarsal seems to be the strongest stabilizer of the Lisfranc joint. Partial lesion of the Lisfranc ligaments requires high clinical suspicion as it can be easily missed

Tendon injuries in both the human and horse represent a challenge due to persistent inflammation combined with inadequate reparative cells and a poorly organised extracellular matrix. The potential of mesenchymal stem cells (MSCs) in regenerating tendon injuries remains to be fully realised. The main mechanism of action by MSCs is considered to be primarily mediated via paracrine mechanisms. This may involve the production and release of extracellular vesicles (EVs) by stem cells with a sub-fraction of these EVs (<100 nm diameter) called exosomes that appear to be the main paracrine effectors. EVs can be readily prepared from MSCs and offer a clinically relevant therapy. However, EVs for tendon repair need to be fully characterised. The horse represents a highly relevant model of tendon and ligament injuries as it shares many features of mechanical loading, function and aetiopathology with the human. We have isolated and characterised EVs from equine MSCs for modulating tendon cell phenotype in an in vitro tendon injury model using IL-1ß. EVs can be isolated from IL-1ß stimulated MSCs although their levels are not significantly increased over controls suggesting that the nature of the stimulated EV cargo may be more important than absolute levels of released EVs

Objectives. Ligaments which heal spontaneously have a healing process that is similar to skin wound healing. Menopause impairs skin wound healing and may likewise impair ligament healing. Our purpose in this study was to investigate the effect of surgical menopause on ligament healing in a rabbit medial collateral ligament model. Methods. Surgical menopause was induced with ovariohysterectomy surgery in adult female rabbits. Ligament injury was created by making a surgical gap in the midsubstance of the medial collateral ligament. Ligaments were allowed to heal for six or 14 weeks in the presence or absence of oestrogen before being compared with uninjured ligaments. Molecular assessment examined the messenger ribonucleic acid levels for collagens, proteoglycans, proteinases, hormone receptors, growth factors and inflammatory mediators. Mechanical assessments examined ligament laxity, total creep strain and failure stress. Results. Surgical menopause in normal medial collateral ligaments initiated molecular changes in all the categories evaluated. In early healing medial collateral ligaments, surgical menopause resulted in downregulation of specific collagens, proteinases and inflammatory mediators at 6 weeks of healing, and proteoglycans, growth factors and hormone receptors at 14 weeks of healing. Surgical menopause did not produce mechanical changes in normal or early healing medial collateral ligaments. With or without surgical menopause, healing ligaments exhibited increased total creep strain and decreased failure stress compared with uninjured ligaments. Conclusions. Surgical menopause did not affect the mechanical properties of normal or early healing medial collateral ligaments in a rabbit model. The results in this preclinical model suggest that menopause may result in no further impairment to the ligament healing process. . Cite this article: Bone Joint Res 2015;4:38–44

The treatment of scapholunate (SL) ligament injuries is addressed by surgical procedures to stabilize the carpal joint. Open techniques include bone-ligament-bone transfers, tenodesis, partial fusions and carpectomies. Innovative procedures using wrist arthroscopy, offer minimally invasive fixation without full exposure of carpal bones; however, the success of the technique and its impact on the reduction on the range of carpal movement is as yet not well known. In this work, the performance of Corella tenodesis technique to repair the SL ligament is evaluated for a wrist type II by numerical methods. Human wrist can be classified based on the lunate morphology: type I for lunate that articulates with radius, scaphoid, capitate and triquetrum, and type II which has an extra surface to articulate with the hamate. A finite element model was constructed from CT-scan images, the model includes cortical and trabecular bones, articular cartilage and ligaments. Three scenarios were simulated representing healthy wrist, SL ligament sectioning and the Corella technique. The performance of the technique was assessed by measure the SL gap in dorsal and volar side as well as the SL angle to be compared to cadaveric studies. In intact position, the SL gap and the SL angle predicted by the numerical model is 2.8 mm and 44.8º, these values are consistent to the standard values reported in cadaveric experiments (2.0 ± 0.8 mm for SL gap and 45.8 ± 9.7 for SL angle). Virtual surgeries may help to understand and evaluate the performance of the techniques at clinical application

Tendon and ligament injuries represent highly prevalent and unmet clinical challenge that may significantly benefit from tissue engineering therapeutic strategies, once optimal cell source and biomolecules regulating tendon homeostasis are properly defined. Herein, we aimed to evaluate the expression of tendon/ligament markers in two novel cell populations, namely human dental pulp stem cells (DPSCs) and periodontal ligament cells (PDLCs), in response to supplementation with TGF-β ligands relevant for tendon development and healing, as well as under standard tri-lineage differentiation conditions. DPSCs and PDLCs were isolated from sound human permanent molars removed for orthodontic reasons. Pulp tissue and periodontal ligament were minced and digested with collagenase (3mg/mL) and cells were expanded in α-MEM supplemented with 10% fetal bovine serum (basal medium). To evaluate the susceptibility of DPSCs and PDLCs to tenogenic induction, cells were seeded at density of 1000 cells/cm. 2. and cultured up to 21 days in basal medium or media supplemented with TGF-β3 (10ng/ml), or GDF-5 (50 ng/ml). Cell response was evaluated weakly by analysis of expression of tendon, bone and cartilage markers, employing real time RT-PCR and immunocytochemistry. A significant increase in collagen I and collagen III expression was observed with the culture progression in all conditions, with abundant matrix being deposited by day 14. A significant upregulation of scleraxis expression was demonstrated in response to supplementation with TGF-β3 in both cell populations, when compared to basal medium and medium with GDF-5. It was concluded that TGF-β3 may represent an effective inducer of stem cell tenogenic differentiation

To study the effect of ligament injuries and surgical repair we investigated the three-dimensional kinematics of the ankle joint complex and the talocrural and the subtalar joints in seven fresh-frozen lower legs before and after sectioning and reconstruction of the ligaments. A foot movement simulator produced controlled torque in one plane of movement while allowing unconstrained movement in the remainder. After testing the intact joint the measurements were repeated after simulation of ligament injuries by cutting the anterior talofibular and calcaneofibular ligaments. The tests were repeated after the Evans, Watson-Jones and Chrisman-Snook tenodeses. The range of movement (ROM) was measured using two goniometer systems which determined the relative movement between the tibia and talus (talocrural ROM) and between the talus and calcaneus (subtalar ROM). Ligament lesions led to increased inversion and internal rotation, predominantly in the talocrural joint. The reconstruction procedures reduced the movement in the ankle joint complex by reducing subtalar movement to a non-physiological level but did not correct the instability of the talocrural joint

Osteoarthritis (OA) is no longer considered a cartilage-centric disease with remodelling of other joint tissues now recognized. While understudied, entheseal pathology is considered a secondary OA feature. A pivotal role for proteinase-activated receptor 2 (PAR2) in OA has been demonstrated previously in cartilage and subchondral bone at early time points, however the entheseal role of PAR2 has not been reported. OA was induced by destabilization of the medial meniscus (DMM) in wild type (WT) and PAR2 deficient (KO) animals. At 4 weeks and one year post surgery, knee joints were harvested for histological analysis. Medial collateral ligament (MCL) width was measured by 2D planimetry analysis. Immunohistochemistry was used to characterize the MCL and anterior cruciate ligament (ACL). Data were expressed as mean±SEM (n=4–6/group) and analysed using Student's t-test, with p<0.05 as the criterion of significance. MCL width increased between 4 weeks and 1 year in WT DMM (0.24 ±0.07 vs 0.40 ±0.008mm respectively, p<0.001). Interestingly, a significant reduction in MCL was observed in KO compared with WT at 1 year (0.23 ±0.005 vs 0.40 ±0.008mm respectively, p <0.001) post-DMM. Further characterization of DMM WT MCL and ACL at 4 weeks showed the presence of F4/80. +. cells in addition to IL-33 and histamine. At one year post-surgery, a cellular infiltrate was observed in MCL DMM WT but absent in KO mice. Histological evaluation revealed an absence of F4/80. +. cells but the presence of a PAR2. +. population, subsequently identified as hypertrophic-like chondrocytes (RUNX2) and chondrocytes-like cells (SOX9). Deletion of PAR2 affords long-term protection against ligament remodelling and demonstrates a critical role for this receptor in both OA joint pathology and ligament injuries. While PAR2 appears to be a credible therapeutic target in OA entheseal pathology, further understanding of the molecular mechanism regulated by this receptor will be required

The function of the knee joint is to allow for locomotion and is comprised of various bodily structures including the four major ligaments; medial collateral ligament (MCL), lateral collateral ligament (LCL), anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL). The primary function of the ligaments are to provide stability to the joint. The knee is prone to injury as a result of osteoarthritis as well as ligamentous and meniscal lesions. Furthermore, compromised joint integrity due to ligamentous injury may be a result of direct and indirect trauma, illness, occupational hazard as well as lifestyle. A device capable of non-invasively determining the condition of the ligaments in the knee joint would be a useful tool to assist the clinician in making a more informed diagnosis and prognosis of the injury. Furthermore, the device would potentially reduce the probability of a misdiagnosis, timely diagnosis and avoidable surgeries. The existing Laxmeter prototype (UK IPN: GB2520046) is a Stress Radiography Device currently limited to measuring the laxity of the MCL and LCL at multiple fixed degrees of knee flexion. Laxity refers to the measure of a ligament's elasticity and stiffness i.e. the condition of the ligament, by applying a known load (200N) to various aspects of the proximal tibial and thereby inducing tibial translation. The extent of translation would indicate the condition of the ligament. The Laxmeter does not feature a load applying component as of yet, however, it allows for the patient to be in the most comfortable and ideal position during radiographic laxity measurement testing. The entire structure is radiolucent and attempts to address the limitations of existing laxity measurement devices, which includes: excessive radiation exposure to the radiographic assistant, little consideration for patient ergonomics and restrictions to cruciate or collateral ligament laxity measurements. The study focusses on further developing and modifying the Laxmeter to allow for: the laxity measurement of all four major ligaments of the knee joint, foldability for improved storage and increased structural integrity. Additionally, a load applicator has been designed as an add-on to the system thereby making the Laxmeter a complete Stress Radiography Device. Various materials including Nylon, Polycarbonate, Ultra High Molecular Weight Polyethylene (UHMWPE) – PE 1000, and Acetal/ POM were tested, using the Low Dose X-ray (Lodox) scanner, to determine their radiolucency. All materials were found to be radiolucent enough for the manufacture of the Laxmeter structure as well as the load applicator in order to identify and measure the translation of the tibia with respect to the stationary femur. The Laxmeter allows for the measurement of the laxity of the MCL and LCL at multiple fixed degrees of flexion by providing the ideal patient position for testing. The next iteration of the device will present an affordable and complete Stress Radiography Device capable of measuring the laxity of all four major ligaments of the knee joint at multiple fixed degrees of flexion. Future work would include aesthetic considerations as well as an investigation into carbon-fibre-reinforced plastics

Knee ligament injury is one of the most frequent sport injuries and ligament reconstruction has been used to restore the structural stability of the joint. Cycling exercises have been shown to be safe for anterior cruciate ligament (ACL) reconstruction and are thus often prescribed in the rehabilitation of patients after ligament reconstruction. However, whether it is safe for posterior cruciate ligament (PCL) reconstruction remains unclear. Considering the structural roles of the PCL, backward cycling may be more suitable for rehabilitation in PCL reconstruction. However, no study has documented the differences in the effects on the knee kinematics between forward and backward pedaling. Therefore, the current study aimed to measure and compare the arthrokinematics of the tibiofemoral joint between forward and backward pedaling using a biplane fluoroscope-to- computed tomography (CT) registration method. Eight healthy young adults participated in the current study with informed written consent. Each subject performed forward and backward pedaling with an average resistance of 20 Nm, while the motion of the left knee was monitored simultaneously by a biplane fluoroscope (ALLURA XPER FD, Philips) at 30 fps and a 14-camera stereophotogrammetry system (Vicon, OMG, UK) at 120 Hz. Before the motion experiment, the knee was CT and magnetic resonance scanned, which enabled the reconstruction of the bones and articular cartilage. The bone models were registered to the fluoroscopic images using a volumetric model-based fluoroscopy-to-CT registration method, giving the 3-D poses of the bones. The bone poses were then used to calculate the rigid-body kinematics of the joint and the arthrokinematics of the articular cartilage. In this study, the top dead center of the crank was defined as 0° so forward pedaling sequence would begin from 0° to 360°. Compared with forward pedaling, for crank angles from 0° to 180°, backward pedaling showed significantly more tibial external rotation. Moreover, both the joint center and contact positions in the lateral compartment were more anterior while the contact positions in the medial compartment was more posterior, during backward pedaling. For crank angles from 180° to 360°, the above-observed phenomena were generally reversed, except for the anterior-posterior component of the contact positions in the medial compartment. Forward and backward pedaling displayed significant differences in the internal/external rotations while the rotations in the sagittal and frontal planes were similar. Compared with forward cycling, the greater tibial external rotation for crank angles from 0° to 180° during backward pedaling appeared to be the main reason for the more anterior contact positions in the lateral compartment and more posterior contact positions in the medial compartment. Even though knee angular motions during forward and backward pedaling were largely similar in the sagittal and frontal planes, significant differences existed in the other components with different contact patterns. The current results suggest that different pedaling direction may be used in rehabilitation programs for better treatment outcome in future clinical applications

This study aimed to overcome the subjective nature of routine assessment of knee laxity and develop a repeatable, objective method using a hand-held force application device (FAD). Eighteen clinicians (physiotherapists, consultants, trainees) volunteered to measure the coronal angular deviation of the right knee of a healthy volunteer using a validated non-invasive infrared measuring system. Effort was taken to ensure the knee flexion angle (∼2°) and hand positions were constant during testing. Three varus and valgus stress tests were conducted, in which maximum angular deviation was determined and subsequently averaged, in the following order of conditions: manual stress without the FAD up to a perceived end-point (before); with the FAD to apply a moment of 18 Nm; and again without the FAD (after). A repeated measures ANOVA was used to analyse the results. All three groups of clinicians produced measurements of valgus laxity with consistent mean values and standard deviations (<1°) for each condition. For varus mean values were consistent but standard deviations were larger. Valgus deviations varied significantly between conditions (p < 0.01), with deviations achieved using the FAD greater than both before (p < 0.01) and after (p < 0.05) indicating that the perceived endpoints were less than that achieved at 18 Nm. However varus perceived endpoints were no different to that achieved at 18 Nm, suggesting that clinicians usually apply a greater valgus moment than varus. Furthermore, the non-significant increase in valgus deviation between before and after (p = 0.123) is suggestive of a training trend, especially for trainees. Our standardised knee laxity assessment may have a role in improving the balancing techniques of TKA and the diagnosis of collateral ligament injuries. Also, by quantifying the technique of senior clinicians, and with use of the FAD, the perceptive skills of more junior trainees may be enhanced

Summary. Tissue grafts fail to recapitulate native tendon function, imposing the need for development of functional regeneration strategies. Herein, we describe advancements in tendon repair and regeneration using functionalised natural and synthetic devices and scaffold-free cell-based therapies. Introduction. Tendon and ligament injuries constitute an unmet clinical need with approximately 100,000 new cases annually in US alone. Tissue grafts are considered the gold standard in clinical practice. However, allografts and xenografts can lead to potential disease transmission, whilst the limited supply of autografts in severe injuries and degenerative conditions restricts their use. To this end, scaffold and scaffold-free therapies are under development to address the tissue grafts shortage. Herein, we describe biophysical, biochemical and biological methods to maintain tendon derived cell phenotype and/or differentiation of other cell types towards tenogenic lineage; development of tendon-equivalent facsimiles; and ultimately functional neotendon formation. Materials and Methods. Growth factor supplementation was assessed as means to either maintain tendon derived stem cell phenotype or differentiate them towards tenocytes. The influence of conditioning media was assessed as means to differentiate skin fibroblasts and stem cells towards tenogenic lineage. Biophysical and biochemical/biological features were assessed as means to maintain tendon derived cell phenotype and directional neotissue formation in rat patellar tendon model. Rich in tendon-specific extracellular matrix cell sheets were produced by appropriate modulation of the in vitro microenvironment. Structural, biophysical and biological analyses were subsequently carried out. Discussion & Future Studies. Treatment with 10 and 100 ng/mL of IGF-1 preserved tendon stem cell multipotency for up to 28 days in culture and minimised changes in marker expression and extracellular matrix molecules production enhancing that way the clinical potential of these cells. Hierarchically assembled collagen scaffolds and anisotropically ordered polymeric substrates of rigidity similar to native tendons facilitate tenocyte phenotype maintenance in vitro, whilst in vivo studies are under way to assess the extent of functional tendon regeneration. Appropriate modulation of the in vitro microenvironment of tenocytes with macromolecules enhances tendon specific extracellular matrix deposition within 6 days in culture, facilitating that way the wide acceptance of cell-sheet technology for tendon repair and regeneration