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Bone remodeling is the balance between osteoblasts and osteoclasts. Bone diseases such as osteoporosis and osteoarthritis are associated with imbalanced bone remodeling. Skeletal injury leads to limited motor function and pain. Neurophilin was initially identified in axons, and its various ligands and roles in bone remodeling, angiogenesis, neuropathic pain and immune regulation were later discovered. Neurophilin promotes osteoblast mineralization and inhibits osteoclast differentiation and its function. Neuropolin-1 provides channels for immune cell chemotaxis and cytokine diffusion and leads to pain. Neuropolin-1 regulates the proportion of T helper type 17 (Th17) and regulatory T cells (Treg cells), and affects bone immunity. Vascular endothelial growth factors (VEGF) combine with neuropilin and promote angiogenesis. Class 3 semaphorins (Sema3a) compete with VEGF to bind neuropilin, which reduces angiogenesis and rejects sympathetic nerves. This review elaborates on the structure and general physiological functions of neuropilin and summarizes the role of neuropilin and its ligands in bone and cartilage diseases. Finally, treatment strategies and future research directions based on neuropilin are proposed., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Objective: This study evaluated single intra-articular injections of Hymovis MO.RE., a hyaluronic acid hexadecyl derivative (HYADD4-G), to manage post-traumatic or degenerative knee or ankle chondropathy in professional soccer players., Patients and Methods: Twenty-five players affected by knee (n = 12) or ankle (n = 13) chondropathy were prospectively enrolled and treated by two single Hymovis MO.RE. (32 mg/4 ml) injections at the beginning of the football season (V0, baseline) and at mid-season (V1, 19-20 weeks thereafter), and were followed-up until the end of the season (V2, after further 19-20 weeks). Knee cases were evaluated using the 2000 IKDC knee subjective examination form and the modified Lysholm scoring system. Ankle cases were evaluated using the American Orthopaedic Foot Ankle Society (AOFAS) ankle-hindfoot score. Patients were also evaluated using a VAS Likert scale and a four-category scale recording both the patient's and the doctor's assessment on joint mobility in degrees and overall treatment efficacy. Adverse events, patient withdrawals and local reaction to injections were also assessed., Results: In knee patients, the 2000 IKDC subjective score improved from 46.8 ± 11.4 at V0 to 83.1 ± 12.5 at V2. Their modified Lysholm score improved from 58.8 ± 8.9 at V0 to 90.6 ± 8.3 at V2. In the ankle patients, the AOFAS score improved from 52.2 ± 5.6 at V0 to 96.4 ± 4.5 at V2. VAS Likert values and subjective evaluations improved at V1 and were maintained at V2. No side effects were recorded., Conclusions: A single Hymovis MO.RE. (32 mg/4 ml) intra-articular injection, repeated after 19-20 weeks, may be a viable option to improve symptoms and function in professional soccer players suffering from knee and ankle chondropathy.

We hypothesized that postoperative malrotation of humeral shaft fractures can alter the bio-mechanical environment of the shoulder; thus, rotator cuff and cartilage degeneration could be induced. Therefore, we designed an animal experiment to evaluate the impact of malrotation deformities after minimally invasive surgery for humeral fractures on the rotator cuff and cartilage, which has rarely been described in previous studies. Twenty-four New Zealand white rabbits were randomly divided into the sham control group (A), negative control group (B) and malrotated group (C). A sham operation with surgical exposure alone was performed in group A. Humeral shaft osteotomy was performed in Group B and C. In Group B, the fractures were fixed in situ with plate -screw system. While in Group C, iatrogenic rotational deformity was created after the proximal end of the fracture being internally rotated by 20 degrees and then subsequently fixed. The animals with bone healing were sacrificed for pathological and biochemical examination. In group C, the modified Mankin scale for cartilage pathology evaluation and the modified Movin scale for tendon both showed highest score among groups with statistical significance (P < 0.05); Disordered alignment and proportion of collagen I/III of rotator cuff were confirmed with picrosirius red staining; Transmission electron microscopy also showed ultrastructural tendon damage. Immunohistochemistry showed that both MMP-1 and MMP-13 expression were significantly higher in group C than groups A and B(P < 0.05). Minimally invasive techniques for humerus shaft fracture might be cosmetically advantageous, but the consequent postoperative malrotation could increase the risk of rotator cuff and cartilage degeneration. This conclusion is supported here by primary evidence from animal experiments., (© 2021. The Author(s).)

Posterior cruciate ligament (PCL) injuries commonly occur in association with participation in sporting or recreational activities or due to a direct trauma. Cartilage and meniscal lesions are prevalent in PCL-injured knees with increasing likelihood and severity based on extent and duration of trauma to the knee. As such, comprehensive diagnostics should be performed to ascertain all related pathology, and patients should be thoroughly educated regarding treatment options, likely sequelae including posttraumatic osteoarthritis, and associated outcomes. Treatments should address the joint as an organ, ensuring stability, alignment, and functional tissue restoration are optimized by the most efficient and effective means possible. Compliance with patient- and procedure-specific postoperative management protocols is critical for optimizing successful outcomes for these complex cases. The objectives of this review article are to highlight the likelihood and importance of osteochondral and meniscal pathology in the PCL-injured knee, and to provide the best current evidence regarding comprehensive evaluation and management for PCL-injured knees with cartilage and/or meniscal comorbidities., Competing Interests: J.P.S. reports grants and personal fees from Arthrex, Inc., grants from DePuy Synthes, other from Journal of Knee Surgery, grants from National Institutes of Health (NIAMS & NICHD), personal fees and other from Thieme, grants from U.S. Department of Defense, other from AO Foundation, other from American Orthopaedic Association, other from AO North America, grants from Coulter Foundation, other from Mid-America Orthopaedic Association, personal fees from Orthopedic Designs North America, personal fees from Smith & Nephew, outside the submitted work. J.L.C. reports grants and personal fees from Arthrex, Inc., personal fees from AthleteIQ, grants from ConforMIS, personal fees from CONMED Linvatec, grants from Coulter Foundation, grants from DePuy Synthes, grants and personal fees from Eli Lilly, other from Journal of Knee Surgery, grants from Merial, other from Midwest Transplant Network, grants, personal fees and other from Musculoskeletal Transplant Foundation, grants from National Institutes of Health (NIAMS and NICHD), grants from Purina, grants from Sites Medical, personal fees and other from Thieme, grants from TissueGen Inc, personal fees from Trupanion, grants from U.S. Department of Defense, grants from Zimmer-Biomet, outside the submitted work., (Thieme. All rights reserved.)

Quantitative magnetic resonance (MR) relaxation parameters demonstrate varying sensitivity to the orientation of the ordered tissues in the magnetic field. In this study, the orientation dependence of multiple relaxation parameters was assessed in cadaveric human cartilage with varying degree of natural degeneration, and compared with biomechanical testing, histological scoring, and quantitative histology. Twelve patellar cartilage samples were imaged at 9.4 T MRI with multiple relaxation parameters, including T 1 , T 2 , CW - T 1ρ , and adiabatic T 1ρ , at three different orientations with respect to the main magnetic field. Anisotropy of the relaxation parameters was quantified, and the results were compared with the reference measurements and between samples of different histological Osteoarthritis Research Society International (OARSI) grades. T 2 and CW - T 1ρ at 400 Hz spin-lock demonstrated the clearest anisotropy patterns. Radial zone anisotropy for T 2 was significantly higher for samples with OARSI grade 2 than for grade 4. The proteoglycan content (measured as optical density) correlated with the radial zone MRI orientation anisotropy for T 2 (r = 0.818) and CW - T 1ρ with 400 Hz spin-lock (r = 0.650). Orientation anisotropy of MRI parameters altered with progressing cartilage degeneration. This is associated with differences in the integrity of the collagen fiber network, but it also seems to be related to the proteoglycan content of the cartilage. Samples with advanced OA had great variation in all biomechanical and histological properties and exhibited more variation in MRI orientation anisotropy than the less degenerated samples. Understanding the background of relaxation anisotropy on a molecular level would help to develop new MRI contrasts and improve the application of previously established quantitative relaxation contrasts., (© 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Stromal cell-derived factor 1 (SDF-1), also known as CXC motif chemokine ligand 12 (CXCL12), is recognized as a homeostatic cytokine with strong chemotactic potency. It plays an important role in physiological and pathological processes, such as the development of multiple tissues and organs, the regulation of cell distribution, and tumour metastasis. SDF-1 has two receptors, CXC chemokine receptor type 4 (CXCR4) and CXC chemokine receptor type 7 (CXCR7). SDF-1 affects the proliferation, survival, differentiation and maturation of chondrocytes by binding to CXCR4 on chondrocytes. Therefore, SDF-1 has been used as an exogenous regulatory target in many studies to explore the mechanism of cartilage development. SDF-1 is also a potential therapeutic target for osteoarthritis (OA) and rheumatoid arthritis (RA), because of its role in pathological initiation and regulation. In addition, SDF-1 shows potent capacity in the repair of cartilage defects by recruiting endogenous stem cells in a cartilage tissue engineering context. To summarize the specific role of SDF-1 on cartilage development and disease, all articles had been screened out in PubMed by May 30, 2020. The search was limited to studies published in English. Search terms included SDF-1; CXCL12; CXCR4; chondrocyte; cartilage; OA; RA, and forty-seven papers were studied. Besides, we reviewed references in the articles we searched to get additional relevant backgrounds. The review aims to conclude the current knowledge regarding the physiological and pathological role of SDF-1 on the cartilage and chondrocyte. More investigations are required to determine methods targeted SDF-1 to cartilage development and interventions to cartilage diseases., (Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Glenoid morphology and dysplasia have been extensively described in conjunction with shoulder arthritis. Dysplastic glenoids have a substantial inherent retroversion, a deficient posteroinferior rim, a short scapular neck, and an inferior inclination of the joint surface. The effect of dysplasia on fracture surgery has not been reported to the same extent., Case Presentation: A 65-year-old man presented with a proximal humeral fracture. The patient was scheduled for osteosynthesis. The head was deemed unrepairable at the time of surgery and the operative plan changed to replace the proximal humerus. A discoid meniscus-like labral extension covering two-thirds of the glenoid was encountered. This finding covered a dysplastic glenoid. The combination of a fracture and a dysplastic glenoid had not been accounted for and made the reconstruction more difficult. The patient received a reverse total shoulder arthroplasty after perioperative considerations regarding reconstruction. At the 2-month follow up, the patient had a satisfactory clinical outcome, with 90° of flexion and minimal residual pain., Conclusion: This case illustrates that elective disorders with dysplasia also present to the fracture team. Careful analysis of preoperative imaging should result in an operative plan taking unexpected findings into account., (© 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Introduction: Chondromalacia patella is the degeneration of articular cartilage on the posterior facet of the patella and may indicate the onset of osteoarthritis. Conservative management is the main treatment option, and surgical intervention is considered the last option in a small percentage of patients. Perineural Injection Treatment (PIT) is a recently developed treatment option that is directed adjacent to the peripheral nerves that are the source of pathology causing neurogenic inflammation and pain. Objective: The objective of this study was to evaluate the efficacy of PIT combined with a home physical therapy program in patients with a diagnosis of chondromalacia patella compared with a control group receiving physical therapy only. Methods: Two patient groups were involved in this randomized clinical trial. The first received PIT combined with physical therapy (PIT + PT group) and the second was managed with physical therapy alone (PT group). Both groups were indicated to follow a 6-week home therapy plan afterward. The Western Ontario and McMaster Osteoarthritis Index was used to assess the patients at baseline and 6 months after therapy interventions. Results: Fifty patients (38 women and 12 men, median age 54.7 ± 14.8 years) were included; sex distribution and age did not differ between groups. Both groups had chondromalacia grade II or III, but the degree of gonarthrosis did not differ significantly between groups. The PIT + PT group outperformed PT group for pain (7.3 ± 3.5 vs. 3.2 ± 2.9 points; p  < 0.010), stiffness (3 ± 1.69 vs. 1.6 ± 1.5 points; p  < 0.010), and functional capacity (23.2 ± 10.7 vs. 11.1 ± 8.9 points; p  < 0.010). Conclusions: Compared with physical therapy alone, PIT plus physical therapy reduced pain and stiffness and restored functional capacity. ClinicalTrials.gov Register Number #NCT03515720.

Purpose: The purpose of this study was to evaluate the extent to which individuals with knee articular cartilage defects (ACDs) have kinesiophobia and pain catastrophizing, and how these psychological factors relate to self-reported knee outcomes., Methods: Thirty-five individuals seeking surgical consultation for an ACD in the knee confirmed with 3.0T MRI and 18 controls without history of knee injury participated in the study. Kinesiophobia was measured with the Tampa Scale of Kinesiophobia (TSK), and scored using the modified 11-item (TSK-11) methods. Pain catastrophizing was measured with the Pain Catastrophizing Scale (PCS). Data were analyzed using descriptive statistics, independent t-tests, chi-squared tests and Spearman's correlation coefficients, as appropriate (α = 0.05)., Results: Participants with ACDs reported higher TSK-11 scores (median 27 [IQR 25-29]) and higher PCS scores (median 10 [IQR 4-18]) than controls (median TSK-11 16 [IQR 14-17], p < 0.001; median PCS 0 [IQR 0-9], p < 0.001). Within those with knee ACDs, higher TSK-11 scores were associated with worse knee pain, function on activities of daily living, sports/recreation, and knee-related quality of life scores (rho = -0.38 to -0.61). Higher pain catastrophizing was associated with worse function with activities of daily living and knee-related quality of life (rho = -0.37 to -0.40)., Conclusions: Kinesiophobia and pain catastrophizing in people with knee ACDs were higher than controls. Higher kinesiophobia and pain catastrophizing were associated with worse function and quality of life. Further study of the impact of these psychological factors on outcomes and prognosis in people with knee ACDs is warranted., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The purpose of this human specimen experimental study was to compare the fixation stability of clinically used bilayer collagen membrane with fibrin glue with trilayer collagen prototype without fibrin glue in chondral defects at the medial or lateral talar shoulder (both matrices from Geistlich Pharma AG, Wollhusen, Switzerland)., Methods: Eleven human specimens were used. The membranes were implanted in standardized chondral defects at the medial and lateral talar shoulder randomized. All tests were performed in load-control 15 kg. Range of motion ROM of each ankle was examined individually before testing. The average ROM was 10° dorsiflexion range 0°-20° and 30° plantarflexion range 20°-45°. 1,000 testing cycles with the defined ROM were performed. Two independent investigators, blinded to membrane and fixation type, visually assessed the membrane fixation integrity for peripheral detachment, area of defect uncovered, membrane constitution and delamination., Results: The clinically used bilayer collagen membrane plus fibrin glue showed higher fixation stability than the trilayer prototype (all p < 0.05). No significant differences occurred between medial and lateral talar shoulder location (all p > 0.05)., Conclusions: The fixation stability of the trilayer collagen prototype without fibrin glue is lower than of the clinically used bilayer membrane with fibrin glue in chondral defects at the medial and lateral talar shoulder in an experimental human specimen test. Clinical use of trilayer collagen prototype without fibrin glue has to be validated by clinical testing to evaluate if the lower stability of fixation is still sufficient., (Copyright © 2020. Published by Elsevier Ltd.)

The prevalence of osteoarthritis (OA) and the burden associated with the disease are steadily increasing worldwide, representing a major public health challenge for the coming decades. The lack of specific treatments for OA has led to it being recognized as a serious disease that has an unmet medical need. Advances in the understanding of OA pathophysiology have enabled the identification of a variety of potential therapeutic targets involved in the structural progression of OA, some of which are promising and under clinical investigation in randomized controlled trials. Emerging therapies include those targeting matrix-degrading proteases or senescent chondrocytes, promoting cartilage repair or limiting bone remodelling, local low-grade inflammation or Wnt signalling. In addition to these potentially disease-modifying OA drugs (DMOADs), several targets are being explored for the treatment of OA-related pain, such as nerve growth factor inhibitors. The results of these studies are expected to considerably reshape the landscape of OA management over the next few years. This Review describes the pathophysiological processes targeted by emerging therapies for OA, along with relevant clinical data and discussion of the main challenges for the further development of these therapies, to provide context for the latest advances in the field of pharmaceutical therapies for OA.

Purpose: To investigate changes in meniscal extrusion during knee flexion before and after pullout fixation for medial meniscus posterior root tear (MMPRT) and determine whether these changes correlate with articular cartilage degeneration and short-term clinical outcomes., Methods: Twenty-two patients (mean age 58.4 ± 8.2 years) diagnosed with type II MMPRT underwent open magnetic resonance imaging preoperatively, 3 months after transtibial fixation and at 12 months after surgery, when second-look arthroscopy was also performed. The medial meniscus medial extrusion (MMME) and the medial meniscus posterior extrusion (MMPE) were measured at knee 10° and 90° flexion at which medial meniscus (MM) posterior translation was also calculated. Articular cartilage degeneration was assessed using International Cartilage Research Society grade at primary surgery and second-look arthroscopy. Clinical evaluations included Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee subjective knee evaluation form, Lysholm score, Tegner activity level scale, and pain visual analogue scale., Results: MMPE at 10° knee flexion was higher 12 months postoperatively than preoperatively (4.8 ± 1.5 vs. 3.5 ± 1.2, p = 0.01). MMPE at 90° knee flexion and MM posterior translation were smaller 12 months postoperatively than preoperatively (3.5 ± 1.1 vs. 4.6 ± 1.3, 7.2 ± 1.7 vs. 8.9 ± 2.0, p < 0.01). Articular cartilage degeneration of medial femoral condyle correlated with MMME in knee extension (r = 0.5, p = 0.04). All clinical scores significantly improved 12 months postoperatively. However, correlations of all clinical scores against decreased MMPE and increased MMME were not detected., Conclusions: MMPRT transtibial fixation suppressed the progression of MMPE and cartilage degeneration and progressed MMME minimally in knee flexion position at 1 year. However, in the knee extension position, MMME progressed and correlated with cartilage degeneration of medial femoral condyle. MMPRT transtibial fixation contributes to the dynamic stability of the MM in the knee flexion position., Level of Evidence: IV.

Objective: Because the literature relating to the influence of degeneration on the viscoelasticity and tissue composition of human lateral menisci remains contradictory or completely lacking, the aim of this study was to fill these gaps by comprehensively characterising the biomechanical properties of menisci with regard to the degree of degeneration., Design: Meniscal tissue from 24 patients undergoing a total knee replacement was collected and the degeneration of each region classified according to Pauli et al. For biomechanical characterisation, compression and tensile tests were performed. Additionally, the water content was determined and infrared (IR) spectroscopy was applied to detect changes in the structural composition, particularly of the proteoglycan and collagen content., Results: With an increasing degree of degeneration, a significant decrease of the equilibrium modulus was detected, while simultaneously the water content and the hydraulic permeability significantly increased. However, the tensile modulus displayed a tendency to decrease with increasing degeneration, which might be due to the significantly decreasing amount of collagen content identified by the IR measurements., Conclusion: The findings of the current study may contribute to the understanding of meniscus degeneration, showing that degenerative processes appear to mainly worsen viscoelastic properties of the inner circumference by disrupting the collagen integrity., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The nonoperative practitioner managing individuals with cartilage defects should use a patient-centered, multifaceted approach that aims to individualize treatment to provide optimal benefit. These include addressing modifiable risk factors for disease progression and instituting interventions such as weight loss, nutrition, physical activity, and potentially regenerative medicine strategies. This review will focus on these nonoperative treatment strategies with a focus on when treatments are necessary, who will benefit from these approaches, why they are specifically appropriate, and, finally, how these treatments directly modify the structure of a patient's cartilage and resulting symptoms., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The joint is an organ with each tissue playing critical roles in health and disease. Intact articular cartilage is an exquisite tissue that withstands incredible biologic and biomechanical demands in allowing movement and function, which is why hyaline cartilage must be maintained within a very narrow range of biochemical composition and morphologic architecture to meet demands while maintaining health and integrity. Unfortunately, insult, injury, and/or aging can initiate a cascade of events that result in erosion, degradation, and loss of articular cartilage such that joint pain and dysfunction ensue. Importantly, articular cartilage pathology affects the health of the entire joint and therefore should not be considered or addressed in isolation. Treating articular cartilage lesions is challenging because left alone, the tissue is incapable of regeneration or highly functional and durable repair. Nonoperative treatments can alleviate symptoms associated with cartilage pathology but are not curative or lasting. Current surgical treatments range from stimulation of intrinsic repair to whole-surface and whole-joint restoration. Unfortunately, there is a relative paucity of prospective, randomized controlled, or well-designed cohort-based clinical trials with respect to cartilage repair and restoration surgeries, such that there is a gap in knowledge that must be addressed to determine optimal treatment strategies for this ubiquitous problem in orthopedic health care. This review article discusses the basic science rationale and principles that influence pathology, symptoms, treatment algorithms, and outcomes associated with articular cartilage defects in the knee., Competing Interests: J.P.S. reports grants and personal fees from Arthrex, Inc., grants from DePuy Synthes, other from Journal of Knee Surgery, grants from National Institutes of Health (NIAMS and NICHD), personal fees and other from Thieme, grants from U.S. Department of Defense, other from AO Foundation, other from American Orthopedic Association, other from AO North America, grants from Coulter Foundation, other from Mid-America Orthopedic Association, personal fees from Orthopedic Designs North America, personal fees from Smith and Nephew outside the submitted work. A.M.S. reports personal fees from Arthrex, Inc., personal fees from Musculoskeletal Transplant Foundation outside the submitted work. J.L.C. reports grants and personal fees from Arthrex, Inc., personal fees from AthleteIQ, grants from ConforMIS, personal fees from CONMED Linvatec, grants from Coulter Foundation, grants from DePuy Synthes, grants and personal fees from Eli Lilly, other from Journal of Knee Surgery, grants from Merial, other from Midwest Transplant Network, grants, personal fees and other from Musculoskeletal Transplant Foundation, grants from National Institutes of Health (NIAMS & NICHD), grants from Purina, grants from Sites Medical, personal fees and other from Thieme, grants from TissueGen Inc, personal fees from Trupanion, grants from U.S. Department of Defense, grants from Zimmer-Biomet, outside the submitted work; In addition, Dr. Cook has a patent US Patent #10,039,277 with royalties paid from Musculoskeletal Transplant Foundation., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Mouse models of osteoarthritis and cartilage degeneration are important and powerful tools for investigating the molecular mechanisms of the disease pathology. Because of the vast number of genetically modified mouse models that are available for research, the ability to use these models is particularly attractive for the mechanobiologic interactions in the pathogenesis of osteoarthritis. However, the very small scale of mouse articular cartilage, where the healthy tissue is only 80 µm in thickness, poses challenges in quantifying mechanical characteristics of the tissue. We introduce here a novel approach that combines experimental and analytical methods to quantify the nuanced mechanical changes during cartilage degeneration at this scale. Cyclic reference point indentation is used to directly test the murine articular cartilage to obtain the force-deformation and the phase-shift characteristics of the tissue. The cartilage zonal thicknesses are confirmed from histology. These data are then fitted to a parallel spring model to determine the depth-dependent tissue stiffness and modulus. Using this approach, we investigated the effects of trypsin degradation on the zonal mechanical behavior of mouse articular cartilage. We observe a decline of the superficial zone stiffness coupled with the loss of the superficial layer. Subsequent degradation by trypsin allowed the identification of middle- and deep- zone properties. Taken together, this approach can be a useful tool for understanding the disease mechanisms of cartilage homeostasis and degeneration, and for monitoring of therapies for osteoarthritis.

Purpose: To determine whether articular cartilage damage noted at the time of primary anterior cruciate ligament reconstruction (ACLR) affects the likelihood of achieving ≥ 90% symmetry for isokinetic extension strength at 6 months after surgery or risk of recurrent ACL injury., Methods: Five hundred and eight patients underwent primary ACLR and diagnostic arthroscopy. All identified cartilage lesions were graded using the Outerbridge system. All patients underwent isokinetic strength testing. The association between cartilage Outerbridge grade and a ≥ 90% Limb Symmetry Index (LSI) and recurrent ACL injury risk at mean 38.7 month follow-up (SD 31.8) was evaluated via multivariate regression analysis., Results: Grade 2 or higher damage was present in 394 (77.5%) of patients, grade 3 or higher in 143 (28.1%) and grade 4 in 83 (16.4%) at time of ACLR. Ipsilateral ACLR graft rupture occurred in 31 (6.1%) of patients. Contralateral ACL injury occurred in 19 (3.7%). Patients with grade 2 or higher damage were significantly less likely to meet an LSI goal of ≥ 90% for fast (300°/s) isokinetic extension. There was no association with slow isokinetic extension. Cartilage lesion severity at or beyond grade 2 had a similar effect on isokinetic testing results regardless of compartment involvement or performance of microfracture. Patients with grade 2-4 cartilage damage were less likely to sustain a second ipsilateral ACL injury or a contralateral native ACL injury., Conclusions: Cartilage damage seen at time of ACL reconstruction is common and associated with lower likelihood of achieving ≥ 90% symmetry for isokinetic extension strength at 6 months after surgery. However, lower recurrent ACL injury rates are seen in patients with concurrent cartilage damage. These data may inform future clinical decisions regarding operative managment of recurrent ACL injuries., Level of Evidence: III.

Background: Autologous chondrocyte implantation (ACI) constitutes an established treatment option for cartilage defects of the knee joint. Experience in the shoulder, however, is limited, and the management of cartilage defects remains a challenge. The purpose of this study was to evaluate the results after ACI with 3-dimensional spheroids of human autologous matrix-associated chondrocytes in the shoulder., Methods: Seven male patients (median age, 42.8 years [range, 18-55 years]) underwent ACI for symptomatic focal grade IV cartilage lesions of the humeral head by an open or arthroscopic approach. Clinical parameters (range of motion, visual analog scale score, Subjective Shoulder Value, Constant score, and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score) and osteoarthritis grades were assessed. Arthroscopic re-evaluation was additionally performed in 5 patients., Results: After a median follow-up period of 32 months (range, 22-58 months), the median Subjective Shoulder Value was 95% (range, 70%-100%) compared with 60% (range, 30%-60%) preoperatively, the visual analog scale score was 0 at rest and was a median of 0 (range, 0-2) during exercise, the median Constant score was 95 points (range, 80-100 points), and the median American Shoulder and Elbow Surgeons score was 97 points (range, 90-100 points). The median preoperative size of the cartilage lesion was 3 cm 2 (range, 2.3-4.5 cm 2 ). Arthroscopically, complete coverage of the cartilage defect was observed in 4 cases whereas a circumferential residual defect of 0.25 cm 2 was found in 1 patient. Grade I osteoarthritis (Samilson and Prieto classification) was observed in 2 cases. One patient had postoperative adhesive capsulitis and required revision surgery., Conclusion: ACI using 3-dimensional spheroids of human autologous matrix-associated chondrocytes for treatment of grade IV articular cartilage lesions of the humeral head achieves satisfactory clinical results during a short- to mid-term follow-up period and leads to successful defect coverage with only minor radiologic degenerative changes. In this case series, ACI proved to constitute a viable treatment in the shoulder joint. However, in consideration of the 2-stage surgical design and the cost intensiveness of this procedure, the indication is restricted to young and active symptomatic patients in our practice., (Copyright © 2019 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Objective: Abnormal joint movement is associated with osteoarthritis (OA). Previous studies using the controlling abnormal joint movement (CAJM) model of OA reported delayed cartilage degeneration; however, none of them focused on gait performance and the localization of matrix metalloproteinase 13 (MMP13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in chondrocytes. Therefore, we aimed to investigate the effect of controlling abnormal joint movement on gait performance and the localization of MMP13 and TIMP-1, using kinematic and histological analyses., Design: Rats were assigned to 2 groups: anterior cruciate ligament transection (ACL-T) group and CAJM group ( n = 5/group); contralateral hind limbs of ACL-T rats were designated as intact. After 1, 2, and 4 weeks, step length was analyzed, and after 2, 4, and 8 weeks, Safranin O-Fast Green staining and immunohistochemical staining for MMP13 and TIMP-1 were performed., Results: Step length did not differ significantly between the groups. However, degeneration of articular cartilage was higher in the ACL-T group than in the intact group ( P < 0.05). There was no significant difference in the CAJM group at all time points. Immunohistochemical analysis of the MMP13/TIMP-1 relationship revealed a significant increase in the expression ratio of MMP13 after 4 weeks in the ACL-T group compared to the CAJM group ( P < 0.05)., Conclusions: Controlling abnormal joint movement may reduce mechanical stress owing to kinematic elements of small articulation including joint instability and delayed cartilage degeneration, despite the lack of kinematic change in step length.

Purpose: To evaluate the time and rate of return to sport (RTS), as well as outcomes, in young and active patients receiving concomitant lateral meniscal allograft transplantation (MAT) and distal femoral varus osteotomy (DFVO) for lateral meniscal deficiency and valgus malalignment., Methods: This was a retrospective study of consecutive patients who underwent concomitant MAT and DFVO by a single surgeon. The exclusion criteria were any concomitant procedures other than cartilage restoration procedures for focal full-thickness cartilage defects of the lateral femoral condyle and less than 2 years of follow-up. At final follow-up, patients were asked to complete a subjective sports questionnaire, the Marx Activity Rating Scale, a visual analog scale (VAS), the Single Assessment Numeric Evaluation, and a satisfaction questionnaire. Changes in patient-reported outcome measures were assessed using nonparametric statistical testing., Results: A total of 21 patients met the inclusion criteria, of whom 17 were included for analysis at an average follow-up of 7.5 years (range, 2.2-13.3 years). The average age at the time of surgery was 23.3 years (range, 16.9-36.2 years), and 76.5% of patients were female patients. The average VAS score decreased from 5.7 preoperatively to 2.6 postoperatively (P = .02). Of the 15 patients who participated in sports within 3 years prior to their surgical procedure, 14 (82.4%) returned to 1 or more sports at an average of 16.9 months (range, 6-36 months); however, only 46.7% were able to return to their preinjury level of participation or higher. Furthermore, 88.2% of patients reported being satisfied with their sport-related outcomes. Direct rates of sport-specific return were as follows: weightlifting, 100%; skiing, 100%; running, 66.7%; and basketball, 50%., Conclusions: In our study population, concomitant MAT and DFVO afforded a high rate of RTS at an average of 16.9 months postoperatively, as well as a significant decrease in VAS pain scores. These findings are essential to note when counseling patients receiving these procedures who wish to resume sports and physical activities so that they may expect an extensive recovery process before they can RTS., Level of Evidence: Level IV, case series., (Copyright © 2019 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: This study was aimed to determine the impact of bioregenerative operations in case of degenerative cartilage lesions within the media knee compartment., Material and Methods: The CartilageRegistry DGOU was founded in 2013. At the deadline August 2016 a total of 1847 patients were included. A total of 23.3% (n = 432) was suffering from a degenerative cartilage lesion in the medial compartment. Follow-up was performed after 6, 12, and 24 months (online evaluation). The patients were asked for their subject feeling as well as the KOOS (Knee injury and Osteoarthritis Outcome Score) was determined., Results: Most of the patients (n = 358) suffered from a single femoral lesion. In 25 cases single tibial and in 49 cases combined defects ("kissing lesions") were addressed by different treatment options: 39.9% autologous chondrocyte transplantation, in 8.1% in combination with a spongiosa plasty. Other treatments were drilling, microfracturing with or without matrix. In 17.9% the surgeons had chosen combined methods. The bioregenerative treatment was combined with a concomitant operation in 39.7% in patients with medial, in 56.0% in patients with a tibial, and in 67.9% in patients with combined defects. The mostly performed additional operations were osteotomies. There were no gender differences at baseline or during follow-up. The history of patients with femoral defects was shorter than in the other groups. The patients with medial defects judged the subjective outcome significant more frequently better after 6, 12, or 24 months compared with the other groups. The KOOS raised from baseline (median 52 points) to a median of 75 after 6, to 78 points after 12, and to 80 points after 24 months. Patients with femoral defects had a better KOOS-outcome in tendency. Revision operations were required in 7.1%., Conclusions: The treatment of degenerative cartilage lesions (respective early OA) by bioregenerative procedures are well-established measures. These treatments are sufficient to produce high patients' satisfaction and acceptable short/midterm results., Competing Interests: The authors declare that they have no conflict of interest./Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Updated three column fixation of tibial plateau fractures (TPFs) arouse the importance of posterior column articular reduction. Complex TPFs with posterolateral (PL) articular injury is difficult to manage. We presented a strategy of combined positions and approaches to treat these injuries. Surgical technique was described and outcome of these were reported., Materials and Methods: From 2014 Jan to 2016 Dec, there were 132 patients of TPFs treated in our institute. Preoperative evaluation included plain films and 2D/3D CT scan to evaluate the involvement of articular surface and associated columns. Inclusion criteria were three column TPFs with PL corner injury. We put patients in prone position first with reverse L incision to manage PL articular impaction and posteromedial (PM) fractures. Then we repositioned the patients in supine to treat anterolateral fixation. Postoperative radiographic analysis, physical examination findings, and patient reported outcome scores from the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire were recorded., Results: Patient demographic information was retrospectively reviewed with a mean follow-up time of 34.4 months (range 24-48 months). The average time to union was 5.2 months (range 4-8months). 13/16 (81%) of patients had satisfactory articular reduction by plain films (less than 2 mm articular step off). All patients demonstrated healed without secondary displacement or infection. All patients demonstrated satisfactory coronal (medial proximal tibia angle 84.68 degrees) and sagittal alignment (posterior proximal tibia angle 84.75 degrees). Condylar width averaged 3.93 mm. 3/16 (19%) of cases required posterolateral columnar plating in addition to posteromedial columnar plating. The knee range of motion averaged 115 degrees (ranged from 0 degrees of extension to140 degrees flexion). The average KOOS score was 83/100 (range 76-90). 3 patients in the series developed a surgical site superficial infection and resolved after debridement and oral antibiotics use. No patient eventually received total knee arthroplasty at the last follow up., Conclusions: Our strategy provides an effective method to treat three column tibial plateau fractures with PL articular injury., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Moderate to severe (grade 3-4) hip joint cartilage injury seems to impair function in patients with femoroacetabular impingement syndrome., Purpose: To investigate whether demographic and radiographic factors were associated with moderate to severe hip joint cartilage injury., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Patients were identified in the Danish Hip Arthroscopy Registry. The outcome variables were acetabular cartilage injury (modified Beck grade 0-2 vs 3-4) and femoral head cartilage injury (International Cartilage Repair Society grade 0-2 vs 3-4). Logistic regressions assessed the association with the following: age (<30 vs 30-50 years); sex; sport activity level (Hip Sports Activity Scale); alpha angle (AA) assessed as normal (AA <55°), cam (55°≤ AA <78°), or severe cam (AA ≥78°); lateral center-edge angle (LCEA) assessed as normal (25°≤ LCEA ≤ 39°), pincer (LCEA >39°), or borderline dysplasia (LCEA <25°); joint space width (JSW) assessed as normal (JSW >4.0 mm), mild reduction (3.1 mm ≤ JSW ≤ 4.0 mm), or severe reduction (2.1 mm ≤ JSW ≤ 3.0 mm)., Results: A total of 1511 patients were included (mean ± SD age: 34.9 ± 9.8 years). Male sex (odds ratio [OR], 4.42), higher age (OR, 1.70), increased AA (cam: OR, 2.23; severe cam: OR, 4.82), and reduced JSW (mild: OR, 2.04; severe: OR, 3.19) were associated ( P < .05) with Beck grade 3-4. Higher age (OR, 1.92), increased Hip Sports Activity Scale (OR, 1.13), borderline dysplasia (OR, 3.08), and reduced JSW (mild: OR, 2.63; severe: OR, 3.04) were associated ( P < .05) with International Cartilage Repair Society grade 3-4., Conclusion: Several demographic and radiographic factors were associated with moderate to severe hip joint cartilage injury. Most notably, increased cam severity and borderline dysplasia substantially increased the risk of grade 3-4 acetabular and femoral head cartilage injury, respectively, indicating that specific deformity may drive specific cartilage injury patterns in the hip joint.

Background: Studies on the effect of partial- and full-thickness chondral damage of the hip on outcomes and the ability to achieve meaningful clinical outcomes are limited., Purpose: To determine the effect of full- and partial-thickness chondral injuries on 2-year outcomes in patients undergoing hip arthroscopic surgery for femoroacetabular impingement syndrome (FAIS) compared with patients without chondral damage, and to identify significant predictors of achieving the patient acceptable symptomatic state (PASS) and minimal clinically important difference (MCID)., Study Design: Case-control study; Level of evidence, 3., Methods: Data from consecutive patients with evidence of chondromalacia at the time of primary hip arthroscopic surgery with routine capsular closure for the treatment of FAIS by a single fellowship-trained surgeon between January 2012 and September 2016 were reviewed. Patients were divided into groups with partial-thickness (grade I-III) or full-thickness (grade IV) chondral defects and matched by age and body mass index (BMI) to patients without chondral injuries. Preoperative and postoperative outcomes were compared among the 3 groups, and a binary logistic regression analysis was utilized to identify significant predictors of achieving the MCID and PASS., Results: There were 634 patients included in the analysis, with a mean age of 34.5 ± 10.9 years and a mean BMI of 25.2 ± 4.7 kg/m 2 . A total of 493 (77.8%) patients had no evidence of chondral damage, 92 (14.5%) patients had partial-thickness chondral defects, and 49 (7.7%) patients had full-thickness chondral defects. There were statistically significant differences in the Hip Outcome Score (HOS)-Activities of Daily Living, HOS-Sports Subscale, modified Harris Hip Score, pain, and satisfaction ( P < .01) among the 3 groups. Patients with grade IV chondromalacia experienced the poorest outcomes and lowest percentage of achieving the PASS. Predictors for achieving any PASS threshold included preoperative alpha angle (odds ratio [OR], 0.96; P = .016), absence of preoperative limping (OR, 7.25; P = .002), absence of preoperative chronic pain (OR, 5.83; P = .019), primary hip arthroscopic surgery (OR, 0.17; P = .050), patients who self-identified as runners (OR, 2.27; P = .037), and Tönnis grade 0 (OR, 2.86; P = .032). Male sex (OR, 2.49; P = .015) was the only predictor of achieving any MCID threshold., Conclusion: Patients with grade IV chondral defects experienced worse functional outcomes, lower satisfaction, and increased pain when compared with both patients without chondral damage or grade I-III chondromalacia at 2-year follow-up. Several predictors were associated with achieving clinically significant function in patients undergoing hip arthroscopic surgery for FAIS.

Clinical Issue: Today's advanced MRI imaging allows for a precise diagnosis and thus better treatment planning of cartilage damage. The phrase "depending on intraoperative findings" is therefore slowly becoming a thing of the past. However, this also increases the demand for an exact interpretation of the imaging, from clinicians and patients alike. This article highlights the importance of a radiologist's role in different constellations., Practical Recommendations: In the case of acute injuries, it is crucial to recognize osteochondral flakes, cartilage delamination, subchondral bone bruising and fractures as well as concomitant injuries. These findings must be instantly communicated to the practitioner. In the case of chronic cartilage damage, grading the extent and size of the damage is decisive in choosing the appropriate therapy method. Possible causes and accompanying injuries must also be analyzed and, if necessary, addressed. Direct communication with the clinical colleague is also useful in correlating the clinical and radiological findings.

Background: In order to answer clinical therapy-oriented questions, reliable and consistent depiction of articular cartilage across technical platforms is necessary., Materials and Methods: Technical standards and developments in cartilage imaging are summarized based on current literature and experience from clinical daily routine., Results: Clinical questions that need to be answered relate to cross-sectional extent, depth, differentiating cartilaginous from bony components of a lesion and to the lesion's location within the compartment. If present, displaced fragments, concomitant meniscal, ligamentous and/or degenerative lesions should be identified. To date, magnetic resonance imaging (MRI) is the workhorse of cartilage imaging and is largely based on moderately T2-weighted and also proton-density (PD)-weighted fat-suppressed turbo-spin-echo sequences. Direct MR- and CT-arthrography are the gold standard to evaluate thin cartilage layers. Recent advances in coil and MR sequence design, increased availability of 3T-MR scanners and more and more sophisticated acceleration techniques allow for better spatial resolution and more robust image contrast at acceptable scan times., Discussion: As abundant as current developments in clinical routine cartilage imaging may be, the radiologist must carefully select the approach best suited to answering the clinical questions.

Background: Osteochondral injuries have been treated by a variety of methods, each having its own drawbacks. The purpose of this study was to determine the biomechanical feasibility of using a hydrogel implant replacement for an osteochondral core defect. The hypothesis of this study was that the contact pressure of the native knee can be recreated with the use of a hydrogel implant., Methods: Six cadaver knees were tested in a knee simulator while contact pressures were measured on the tibial plateau. Pressure data was collected in the intact knee, after coring of the condyle and after insertion of a hydrogel implant. Following 1000 gait cycles of fatigue testing, each knee was taken through axial loading indentation testing where the stiffness of the in situ implant was compared to the contralateral condyle., Findings: While coring significantly reduced the peak pressure at the coring site from 1.8 MPa in the intact knee to 0.0 MPa after coring, implant insertion significantly increased it to 1.2 MPa. There was no significant difference in the peak pressures or the average pressures at the hole location between the intact knee and following implant insertion. After fatigue testing, no macroscopic loosening or implant damage was observed. Based on indentation testing, the stiffness of the medial condyle, 157 N/mm, was significantly less than the lateral condyle, 696 N/mm., Interpretation: The insertion of the hydrogel implant was able to achieve restoration of contact pressures in the knee supporting the viability of hydrogel implants in the treatment of osteochondral lesions of the knee., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: No study has yet assessed the effect of medial open-wedge high tibial osteotomy (MOWHTO) on the patellofemoral joint according to postoperative alignment., Purpose: To evaluate the effect of MOWHTO on the patellofemoral joint according to postoperative alignment by comparing the cartilage status before and after surgery and assessing the clinical and radiological outcomes., Study Design: Cohort study; Level of evidence, 3., Methods: A total of 135 patients who underwent MOWHTO were retrospectively investigated. The patients were divided into 3 groups according to the postoperative weightbearing line ratio (WBLR): undercorrection (WBLR <58.3%, lowest quartile), acceptable correction (WBLR of 58.3%-66.3%, middle 2 quartiles), and overcorrection (WBLR >66.3%, highest quartile). The postoperative change in the cartilage status was assessed arthroscopically during implant removal at 2 years after MOWHTO. The clinical and radiological outcomes were evaluated at a mean follow-up of 52.1 months. A regression analysis was performed to identify the factors affecting the deterioration of the patellofemoral joint cartilage status. A receiver operating characteristic curve was employed to identify the cutoff point for the postoperative WBLR associated with the deterioration of the cartilage status in the patellofemoral joint., Results: Of all patients, progression of cartilage degeneration was noted in 39.3% for femoral trochlea and 23.7% for patella. The incidence of cartilage progression was significantly higher in the overcorrection group than in the undercorrection and acceptable correction groups (femoral trochlea: undercorrection group = 30.3%, acceptable correction group = 32.4%, and overcorrection group = 61.8% [ P = .008]; patella: undercorrection group = 15.2%, acceptable correction group = 17.7%, and overcorrection group = 44.1% [ P = .005]). The functional outcomes, including Lysholm knee score, Knee injury and Osteoarthritis Outcome Score (Pain, Symptoms, and Activities of Daily Living subscales), and Shelbourne and Trumper score, were significantly worse in the overcorrection group. The regression analysis showed that only the postoperative WBLR had a significant effect on cartilage deterioration. The cutoff point for the postoperative WBLR associated with progression of the International Cartilage Repair Society grade was 62.1% for the femoral trochlea (sensitivity = 61.5%, specificity = 62.7%, accuracy = 66.2%) and 62.2% for the patella (sensitivity = 59.4%, specificity = 60.2%, accuracy = 67.8%)., Conclusion: The patellofemoral joint was adversely affected by MOWHTO. Overcorrection causing excessive valgus alignment led to further progression of degenerative changes in the patellofemoral joint and inferior clinical outcomes. The postoperative WBLR can be used as a predictive factor for deterioration of the cartilage status in the patellofemoral joint after MOWHTO.

Background/aim: Evaluating the relationship of patellar chondromalacia with obesity, infrapatellar fat pad (IFP) volume and popliteal artery intima-media thickness (IMT)., Materials and Methods: A total of203 patients with different degree of patellar chondromalacia (103 male, 100 female) and 52 control subjects (19 male, 33 female) were included and grouped according to sex, age, body surface area (BSA), body mass index (BMI) and patellar chondromalacia classification. All measurements were completed with 3T magnetic resonance imaging (MRI). Articular cartilage and IFP volume were measured in saggital plane using double echo steady state (DESS) and DIXON sequences, respectively. Patellar cartilage damage was graded using modified outerbridge classification, and the relations among cartilage volume and BMI, BSA, IFP, IMT were statistically assessed., Results: Popliteal artery IMT showed an independent association with the prevalence of cartilage defects and IFP volumes (P ˂ 0.001). There was an association between BMI and IFP volumes (P ˂ 0.001). However, no differences were observed between IFP volume and different chondromalacia groups. When IFP measurements were corrected using individual BMI and BSA values, a positive correlation was found between control and advanced chondromalacia groups (P ˂ 0.001)., Conclusion: This study demonstrates the relationship among obesity, IMT and chondromalacia and highlights this potential circle to develop effective treatments and inhibit the progression of chondromalacia., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Meniscal tears have a poor healing capacity, and damage to the meniscus is associated with significant pain, disability, and progressive degenerative changes in the knee joint that lead to osteoarthritis. Therefore, strategies to promote meniscus repair and improve meniscus function are needed. The objective of this study was to generate porcine meniscus-derived matrix (MDM) scaffolds and test their effectiveness in promoting meniscus repair via migration of endogenous meniscus cells from the surrounding meniscus or exogenously seeded human bone marrow-derived mesenchymal stem cells (MSCs). Both endogenous meniscal cells and MSCs infiltrated the MDM scaffolds. In the absence of exogenous cells, the 8% MDM scaffolds promoted the integrative repair of an in vitro meniscal defect. Dehydrothermal crosslinking and concentration of the MDM influenced the biochemical content and shear strength of repair, demonstrating that the MDM can be tailored to promote tissue repair. These findings indicate that native meniscus cells can enhance meniscus healing if a scaffold is provided that promotes cellular infiltration and tissue growth. The high affinity of cells for the MDM and the ability to remodel the scaffold reveals the potential of MDM to integrate with native meniscal tissue to promote long-term repair without necessarily requiring exogenous cells.

Objective: To determine biomechanical effects of knee cartilage defect perimeter morphology based on cartilage strain and opposing subchondral bone contact., Design: Articular cartilage defects were created in 5 bovine femoral condyles: group 1, 45° inner bevel with 8-mm rim; group 2, vertical with 8-mm rim; and group 3, 45° outer bevel with 8-mm base. Samples were placed into a custom-machined micro-computed tomography tube and subjected to 800 N of axial loading. DICOM data were used to calculate cartilage thickness 4 and 6 mm from the center, distance between tibial cartilage surface and femoral subchondral bone, and contact width between tibial cartilage and subchondral bone. Strain 4 mm from the center and both absolute and change in distance (mm) to subchondral bone were compared between groups 1 and 2 using paired t tests. Strain at 6 mm and distance changed, loaded distance, and contact width (mm) were compared between groups using the Friedman test with post hoc analysis using Wilcoxon signed rank test., Results: No significant differences in rim strain were noted between groups 1 and 2 at 4 mm ( P = 0.10) and between groups 1, 2, and 3 at 6 mm ( P = 0.247) from the defect center. The loaded distance was significantly different between groups 1 and 3 ( P = 0.013). No significant change in distance to the subchondral bone was found between groups ( P = 0.156). The difference in subchondral bone contact area approached but did not reach significance ( P = 0.074)., Conclusion: When debriding focal articular cartilage defects, establishment of an inner bevel decreases tissue deformation and contact with opposing subchondral bone.

Background: The addition of a type I/III collagen membrane in cartilage defects treated with microfracture has been advocated for cartilage repair, termed "autologous matrix-induced chondrogenesis" (AMIC)., Purpose: To examine the current clinical evidence regarding AMIC for focal chondral defects., Study Design: Systematic review., Methods: A systematic review was performed by searching PubMed, ScienceDirect, and Cochrane Library databases. Inclusion criteria were clinical studies of AMIC for articular cartilage repair, written in English. Relative data were extracted and critically analyzed. PRISMA guidelines were applied, the methodological quality of the included studies was assessed by the modified Coleman Methodology Score (CMS), and aggregate data were generated., Results: Twenty-eight clinical articles were included: 12 studies (245 patients) of knee cartilage defects, 12 studies (214 patients) of ankle cartilage defects, and 4 studies (308 patients) of hip cartilage defects. The CMS demonstrated a suboptimal study design in the majority of published studies (knee, 57.8; ankle, 55.3; hip, 57.7). For the knee, 1 study reported significant clinical improvements for AMIC compared with microfracture for medium-sized cartilage defects (mean defect size 3.6 cm 2 ) after 5 years (level of evidence, 1). No study compared AMIC with matrix-assisted autologous chondrocyte implantation (ACI) in the knee. For the ankle, no clinical trial was available comparing AMIC versus microfracture or ACI. In the hip, only one analysis (level of evidence, 3) compared AMIC with microfracture for acetabular lesions. For medium-sized acetabular defects, one study (level of evidence, 3) found no significant differences between AMIC and ACI at 5 years. Specific aspects not appropriately discussed in the currently available literature include patient-related factors, membrane fixation, and defect properties. No treatment-related adverse events were reported., Conclusion: This systematic review reveals a paucity of high-quality, randomized controlled studies testing the AMIC technique versus established procedures such as microfracture or ACI. Evidence is insufficient to recommend joint-specific indications for AMIC. Additional nonbiased, high-powered, randomized controlled clinical trials will provide better clinical and structural long-term evidence, thus helping to define possible indications for this technique.

Background: In this study, we investigate the in vitro and in vivo chondrogenic capacity of a novel photopolymerizable cartilage mimetic hydrogel, enhanced with extracellular matrix analogs, for cartilage regeneration., Purpose: To (1) determine whether mesenchymal stem cells (MSCs) embedded in a novel cartilage mimetic hydrogel support in vitro chondrogenesis, (2) demonstrate that the proposed hydrogel can be delivered in situ in a critical chondral defect in a rabbit model, and (3) determine whether the hydrogel with or without MSCs supports in vivo chondrogenesis in a critical chondral defect., Study Design: Controlled laboratory study., Methods: Rabbit bone marrow-derived MSCs were isolated, expanded, encapsulated in the hydrogel, and cultured in chondrogenic differentiation medium for 9 weeks. Compressive modulus was evaluated at day 1 and at weeks 3, 6, and 9. Chondrogenic differentiation was investigated via quantitative polymerase reaction, safranin-O staining, and immunofluorescence. In vivo, a 3 mm-wide × 2-mm-deep chondral defect was created bilaterally on the knee trochlea of 10 rabbits. Each animal had 1 defect randomly assigned to be treated with hydrogel with or without MSCs, and the contralateral knee was left untreated. Hence, each rabbit served as its own matched control. Three groups were established: group A, hydrogel (n = 5); group B, hydrogel with MSCs (n = 5); and group C, control (n = 10). Repair tissue was evaluated at 6 months after intervention., Results: In vitro, chondrogenesis and the degradable behavior of the hydrogel by MSCs were confirmed. In vivo, the hydrogel could be delivered intraoperatively in a sterile manner. Overall, the hydrogel group had the highest scores on the modified O'Driscoll scoring system (group A, 17.4 ± 4.7; group B, 13 ± 3; group C, 16.7 ± 2.9) ( P = .11) and showed higher safranin-O staining (group A, 49.4% ± 20%; group B, 25.8% ± 16.4%; group C, 36.9% ± 25.2%) ( P = .27), although significance was not detected for either parameter., Conclusion: This study provides the first evidence of the ability to photopolymerize this novel hydrogel in situ and assess its ability to provide chondrogenic cues for cartilage repair in a small animal model. In vitro chondrogenesis was evident when MSCs were encapsulated in the hydrogel., Clinical Relevance: Cartilage mimetic hydrogel may offer a tissue engineering approach for the treatment of osteochondral lesions.

Background: Healthy cartilage is essential for optimal joint function. Although, articular cartilage defects are highly prevalent in the active population and hamper joint function, the effect of articular cartilage defects on knee loading is not yet documented. Therefore, the present study compared knee contact forces and pressures between patients with tibiofemoral cartilage defects and healthy controls. Potentially this provides additional insights in movement adaptations and the role of altered loading in the progression from defect towards OA., Methods: Experimental gait data collected in 15 patients with isolated cartilage defects (8 medial involvement, 7 lateral-involvement) and 19 healthy asymptomatic controls was processed using a musculoskeletal model to calculate contact forces and pressures. Differences between two patient groups and controls were evaluated using Kruskal-Wallis tests and individually compared using Mann-Whitney-U tests (alpha <0.05)., Findings: The patients with lateral involvement walked significantly slower compared to the healthy controls. No movement adaptations to decrease the loading on the injured condyle were observed. Additionally, the location of loading was not significantly affected., Interpretation: The current results suggest that isolated cartilage defects do not induce significant changes in the knee joint loading distribution. Consequently, the involved condyle will capture a physiological loading magnitude that should however be distributed over the cartilage surrounding the defect. This may cause local degenerative changes in the cartilage and in combination with inflammatory responses, might play a key role in the progression from articular cartilage defect to a more severe OA phenotype., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study aimed to develop a new histological scoring system for use in a partial-thickness cartilage repair animal model. Although previous papers have investigated the regeneration of articular cartilage, the good results achieved in small animals have not been replicated in large animal models or humans, possibly because of the frequent use of models with perforation of the subchondral bone plates. Partial-thickness lesions spare the subchondral bone, and this pattern is the most frequent in humans; therefore, new therapies should be tested using this model. However, no specific histological score exists to evaluate partial-thickness model results., Methods: Histological sections from 30 ovine knees were reviewed to develop a new scoring system. The sections were subjected to H&E, Safranin O, and Masson's trichrome staining., Results: This paper describes a new scoring tool that is divided into sections in detail: repair of tissue inside the lesion, cartilage around the lesion and degenerative changes at the base of the lesion. Scores range from 0 to 21; a higher score indicates better cartilage repair., Discussion: Unlike existing tools, this new scale does not assign points for the positioning of a tidemark; we propose evaluation of the degenerative changes to the subchondral bone and calcified cartilage layer. It is necessary to remove the whole joint to access and study the evolution of the lesion as well as the surrounding tissue., Conclusion: This article emphasizes the importance of a partial-thickness animal model of cartilage repair and presents a new histological scoring system.

Objective To test different fixation methods of a 3-dimensionally woven poly(ϵ-caprolactone) (PCL) scaffold within chondral defects of a weightbearing large animal model. Methods Full thickness chondral defects were made in the femoral condyles of 15 adult male Yucatan mini-pigs. Two surgical approaches were compared including total arthrotomy (traditional) and a retinaculum-sparing, minimally invasive surgery (MIS) approach. Following microfracture (MFX), scaffolds were placed without fixation or were fixed with fibrin glue, suture, or subchondral anchor. Experimental endpoints were between 1 and 6 weeks. Micro-computed tomography and histology were used to assess samples. Results The MIS approach was superior as the traditional approach caused medial condyle cartilage wear. One of 13 (7.7%) of scaffolds without fixation, 4 of 11 (36.3%) fibrin scaffolds, 1 of 4 (25%) of sutured scaffolds, and 9 of 9 (100%) of anchor-fixed scaffolds remained in place. Histology demonstrated tissue filling with some overgrowth of PCL scaffolds. Conclusions Of the methods tested, the MIS approach coupled with subchondral anchor fixation provided the best scaffold retention in a mini-pig chondral defect model. This finding has implications for fixation strategies in future animal studies and potential future human use.

Purpose: Chondral lesion is a pathology with high prevalence, reaching as much as 63% of general population and 36% among athletes. The ability of human Dental Pulp Stem Cells (DPSCs) to differentiate into chondroblasts in vitro suggests that this stem cell type may be useful for tissue bioengineering. However, we have yet to identify a study of large animal models in which DPSCs were used to repair articular cartilage. Therefore, this study aimed to describe a novel treatment for cartilage lesion with DPSCs on a large animal model., Methods: Mesenchymal stem cells (MSC) were obtained from deciduous teeth and characterized by flow cytometry. DPSCs were cultured and added to a collagen type I/III biomaterial composite scaffold. Brazilian miniature pig (BR-1) was used. A 6-mm diameter, full-thickness chondral defect was created in each posterior medial condyle. The defects were covered with scaffold alone or scaffold + DPSCs on the contralateral side. Animals were euthanized 6 weeks post-surgery. Cartilage defects were analyzed macroscopically and histology according to modified O'Driscoll scoring system., Results: Flow cytometry confirmed characterization of DPSCs as MSCs. Macroscopic and histological findings suggested that this time period was reasonable for evaluating cartilage repair. To our knowledge, this study provides the first description of an animal model using DPSCs to study the differentiation of hyaline articular cartilage in vivo., Conclusion: The animals tolerated the procedure well and did not show clinical or histological rejection of the DPSCs, reinforcing the feasibility of this descriptive miniature pig model for pre-clinical studies.

Introduction: The aim of the study was to assess the relationship between symptomatic osteochondral lesions of the talus (OLTs) and age, body mass index (BMI), quality of life (QOL), size and anatomic location., Methods: Fifty-two patients with chronic OLTs were analyzed including BMI, Visual Analogue Scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS), Short-Form Health Survey (SF-12 divided into Mental (MCS) and Physical (PCS) score) and the 12-Item General Health Questionnaire (GHQ-12). Every patient underwent magnetic resonance imaging (MRI) and computed tomography (CT) examinations. We carried out a sub-analysis by dividing the talus into 6 areas, 3 vertical (medial, central and lateral group) and 3 horizontal (anterior, middle and posterior group)., Results: There were 31 (60%) male and 21 (40%) female patients. Mean MCS and PCS resulted respectively 43.9 and 35.2. OLTs were located as follows: medial 20 (38.50%); central 13 (24.0%); and lateral 19 (36.50%); anterior 24 (46.15%); middle 16 (30.77%); and posterior 12 (23.08%). No significant differences were found among different groups with the exception of the anterior and posterior group for MCS (p=0.021). In the central group we identified a negative correlation (R=-0.672) between aging and AOFAS and a positive correlation between BMI and lesion size. We found a positive correlation between CT and MRI in each group., Conclusions: OLTs impact patients' quality of life particularly in the physical component. Additionally, in patients with central lesions we found a positive linear correlation between lesion size and BMI and a worsening of the ankle with increasing age., (Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Gene therapy refers to the use of viral and non-viral vectors to deliver nucleic acids to tissues of interest using direct (in vivo) or transduced cell-mediated (ex vivo) approaches. Over the past few decades, strategies have been adopted to express therapeutic transgenes at sites of injury to promote or facilitate repair of bone and cartilage. Targets of interest have typically included secreted proteins such as growth factors and anti-inflammatory mediators; however, work has also begun to focus intracellularly on signaling components, transcription factors and small, regulatory nucleic acids such as microRNAs (miRNAs). In recent years, a number of single therapeutic gene approaches (termed 'monotherapies') have proven effective in preclinical models of disease, and several are being evaluated in clinical trials. In particular, an ex vivo TGF-β1 gene therapy was approved in Korea in 2017 for treatment of moderate-to-severe osteoarthritis (OA). The ability to utilize viral vectors for context-specific and combinatorial gene therapy is also being investigated, and these strategies are likely to be important in more robustly addressing the complexities of tissue repair and regeneration in skeletal disease. In this review, we provide an overview of viral gene therapies being developed for treatment of bone and cartilage pathologies, with an emphasis on emerging combinatorial strategies as well as those targeting intracellular mediators such as miRNAs., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose: The aim of this retrospective study was to evaluate the clinical and radiological results of a nano-composite multi-layered three-dimensional biomaterial scaffold for treatment of osteochondral lesions (OCL) of the knee. It was a particular radiological interest to analyse the osseointegration, filling of the defects and the bone tracer uptake (BTU), and it was hypothesised that this scaffold, which was created to mimic the entire osteo-cartilaginous unit, is integrated within the bone 12 months postoperatively and comes along with improved patients symptoms and function., Methods: Fourteen patients (male:female = 11:3, mean age ± SD 33.1 ± 10.7 years) treated for OCL (size 1.0-3.5 cm 2 ) were clinically and radiologically evaluated at 1 year postoperatively. The data were prospectively collected including SPECT/CT, Tegner and Lysholm scores. BTU was anatomically localised and volumetrically quantified in SPECT/CT. Defect filling was analysed in CT. Spearman's rho and Wilcoxon test were used for correlation of BTU in SPECT/CT and clinical scores (p < 0.05)., Results: A significant improvement in Lysholm knee score (p < 0.001) and slight deterioration in Tegner score were found (p < 0.01). A complete filling of the defect was shown in 14%, a partial filling in 14% and only minor filling was seen in 72%. A significant correlation (p < 0.001) was found between location of osteochondral lesions and increased BTU. At the lesion sites pre- and postoperative BTU was markedly increased and did not show any decrease at 12-month follow-up. Median Tegner and mean Lysholm scores did not correlate with BTU at any time., Conclusions: Treatment of OCL in the knee joint with a nano-composite multi-layered three-dimensional biomaterial scaffold resulted in a significant clinical improvement at 1-year follow-up. However, osseointegration was still ongoing at 12-month follow-up., Level of Evidence: Case series, Level IV.

The control of the different angiogenic process is an important point in osteochondral regeneration. Angiogenesis is a prerequisite for osteogenesis in vivo; insufficient neovascularization of bone constructs after scaffold implantation resulted in hypoxia and cellular necrosis. Otherwise, angiogenesis must be avoided in chondrogenesis; vascularization of the cartilage contributes to structural damage and pain. Finding a balance between these processes is important to design a successful treatment for osteochondral regeneration. This chapter shows the most important advances in the control of angiogenic process for the treatment of osteochondral diseases focused on the administration of pro- or anti-angiogenic factor and the design of the scaffold.

The size of full-thickness focal cartilage defect is accepted to be predictive of its fate, but at which size threshold treatment is required is unclear. Clarification of the mechanism behind this threshold effect will help determining when treatment is required. The objective was to investigate the effect of defect size on strains in the collagen fibers and the non-fibrillar matrix of surrounding cartilage. These strains may indicate matrix disruption. Tissue deformation into the defect was expected, stretching adjacent superficial collagen fibers, while an osteochondral implant was expected to prevent these deformations. Finite element simulations of cartilage/cartilage contact for intact, 0.5 to 8mm wide defects and 8mm implant cases were performed. Impact, a load increase to 2MPa in 1ms, and creep loading, a constant load of 0.5MPa for 900s, scenarios were simulated. A composition-based material model for articular cartilage was employed. Impact loading caused low strain levels for all models. Creep loading increased deviatoric strains and collagen strains in the surrounding cartilage. Deviatoric strains increased gradually with defect size, but the surface area at which collagen fiber strains exceeded failure thresholds, abruptly increased for small increases of defect size. This was caused by a narrow distribution of collagen fiber strains resulting from the non-linear stiffness of the fibers. We postulate this might be the mechanism behind the existence of a critical defect size. Filling of the defect with an implant reduced deviatoric and collagen fiber strains towards values for intact cartilage., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to determine the probability of structural worsening of knee cartilage and whole joint degeneration over 4-8 years based on cartilage T 2 Z-scores at baseline., Design: Right knees with Kellgren-Lawrence (KL) grades of 0-2 in 587 participants from the Osteoarthritis Initiative were studied. 3T MR images were used to perform baseline cartilage T 2 quantification and assess 4-year changes in cartilage morphology (WORMS scoring) in 5 regions. Changes in joint space narrowing (JSN) and KL were assessed over 8 years. T 2 Z-scores were based on a reference database of knees without morphologic cartilage degeneration at baseline. Odds ratios for, and predicted probabilities of any worsening in WORMS cartilage, JSN and KL grade were obtained from logistic regression models., Results: A one-unit increase in the baseline medial femur T 2 Z-score was associated with cartilage worsening in the same region (OR = 1.59; P < 0.0001) and in any region (OR = 1.37; P < 0.0001), and with worsening JSN (OR = 1.82; P < 0.0001) and KL grades (OR = 1.69; P < 0.0001). Predicted probabilities of worsening in knees with a medial femur T 2 Z-score from 2-4 were 38% for medial femur cartilage WORMS, 70% for any cartilage region, 28% for increasing JSN and 31% for increasing KL grade., Conclusion: Knees with elevated cartilage T 2 (especially in the medial femur and those that are 2 to 4 SDs above the mean reference values) are significantly more likely to have structural worsening over 4 to 8 years. Knowing cartilage T 2 Z-scores may aid in targeting prevention efforts at early stages of osteoarthritis., Level of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1128-1136., (© 2017 International Society for Magnetic Resonance in Medicine.)

The S100 protein family comprises more than 20 members of small calcium binding proteins operating as Ca2 +-activated switches that interact and modulate the activity of a large number of targets. S100A1 and S100B, two members of this family, have been recently associated with the differentiation status of human articular chondrocytes. Both proteins are homogeneously expressed in all cartilage zones, their expression decreases during chondrocyte dedifferentiation, and can be induced under conditions promoting redifferentiation. Although S100 proteins have a broad range of extra- and intracellular roles, functional studies of S100 proteins expressed in chondrocytes have focused on their extracellular roles linked to catabolic processes. The intracellular roles of S100A1 and S100B in chondrocytes remain largely unexplored, yet the few studies addressing their intracellular activity point toward potentially important functions in chondrocyte biology. This review summarizes reported intracellular S100A1 and S100B regulatory functions described in other cell types that could be also involved in the regulation of chondrogenic processes in cartilage. Potential roles of S100A1 and S100B in the TGF-β-SMAD, the cAMP-PKA-CREB, and the PI3K-AKT pathways, Ca2+ homeostasis, cytoskeleton dynamics, the calcineurin-NFAT pathway, interactions with the p53 family, and the Hippo pathway are examined in the context of chondrocyte biology. Based on the plethora of interactions of S100A1 and S100B with different molecular partners playing essential roles in chondrocyte biology, and the staggering complexity and ubiquity of cross-talk among these partners, we hypothesize that these S100 proteins play fundamental roles in the spatial and temporal regulation of chondrogenesis. J. Cell. Physiol. 232: 1979-1987, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Purpose: Lateral epicondylitis is generally considered an extra-articular condition. The role of minor instability in the aetiology of lateral elbow pain has rarely been considered. The aim of this study was to evaluate the correlation of lateral ligamentous laxity with aspects of intra-articular lateral elbow pathology and investigate the role of minor instability in lateral elbow pain., Methods: Thirty-five consecutive patients aged between 20 and 60 years with recalcitrant lateral epicondylitis who had failed conservative therapy and had no previous trauma or overt instability, were included. The presence of three signs of lateral ligamentous patholaxity and five intra-articular findings were documented during arthroscopy. The relative incidence of each of these was calculated, and the correlation between patholaxity and intra-articular pathology was evaluated., Results: At least one sign of lateral ligamentous laxity was observed in 48.6% of the studied cohort, and 85.7% demonstrated at least one intra-articular abnormal finding. Radial head ballottement was the most common sign of patholaxity (42.9%). Synovitis was the most common intra-articular aspect of pathology (77.1%), followed by lateral capitellar chondropathy (40.0%). A significant correlation was found between the presence of lateral ligamentous patholaxity signs and capitellar chondropathy (p = 0.0409), as well as anteromedial synovitis (p = 0.0408)., Conclusions: Almost one half of patients suffering from recalcitrant lateral epicondylitis display signs of lateral ligamentous patholaxity, and over 85% demonstrate at least one intra-articular abnormality. The most frequent intra-articular findings are synovitis and lateral capitellar chondropathy, which correlate significantly with the presence of lateral ligamentous patholaxity. The fact that several patients demonstrated multiple intra-articular findings in relation to laxity provides support to a sequence of pathologic changes that may result from a symptomatic minor instability of the lateral elbow (SMILE) condition., Level of Evidence: III.

Objective: Whether meniscal extrusion and bone marrow lesions (BMLs) are independently associated with the risk of knee osteoarthritis (OA) is unknown., Methods: Data was extracted from the Osteoarthritis Initiative (OAI) cohort. Participants were grouped according to the absence (Kellgren-Lawrence (KL) grade ≤ 1, n = 2120) or presence (KL ≥ 2, n = 2249) of radiographic OA (ROA). Baseline meniscal extrusion and tibial BMLs were assessed. Tibial plateau cartilage volume was assessed at baseline and 72 months, while radiographic disease was assessed at baseline and 48 months. Total knee replacement (TKR) was assessed at 72 months., Results: In those with ROA, the presence of a baseline meniscal extrusion (independent of BMLs) was associated with accelerated cartilage volume loss (medial tibia: -2.1%/annum vs -1.5%; lateral: -2.6%/annum vs -1.6%; both P < 0.001), progressive ROA and TKR (Odds ratio (OR) range 1.4-1.8; 95% CI range 1.1-2.9). The presence of a baseline BML was associated with accelerated cartilage volume loss (medial tibia: -2.1%/annum vs -1.6%; lateral: -1.9%/annum vs -1.6%; P ≤ 0.02), progressive ROA and joint replacement (OR range 1.5-2.4; 95% CI range 1.1-3.4). In those with no ROA, a baseline medial meniscal extrusion was associated with accelerated cartilage volume loss (medial tibia: -2.1%/annum vs -1.2%, P < 0.001), and a baseline medial BML with incident ROA (OR 1.7, 95% CI 1.1 to 2.9)., Conclusions: The presence of baseline meniscal extrusion and BMLs are associated with incident and progressive knee of each other (OA) and represent important structural targets for the treatment and prevention of knee OA., (Copyright © 2017. Published by Elsevier Ltd.)

This study compared patients who failed a cartilage restoration procedure and underwent ipsilateral knee arthroplasty with matched control subjects undergoing knee arthroplasty without prior cartilage restoration. Although patients with a failed cartilage procedure derived benefit from knee arthroplasty, their magnitude of improvement and final outcomes scores were lower than the matched control subjects. In this cohort, the cartilage patients also experienced little to no benefit from cartilage restoration, suggesting that unmeasured shared patient characteristics may play a role. This information can be used to counsel this difficult patient population on expected outcomes following arthroplasty procedures. Further research identifying characteristics of responders to treatment remains critical to refine clinical decision-making for this difficult patient group., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To determine compartment-specific loading patterns during gait, quantified as joint reaction forces (JRF), of individuals with knee articular cartilage defects (ACD) compared to healthy controls (HC)., Methods: Individuals with ACDs and HC participated. Individuals with ACDs were divided into groups according to ACD location: PF (only a patellofemoral ACD), TF (only a tibiofemoral ACD), and MIX (both PF and TF ACDs). Participants underwent three-dimensional gait analysis at self-selected speed. TF joint reaction force (TF-JRF) was calculated using inverse dynamics. PF joint reaction force (PF-JRF) was derived from estimated quadriceps force (F QUAD ) and knee flexion angle. Primary variables of interest were the PF- and TF-JRF peaks (body weight [×BW]). Related secondary variables (gait speed, quadriceps strength, knee function, activity level) were evaluated as covariates., Results: First peak PF-JRF and TF-JRF were similar in the TF and MIX groups (0.75-1.0 ×BW, P = 0.6-0.9). Both peaks were also similar in the PF and HC groups (1.1-1.3 ×BW, P = 0.7-0.8), and higher than the TF and MIX groups (P = 0.004-0.02). For the second peak PF-JRF, only the HC group was higher than the TF group (P = 0.02). The PF group walked at a similar speed as the HC group; both groups walked faster than the TF and MIX groups (P < 0.001). With gait speed and quadriceps strength as covariates, no differences were observed in JRF peaks., Conclusions: The results suggest the presence of a TF ACD (TF and MIX groups), but not a PF ACD (PF group), may affect joint loading patterns during walking. Walking slower may be a protective gait modification to reduce load., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to assess cross-sectional and longitudinal effects of meniscal lesions on adjacent cartilage T 1ρ and T 2 relaxation times, patient-reported outcomes and gait biomechanics., Design: Thirty patients with no cartilage morphological defects reported by Whole Organ MRI Score (WORMS) magnetic resonance imaging (MRI) grading and no radiographic osteoarthritis (OA) (Kellgren--Lawrence (KL) ≤ 1) were selected, 15 with posterior meniscus horn lesions and 15 matched controls without meniscal lesions. All were imaged on a 3T MR scanner for three consecutive years, except those who dropped from the study. Sagittal and frontal plane kinematic gait data were acquired at baseline. The Knee Injury and Osteoarthritis Outcome Score (KOOS) survey was taken each time. All images were automatically segmented and registered to an atlas for voxel-by-voxel cross-sectional and longitudinal analyses., Results: Relaxation time comparisons between groups showed elevated T 1ρ of the lateral tibia (LP) and elevated T 2 of the medial tibia (MT) and LT at 1 and 2 years in the lesion group. Longitudinal comparisons within each group revealed greater relaxation time elevations over one and 2 years in the group with lesions. KOOS Quality of Life (QOL) was significantly different between the groups at all time points (P < 0.05), as were other KOOS subcategories. No significant differences in the frontal or sagittal biomechanics were observed between the groups at baseline., Conclusions: Individuals with healthy cartilage and posterior meniscal horn lesions have increased relaxation times when compared to matched controls, increased relaxation time changes over 2 years, and consistently report a lower KOOS QOL, yet show no difference in gait biomechanics., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)