Lower cell number, lateral defect location and milder grade are associated with improved autologous chondrocyte implantation outcome.

PURPOSE: To investigate patient demographic, injury and surgery/treatment-associated factors that can influence the patient-reported outcome (Lysholm score), following autologous chondrocyte implantation (ACI) in a large, 'real-world', nonuniform, prospective data examined retrospectively. METHODS: Knee patients treated at the Robert Jones and Agnes Hunt Orthopaedic Hospital, UK, using ACI between 1996 and 2020 were eligible. All longitudinal postoperative Lysholm scores collected between 1 and 23 years after ACI treatment and before any second major procedure (e.g., arthroplasty) were included. Multilevel longitudinal models were built investigating the association of short-term (1 year) or long-term trends in Lysholm score with baseline demographic, clinical and cell-culture variables, namely age, gender, smoker status, body mass index, baseline Lysholm score, time from surgery, defect grade, diameter and location, number of defects, previous microfracture, patch/scaffold type, associated procedure(s), number of cells implanted and their passage number. RESULTS: Following filtering, 306 of the 427 knee ACI procedures reviewed were suitable for inclusion. Factors shown to result in higher postoperative Lysholm scores in the short term were lower patient age, higher baseline Lysholm scores, fewer implanted cells and a lateral femoral defect location. The factor which was associated with higher long-term postoperative Lysholm scores was a milder defect grade. Additionally, the failure rate in this cohort was explored and it was found that 73/306 (24%) of patients experienced joint failure according to our definition. Furthermore, the outcome was not influenced by coincidental procedures in this cohort of patients. CONCLUSIONS: This study has identified a number of baseline factors associated with patient-reported outcomes following ACI and shows that treatment of associated pathology at the time of surgery potentially restores patient outcomes to a similar level as those with no associated pathologies. LEVEL OF EVIDENCE: Level IV.

Patient-Specific Distal Femoral Guides Optimize Cartilage Topography Matching in Osteochondral Allograft Transplantations.

BACKGROUND: Osteochondral allograft (OCA) transplantation is an important surgical technique for full-thickness chondral defects in the knee. For patients undergoing this procedure, topography matching between the donor and recipient sites is essential to limit premature wear of the OCA. Currently, there is no standardized process of donor and recipient graft matching. PURPOSE: To evaluate a novel topography matching technique for distal femoral condyle OCA transplantation using 3-dimensional (3D) laser scanning to create 3D-printed patient-specific instrumentation in a human cadaveric model. STUDY DESIGN: Descriptive laboratory study. METHODS: Human cadaveric distal femoral condyles (n = 12) underwent 3D laser scanning. An 18-mm circular osteochondral recipient defect was virtually created on the medial femoral condyle (MFC), and the position and orientation of the best topography-matched osteochondral graft from a paired donor lateral femoral condyle (LFC) were determined using an in silico analysis algorithm minimizing articular step-off distances between the edges of the graft and recipient defect. Distances between the entire surface of the OCA graft and the underneath surface of the MFC were evaluated as surface mismatch. Donor (LFC) and recipient (MFC) 3D-printed patient-specific guides were created based on 3D reconstructions of the scanned condyles. Through use of the guides, OCAs were harvested from the LFC and transplanted to the reamed recipient defect site (MFC). The post-OCA recipient condyles were laser scanned. The 360° articular step-off and cartilage topography mismatch were measured. RESULTS: The mean cartilage step-off and graft surface mismatch for the in silico OCA transplant were 0.073 ± 0.029 mm (range, 0.005-0.113 mm) and 0.166 ± 0.039 mm (range, 0.120-0.243 mm), respectively. Comparatively, the cadaveric specimens postimplant had significantly larger step-off differences (0.173 ± 0.085 mm; range, 0.082-0.399 mm; P = .001) but equivalent graft surface topography matching (0.181 ± 0.080 mm; range, 0.087-0.396 mm; P = .678). All 12 OCA transplants had mean circumferential step-off differences less than a clinically significant cutoff of 0.5 mm. CONCLUSION: These findings suggest that the use of 3D-printed patient-specific guides for OCA transplantation has the ability to reliably optimize cartilage topography matching for LFC to MFC transplantation. This study demonstrated substantially lower step-off values compared with previous orthopaedic literature when also evaluating LFC to MFC transplantation. Using this novel technique in a model performing MFC to MFC transplantation has the potential to yield further enhanced results due to improved radii of curvature matching. CLINICAL RELEVANCE: Topography-matched graft implantation for focal chondral defects of the knee in patients improves surface matching and has the potential to improve long-term outcomes. Efficient selection of the allograft also allows improved availability of the limited allograft sources.

Effects of different combinations of mechanical loading intensity, duration, and frequency on the articular cartilage in mice.

BACKGROUND: Understanding how healthy articular cartilage responds to mechanical loading is critical. Moderate mechanical loading has positive effects on the cartilage, such as maintaining cartilage homeostasis. The degree of mechanical loading is determined by a combination of intensity, frequency, and duration; however, the best combination of these parameters for knee cartilage remains unclear. This study aimed to determine which combination of intensity, frequency, and duration provides the best mechanical loading on healthy knee articular cartilage in vitro and in vivo. METHODS AND RESULTS: In this study, 33 male mice were used. Chondrocytes isolated from mouse knee joints were subjected to different cyclic tensile strains (CTSs) and assessed by measuring the expression of cartilage matrix-related genes. Furthermore, the histological characteristics of mouse tibial cartilages were quantified using different treadmill exercises. Chondrocytes and mice were divided into the control group and eight intervention groups: high-intensity, high-frequency, and long-duration; high-intensity, high-frequency, and short-duration; high-intensity, low-frequency, and long-duration; high-intensity, low-frequency, and short-duration; low-intensity, high-frequency, and long-duration; low-intensity, high-frequency, and short-duration; low-intensity, low-frequency, and long-duration; low-intensity, low-frequency, and short-duration. In low-intensity CTSs, chondrocytes showed anabolic responses by altering the mRNA expression of COL2A1 in short durations and SOX9 in long durations. Furthermore, low-intensity, low-frequency, and long-duration treadmill exercises minimized chondrocyte hypertrophy and enhanced aggrecan synthesis in tibial cartilages. CONCLUSION: Low-intensity, low-frequency, and long-duration mechanical loading is the best combination for healthy knee cartilage to maintain homeostasis and activate anabolic responses. Our findings provide a significant scientific basis for exercise and lifestyle instructions.

Sensitivity of knee cartilage biomechanics in finite element analysis to selected Musculoskeletal models.

Knee joint kinematics and kinetics analyzed by musculoskeletal (MS) modeling are often utilized in finite element (FE) models, estimating tissue-level mechanical responses. We compared knee cartilage stresses, strains, and centers of pressure of FE models driven by two widely used MS models, implemented in AnyBody and OpenSim. Minor discrepancies in the results were observed between the models. AnyBody-driven FE models showed slightly higher stresses in the medial tibial cartilage, while OpenSim-driven FE models estimated more anterior and lateral center of pressure. Recognizing these differences in the MS-FE models is important to ensure reliable analysis of cartilage mechanics and failure and simulation of rehabilitation.

Tibial and femoral articular cartilage exhibit opposite outcomes for T1ρ and T2* relaxation times in response to acute compressive loading in healthy knees.

Abnormal loading is thought to play a key role in the disease progression of cartilage, but our understanding of how cartilage compositional measurements respond to acute compressive loading in-vivo is limited. Ten healthy subjects were scanned at two timepoints (7 ± 3 days apart) with a 3 T magnetic resonance imaging (MRI) scanner. Scanning sessions included T1ρ and T2* acquisitions of each knee in two conditions: unloaded (traditional MRI setup) and loaded in compression at 40 % bodyweight as applied by an MRI-compatible loading device. T1ρ and T2* parameters were quantified for contacting cartilage (tibial and femoral) and non-contacting cartilage (posterior femoral condyle) regions. Significant effects of load were found in contacting regions for both T1ρ and T2*. The effect of load (loaded minus unloaded) in femoral contacting regions ranged from 4.1 to 6.9 ms for T1ρ, and 3.5 to 13.7 ms for T2*, whereas tibial contacting regions ranged from -5.6 to -1.7 ms for T1ρ, and -2.1 to 0.7 ms for T2*. Notably, the responses to load in the femoral and tibial cartilage revealed opposite effects. No significant differences were found in response to load between the two visits. This is the first study that analyzed the effects of acute loading on T1ρ and T2* measurements in human femoral and tibial cartilage separately. The results suggest the effect of acute compressive loading on T1ρ and T2* was: 1) opposite in the femoral and tibial cartilage; 2) larger in contacting regions than in non-contacting regions of the femoral cartilage; and 3) not different visit-to-visit.

Dense Multi-Scale Graph Convolutional Network for Knee Joint Cartilage Segmentation.

In this paper, we propose a dense multi-scale adaptive graph convolutional network (DMA-GCN) method for automatic segmentation of the knee joint cartilage from MR images. Under the multi-atlas setting, the suggested approach exhibits several novelties, as described in the following. First, our models integrate both local-level and global-level learning simultaneously. The local learning task aggregates spatial contextual information from aligned spatial neighborhoods of nodes, at multiple scales, while global learning explores pairwise affinities between nodes, located globally at different positions in the image. We propose two different structures of building models, whereby the local and global convolutional units are combined by following an alternating or a sequential manner. Secondly, based on the previous models, we develop the DMA-GCN network, by utilizing a densely connected architecture with residual skip connections. This is a deeper GCN structure, expanded over different block layers, thus being capable of providing more expressive node feature representations. Third, all units pertaining to the overall network are equipped with their individual adaptive graph learning mechanism, which allows the graph structures to be automatically learned during training. The proposed cartilage segmentation method is evaluated on the entire publicly available Osteoarthritis Initiative (OAI) cohort. To this end, we have devised a thorough experimental setup, with the goal of investigating the effect of several factors of our approach on the classification rates. Furthermore, we present exhaustive comparative results, considering traditional existing methods, six deep learning segmentation methods, and seven graph-based convolution methods, including the currently most representative models from this field. The obtained results demonstrate that the DMA-GCN outperforms all competing methods across all evaluation measures, providing DSC=95.71% and DSC=94.02% for the segmentation of femoral and tibial cartilage, respectively.

The Statistical Fragility of Marrow Stimulation for Cartilage Defects of the Knee: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: Marrow stimulation is used to address knee cartilage defects. In this study, we used the fragility index (FI), reverse fragility index (rFI), and fragility quotient (FQ) to evaluate statistical fragility of outcomes reported in randomized controlled trials (RCTs) evaluating marrow stimulation. DESIGN: PubMed, Embase, and MEDLINE were queried for recent RCTs (January 1, 2010-September 5, 2023) assessing marrow stimulation for cartilage defects of the knee. The FI and rFI were calculated as the number of outcome event reversals required to alter statistical significance for significant and nonsignificant outcomes, respectively. The FQ was determined by dividing the FI by the study sample size. RESULTS: Across 155 total outcomes from 21 RCTs, the median FI was 3 (interquartile range [IQR], 2-5), with an associated median FQ of 0.067 (IQR, 0.033-0.010). Thirty-two outcomes were statistically significant, with a median FI of 2 (IQR, 1-3.25) and FQ of 0.050 (IQR, 0.025-0.069). Ten of the 32 (31.3%) outcomes reported as statistically significant had an FI of 1. In total, 123 outcomes were nonsignificant, with a median rFI of 3 (IQR, 2-5). Studies assessing stem cell augments were the most fragile, with a median FI of 2. In 55.5% of outcomes, the number of patients lost to follow-up was greater than or equal to the FI. CONCLUSION: Statistical findings in RCTs evaluating marrow stimulation for cartilage defects of the knee are statistically fragile. We recommend combined reporting of P-values with FI and FQ metrics to aid in the interpretation of clinical findings in comparative trials assessing cartilage restoration.

Cartilage regeneration is related to superior mid-term patient-reported outcomes after open-wedge high tibial osteotomy.

PURPOSE: Medial open-wedge high tibial osteotomy (OWHTO) is related to cartilage improvement in the medial compartment. This study aimed to evaluate factors associated with cartilage improvement and patient-reported outcomes (PRO) after OWHTO. It was hypothesised that cartilage improvement is associated with favourable PRO. METHODS: This retrospective study included 94 patients who underwent OWHTO. The mean follow-up period was 5 years. The weight-bearing line ratio (WBLR) was defined as the ratio of the distance from the medial tibial edge to the tibial insertion of the weight-bearing line and the tibial width. The International Cartilage Research Society grade evaluated the medial femoral condyle (MFC) and medial tibial plateau (MTP) at initial and second-look arthroscopy, and cartilage improvement after OWHTO was assessed. Postoperative knee injury and osteoarthritis outcome scores (KOOS) were compared between the groups with improved and non-improved cartilage. Additionally, factors related to cartilage improvement and postoperative KOOS scores were analysed. RESULTS: Regarding the MFC, KOOS pain, symptoms, activities of daily living (ADL) and quality of life (QOL) were significantly higher in the cartilage-improved group than in the non-improved group (p = 0.012, 0.003, 0.001, 0.006), and cartilage improvement was significantly related to KOOS pain, ADL and QOL (p = 0.021, 0.039, 0.013). In addition, the postoperative WBLR was associated with cartilage improvement, with a cutoff value of 54.0% (p = 0.046). Regarding the MTP, KOOS ADL and QOL (p = 0.026, 0.022) were significantly higher in the cartilage-improved group than in the nonimproved group. Body mass index (BMI) was significantly related to the postoperative QOL (p = 0.018) and associated with cartilage improvement, with a cutoff value of 25.9 kg/m2 (p = 0.002). CONCLUSION: A postoperative WBLR greater than 54.0% and a preoperative BMI below 25.9 kg/m2 were associated with cartilage improvement, positively impacting PRO after OWHTO. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Changes in tissue sodium concentration and sodium relaxation times during the maturation of human knee cartilage: Ex vivo 23 Na MRI study at 10.5 T.

PURPOSE: To evaluate the influence of skeletal maturation on sodium (23 Na) MRI relaxation parameters and the accuracy of tissue sodium concentration (TSC) quantification in human knee cartilage. METHODS: Twelve pediatric knee specimens were imaged with whole-body 10.5 T MRI using a density-adapted 3D radial projection sequence to evaluate 23 Na parameters: B1 + , T1 , biexponential T 2 * $$ {\mathrm{T}}_2^{\ast } $$ , and TSC. Water, collagen, and sulfated glycosaminoglycan (sGAG) content were calculated from osteochondral biopsies. The TSC was corrected for B1 + , relaxation, and water content. The literature-based TSC (TSCLB ) used previously published values for corrections, whereas the specimen-specific TSC (TSCSP ) used measurements from individual specimens. 23 Na parameters were evaluated in eight cartilage compartments segmented on proton images. Associations between 23 Na parameters, TSCLB - TSCSP difference, biochemical content, and age were determined. RESULTS: From birth to 12 years, cartilage water content decreased by 18%; collagen increased by 59%; and sGAG decreased by 36% (all R2 ≥ 0.557). The short T 2 * $$ {\mathrm{T}}_2^{\ast } $$ ( T 2 * S $$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ ) decreased by 72%, and the signal fraction relaxing with T 2 * S $$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ ( fT 2 * S $$ {{\mathrm{fT}}_2^{\ast}}_{\mathrm{S}} $$ ) increased by 55% during the first 5 years but remained relatively stable after that. TSCSP was significantly correlated with sGAG content from biopsies (R2 = 0.739). Depending on age, TSCLB showed higher or lower values than TSCSP . The TSCLB - TSCSP difference was significantly correlated with T 2 * S $$ {{\mathrm{T}}_2^{\ast}}_{\mathrm{S}} $$ (R2 = 0.850), fT 2 * S $$ {{\mathrm{fT}}_2^{\ast}}_{\mathrm{S}} $$ (R2 = 0.651), and water content (R2 = 0.738). CONCLUSION: TSC and relaxation parameters measured with 23 Na MRI provide noninvasive information about changes in sGAG content and collagen matrix during cartilage maturation. Cartilage TSC quantification assuming fixed relaxation may be feasible in children older than 5 years.

A New Zn(II) Compound: Luminescent Property and Promoting Knee Cartilage Repair by Modulating Iron Death.

The hydrothermal reactions of bis{6-{5-methyl-1 H,7 H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one}}methane (L) and Zn(NO3)2·6H2O at 180 ℃ afforded a novel Zn(II) coordination polymer (CP), that is, {[Zn2(L)(µ2-O)2]·3H2O}n (1), which further characterized via Single crystal X-ray diffraction (SCXRD), elemental analysis (EA), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA). Besides, this CP reveals strong luminescence that may be caused by the charge transfer within the ligand. In biological study, the new compound was evaluated for its protective effect on chondrocytes. This compound significantly up-regulated GPX4 and down-regulated HO-1 mRNA levels, thereby inhibiting iron death in chondrocytes.

Repeatability of Quantitative Knee Cartilage T1 , T2 , and T1ρ Mapping With 3D-MRI Fingerprinting.

BACKGROUND: Three-dimensional MR fingerprinting (3D-MRF) techniques have been recently described for simultaneous multiparametric mapping of knee cartilage. However, investigation of repeatability remains limited. PURPOSE: To assess the intra-day and inter-day repeatabilities of knee cartilage T1 , T2 , and T1ρ maps using a 3D-MRF sequence for simultaneous measurement. STUDY TYPE: Prospective. SUBJECTS: Fourteen healthy subjects (35.4 ± 9.3 years, eight males), scanned on Day 1 and Day 7. FIELD STRENGTH/SEQUENCE: 3 T/3D-MRF, T1 , T2 , and T1ρ maps. ASSESSMENT: The acquisition of 3D-MRF cartilage (simultaneous acquisition of T1 , T2 , and T1ρ maps) were acquired using a dictionary pattern-matching approach. Conventional cartilage T1 , T2 , and T1ρ maps were acquired using variable flip angles and a modified 3D-Turbo-Flash sequence with different echo and spin-lock times, respectively, and were fitted using mono-exponential models. Each sequence was acquired on Day 1 and Day 7 with two scans on each day. STATISTICAL TESTS: The mean and SD for cartilage T1 , T2 , and T1ρ were calculated in five manually segmented regions of interest (ROIs), including lateral femur, lateral tibia, medial femur, medial tibia, and patella cartilages. Intra-subject and inter-subject repeatabilities were assessed using coefficient of variation (CV) and intra-class correlation coefficient (ICC), respectively, on the same day and among different days. Regression and Bland-Altman analysis were performed to compare maps between the conventional and 3D-MRF sequences. RESULTS: The CV in all ROIs was lower than 7.4%, 8.4%, and 7.5% and the ICC was higher than 0.56, 0.51, and 0.52 for cartilage T1 , T2 , and T1ρ , respectively. The MRF results had a good agreement with the conventional methods with a linear regression slope >0.61 and R2 > 0.59. CONCLUSION: The 3D-MRF sequence had high intra-subject and inter-subject repeatabilities for simultaneously measuring knee cartilage T1 , T2 , and T1ρ with good agreement with conventional sequences. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

A systematic review demonstrating correlation of MRI compositional parameters with clinical outcomes following articular cartilage repair interventions in the knee.

Objective: Compositional-MRI parameters enable the assessment of cartilage ultrastructure. Correlation of these parameters with clinical outcomes is unclear. This systematic review investigated the correlation of various compositional- MRI parameters with clinical outcome measures following cartilage repair or regeneration interventions in the knee. Design: This study was registered with PROSPERO and reported in accordance with PRISMA. PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials, and Embase databases were searched. All studies, regardless of type, that presented correlation of compositional- MRI parameters with clinical outcome measures were included. Two researchers independently performed data extraction and QUADAS-2 analysis. Compositional-MRI parameter change following intervention and correlation with clinical outcome measures were evaluated. Results: 19 studies were included. Risk of bias was generally low. 5 different compositional parameters were observed from the included studies. However, due to the significant variability in the reporting of compositional-MRI parameters across studies, meta-analyses were possible only for T2 values and T2 index values (T2 value of repair cartilage relative to normal cartilage). Correlation of T2 values of repair cartilage with clinical outcome score was r â€‹= â€‹0.33 [0.15, 0.52]. Correlation of T2 index with clinical outcome score was r â€‹= â€‹0.52 [0.32, 0.77]. Conclusions: Correlation between T2 values and clinical outcome scores following knee cartilage repair were found. The heterogeneity of the correlations extracted from the included studies limited the scope for the meta-analysis. Thus, standardised, high-quality studies are required for better assessment of correlation between compositional MRI parameters and clinical outcome measures after cartilage repair. Registration number: PROSPERO CRD42021287364.Study protocol available on PROSPERO website.

The biomechanical and functional outcomes of autologous chondrocyte implantation for articular cartilage defects of the knee: A systematic review.

PURPOSE: Autologous chondrocyte implantation (ACI) is primarily performed in active, young patients to treat knee pain and functional limitations resulting from articular cartilage injury. Nevertheless, the functional outcomes of ACI remain poorly understood. This systematic review aimed to evaluate the biomechanical and functional outcomes of ACI. METHODS: Ovid MEDLINE, Embase, and Web of Science were systematically searched using the terms 'Knee OR Knee joint AND Autologous chondrocyte implantation OR ACI'. Inclusion and exclusion criteria were used to screen publications by title, abstract, and full text. Study quality and bias were assessed by two reviewers. Means and standard deviations of all collected variables were calculated and presented in the review. PROSPERO ID: CRD42021238768. RESULTS: Nineteen articles including 20 ACI cohorts were included. In general, the average range of motion (ROM) improved with clinical (>5°) and statistical significance (p < 0.05) postoperatively: 130.5 ± 14.8° to 136.1 ± 10.2°. Knee strength significantly improved within the first two postoperative years but remained poorer than control groups at final follow-up. No statistical differences were found between ACI and control groups in their ability to perform functional activities like the 6-minute walk test. CONCLUSION: Knee range of motion generally improved following ACI. Although, some studies reported that knee strengths remained significantly poorer than healthy controls, particularly >2-years postoperatively, implying that longer-term strength training may benefit patients.However, the volume of research and current level of evidence remain low, thus further research is required to better understand the impact of ACI on knee function and guide future rehabilitative protocols.

MicroRNA Signatures in Cartilage Ageing and Osteoarthritis.

Osteoarthritis is the most common degenerative joint disorder. MicroRNAs are gene expression regulators that act post-transcriptionally to control tissue homeostasis. Microarray analysis was undertaken in osteoarthritic intact, lesioned and young intact cartilage. Principal component analysis showed that young intact cartilage samples were clustered together; osteoarthritic samples had a wider distribution; and osteoarthritic intact samples were separated into two subgroups, osteoarthritic-Intact-1 and osteoarthritic-Intact-2. We identified 318 differentially expressed microRNAs between young intact and osteoarthritic lesioned cartilage, 477 between young intact and osteoarthritic-Intact-1 cartilage and 332 between young intact and osteoarthritic-Intact-2 cartilage samples. For a selected list of differentially expressed microRNAs, results were verified in additional cartilage samples using qPCR. Of the validated DE microRNAs, four-miR-107, miR-143-3p, miR-361-5p and miR-379-5p-were selected for further experiments in human primary chondrocytes treated with IL-1ß. Expression of these microRNAs decreased in human primary chondrocytes treated with IL-1ß. For miR-107 and miR-143-3p, gain- and loss-of-function approaches were undertaken and associated target genes and molecular pathways were investigated using qPCR and mass spectrometry proteomics. Analyses showed that WNT4 and IHH, predicted targets of miR-107, had increased expression in osteoarthritic cartilage compared to young intact cartilage and in primary chondrocytes treated with miR-107 inhibitor, and decreased expression in primary chondrocytes treated with miR-107 mimic, suggesting a role of miR-107 in chondrocyte survival and proliferation. In addition, we identified an association between miR-143-3p and EIF2 signalling and cell survival. Our work supports the role of miR-107 and miR-143-3p in important chondrocyte mechanisms regulating proliferation, hypertrophy and protein translation.

Multi-frame biomechanical and relaxometry analysis during in vivo loading of the human knee by spiral dualMRI and compressed sensing.

PURPOSE: Knee cartilage experiences repetitive loading during physical activities, which is altered during the pathogenesis of diseases like osteoarthritis. Analyzing the biomechanics during motion provides a clear understanding of the dynamics of cartilage deformation and may establish essential imaging biomarkers of early-stage disease. However, in vivo biomechanical analysis of cartilage during rapid motion is not well established. METHODS: We used spiral displacement encoding with stimulated echoes (DENSE) MRI on in vivo human tibiofemoral cartilage during cyclic varus loading (0.5 Hz) and used compressed sensing on the k-space data. The applied compressive load was set for each participant at 0.5 times body weight on the medial condyle. Relaxometry methods were measured on the cartilage before (T1ρ , T2 ) and after (T1ρ ) varus load. RESULTS: Displacement and strain maps showed a gradual shift of displacement and strain in time. Compressive strain was observed in the medial condyle cartilage and shear strain was roughly half of the compressive strain. Male participants had more displacement in the loading direction compared to females, and T1ρ values did not change after cyclic varus load. Compressed sensing reduced the scanning time up to 25% to 40% when comparing the displacement maps and substantially lowered the noise levels. CONCLUSION: These results demonstrated the ease of which spiral DENSE MRI could be applied to clinical studies because of the shortened imaging time, while quantifying realistic cartilage deformations that occur through daily activities and that could serve as biomarkers of early osteoarthritis.

Intraoperative Acoustic Evaluation of Living Human Knee Cartilage-Comparison with Respect to Cartilage Degeneration and Aging.

OBJECTIVE: The objective of the study was to evaluate the mechanical properties of living human knee cartilage using our ultrasonic device, and to compare the measurements with respect to cartilage degeneration and aging. DESIGN: A total of 95 knees which had undergone arthroscopic knee surgery, from 88 patients, were included in the study, with informed consent. All procedures were reviewed and approved by the ethical committee of our hospital. In the study group, there were 41 men, 47 women, 39 right knees, and 56 left knees. The conditions primarily included knee osteoarthritis and anterior cruciate ligament rupture. The mean operative age was 44.1 years old (range = 10-83). We compared mechanical properties of the knee cartilage with respect to aging and gender, in comparison with normal cartilage. A P value of <0.05 represented statistical significance. RESULTS: In the context of the International Cartilage Repair Society (ICRS) classification of cartilage degeneration (grade 0-3), the signal intensity in grade 0 was significantly larger than that in grade 1, 2, or 3. The thickness in grade 0 was significantly higher than that in grade 1, 2, or 3. Normal cartilage in older women had the lowest signal intensity and the least cartilage thickness among all the groups. CONCLUSION: The ultrasonic system we developed was able to detect early degenerative changes in living cartilage in knees. The lowest signal intensity and least cartilage thickness in normal cartilage among older women were correlated to a large prevalence of knee osteoarthritis in women. LEVEL OF EVIDENCE: Level IV, case series.

Clinical Efficacy of Intra-Articular Injection with P-PRP Versus that of L-PRP in Treating Knee Cartilage Lesion: A Randomized Controlled Trial.

OBJECTIVE: Platelet-rich plasma（PRP), with different concentration of leukocytes, may lead to varying effects in the treatment of cartilage lesions. So far, current research has not shown enough evidence on this. To evaluate the clinical efficacy and safety of intra-articular injection with pure platelet-rich plasma (P-PRP) versus those of leukocyte platelet-rich plasma (L-PRP) in treating knee cartilage lesions, we conducted a double-blind, randomized controlled clinical trial with a larger sample and longer follow-up period. METHODS: From October 2019 to October 2020, 95 patients were invited to participate in our study, and 60 (63.2%) were randomized to P-PRP (n = 30) or L-PRP (n = 30) groups. Patients from the two groups were treated with knee intra-articular injections of P-PRP or L-PRP. Visual analog scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were assessed using an unpaired t-test for independent samples preoperatively and at 6 weeks, 12 weeks, 6 months, and 12 months after intervention. RESULTS: We followed up 27 cases in the P-PRP group and 26 cases in the L-PRP group. No significant differences in VAS and WOMAC scores were found between the two groups before the intervention (p > 0.05). The WOMAC Pain and VAS-Motions scores of the P-PRP group were significantly lower than those of the L-PRP group at 6 weeks after the intervention (p < 0.05). While the long-term clinical efficacy of both injections was similar and weakened after 12 months, more adverse events were found in the L-PRP group. CONCLUSIONS: The short-term results demonstrate a positive effect in reducing pain and improving function in patients with knee cartilage lesions in the two groups. While the P-PRP injection showed better clinical efficacy in the early phase of postoperative rehabilitation and resulted in fewer adverse events, long-term follow-up showed similar and weakened efficacy after 12 months. TRIAL REGISTRATION: ChiCTR1900026365. Registered on October 3, 2019, http://www.chictr.org.cn/showproj.aspx?proj=43911.

A numerical model for fibril remodeling in articular cartilage.

BACKGROUND: Collagen fibrils of articular cartilage have a distinct organization in mature human knee joints. It seems that a mechanobiological process drives the remodeling of newborn collagen fibrils with maturation. Therefore, the goal of the present study was to develop a collagen fibril remodeling algorithm that describes the unique collagen fibril organization in a 3D knee model. METHOD: A fibril-reinforced, biphasic cartilage model was used with a cuboid and a 3D human knee joint geometries. An isotropic collagen fibril distribution was assigned to the cartilage at the start of the analysis. Each fibril was rotated towards the direction that resulted in a maximum stretch at each time increment of the loading cycle. RESULTS: The resulting pattern for the collagen fibrils was compared with split line patterns of porcine knee joint cartilage and also data published in the literature. Fibrils on the articular surface had a radial pattern towards the geometrical centroid of the tibial and femoral cartilage. In the tibiofemoral contact regions of superficial zone, fibrils were oriented circumferentially and randomly. In the porcine samples, the split-line patterns were similar to those obtained theoretically. Depth-wise organization of fibril network was characterized by fibrils perpendicular to the subchondral bone in the deeper layers, and fibrils parallel to the surface of cartilage in the superficial zone. CONCLUSIONS: The maximum stretch criterion, coupled with a biphasic constitutive model, successfully predicted the collagen fibril organization observed in the articular cartilage throughout the depth and on the articular surface.

Analysis of Knee Joint Stress During Drop Jump Landing in Females with Generalised Joint Hypermobility / 医用生物力学

Objective To analyze the differences of von Mises stress distribution in knee cartilage and meniscus in female with generalised joint hypermobility (GJH) and healthy female during drop jump landing. Methods The kinematic and ground reaction force (GRF) characteristics of knee joint in female with GJH and healthy female at the moment of peak vertical GRF (VGRF) during loading phase of drop jump landing were collected. The knee joint reaction force was calculated via inverse dynamics, and the combined force of knee joint along long axis of the femur was applied as the load. Based on three-dimensional (3D) finite element model of a female knee joint, numerical simulations were performed separately during drop jump landing of subjects in two groups, and von Mises stresses and stress distribution of knee cartilage and meniscus were calculated. Results At the moment of peak VGRF during drop jump landing, knee flexion and valgus angles in GJH group and control group showed a statistical significance (P<0. 05). Compared with control group, knee flexion angle decreased and valgus angle increased in GJH group. During drop jump landing, GJH group bore larger stress inside the knee joint, and stress distribution in weight-bearing areas of the medial and lateral tibiofemoral compartments was uneven, while the lateral femoral cartilage lateral condyle, the anterior and middle lateral of lateral tibial cartilage, the anterior angle and body lateral margin of lateral meniscus were stress concentration sites. Conclusions For females with GJH, the stability of knee joint decreases and force lines change in jumping events, due to the increased range of motion of knee joint and relaxation of joint capsule, which increases the risk of cartilage and meniscal injury in lateral knee joint. During jumping sports, females with GJH should especially prevent knee joint injury caused by altered force lines in frontal plane of knee joint.

Toward New Assessment of Knee Cartilage Degeneration.

OBJECTIVE: Assessment of human joint cartilage is a crucial tool to detect and diagnose pathological conditions. This exploratory study developed a workflow for 3D modeling of cartilage and bone based on multimodal imaging. New evaluation metrics were created and, a unique set of data was gathered from healthy controls and patients with clinically evaluated degeneration or trauma. DESIGN: We present a novel methodology to evaluate knee bone and cartilage based on features extracted from magnetic resonance imaging (MRI) and computed tomography (CT) data. We developed patient specific 3D models of the tibial, femoral, and patellar bones and cartilages. Forty-seven subjects with a history of degenerative disease, traumatic events, or no symptoms or trauma (control group) were recruited in this study. Ninety-six different measurements were extracted from each knee, 78 2D and 18 3D measurements. We compare the sensitivity of different metrics to classify the cartilage condition and evaluate degeneration. RESULTS: Selected features extracted show significant difference between the 3 groups. We created a cumulative index of bone properties that demonstrated the importance of bone condition to assess cartilage quality, obtaining the greatest sensitivity on femur within medial and femoropatellar compartments. We were able to classify degeneration with a maximum recall value of 95.9 where feature importance analysis showed a significant contribution of the 3D parameters. CONCLUSION: The present work demonstrates the potential for improving sensitivity in cartilage assessment. Indeed, current trends in cartilage research point toward improving treatments and therefore our contribution is a first step toward sensitive and personalized evaluation of cartilage condition.