Knee Cartilage Research Articles

Second generation multiple channeling using platelet-rich plasma enhances cartilage repair through recruitment of endogenous MSCs in bone marrow.

In the treatment of cartilage defects, a key factor is the adequate and specific recruitment of endogenous stem cells to the site of injury. However, the limited quantity and capability of endogenous bone marrow stem cells (BM MSCs) often result in the formation of fibrocartilage when using bone marrow stimulation (BMS) procedures. We engineered second-generation platelet-rich plasma (2G PRP) with defibrinogenating and antifibrinolytic agents for injection into the condyle of the right femur, followed by multiple channeling (MCh) 5 days later. This approach aims to enhance repair by promoting the local proliferation and migration of BM MSCs to the full-thickness knee cartilage defect (ftKD). In our in vitro study, 2G PRP increased the number of endogenous BM MSCs and their ability to migrate toward an IL-1β-induced inflammatory condition. This significance was further confirmed by in vivo proliferation results after injection of 2G PRP into the condyle of rats. Fifty-four healthy male Sprague-Dawley rats were divided into 3 groups (ftKD, MCh, 2G MCh) for 3 time points (2 weeks, 4 weeks, 8 weeks). The 2G MCh (2G PRP injection + MCh) groups significantly improved cartilage formation at 4 and 8 weeks compared to the ftKD and MCh groups. The 2G MCh initiated cartilage repair earlier than MCh and significantly enhanced up to 8 weeks. This study demonstrated that 2G PRP increased the number of BM MSCs through the enhancement of proliferation and recruitment into the injured site, thereby improving articular cartilage repair.

Effect of patient specificity on predicting knee cartilage degeneration in obese adults: Musculoskeletal finite-element modeling of data from the CAROT trial.

Obesity is a known risk factor for development of osteoarthritis (OA). Numerical tools like finite-element (FE) models combined with degenerative algorithms have been developed to understand the interplay between OA and obesity. Inthisstudy,we aimed to predict knee cartilage degeneration in a cohort of obese adults to investigate the importance of patient-specific information on degeneration predictions. We used a validated FE modeling approach and three different age-dependent functions (step-wise, exponential, and linear) to simulate cartilage degradation under overloading in the knee joint. Gait motion analysis and magnetic resonance imaging data from 115 obese individuals with knee OA were used for musculoskeletal and FE modeling. Cartilage degeneration predictions were contrasted with Kellgren-Lawrence (KL)and Boston-Leeds Osteoarthritis Knee Score (BLOKS) grades. The findings show that overall, the similarities between numerical predictions and clinical measures were better for the medial (average area under the curve(AUC) = 0.62) compared to the lateral compartment (average AUC = 0.52) of the knee. Classification results for KL grades, full patient-specific models and patient-specific geometry with generic gait data showed higher AUC values (AUC = 0.71 and AUC = 0.68, respectively) compared to generic geometry and patient-specific gait (AUC = 0.48). For BLOKS grades, AUC values for both full patient-specific models and for patient-specific geometry with generic gait locomotion were higher (AUC = 0.66 and AUC = 0.64, respectively) compared to when the generic geometry and patient-specific gait were used (AUC = 0.53). In summary, our study highlights the importance of considering individual information in knee OA prediction. Nevertheless, our findings suggest that personalized gait play a smaller role in the OA prediction and classification capacity than personalized joint geometry.

Improving Accuracy and Reproducibility of Cartilage T2 Mapping in the OAI Dataset Through Extended Phase Graph Modeling.

The Osteoarthritis Initiative (OAI) collected extensive imaging data, including Multi-Echo Spin-Echo (MESE) sequences for measuring knee cartilage T2 relaxation times. Mono-exponential models are used in the OAI for T2 fitting, which neglects stimulated echoes and B1 inhomogeneities. Extended Phase Graph (EPG) modeling addresses these limitations but has not been applied to the OAI dataset. To assess how different fitting methods, including EPG-based and exponential-based approaches, affect the accuracy and reproducibility of cartilage T2 in the OAI dataset. Retrospective. From OAI dataset, 50 subjects, stratified by osteoarthritis (OA) severity using Kellgren-Lawrence grades (KLG), and 50 subjects without OA diagnosis during OAI duration were selected (each group: 25 females, mean ages ~61 years). 3-T, two-dimensional (2D) MESE sequence. Femoral and tibial cartilages were segmented from DESS images, subdivided into seven sub-regions, and co-registered to MESE. T2 maps were obtained using three EPG-based methods (nonlinear least squares, dictionary matching, and deep learning) and three mono-exponential approaches (linear least squares, nonlinear least squares, and noise-corrected exponential). Average T2 values within sub-regions were obtained. Pair-wise agreement among fitting methods was evaluated using the stratified subjects, while reproducibility using healthy subjects. Each method's T2 accuracy and repeatability varying signal-to-noise ratio (SNR) were assessed with simulations. Bland-Altman analysis, Lin's concordance coefficient, and coefficient of variation assessed agreement, repeatability, and reproducibility. Statistical significance was set at P-value <0.05. EPG-based methods demonstrated superior T2 accuracy (mean absolute error below 0.5 msec at SNR > 100) compared to mono-exponential methods (error > 7 msec). EPG-based approaches had better reproducibility, with limits of agreement 1.5-5 msec narrower than exponential-based methods. T2 values from EPG methods were systematically 10-17 msec lower than those from mono-exponential fitting. EPG modeling improved agreement and reproducibility of cartilage T2 mapping in subjects from the OAI dataset. 3 TECHNICAL EFFICACY: Stage 1.

Induced magnetic field and thermal regulation of synovial fluid flow through irregular surfaces with first-order slip and gold nanoparticles

ABSTRACT The current computational exploration develops a poroelastic model of the knee cartilage to elevate its temperature under cyclic sinusoidal loading. A contributing factor to the rise in temperature is this tissue’s viscous dissipation, which converts some of the mechanical energy supplied into heat. The manipulation of cartilage temperature is mostly reliant on the movement of synovial fluid inside the space between joints and within the permeable cartilage. We developed the region flow model in the presence of induced magnetic fields and gold nanoparticles, which enhanced the efficiency of joint lubrication by boosting the load-carrying capacity. We dealt with the problem for two different models. Model 1 assumes that viscosity is exponentially dependent on concentration. The shear thinning index in Model 2 is regarded as a concentration-dependent variable. We introduce these models for a complex wavy surface, where the first-order slip effect occurs. We modified the governing problem by assuming a long wavelength and a low Reynolds number. We followed up with a computational analysis utilizing the Rung–Kutta–Merson approach with Newton iteration in a shooting and matching strategy. We have conducted detailed comparisons between Model 1 and Model 2. The graphical findings have been shown for the distributions of velocity, temperature, and nanoparticle concentration. Additionally, the pressure gradients, streamlines, and axially generated magnetic fields have also been included. These results are presented for numerous physical parameters. The mechanics of trapping are thoroughly examined through the use of streamlines.

An Adhesive Hydrogel Technology for Enhanced Cartilage Repair: A Preliminary Proof of Concept.

Knee cartilage has limited natural healing capacity, complicating the development of effective treatment plans. Current non-cell-based therapies (e.g., microfracture) result in poor repair cartilage mechanical properties, low durability, and suboptimal tissue integration. Advanced treatments, such as autologous chondrocyte implantation, face challenges including cell leakage and inhomogeneous distribution. Successful cell therapy relies on prolonged retention of therapeutic biologicals at the implantation site, yet the optimal integration of implanted material into the surrounding healthy tissue remains an unmet need. This study evaluated the effectiveness of a newly developed photo-curable adhesive hydrogel for cartilage repair, focusing on adhesion properties, integration performance, and ability to support tissue regeneration. The proposed hydrogel design exhibited significant adhesion strength, outperforming commercial adhesives such as fibrin-based glues. An in vivo goat model was used to evaluate the hydrogels' adhesion properties and long-term integration into full-thickness cartilage defects over six months. Results showed that cell-free hydrogel-treated defects achieved superior integration with surrounding tissue and enhanced cartilage repair, with notable lateral integration. In vitro results further demonstrated high cell viability, robust matrix production, and successful cell encapsulation within the hydrogel matrix. These findings highlight the potential of adhesive hydrogel formulations to improve the efficacy of cell-based therapies, offering a potentially superior treatment for knee cartilage defects.

Impact of core muscle strengthening on knee pain, patient outcomes, physical function, and cartilage thickness in knee osteoarthritis: Protocol for a randomized controlled trial

Knee Osteoarthritis (KOA) is a degenerative condition that significantly impacts individuals, causing disability. Routine rehabilitation methods primarily involve knee and hip strengthening exercises. While there is limited evidence supporting the potential benefits of core muscle strengthening in KOA rehabilitation, further research is needed to examine the effects of a structured core muscle strengthening protocol on pain, functional abilities, quality of life, and knee cartilage health. This double-blind, randomized controlled trial seeks to investigate the impact of integrating core muscle strengthening into routine rehabilitation. The study will randomly assign 80 participants to either routine rehabilitation or experimental groups, with both groups receiving routine rehabilitation combined with core strengthening exercises in the experimental group over a twelve-week period. The outcomes measured will include pain levels, patient-reported outcomes, physical functional abilities, core muscle and leg muscle strength, and cartilage height of the femur and tibia. Follow-up assessments will occur in the 4th, 8th, and 12th weeks. This novel study aims to provide valuable insights into the role of core strengthening in KOA rehabilitation, potentially influencing rehabilitation approaches and managing disease progression.•Incorporating core muscle strengthening into routine rehabilitation for KOA could open new possibilities for KOA management.•This study employs outcome measures recommended by OARSI for a thorough evaluation.•Additionally, it will investigate the impact on cartilage health, offering fresh insights into disease progression and the effects of exercise

Does scaffold enhancement show significant superiority over microfracture alone for treating knee chondral defects? A systematic review and meta-analysis of randomised clinical trials.

Chondral and osteochondral lesions in the knee are common conditions that significantly impair individuals' well-being and can lead to osteoarthritis, imposing substantial burdens on healthcare systems. The limited natural healing capacity of articular cartilage necessitates innovative treatment strategies. Microfracture (MF) is a widely used technique for knee chondral defects, but its long-term efficacy is often inadequate. Although recent randomised controlled trials have compared microfractures with scaffold-enhanced therapies, a comprehensive systematic review and meta-analysis are lacking. An extensive literature search was conducted in PubMed and EMBASE databases following PRISMA guidelines. Inclusion criteria focused on randomised controlled trials (RCTs) comparing microfractures alone to matrix-induced chondrogenesis for knee chondral defects with at least a 12-month follow-up. Ten randomised controlled trials conducted between 2013 and 2024, enroling 378 patients, were included. The meta-analysis showed no significant superiority of scaffolds over MF (p > 0.05) in International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome, Visual Analog Scale, and Magnetic Resonance Observation of Cartilage Repair Tissue scores at 12 and 24 months. However, individual studies suggested the potential benefits of scaffolds, especially in long-term outcomes. Clinical improvements from MF typically decline after 2-3 years, underscoring the need for long-term follow-up in future research. Our meta-analysis shows no significant difference between MF and MF with scaffold in treating knee cartilage defects, though some long-term RCTs demonstrate statistically significant differences. The absence of a universally accepted algorithm for analysing knee chondral defects limits this study. Establishing reliable guidelines and standardised study protocols is essential to improve long-term patient outcomes and the quality of future papers. Level I.

Text mining approach for feature extraction and cartilage disease grade classification using knee MRI radiology reports

MRI radiology reporting processes can be improved by exploiting structured and semantically labelled data that can be fed to artificial intelligence (AI) tools. AI-based tools assisting radiology reporting can help to automatically individuate cartilage grading in textual magnetic resonance imaging (MRI) reports, thus supporting clinicians' decisions regarding medical imaging utilisation, diagnosis and treatment. In this study, we extracted information (clinical findings, observations, anatomical regions, etc.) and classified knee cartilage degradation from medical reports utilising transfer-learning techniques applied to the Bidirectional Encoder Representations from Transformers (BERT) model and its variants, pre-trained on an Italian-language corpus. To realise this objective, we used a dataset of 750 MRI knee reports written by three radiologists who contributed to a manual annotation process to perform text classification (TC) and named entity recognition (NER) tasks. The dataset was obtained from an internal database of the IRCCS SYNLAB SDN. Seventy percent of the dataset was used for training, 10% was used for validation and 20% was used for testing. The best-performing configurations for NER and TC tasks were based on the pre-trained BERT model. The macro F1-scores obtained with the NER and TC models are 0.89 and 0.81, respectively. The accuracies calculated on the test set for both tasks are 0.96 and 0.99, respectively.

Walking recovers cartilage compressive strain in vivo

BackgroundArticular cartilage is a fiber reinforced hydrated solid that serves a largely mechanical role of supporting load and enabling low friction joint articulation. Daily activities that load cartilage, lead to fluid exudation and compressive axial strain. To date, the only mechanism shown to recover this cartilage strain in vivo is unloading (e.g., lying supine). Based on recent work in cartilage explants, we hypothesized that loaded joint activity (walking) would also be capable of strain recovery in cartilage. MethodsEight asymptomatic young adults performed a fixed series of tasks, each of which was followed by magnetic resonance imaging to track changes in their knee cartilage thickness. The order of tasks was as follows: 1) stand for 30 ​min, 2) walk for 10 ​min, 3) stand for 30 ​min, and 4) lie supine for 50 ​min. The change in cartilage thickness was used to compute the axial cartilage strain. ResultsStanding produced an average axial strain of −5.1 ​% (compressive) in the tibiofemoral knee cartilage, while lying supine led to strain recovery. In agreement with our hypothesis, walking also led to cartilage strain recovery. Interestingly, the recovery rate during walking (0.19 ​% strain/min) was nearly 3-fold faster than lying supine (0.07 ​% strain/min). ConclusionsThis study represents the first in vivo demonstration that joint activity is capable of recovering compressive strain in cartilage. These findings indicate that joint activities such as walking may play a key role in maintaining and recovering cartilage strain, with implications for maintaining cartilage health and preventing or delaying cartilage degeneration.

Quantitative Evaluation of Knee Cartilage in Professional Martial Arts Athletes Using T2 Mapping: A Comparative Study.

Although the relationship between high-impact sports like football and basketball and the development of knee osteoarthritis is well established, the effect of martial arts on the knee joint remains unclear. To compare the imaging abnormalities of knee joints and T2 relaxation times of cartilage in professional martial arts athletes and healthy controls. Cross-sectional study. Hospital imaging center. Nine asymptomatic professional martial arts athletes and 18 healthy volunteers. We performed 3T magnetic resonance imaging of the knee on both legs of athletes and the dominant leg of controls. The magnetic resonance imaging protocol included conventional sequences used for morphological assessment (cartilage, meniscus, ligaments, joint effusion, and bone marrow edema) and T2 mapping used for quantitatively evaluating the cartilage. Knee cartilage was manually divided into 8 regions, and T2 relaxation times of the corresponding subregions were measured. Fisher exact test and t test were used to compare the frequency of lesions and cartilage T2 values both between groups and between the athletes' limbs. P < .05 was considered significant. Professional martial arts athletes exhibited significantly higher frequencies of cartilage (55.6% vs 11.1%, P = .023) and ligament lesions (66.7% vs 16.7%, P = .026) compared with the control group. Athletes showed higher T2 values in 3 distinct cartilage segments: the central weight-bearing segment of the medial femoral condyle (P = .006), the medial tibial plateau (P = .012), and the trochlea (P = .032), when compared with the controls. Additionally, the dominant leg of athletes showed significantly higher T2 values compared with the nondominant leg. The findings demonstrated the impact of martial arts on the knee joint, characterized by higher prevalence of lesions and elevated cartilage T2 values, particularly in the medial compartment. The dominant legs of martial arts athletes seem to have higher risk of cartilage degeneration due to the observed interlimb differences in T2 values.

Treatment with a superoxide dismutase mimetic for joint preservation during 35 and 75 days in orbit aboard the International Space Station, and after 120 days recovery on Earth.

Reduced weight-bearing during spaceflight has been associated with musculoskeletal degradation that risks astronaut health and performance in transit and upon reaching deep space destinations. Previous rodent experiments aboard the international space station (ISS) have identified that the spaceflight-induced molecular arthritic phenotype was characterized with an increase in oxidative stress. This study evaluated if treatment with a superoxide dismutase (SOD) mimetic on orbit could prevent spaceflight-induced damage to the knee and hip articular cartilage, and the menisci in rodents. Cartilage and meniscal degradation in mice were measured via microCT, histology, and transcriptomics after: (1) ∼ 35 days on the ISS, (2) ∼ 35 days on the ISS followed by 120 days weight-bearing readaptation on Earth or (3) ∼ 75 days on the ISS. The study had a limited sample size, so both significant effects and generalized patterns are reported. After 35 days aboard the ISS, cartilage volume at the tibial-femoral cartilage-cartilage contact point decreased, meniscal volume decreased concurrent with an increase in pro-osteoarthritic signaling in the joint soft tissue. Similarly, a decrease in cortical and trabecular bone volume of the tibia was observed. While treatment with the SOD mimetic preserved the trabecular bone, articular cartilage and the menisci after 35 days aboard the ISS, but had limited efficacy retaining that recovery after 120 days of weight bearing, and after 75 days on orbit. Antioxidants including BuOE may serve as a potential countermeasure option to protect musculoskeletal health during spaceflight missions, and continued use may be necessary upon reaching a destination.

Weightlessness damaged the ultrastructure of knee cartilage and quadriceps muscle, aggravated the degeneration of cartilage

Weightlessness damaged the ultrastructure of knee cartilage and quadriceps muscle, aggravated the degeneration of cartilage

Trends in knee cartilage repair procedures in the United States, 2010 to 2020

IntroductionSurgical intervention of knee articular cartilage injuries may prevent degeneration in symptomatic patients. ObjectiveThis study aims to analyze trends, demographics, and yearly incidence of four different knee cartilage repair procedures in the U.S. from 2010 to 2020. MethodsThe PearlDiver database was queried for patients who underwent knee microfracture, autologous chondrocyte implantation (ACI), osteochondral autograft transfer (OAT) and osteochondral allograft transplantation (OCA) procedures from 2010 to 2020. Student t and χ-square tests were used for statistical comparisons and analysis of data trends. Regression models and Compound Annual Growth Rates (CAGR) further assessed trends of each procedure. Results220,674 patients from 2010 to 2020 were included in this study. Microfracture incurred a 62.4% decrease in occurrence (P < 0.001). Incidence of OCA trended upwards (37.7%; P = 0.065) whilst OAT procedures significantly decline (53.9%; P < 0.001). ACI procedure numbers remained relatively stable (11.2% increase; P = 0.847). ConclusionsThe incidence of microfracture significantly decreased in the United States from 2010 to 2020. There was a positive trend in the incidence of OCA cases, whilst the number of OAT cases decreased significantly. The number of ACI cases performed per year did not change significantly over the study period with the exception of an increase from 2017-2019. Microfracture procedures were performed in an older patient population than the other cartilage procedures. Males were more likely to undergo the four cartilage preservation surgeries compared to females. Similar studies should be carried out in other large health databases to confirm the external validity of these trends across the United States.

Future Potential of Stem Cells Conditioned Medium (Secretome) in Knee Cartilage Healing: A Systematic Review

Future Potential of Stem Cells Conditioned Medium (Secretome) in Knee Cartilage Healing: A Systematic Review

Systemic Inflammation In Asymptomatic Hyperuricemia With Sonographic Crystal Deposits, Including A Comparison With Normouricemia And Gout.

To describe the inflammatory profile of asymptomatic hyperuricemia (AH) with ultrasound evidence of monosodium urate (MSU) crystals (AH-MSUpos), vs AH without deposits (AH-MSUneg), intercritical gout, and normouricemia. Based on serum urate levels, musculoskeletal ultrasound, and history of flares, we divided 122 participants into four groups: normouricemia, AH-MSUneg, AH-MSUpos, and intercritical gout. We tested four ultrasound definitions for MSU deposition in AH: grade 2-3 (G2-3) double contour and/or tophi, G1-3 double contour and/or tophi, G1-3 Stewart scheme (double contour sign in knee cartilage and/or first metatarsophalangeal joint and/or tophi in first metatarsophalangeal joint), and G2-3 Stewart scheme. Serum acute phase reactants, cytokines, pyroptosis derivates, and neutrophil-related proteins were measured and compared between groups. A linear regression model was fitted to correlate crystal and inflammatory burden (measured by ultrasound) with inflammatory markers in hyperuricemics. Rates of MSU deposition in AH ranged from 26.0% to 68.8%, depending on the definition used. Levels of CRP, leukocytes, IL-1RA, IL-6, sIL-6R, IL-18, TNF-α, TGF-β, and galectin-3 were higher in hyperuricemics vs normouricemics. Sex, obesity, and comorbidity scores influenced some comparisons. We saw no differences comparing AH-MSUpos vs AH-MSUneg groups, except for higher calprotectin using G1-3 sonographic definitions and higher CRP and TGF-β when restricted to women and obese participants. Hyperuricemia is associated with substantial inflammation and some degree of active pyroptosis. Four different ultrasound definitions for AH with MSU deposits yielded similar findings, although we noted some differences in calprotectin, CRP, and TGF-β. Sex, obesity, and comorbidities influenced some inflammatory responses.

Effectiveness of Arthroscopic Microfracture Combined with Platelet-Rich Plasma Complex in the Treatment of Knee Cartilage Injury

Effectiveness of Arthroscopic Microfracture Combined with Platelet-Rich Plasma Complex in the Treatment of Knee Cartilage Injury

Performance of MR learned pulse sequences for 3D bi-exponential, stretched-exponential, and mono-exponential T2 and T1ρ mapping of knee cartilage.

To compare the performance of a learned magnetization-prepared gradient echo (L-MPGRE) sequence against a commonly used sequence for 3D T2 and T1ρ mapping of the knee joint, the magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (MAPSS), on bi-exponential (BE), stretched-exponential (SE), and mono-exponential (ME) relaxation models. We used a combined differentiable and non-differentiable optimization to learn pulse sequence structure and its parameters for 3D T2 and T1ρ mapping of the knee joint using ME, SE, and BE models. The learned pulse sequence framework was used to improve quantitative accuracy and SNR and to reduce filtering effects. We compare the measured multi-compartment values between the two sequences (n = 8), and their repeatability (n = 4) in healthy volunteers (n = 12 total). The voxel-wise median absolute percentage difference (MAPD) between the T2 and T1ρ maps obtained with each sequence was 18.6% and 19.9%, respectively. The T2 and T1ρ repeatability tests showed a MAPD of 18.5% and 19.1% for MAPSS, and 16.8% and 15.5% for L-MPGRE. Bland-Altman region of interest (ROI)-wise analysis shows that bias is small, close to -1.5%, and the coefficient of variation is around 5.5% when comparing ROIs from both sequences. The L-MPGRE sequences can be used as a replacement for MAPSS for T2 and T1ρ mapping in the knee cartilage with advantages, achieving similar accuracy and 15% better repeatability in only half of its scan time.

Loss of collagen content is localized near cartilage lesions on the day of injurious loading and intensified on day 12.

Joint injury can lead to articular cartilage damage, excessive inflammation, and post-traumatic osteoarthritis (PTOA). Collagen is an essential component for cartilage function, yet current literature has limited understanding of how biochemical and biomechanical factors contribute to collagen loss in injured cartilage. Our aim was to investigate spatially dependent changes in collagen content and collagen integrity of injured cartilage, with an explant model of early-stage PTOA. We subjected calf knee cartilage explants to combinations of injurious loading (INJ), interleukin-1α-challenge (IL) and physiological cyclic loading (CL). Using Fourier transform infrared microspectroscopy, collagen content (Amide I band) and collagen integrity (Amide II/1338 cm-1 ratio) were estimated on days 0 and 12 post-injury. We found that INJ led to lower collagen content near lesions compared to intact regions on day 0 (p < 0.001). On day 12, near-lesion collagen content was lower compared to day 0 (p < 0.05). Additionally, on day 12, INJ, IL, and INJ + IL groups exhibited lower collagen content along most of tissue depth compared to free-swelling control group (p < 0.05). CL groups showed higher collagen content along most of tissue depth compared to corresponding groups without CL (p < 0.05). Immunohistochemical analysis revealed higher MMP-1 and MMP-3 staining intensities localized within cell lacunae in INJ group compared to CTRL group on day 0. Our results suggest that INJ causes rapid loss of collagen content near lesions, which is intensified on day 12. Additionally, CL could mitigate the loss of collagen content at intact regions after 12 days.

Differential analysis of the impact of lesions’ location on clinical and radiological outcomes after the implantation of a novel aragonite-based scaffold to treat knee cartilage defects

Abstract Purpose There is limited comparative evidence on patient outcomes following cartilage repair in various knee compartments. The aim of this study was to compare clinical and imaging outcomes after treating cartilage defects in femoral condyles and trochlea with either an aragonite-based scaffold or surgical standard of care (SSoC, i.e., debridement/microfractures) in a large multicentre randomized controlled trial. Methods 247 patients with up to three knee joint surface lesions (ICRS grade IIIa or above) in the femoral condyles, trochlea or both (“mixed”), were enrolled and randomized to surgery with either a cell-free aragonite scaffold or SSoC. Patients were followed for up to 48 months by analysing subjective scores (KOOS and IKDC), radiological outcomes (defect filling on MRI), as well as treatment failure rates and adverse events. A differential analysis of outcomes for condylar, trochlear and mixed lesions was performed. Results The scaffold group significantly outperformed the SSoC group regardless of lesion location with statistically significantly better KOOS Overall scores at 24 months (all p ≤ 0.0009) and 48 months (all p ≤ 0.02). Similar results were observed for KOOS subscales and IKDC scores. For KOOS responder rates, superiority of the implant group was demonstrated at 24, 36, and 48 months (all p ≤ 0.004). Higher defect filling on MRI for implants was observed for all locations. Lower treatment failure rates for the implant were observed in condylar and mixed lesions. Conclusion The aragonite-based scaffold was safe and effective regardless of the defect location, providing superior clinical and radiological outcomes compared to SSoC up to four years follow-up. Level of evidence I – Randomized controlled trial.

Injectable decellularized Wharton's jelly hydrogel containing CD56+ umbilical cord mesenchymal stem cell-derived exosomes for meniscus tear healing and cartilage protection

Traditional meniscectomy or suture for meniscal tear usually leads to failed self-healing, cartilage degeneration and worse osteoarthritis. The strategies that facilitate the healing process of torn meniscus and safeguard knee cartilage against degeneration will be promising for clinical therapy. The CD56+ umbilical cord mesenchymal stem cells (UCSCs) (CD56+UCSCs) were sorted from Wharton's jelly using flow cytometer. Then, the modified decellularized Wharton's Jelly hydrogel (DWJH) was combined with isolated CD56+Exos from CD56+UCSCs to fabricate DWJH/CD56+Exos. The in vitro studies were performed to characterize the DWJ (decellularized Wharton's Jelly). The injectability and rheological properties were assessed by shear rate and frequency sweep analysis. The biocompatibility and chondrogenic differentiation inducibility of DWJH/CD56+Exos were performed on human bone marrow mesenchymal stem cells (hBMSCs) and RAW 264.7 cells. The release dynamics was evaluated in vitro and in vivo experiments. As for the in vivo experiments, the operated rats that subjected to a 2 mm full-thickness longitudinal tear in right medial anterior meniscus were injected a single dose of DWJH/CD56+Exos. At 4 and 8 weeks postoperatively, torn meniscus healing and articular cartilage degeneration were evaluated by hematoxylin and eosin (H&E), safranin O/fast green (SO&FG), and Sirius red staining. In in vitro experiments, the injectable DWJH/CD56+Exos demonstrated excellent biocompatibility, exosome releasing efficiency, injectable property and chondrogenic inducibility. The results of in vivo experiments revealed that DWJH/CD56+Exos degraded over time, promoted meniscal chondrogenesis, organized meniscal extracellular matrix remodeling, safeguard articular cartilage and inhibited secondary cartilage degeneration, which accelerated further facilitated torn meniscus healing. The novel injectable DWJH/CD56+Exos promoted meniscal tear healing by promoting meniscal chondrogenesis, safeguarding articular cartilage, and inhibiting secondary cartilage degeneration.