Cartilage Lesions Research Articles

Effects of alendronate on cartilage lesions and micro-architecture deterioration of subchondral bone in patellofemoral osteoarthritic ovariectomized rats with patella-baja

BackgroundPatellofemoral osteoarthritis (PFJOA) is a subtype of knee OA, which is one of the main causes of anterior knee pain. The current study found an increased prevalence of OA in postmenopausal women, called postmenopausal OA. Therefore, we designed the ovariectomized rat model of patella baja-induced PFJOA. Alendronate (ALN) inhibits osteoclast-mediated bone loss, and has been reported the favorable result of a potential intervention option of OA treatment. However, the potential effects of ALN treatment on PFJOA in the ovariectomized rat model are unknown and need further investigation prior to exploration in the clinical research setting. In this study, the effects of ALN on articular cartilage degradation and subchondral bone microstructure were assessed in the ovariectomized PFJOA rat model for 10 weeks.MethodsPatella baja and estrogen withdrawal were induced by patellar ligament shortening (PLS) and bilateral ovariectmomy surgeries in 3-month-old female Sprague–Dawley rats, respectively. Rats were randomly divided into five groups (n = 8): Sham + V; OVX + V, Sham + PLS + V, OVX + PLS + V, OVX + PLS + ALN (ALN: 70 μg/kg/week). Radiography was performed to evaluate patellar height ratios, and the progression of PFJOA was assessed by macroscopic and microscopic analyses, immunohistochemistry and micro-computed tomography (micro-CT).ResultsOur results found that the patella baja model prepared by PLS can successfully cause degeneration of articular cartilage and subchondral bone, resulting in changes of PFJOA. OVX caused a decrease in estrogen levels in rats, which aggravated the joint degeneration caused by PFJOA. Early application of ALN can delay the degenerative changes of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent, improve and maintain the micrometabolism and structural changes of cartilage and subchondral bone.ConclusionThe early application of ALN can delay the destruction of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent.

Is Osteoarthritis a Vascular Disease?

Osteoarthritis (OA) is now considered as a multifaceted disease affecting various articular tissues, including cartilage, bone, synovium, and surrounding ligaments. The pathophysiology strongly implicates intricate chemical communication, primarily through cytokines, leading to the production of degradative enzymes in cartilage, inflammatory peptides in synovium, and structural changes in bone, resulting in characteristic clinical features such as joint deformities and loss of cartilage space seen on X-rays. Recent studies highlight the previously underestimated role of subchondral bone in OA, revealing its permeability to cytokines and raising questions about the influence of abnormal perfusion on OA pathophysiology, suggesting a vascular component in the disease's etiology. In essence, alterations in bone perfusion, including reduced venous outflow and intraosseous hypertension, play a crucial role in influencing the physicochemical environment of subchondral bone, impacting osteoblast cytokine expression and contributing to trabecular remodeling, changes in chondrocyte phenotype, and ultimately cartilage matrix degeneration in OA. Dynamic contrast (gadolinium) enhanced magnetic resonance imaging (DCE-MRI) was used to quantify perfusion kinetics in normal and osteoarthritic subchondral bone, demonstrating that decreased perfusion temporally precedes and spatially correlates with cartilage lesions in both young Dunkin-Hartley (D-H) guinea pigs and humans with osteoarthritis. Pharmacokinetic analysis of DCE-MRI generated data reveals decreased tracer clearance and outflow obstruction in the medial tibial plateau of osteoarthritic guinea pigs, coinciding with progressive cartilage degradation, loss of Safranin O staining, and increased expression of matrix metalloproteinases and interleukin-1. Positron emission tomographic (PET) scanning using 18F-Fluoride reveals a relationship among bone blood flow, cartilage lesions, and 18F-Fluoride influx rate in OA, highlighting the intricate relationships between decreased perfusion, altered bone metabolism, and the progression of osteoarthritis. These findings, supported by 18F-Fluoride PET data, suggest the presence of venous stasis associated with outflow obstruction, emphasizing the role of decreased subchondral bone perfusion in the pathophysiology of OA and its association with reduced osteoblast activity and advanced cartilage degeneration.

Reliability and Accuracy of the Outerbridge Classification in Staging of Cartilage Defects.

The decision on whether or not and how to treat a local cartilage defect is still made intraoperatively based on the visual presentation of the cartilage and findings from indentations with an arthroscopic probe. The treatment decision is then usually based on grading according to established classifications systems, which, therefore, need to have high reliability and accuracy. The aim of the present study was to evaluate the reliability and accuracy of the Outerbridge classification in staging cartilage defects. We performed an observer arthroscopic study using the Outerbridge classification on seven fresh-frozen human cadaveric knees, which collectively exhibited nine cartilage defects. To evaluate accuracy, defect severity was verified through histological examination. Interrater and intrarater reliabilites were calculated using Cohen's kappa and the intra-class correlation coefficient (ICC 3.1). The interrater and intrarater reliability for the Outerbridge classification ranged from poor to substantial, with 0.24 ≤ κ ≤ 0.70 and κ = 0.55 to κ = 0.66, respectively. The accuracy evaluated by comparison with the histological examination was 63% overall. The erroneous evaluations were, however, still often at the discrimination of grade 2 and 3. We did not find any relationship between higher experience and accuracy or intraobserver reliability. Taken together, these results encourage surgeons to further use diagnostic arthroscopy for evaluating cartilage lesions. Nevertheless, especially in grade 2 and 3, deviations from the histology were observed. This is, however, the point where a decision is made on whether to surgically address the defect or not. Diagnostic arthroscopy is the standard for cartilage lesion assessment, yet interobserver reliability is fair to substantial. Caution is warranted in interpreting varied observer results. The accuracy of the "simpler" Outerbridge classification is insufficient compared to histological examinations, highlighting the need for improved techniques in guideline-based intraoperative decision-making.

In Situ Remodeling of Efferocytosis via Lesion-Localized Microspheres to Reverse Cartilage Senescence.

Efferocytosis, an intrinsic regulatory mechanism to eliminate apoptotic cells, will be suppressed due to the delayed apoptosis process in aging-related diseases, such as osteoarthritis (OA). In this study, cartilage lesion-localized hydrogel microspheres are developed to remodel the in situ efferocytosis to reverse cartilage senescence and recruit endogenous stem cells to accelerate cartilage repair. Specifically, aldehyde- and methacrylic anhydride (MA)-modified hyaluronic acid hydrogel microspheres (AHM), loaded with pro-apoptotic liposomes (liposomes encapsulating ABT263, A-Lipo) and PDGF-BB, namely A-Lipo/PAHM, are prepared by microfluidic and photo-cross-linking techniques. By a degraded porcine cartilage explant OA model, the in situ cartilage lesion location experiment illustrated that aldehyde-functionalized microspheres promote affinity for degraded cartilage. In vitro data showed that A-Lipo induced apoptosis of senescent chondrocytes (Sn-chondrocytes), which can then be phagocytosed by the efferocytosis of macrophages, and remodeling efferocytosis facilitated the protection of normal chondrocytes and maintained the chondrogenic differentiation capacity of MSCs. In vivo experiments confirmed that hydrogel microspheres localized to cartilage lesion reversed cartilage senescence and promoted cartilage repair in OA. It is believed this in situ efferocytosis remodeling strategy can be of great significance for tissue regeneration in aging-related diseases.

Acellular Aragonite-Based Scaffold for the Treatment of Joint Surface Lesions of the Knee: A Minimum 5-Year Follow-Up Study.

A novel aragonite-based scaffold has been developed. In this study, mid-term clinical and magnetic resonance imaging (MRI) results on 12 patients affected by isolated chondral or osteochondral lesions of the knee treated by the scaffold implantation have been evaluated at a mean follow-up of 6.5 (range: 5-8) years. The study population consisted of 3 females and 9 males, mean age 34.4 (20-51) years. The lesion was located on the medial femoral condyle, the trochlea, and the lateral femoral condyle in 5, 5, and 2 patients, respectively. In all cases, a single lesion over grade 3 of the International Cartilage Restoration and Joint Preservation Society (ICRS) classification was treated: in 9 cases by implantation of one plug, and in 2 cases with 2 plugs; the mean size of the lesion was 2.5 cm2 (1-7). One patient failed and was revised with a custom-made metal implant (Episealer). Overall, Knee Injury and Osteoarthritis Outcome Score (KOOS) significantly improved from 45 ± 13 preoperatively to 86 ± 13 at final follow-up. All KOOS subscales improved significantly: pain subscale increased from 48 ± 12 to 92 ± 11; symptoms from 66 ± 13 to 91 ± 13; activity of daily living (ADL) from 60 ± 19 to 90 ± 21; sport from 23 ± 20 to 75 ± 20; finally, quality of life (QoL) increased from 27 ± 14 to 77 ± 19. Long-term MRI MOCART score was 64. This study shows continued significant clinical improvement and good magnetic resonance imaging (MRI) findings with a minimum 5 years follow-up after implantation of a novel aragonite derived scaffold for the treatment of cartilage lesions of the knee. One patient failed and was revised with a custom-made metal implant (Episealer).

Gait characteristics of patients with symptomatic cartilage lesions of the knee

IntroductionLittle is known about the impact of articular cartilage lesions on knee joint biomechanics. ObjectivesThis investigation aimed to determine the gait characteristics of patients with symptomatic articular cartilage defects of the knee. MethodsGait analyses were performed at a regional joint preservation center. Assessments were completed on a treadmill with a 15-camera 3D motion-capture system. Participants walked for 2 minutes at a self-selected speed at 0° inclination. The resulting kinematic and spatiotemporal parameters were averaged across 20 consecutive gait cycles. Paired t tests or Wilcoxon ranked tests were performed on the data to compare biomechanical parameters between knees (α = 0.05). ResultsPatients (n = 30) walked at an average speed of 3.0 ± 0.7 km/h with a cadence of 60.4 ± 16.2 steps/min. Step lengths were comparable between limbs (P = .595). Maximum flexion during swing did not differ between knees (P = .507), but were lower than previously reported healthy adults. In the frontal plane, both knees remained in adduction throughout the gait cycle (P = .385). The maximal adduction reported in both knees were greater than previously reported for healthy adults. Maximal internal-external rotation patterns were comparable in stance (P = .475) and swing (P = .762) and to previous literature. ConclusionsGait characteristics were generally comparable between injured and contralateral knees of patients with symptomatic cartilage lesions of the knee. However, some parameters of gait in the sagittal and frontal plane were pathological when compared to previously published data from healthy adults.

Osteochondral Allograft Transplantation in the Knee

Osteochondral injuries of the knee can be a frequent source of debilitating pain and dysfunction. Significant chondral (>1.5-2 cm2) lesions of the femoral condyles can be especially difficult to manage with nonsurgical measures. Fresh osteochondral allograft (OCA) transplantation has been shown to be a reliable surgical procedure to manage a wide array of high-grade focal chondral lesions, with or without subchondral bone involvement. OCA transplantation affords the transfer of a size-matched allograft of mature hyaline cartilage with its associated subchondral bony scaffold. Indications include primary or secondary management of large, high-grade chondral or osteochondral defects secondary to trauma, developmental malformation, osteonecrosis, or other focal degenerative disease. Contraindications include end-stage osteoarthritis, uncorrected malalignment, ligament or meniscus deficiency, and inflammatory joint disease. Improvements in surgical technique, allograft storage, and tissue availability have created more reproducible clinical results and increased chondrocyte viability. Long-term (>10 year) graft survival rates have been shown to be between 70% and 91%, and the procedure has been shown to be cost-effective based on cost per quality-adjusted life year. Finally, OCA transplantation has been shown to provide excellent return to play rate for athletes with medium-to-large cartilage lesions. OCA transplantation is therefore an important option in the treatment algorithm of articular cartilage injuries.

Single-stage autologous chondrocyte coimplantation on a hyaluronan scaffold for the treatment of knee cartilage lesions: a case series of 16 patients with clinical outcomes up to 5 years

IntroductionThe direct reimplantation of autologous primary articular chondrocytes in a single-stage procedure for knee cartilage lesions is a novel approach, yet to be extensively reported. This study aimed to evaluate the clinical outcomes and reinterventions over a 5-year period post-surgery. MethodsA prospective case series involving 16 patients (4 female, 12 male) with single or multiple focal knee cartilage lesions was conducted. The mean age at baseline was 36.8 (±11.5) years. The mean total lesion size was 4.5 (±2.3) cm2 Patients underwent surgery where articular chondrocytes and mononuclear bone marrow cells were isolated, mixed, and seeded onto a hyaluronan-based scaffold within the lesion. A structured physical therapy regimen was followed, and patients were assessed using Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) Subjective questionnaires at various intervals. Overall, patient-reported outcomes improved over the first 3 years post-surgery, with slight declines thereafter. ResultsSignificant improvements over baseline were noted for various KOOS parameters and IKDC Subjective scores at different follow-up points. Reinterventions were required for two patients, one receiving intra-articular injections with mesenchymal stromal cells and another undergoing knee washout for septic arthritis while a meniscus implant was removed. Patient satisfaction at final follow-up was generally favorable. Despite a significant intraoperative cell isolation time of approximately 1.5 hours, the procedure demonstrated safety and efficacy, with an average of ±0.9 million articular chondrocytes obtained per case. ConclusionsThis study underscores the potential of coimplantation of intraoperatively isolated articular chondrocytes and bone marrow cells on a hyaluronan scaffold as a promising strategy for treating symptomatic knee cartilage lesions.

High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells.

Cartilage defects are some of the most common causes of arthritis. Cartilage lesions caused by inflammation, trauma or degenerative disease normally result in osteochondral defects. Previous studies have shown that decellularized extracellular matrix (ECM) derived from autologous, allogenic, or xenogeneic mesenchymal stromal cells (MSCs) can effectively restore osteochondral integrity. To determine whether the decellularized ECM of antler reserve mesenchymal cells (RMCs), a xenogeneic material from antler stem cells, is superior to the currently available treatments for osteochondral defects. We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70% confluence; 50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition. Decellularized sheets of adipocyte-derived MSCs (aMSCs) and antlerogenic periosteal cells (another type of antler stem cells) were used as the controls. Three weeks after ascorbic acid stimulation, the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints. The defects were successfully repaired by applying the ECM-sheets. The highest quality of repair was achieved in the RMC-ECM group both in vitro (including cell attachment and proliferation), and in vivo (including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues). Notably, the antler-stem-cell-derived ECM (xenogeneic) performed better than the aMSC-ECM (allogenic), while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells. Decellularized xenogeneic ECM derived from the antler stem cell, particularly the active form (RMC-ECM), can achieve high quality repair/reconstruction of osteochondral defects, suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

MiR-708–5p deficiency involves the degeneration of mandibular condylar chondrocytes via the TLR4/NF-κB pathway

ObjectiveAgeing and aberrant biomechanical stimulation are two major risk factors for osteoarthritis (OA). One of the main characteristics of aged cartilage is cellular senescence. One of the main characteristics of osteoarthritic joints is cartilage degeneration. The cells in the temporomandibular joint (TMJ) cartilage are zonally arranged. The deep zone cells are differentiated from the superficial zone cells (SZCs). The purpose of the present study was to investigate whether degenerative shear stress (SS) stimulates the senescence programme in TMJ SZCs, and to determine which miRNA is involved in this process. MethodSZCs were isolated from the TMJ condyles of 3-week-old rats and treated with continuous passaging or SS. RNA sequencing was conducted to identify miRNA(s) that overlap with those involved in the replication senescence process and the SS-induced degeneration programme. Unilateral anterior crossbite (UAC), which is TMJ-OA inducible, was applied to 2-month-old and 12-month-old mice for 3 weeks. The effect of TMJ local injection of agomiR-708-5p was evaluated histologically. ResultsBoth replication and SS treatment induced SZC senescence. miR-708-5p was identified. Knocking down miR-708-5p in SS treated SZCs led to more severe senescence by alleviating the inhibitory impact of miR-708-5p on the TLR4/NF-κB pathway. miR-708-5p expression in mouse TMJ cartilage decreased with age. UAC induced more severe osteoarthritic cartilage lesions in 12-month-old mice than in 2-month-old mice. Injection of agomiR-708-5p suppressed UAC-induced osteoarthritic cartilage lesions. ConclusionsAge-related miR-708-5p deficiency is involved in the mechanically stimulated OA process. Intra-articular administration of agomiR-708-5p is a promising new strategy for OA treatment. Data availabilityThe small RNA and mRNA sequencing data included in this study are available in the NCBI Gene Expression Omnibus (GEO) database (accession numbers GSE236980, GSE236977, and GSE 236978).

Quantitative Magnetic Resonance Imaging of Lateral Compartment Articular Cartilage After Lateral Extra-articular Tenodesis

Background: Concerns have arisen that anterior cruciate ligament reconstruction (ACLR) with lateral extra-articular tenodesis (LET) may accelerate the development of posttraumatic osteoarthritis in the lateral compartment of the knee. Purpose/Hypothesis: The purpose of this study was to evaluate whether the augmentation of ACLR with LET affects the quality of lateral compartment articular cartilage on magnetic resonance imaging (MRI) at 2 years postoperatively. We hypothesized that there would be no difference in T1rho and T2 relaxation times when comparing ACLR alone with ACLR + LET. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A consecutive subgroup of patients at the Fowler Kennedy Sport Medicine Clinic participating in the STABILITY 1 Study underwent bilateral 3-T MRI at 2 years after surgery. The primary outcome was T1rho and T2 relaxation times. Articular cartilage in the lateral compartment was manually segmented into 3 regions of the tibia (lateral tibia [LT]–1 to LT-3) and 5 regions of the femur (lateral femoral condyle [LFC]–1 to LFC-5). Analysis of covariance was used to compare relaxation times between groups, adjusted for lateral meniscal tears and treatment, cartilage and bone marrow lesions, contralateral relaxation times, and time since surgery. Semiquantitative MRI scores according to the Anterior Cruciate Ligament OsteoArthritis Score were compared between groups. Correlations were used to determine the association between secondary outcomes (including results of the International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, Lower Extremity Functional Scale, 4-Item Pain Intensity Measure, hop tests, and isokinetic quadriceps and hamstring strength tests) and cartilage relaxation. Results: A total of 95 participants (44 ACLR alone, 51 ACLR + LET) with a mean age of 18.8 years (61.1% female [58/95]) underwent 2-year MRI (range, 20-36 months). T1rho relaxation times were significantly elevated for the ACLR + LET group in LT-1 (37.3 ± 0.7 ms vs 34.1 ± 0.8 ms, respectively; P = .005) and LFC-2 (43.9 ± 0.9 ms vs 40.2 ± 1.0 ms, respectively; P = .008) compared with the ACLR alone group. T2 relaxation times were significantly elevated for the ACLR + LET group in LFC-1 (51.2 ± 0.7 ms vs 49.1 ± 0.7 ms, respectively; P = .03) and LFC-4 (45.9 ± 0.5 ms vs 44.2 ± 0.6 ms, respectively; P = .04) compared with the ACLR alone group. All effect sizes were small to medium. There was no difference in Anterior Cruciate Ligament OsteoArthritis Scores between groups (P = .99). Weak negative associations (rs = –0.27 to –0.22; P < .05) were found between relaxation times and quadriceps and hamstring strength in the anterolateral knee, while all other correlations were nonsignificant (P > .05). Conclusion: Increased relaxation times demonstrating small to medium effect sizes suggested early biochemical changes in articular cartilage of the anterolateral compartment in the ACLR + LET group compared with the ACLR alone group. Further evidence and long-term follow-up are needed to better understand the association between these results and the potential risk of the development of osteoarthritis in our patient cohort.

Modern low-field MRI.

This narrative review explores recent advancements and applications of modern low-field (≤ 1 Tesla) magnetic resonance imaging (MRI) in musculoskeletal radiology. Historically, high-field MRI systems (1.5T and 3T) have been the standard in clinical practice due to superior image resolution and signal-to-noise ratio. However, recent technological advancements in low-field MRI offer promising avenues for musculoskeletal imaging. General principles of low-field MRI systems are being introduced, highlighting their strengths and limitations compared to high-field counterparts. Emphasis is placed on advancements in hardware design, including novel magnet configurations, gradient systems, and radiofrequency coils, which have improved image quality and reduced susceptibility artifacts particularly in musculoskeletal imaging. Different clinical applications of modern low-field MRI in musculoskeletal radiology are being discussed. The diagnostic performance of low-field MRI in diagnosing various musculoskeletal pathologies, such as ligament and tendon injuries, osteoarthritis, and cartilage lesions, is being presented. Moreover, the discussion encompasses the cost-effectiveness and accessibility of low-field MRI systems, making them viable options for imaging centers with limited resources or specific patient populations. From a scientific standpoint, the amount of available data regarding musculoskeletal imaging at low-field strengths is limited and often several decades old. This review will give an insight to the existing literature and summarize our own experiences with a modern low-field MRI system over the last 3years. In conclusion, the narrative review highlights the potential clinical utility, challenges, and future directions of modern low-field MRI, offering valuable insights for radiologists and healthcare professionals seeking to leverage these advancements in their practice.

Sex does not influence the long-term outcome of matrix-assisted autologous chondrocyte transplantation.

Regenerative techniques for articular cartilage lesions demonstrated heterogeneous clinical results. Several factors may influence the outcome, with sex being one of the most debated. This study aimed at quantifying the long-term influence of sex on the clinical outcome obtained with a regenerative procedure for knee chondral lesions. Matrix-assisted autologous chondrocyte transplantation (MACT) was used to treat 235 knees which were prospectively evaluated with the International Knee Documentation Committee (IKDC), EuroQol visual analogue scale,and Tegner scores at 14-year mean follow-up. A multilevel analysis was performed with the IKDC subjective scores standardised according to the age/sex category of each patientand/or the selection of a match-paired subgroup to compare homogeneous men and women patients. At 14 years, men and women showed a failure rate of 10.7% and 28.8%, respectively (p < 0.0005). An overall improvement was observed in both sexes. Women had more patellar lesions and men more condylar lesions (p = 0.001), and the latter also presented a higher preinjury activity level (p < 0.0005). Men had significantly higher IKDC subjective scores at all follow-ups (at 14 years: 77.2 ± 18.9 vs.62.8 ± 23.1; p < 0.0005). However, the analysis of homogeneous match-paired populations of men and women, with standardised IKDC subjective scores, showed no differences between men and women (at 14 years: -1.6 ± 1.7 vs. -1.9 ± 1.6). Men and women treated with MACT for knee chondral lesions presented a significant improvement and stable long-term results. When both sexes are compared with homogeneous match-paired groups, they have similar results over time. However, women present more often unfavourable lesion patterns, which proved more challenging in terms of long-term outcome after MACT. Level II.

Covalent Conjugation of Small Molecule Inhibitors and Growth Factors to a Silk Fibroin-Derived Bioink to Develop Phenotypically Stable 3D Bioprinted Cartilage.

Implantation of a phenotypically stable cartilage graft could represent a viable approach for repairing osteoarthritic (OA) cartilage lesions. In the present study, we investigated the effects of modulating the bone morphogenetic protein (BMP), transforming growth factor beta (TGFβ), and interleukin-1 (IL-1) signaling cascades in human bone marrow stromal cell (hBMSC)-encapsulated silk fibroin gelatin (SF-G) bioink. The selected small molecules LDN193189, TGFβ3, and IL1 receptor antagonist (IL1Ra) are covalently conjugated to SF-G biomaterial to ensure sustained release, increased bioavailability, and printability, confirmed by ATR-FTIR, release kinetics, and rheological analyses. The 3D bioprinted constructs with chondrogenically differentiated hBMSCs were incubated in an OA-inducing medium for 14 days and assessed through a detailed qPCR, immunofluorescence, and biochemical analyses. Despite substantial heterogeneity in the observations among the donors, the IL1Ra molecule illustrated the maximum efficiency in enhancing the expression of articular cartilage components, reducing the expression of hypertrophic markers (re-validated by the GeneMANIA tool), as well as reducing the production of inflammatory molecules by the hBMSCs. Therefore, this study demonstrated a novel strategy to develop a chemically decorated, printable and biomimetic SF-G bioink to produce hyaline cartilage grafts resistant to acquiring OA traits that can be used for the treatment of degenerated cartilage lesions.

Autologous Chondrocyte Implantation Is Not Better Than Arthroscopic Debridement for the Treatment of Symptomatic Cartilage Lesions of the Knee: Two-Year Results From a Randomized-Controlled Trial

PurposeTo compare the functional and patient reported outcome measures (PROMs) after autologous chondrocyte implantation (ACI) and arthroscopic debridement (AD) in symptomatic, isolated cartilage injuries larger than 2cm2 in patients aged 18–50 years. MethodsTwenty-eight patients were included and randomized to ACI (n=15) or AD (n=13), and followed for two years. The primary outcome was the change in the Knee injury and Osteoarthritis Outcome Score (KOOS) Quality of Life (QoL) subscale. ResultsThe mean age at inclusion was 34.1 (standard deviation (SD) 8.5) years. There were 19 (68%) males. The mean size of the lesion was 4.2 (SD 1.7) cm2. There was a statistically significant and clinically meaningful improvement in PROMs from baseline to two years in both groups. The improvement from baseline to final follow-up for the primary endpoint (the KOOS QoL subscale) was larger for the AD group (39.8, SD 9.4) compared to the ACI group (23.8, SD 6.7), but this difference was not statistically significant (p=0.17). However, according to a mixed linear model there were statistically significantly higher scores in the AD group for several KOOS sub-scales at several time-points, including KOOS QoL, KOOS pain and KOOS sport and recreation at two years. ConclusionsThis study indicates that AD followed by supervised physiotherapy is equal to or better than ACI followed by supervised physiotherapy in patients with isolated cartilage lesions of the knee larger than 2 cm2. The improvement in DASH score from baseline to two years was clinically meaningful for both groups (23.8 points for ACI and 39.8 points AD), and larger for the AD group by 16 points.

Influence of leg axis alignment on MRI T2* mapping of the knee in young professional soccer players

BackgroundInvestigation of the association between leg axis alignment and biochemical MRI in young professional soccer players in order to identify a potential influence of the leg axis on cartilage regions at risk.MethodsSixteen professional soccer players (21 ± 3 years) underwent static and dynamic leg axis analysis via radiation free DIERS formetric 4 D as well as 3-T MRI examination of both knees. Quantitative T2* mapping of the knee cartilage was performed and T2* values were evaluated as 144 regions of interest. Subgroup analysis was performed in players with severe varus alignment (> 6°).ResultsAnalysis of the leg axis geometry revealed a mean static alignment of 6.6° ± 2.5 varus and a mean dynamic alignment of 5.1° ± 2.6 varus. Quantitative T2* mapping showed significantly increased T2* values in the superficial cartilage layer compared to the deeper region (p < 0.001) as well as a significant increase in relaxation times in the femoral cartilage from anterior to intermediate to posterior (p < 0.001). Combination of both methods revealed a significant correlation for the degree of varus alignment and the femoral, posterior, deep region of the medial knee compartment (r = 0.4; p = 0.03). If severe varus alignment was present this region showed a significant increase in relaxation time compared to players with a less pronounced leg axis deviation (p = 0.003).ConclusionThis study demonstrates that varus alignment in young soccer players is associated with elevated T2* relaxation times in the deep cartilage layer of the medial, posterior, femoral compartment and might therefore be a contributing factor in the early pathogenesis of manifest cartilage lesions. Therefore, these findings should be considered in the development of preventive training programs.

An Unusual Case of Oligometastases in a Patient with Renal Cell Carcinoma: Insights from 18F-FDG PET/CT.

Renal cell carcinoma (RCC) is a significant cause of mortality worldwide. To date, many atypical metastatic sites have been observed and reported in patients with RCC. However, to the best of our knowledge, there have been no reported cases of thyroid cartilage metastasis in the context of RCC metastasis. Herein, we present the case of a 68-year-old man who developed left arm pain that led to an RCC diagnosis. First, evaluation by pan-computed tomography (CT) denoted right kidney RCC and identified left humeral metastasis. Subsequently, 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) was performed after right nephrectomy and left humeral lesion excision and fixation. Interestingly, few intramedullary hypermetabolic lesions were observed in addition to a single intensely hypermetabolic thyroid cartilage lesion indicative of oligometastases. This case underscores the importance of 18F-FDG PET/CT in the evaluation of RCC disease for baseline staging and beyond.

Continuous Low-Intensity Ultrasound Improves Cartilage Repair in Rabbit Model of Subchondral Injury.

Subchondral drilling (SD), a bone marrow stimulation technique, is used to repair cartilage lesions that lack regenerative potential. Cartilage repair outcomes upon SD are typically fibrocartilaginous in nature with inferior functionality. The lack of cues to foster the chondrogenic differentiation of egressed mesenchymal stromal cells upon SD can be attributed for the poor outcomes. Continuous low-intensity ultrasound (cLIUS) at 3.8 MHz is proposed as a treatment modality for improving cartilage repair outcomes upon marrow stimulation. Bilateral defects were created by SD on the femoral medial condyle of female New Zealand white rabbits (n = 12), and the left joint received cLIUS treatment (3.8 MHz, 3.5 Vpp, 8 min/application/day) and the contralateral right joint served as the control. On day 7 postsurgery, synovial fluid was aspirated, and the cytokine levels were assessed by Quantibody™ assay. Rabbits were euthanized at 8 weeks and outcomes were assessed macroscopically and histologically. Defect areas in the right joints exhibited boundaries, incomplete fill, irregular cartilage surfaces, loss of glycosaminoglycan (GAG), and absence of chondrocytes. In contrast, the repaired defect area in the joints that received cLIUS showed complete fill, positive staining for GAG with rounded chondrocyte morphology, COL2A1 staining, and columnar organization. Synovial fluid collected from cLIUS-treated left knee joints had lower levels of IL1, TNFα, and IFNγ when compared to untreated right knee joints, alluding to the potential of cLIUS to mitigate early inflammation. Further at 8 weeks, left knee joints (n = 12) consistently scored higher on the O'Driscoll scale, with a higher percent hyaline cartilage score. No adverse impact on bone or change in the joint space was noted. Upon a single exposure of cLIUS to TNFα-treated cells, nuclear localization of pNFκB and SOX9 was visualized by double immunofluorescence and the expression of markers associated with the NFκB pathway was assayed by quantitative real-time polymerase chain reaction. cLIUS extends its chondroprotective effects by titrating pNFκB levels, preventing its nuclear translocation, while maintaining the expression of SOX9, the collagen II transcription factor. Our combined results demonstrate that healing of chondral defects treated with marrow stimulation by SD can be accelerated by employing cLIUS regimen that possesses chondroinductive and chondroprotective properties. Impact statement Repair of cartilage represents an unsolved biomedical burden. In vitro, continuous low-intensity ultrasound (cLIUS) has been demonstrated to possess chondroinductive and chondroprotective potential. To our best knowledge, the use of cLIUS to improve cartilage repair outcomes upon marrow stimulation, in vivo, has not been reported and our work reported here fills that gap. Our results demonstrated enhanced cartilage repair outcomes under cLIUS (3.8 MHz) in a rabbit model of subchondral injury by subchondral drilling. Enhanced repair stemmed from mesenchymal stem cell differentiation in vivo and the subsequent synthesis of articular cartilage-specific matrix.

Fifteen out of 16 elite athletes showed concomitant low-grade cartilage lesions of the ankle with unstable syndesmotic injuries: concerns from a prospective case series

ObjectivesThis study aimed to determine the incidence rate and characterise the location and severity of cartilage lesions in the ankle in elite athletes undergoing suture-button stabilisation for unstable distal syndesmotic...

Evaluating the Morphology of Unique Superficial Fissured Cartilage Lesions at the Femoral Head-Neck Junction in Patients with Femoroacetabular Impingement Syndrome.

While an association between femoroacetabular impingement (FAI) and osteoarthritis (OA) has been reported, the mechanistic differences and transition between the 2 conditions is not fully understood. In FAI, cartilage lesions at the femoral head-neck junction can sometimes be visualized during hip arthroscopy. The purpose of this study was to describe a unique dimpled pattern of superficial fissured cartilage lesions on the femoral head-neck junction at impingement site in patients with FAI syndrome (FAIS) and to evaluate the clinical, histological, and genetic phenotype of this cartilage. We hypothesized that the cartilage lesions may indicate risk for, or predict occurrence of, OA. Controlled laboratory study. Six hips (6 patients; mean age, 34.2 ± 12.9 years; range, 19-54 years) with dimpled or fissured cartilage were included among patients who underwent hip arthroscopy for treatment of FAIS from October 2020 through December 2021. This affected cartilage (dimple-pattern group) and normal cartilage (control group) on the femoral head-neck junction were collected from the same patients and evaluated for histological quantification by Mankin scores and expression of proteins related to cartilage degeneration (eg, matrix metalloproteinase [MMP]-1, MMP-2, MMP-3, MMP-10, and MMP-12, tissue inhibitor of metalloproteinase [TIMP]-1 and TMP-2, aggrecan neopepitope CS846, and hyaluronic acid [HA]) with the use of Milliplex Multiplex Assays. All 6 hips were of the mixed FAI subtype. Preoperatively, 4 of 6 hips had Tönnis grade 1 radiographic changes, which was associated with greater femoral head chondral damage visualized intraoperatively. Mankin scores for the normal cartilage group and the dimple-pattern group were 0.67 ± 0.82 and 3.3 ± 0.82, respectively. Dimple pattern fissured cartilage showed a significant increase in Mankin score (P = .031) and a significant increase in protein expression of CS846 (P = .031) compared with normal cartilage. There were no significant differences in MMPs, TIMPs, or HA levels between the 2 groups. The dimple pattern fissured cartilage, compared to normal cartilage, showed histologically significant cartilage degeneration and a significant increase in protein expression of CS846, a biomarker for early OA. This lesion serves as helpful visual indicator of early degeneration of the cartilage of femoral head-neck junction caused by FAIS.