Cartilage Surface Research Articles

Nonlinear Stress-Induced Transformations in Collagen Fibrillar Organization, Disorder and Strain Mechanisms in the Bone-Cartilage Unit.

By developing a 3D X-ray modeling and spatially correlative imaging method for fibrous collagenous tissues, this study provides a comprehensive mapping of nanoscale deformation in the collagen fibril network across the intact bone-cartilage unit (BCU), whose healthy functioning is critical for joint function and preventing degeneration. Extracting the 3D fibril structure from 2D small-angle X-ray scattering before and during physiological compression reveals of dominant deformation modes, including crystallinity transitions, lateral fibril compression, and reorientation, which vary in a coupled, nonlinear, and correlated manner across the cartilage-bone interface. A distinct intermolecular arrangement of collagen molecules, and enhanced molecular-level disorder, is found in the cartilage (sliding) surface region. Just below, fibrils accommodate tissue strain by reorientation, which transitions molecular-level kinking or loss of crystallinity in the deep zone. Crystalline fibrils laterally shrink far more (20×) than they contract, possibly by water loss from between tropocollagen molecules. With the calcified plate acting as an anchor for surrounding tissue, a qualitative switch occurs in fibrillar deformation between the articular cartilage and calcified regions. These findings significantly advance this understanding of the complex, nonlinear ultrastructural dynamics at this critical interface, and opens avenues for developing targeted diagnostic and therapeutic strategies for musculoskeletal disorders.

Correlation between proprioception, functionality, patient-reported knee condition and joint acoustic emissions.

Non-invasive assessment of joint status using acoustic emissions (AE) is a growing research area that has the potential to translate into clinical practice. The purpose of this study is to investigate the correlation of the knee's AE with measures of proprioception, self-assessment, and performance, as it can be hypothesised that, AE parameters will correlate with joint function metrics due to AE being recorded during interaction of the articular surfaces. Threshold to detect passive motion (TTDPM), Knee Osteoarthritis Outcome Scores (KOOS) and 5 times sit-to-stand test (5STS) were collected from 51 participant. Knee AE were recorded during cycling with 30 and 60 rpm cadences using two sensors in different frequency ranges and three modes of AE event detection. Weak (0.297, p = 0.048) to moderate (0.475, p = 0.001) Spearman's correlations were observed between longer 5STS time and AE parameters (i.e. higher median absolute energy, signal strength, longer AE event rise time and duration). Similarly, AE parameters shown correlation with lower KOOS, especially in the "Function in Sports and Recreation" and "Activities of Daily Living" subscales with correlation coefficients for higher median amplitude up to 0.441, p = 0.001 and 0.403, p = 0.004, respectively. The correlation with the TTDPM was not detected for most of the AE parameters. Additionally, a lower frequency sensor and 60 rpm cadence AE recordings showed higher correlations. Considering that this study included subjects from the general population and the number of participants with KOOS <70 was relatively small, higher correlations might be expected for clinically confirmed OA cases. Additionally, different ICCs might be expected for alternative signal parameters and proprioception assessment methods. Overall, the study confirms that AE monitoring offers an additional modality of joint assessment that reflects interaction between cartilage surfaces and can complement orthopaedic diagnostics, especially in the context of remote monitoring, drug testing, and rehabilitation.

Refixation of osteochondral flake fractures after patellar dislocation-The parachute technique

Patellar dislocations are acommon occurrence in orthopedic practice, often accompanied by osteochondral fractures of the retropatellar cartilage surface, known as flake fractures, in up to 58% of cases. The parachute technique represents asimple and cost-effective surgical option aimed at restoring osteochondral integration and preserving native cartilage. Flake fracture of the patella with osteochondral fragments. Patella fracture. By utilizing transpatellar, absorbable sutures, astable osteochondral interface is achieved without penetrating the fragment itself. Postoperative treatment involves partial weight-bearing with amaximum of 20 kg for 6weeks in full knee extension. In addition, the range of motion of knee flexion is limited to30° and is increased by30° every 2weeks. To examine the short- to medium-term clinical outcomes, all patients with acute patellar dislocation treated using the parachute technique between 01/2012 and 11/2022 were included. Clinical outcomes were assessed using the visual analog scale (VAS), Tegner Activity Scale (TAS), Kujala Score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and International Knee Documentation Committee (IKDC). Out of 20patients, 19 (10men, 11right-sided, 95% follow-up rate) could be recruited for postoperative evaluation. The average follow-up period was 62.5 ± 20.5 months. The clinical outcome scores yielded the following results: VAS 0.5 ± 1.6, TAS 5.8 ± 2.2, Kujala 89.4 ± 12.5, KOOS 87.8 ± 14.1, and IKDC 86.7 ± 14.3. Overall, 18patients (90.0%) expressed willingness to undergo the procedure again. At the time of follow-up, 19patients (95.0%) were satisfied with the surgical outcome. One patient (23-year-old man) required revision. None of the included patients suffered from the recurrence of patellar dislocation. In summary, the parachute technique demonstrated excellent clinical function in the short- to medium-term follow-up for acute patellar dislocation.

Early signs of osteoarthritis in differing rat osteochondral defects.

Preclinical models of osteochondral defects (OCDs) are fundamental test beds to evaluate treatment modalities before clinical translation. To increase the rigor and reproducibility of translational science for a robust "go or no-go," we evaluated disease progression and pain phenotypes within the whole joint for two OCD rat models with same defect size (1.5x 0.8 mm) placed either in the trochlea or medial condyle of femur. Remarkably, we only found subtle transitory changes to gaits of rats with trochlear defect without any discernible effect to allodynia. At 8-weeks post-surgery, anatomical evaluations of joint showed early signs of osteoarthritis with EPIC-microCT. For the trochlear defect, cartilage attenuation was increased in trochlear, medial, and lateral compartments of the femur. For condylar defect, increased cartilage attenuation was isolated to the medial condyle of the femur. Further, the medial ossicle showed signs of deterioration as indicated with decreased bone mineral density and increased bone surface area to volume ratio. Thus, OCD in a weight-bearing region of the femur gave rise to more advanced osteoarthritis phenotype within a unilateral joint compartment. Subchondral bone remodeling was evident in both models without any indication of closure of the articular cartilage surface. We conclude that rat OCD, placed in the trochlear or condylar region of the femur, leads to differing severity of osteoarthritis progression. As found herein, repair of the defect with fibrous tissue and subchondral bone is insufficient to alleviate onset of osteoarthritis. Future therapies using rat OCD model should address joint osteoarthritis in addition to repair itself.

Timing of cartilage articulation following impact injury affects the response of surface zone chondrocytes.

Post-traumatic osteoarthritis develops following an inciting injury to a joint and results in cartilage degeneration. Mechanical loading, including articulation, drives anabolic responses in cartilage clinically, in vivo, and in vitro. Tribological articulation, or sliding of cartilage on a glass counterface, has long been used as an in vitro tool to study cartilage tissue behavior. However, it is unclear if tribological articulation affects chondrocyte fate following injury, and if the timing of articulation impacts the resultant effect. The goal of this study was to investigate the effect of tribological articulation on injured cartilage tissue at two time points: (i) performed immediately after injury and (ii) 24 h after injury. Neonatal bovine femoral cartilage explants were injured using a rapid spring-loaded impactor and subsequently subjected to tribological articulation. Cell death due to impact injury was highest near the articular surface, suggesting a strain-dependent mechanism. Immediate articulation following injury mitigated cell death compared to injury alone or delayed articulation; markers for both general cell death and early-stage apoptosis were markedly decreased in the explants that were immediately slid. Interestingly, mitigation of cell death due to sliding was most predominant at the cartilage surface. Tribological articulation is known to create fluid flow within the tissue, predominantly at the articular surface, which could drive the protective response seen here. Altogether, this work shows that perturbations to the cellular environment immediately following cartilage injury significantly impact chondrocyte fate.

The degenerated glenohumeral joint.

This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated. Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA). Cartilage degeneration of the humeral head was associated with the histological presentation of: 1) pannus overgrowing the cartilage surface; 2) pores in the subchondral bone plate; and 3) chondrocyte clusters in OmA patients. In contrast, hyperplasia of the synovial lining layer was revealed as a significant indicator of inflammatory processes predominantly in CTA. The abundancy of collagen I, collagen II, and the C1,2C neoepitope correlated significantly with the histopathological degeneration of humeral head cartilage. No evidence for differences in MMP levels between OmA and CTA patients was found. This study provides a comprehensive histological characterization of humeral cartilage and synovial tissue within the glenohumeral joint, both in normal and diseased states. It highlights synovitis and pannus formation as histopathological hallmarks of OmA and CTA, indicating their roles as drivers of joint inflammation and cartilage degradation, and as targets for therapeutic strategies such as rotator cuff reconstruction and synovectomy.

PETAL – LIKE OTOPLASTY IN THE TREATMENT OF PROTRUDING EARS

Introduction. Approximately 5% of humanity suffers from inborn protruding ears, and usually this condition causes marked psychosomatic disorders. Despite years of experience gained in aesthetic surgery, optimal technique of otoplasty is yet to be elaborated. The Aim of the Research. To develop a method of surgical correction of congenital bulging ears in order to optimize the immediate and long-term results of otoplasty. Material and methods. We have analysed the outcomes of 120 patients operated for congenital protruding ears at Lviv City Cosmetologic Hospital between 2020 and 2023. Distance between mastoid process and the concha exceeding 20 mm, and auriculo-cephalic angle over 30° were used as objective criteria of protruding ears. Surgical improvement of tall concha and increased auriculo-cephalic angle were identified as key vectors in elaboration of the original otoplasty technique. Results of the Research. With local anaesthesia, an S-shaped incision is made to the depth of perichondrium of posterior surface of the cartilage of the ear. Once subcutaneous dissection is completed, preoperative markup is transferred with injection needles from anterior surface to posterior surface of the conchal cartilage. A full depth arch-shaped incision of conchal cartilage is made. Perichondrium and skin of anterior surface of the concha are mobilized with a raspatory, from the chondral «petal» to the margin of external meatus. Basis of the chondral «petal» is dissected by 2/3 of its depth along the vertical axis between the pedicle of the helix, and the antitragus. In order to reliably fix the auricula, the cartilage is stitched to the mastoid process with three mattress sutures on the ventral surface of the «petal». Finally, excessive skin is carefully resected, and the wound is closed with continuous suture, with dead space elimination for hematoma prevention. Our technique has the following significant advantages: Unique conchal cartilage is kept entirely, therefore it can be used as auto-transplant in the future. The technique does not significantly affect the rheology of auricula. With this technique correction and modification of antihelical curve and radius is possible; if necessary, width of auricula can be corrected, and auricular height to width ratio can be modified. The proposed «petal» technique significantly reduces the rate of postoperative complications, such as recurrent protruding ears. Postoperatively, the size of external meatus is not reduced, hence no hearing deterioration. The outcomes of the technique we have developed were assessed 6 months after otoplasty as good, satisfactory and unsatisfactory. Good outcome: preservation of symmetry and anatomical «standard» of both auriculas, no recurrence throughout follow-up, and no impairment of sensation in the external ear. Satisfactory outcome: anatomical «standard» of the organ is preserved, with permissible error of up to 3 mm in the symmetrical points on the right and left auriculas, not requiring additional correction. Conclusions. 98 (81,3%) patients operated by the proposed «petal» technique assessed their otoplasty outcome as good, 17 (14,3%) of patients assessed the outcome of surgery as satisfactory. 5 (4,3%) patients were not satisfied with the outcome of surgery. These patients were operated during the early period of development of the technique.

Lymphocyte-Derived Engineered Apoptotic Bodies with Inflammation Regulation and Cartilage Affinity for Osteoarthritis Therapy.

Apoptotic bodies as plentiful extracellular vesicles generated from apoptotic cells play a central role in signal transduction and homeostasis regulation and simultaneously switch death to regeneration to a certain extent. Herein, we designed engineered apoptotic bodies derived from T cells to have the capacity of inflammation regulation and cartilage affinity. The engineered apoptotic bodies as a natural anti-inflammation factor were encapsulated into lubricating hydrogel microspheres to achieve an injectable microsphere complex for the treatment of osteoarthritis (OA). In the above therapeutic system, the engineered apoptotic bodies acted as a biochemical cue to regulate the inflammatory microenvironment and promote chondrocyte cartilage homeostasis, whereas the lubricating hydrogel microspheres served as a biophysical stimulation to effectively reduce the friction of the cartilage surface, restore the cartilage stress, and control the slow delivery of the encapsulated engineered apoptotic bodies by friction degradation. Consequently, the current work creates an injectable and multifunctional therapeutic microsphere to advance cartilage remodeling and OA therapy.

Osteoarthritis early-, mid- and late-stage progression in the rat medial meniscus transection model.

Osteoarthritis is a degenerative disease of synovial joints affecting all tissues, including articular cartilage and subchondral bone. Osteoarthritis animal models can recapitulate aspects of human disease progression and are used to test efficacy of drugs, biomaterials, and cell therapies. The rat medial meniscus transection (MMT) model is a surgically induced posttraumatic osteoarthritis model commonly used for preclinical therapeutic screening. We describe herein, the qualitative and quantitative changes to articular cartilage, subchondral bone, and formation of osteophytes at early-, mid-, and late-stages of osteoarthritis progression. Tibia of MMT-operated animals showed proteoglycan loss and fibrillation along articular cartilage surfaces as early as 3-weeks post-surgery. With contrast-enhanced micro-CT technique, quantitative, 3-dimensional analysis of the tibia showed that the articular cartilage thickened at 3- and 6-weeks post-surgery and decreased at 12-weeks post-surgery. This decreased cartilage thickness corresponded with increased lesions in the articular cartilage that led to its full degradation and exposing the subchondral bone layer. Further, subchondral bone thickening was significant at 6-weeks post-surgery and followed cartilage damage. Osteophytes were found as early as 3-weeks post-surgery and coincided with articular cartilage degradation. Cartilaginous osteophytes preceded mineralization, suggesting endochondral ossification. The rat MMT model has predominantly been used out to 3-weeks, and most studies determined the effect of therapies to delay or prevent the onset of osteoarthritis. We provide evidence that an extension of the rat MMT model out to 6- and 12-weeks more resembled severe phenotypes of human osteoarthritis. Thus, evaluating novel therapeutics at late-stage will be important for eventual clinical translation.

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

Long-term exposure to weightlessness can result in bone and muscle degradation, significantly impacting musculoskeletal function. Recent studies have also indicated damage to articular cartilage due to weightlessness. This study aims to observe the effects of simulated weightlessness on the cartilage microstructure of the quadriceps muscle and the muscular knee joint in rats. A total of 30 rats were used in this study, of which 20 rats were subjected to simulated weightlessness by tail suspension, which may be suitable for clinical long-term bedridden patients. At 14 and 28 days, the microscopic morphology of knee cartilage and quadriceps femoris muscle was observed by transmission electron microscopy, and the collagen and water content of cartilage was evaluated by magnetic resonance imaging. The mitochondrial activity of knee muscle and the levels of inflammatory factors in synovial fluid were detected by enzyme-linked immunosorbent assay (ELISA). Biomechanical and histological evaluation of cartilage was performed. On day 14, T2 mapping revealed no significant loading effect. However, transmission electron microscopy revealed altered mitochondrial inner membrane structure in cartilage, with vacuolization, disrupted endoplasmic reticulum, alongside mitochondrial ultrastructural damage in muscle. ELISA results showed that a large number of mitochondria in muscle were inactivated, and the levels of inflammatory factors in synovial fluid were increased. The staining results showed slight fracture of the cartilage surface and the type II collagen-positive cells were reduced. Nanoindentation showed that the cartilage microsurface was uneven, and the elastic modulus and hardness were decreased. On day 28, T2 mapping analysis indicated increased cartilage T2 values. Transmission electron microscopy showed alterations in the structure of the mitochondrial inner membrane in cartilage, severe vacuolization, disrupted endoplasmic reticulum, and substantial mitochondrial damage in muscle tissue. Muscle mitochondrial activity was markedly decreased, inflammatory factors levels were elevated, and the cartilage surface exhibited severe damage. The type II collagen positive cells were further reduced, the micro-surface of cartilage was uneven, and the elastic modulus and hardness were significantly decreased. The weightless environment resulted in the damage of endoplasmic reticulum and mitochondria of cartilage, mitochondrial damage of quadriceps muscle, inactivation of muscle mitochondria (P=0.01), increased intra-articular inflammation (P=0.01), decreased elastic modulus and hardness (P=0.03), and damaged cartilage surface, which aggravated cartilage degeneration.

Kinematic Interactions Between Bones, Patellar Tendon, And Cartilage Surfaces During Cycling By Three-dimensional Fluoroscopic Imaging

Kinematic Interactions Between Bones, Patellar Tendon, And Cartilage Surfaces During Cycling By Three-dimensional Fluoroscopic Imaging

Enzyme-responsive microgel with controlled drug release, lubrication and adhesion capability for osteoarthritis attenuation

The treatment of osteoarthritis (OA) remains challenging due to the narrow therapeutic window and rapid clearance of therapeutic agents, even with intra-articular administration, resulting in a low treatment index. Recent advancements in local drug delivery systems have yet to overcome the issues of uncontrolled burst release and short retention time, leading to suboptimal OA treatment outcome. Herein, we developed a methacrylate-crosslinking hyaluronic acid (HA) microgel (abbreviated as CXB-HA-CBP) that covalently conjugates the anti-inflammatory drug celecoxib (CXB) via a metalloproteinase-2 (MMP-2)-responsive peptide linker (GGPLGLAGGC) and a collagen II binding peptide (WYRGRLC). The GGPLGLAGGC linker is specifically cleaved by the overexpressed MMP-2 enzyme within the OA joint, enabling the sustained and on-demand release of CXB entity. The synergistic action of CXB and HA effectively inhibited macrophage activation and reduced the production of pro-inflammatory cytokines, protecting chondrocytes from damage. Furthermore, the collagen II peptide introduced on the microgel surface enabled a cartilage-binding function to form an artificial lubrication microgel layer on the cartilage surface to reduce cartilage wear. The CXB-HA-CBP microgel showed an extended retention time of up to 18 days in the affected joint, leading to an effective OA treatment in rats. This sophistically designed microgel, characterized by the prolonged retention time, sustained drug delivery, and enhanced lubrication, presents a promising biomedicine for OA treatment. Statement of SignificanceA new methacrylate-crosslinking hyaluronic acid (HA) microgel, covalently conjugated with the celecoxib (CXB)-GGPLGLAGGC and the collagen II binding peptide (CBP, peptide sequence: WYRGRLC), was developed. The overexpressed MMP-2 in OA joint cleaved the GGPLGLAGGC linker to trigger the CXB moiety release. Besides, the CBP on the surface of microgels enabled a cartilage-attaching ability, resulting in a prolonged retention time and an improved lubrication property in joint. This advanced drug-loading microgel remarkably reduced macrophage activation and pro-inflammation cytokine production, while protecting the chondrocytes via a dual action of CXB and HA. This study demonstrated that the enzyme-responsive drug-loading microgel could serve as an platform to efficiently attenuate osteoarthritis.

Histopathology of Idiopathic Condylar Resorption Differs From Temporomandibular Joint-Only Juvenile Idiopathic Arthritis

BackgroundIdiopathic condylar resorption (ICR) is a rare condition of unknown etiology characterized by progressive decrease in volume and pathologic remodeling of a previously normal mandibular condyle. Juvenile Idiopathic Arthritis (JIA) affecting only the temporomandibular joint (TMJ-only JIA) is characterized by synovitis and destruction of TMJ tissues without involvement of other joints. It is often difficult to differentiate the two conditions because they exhibit similar phenotypes. PurposeTo compare histology of resected condylar specimens from patients with ICR and TMJ-only JIA. Specific aims were: 1) To correlate longitudinal clinical data with histopathology of resected condyle specimens, 2) To compare resorption patterns between the two disease processes. Study design, setting, sampleThis was a retrospective cohort study of patients treated at Massachusetts General Hospital (MGH) from 1999 through 2023. Predictor/exposure/independent variablePrimary predictor variable was the diagnosis (ICR or JIA). Secondary predictor variables included age, gender, race, putative contributing factors, and laboratory studies. Main outcome variable(s)Primary outcome variable was presence or absence of inflammatory infiltrates in bone and synovial specimens. Secondary outcome variables were structural integrity and morphologic characteristics of the condylar cartilage and bone. AnalysesSpearman correlation was used to assess the relationship between histological scores and age, gender, and possible associated contributing factors. A p-value < 0.05 was considered statistically significant. ResultsThirty-five subjects (67 specimens) were included in Group 1 (ICR). Eight subjects (15 specimens) were included in Group 2 (TMJ-only JIA). The histopathologic findings in ICR consisted of severe and irregular cartilage surface disruption, fibrocartilage degeneration, and subchondral bone with no inflammatory infiltrate. Degeneration was observed to begin at the anterior pole of the condyle and progress eventually to total resorption to the sigmoid notch. TMJ-only JIA was notable for more severe condylar degeneration and inflammation in the bone and synovia. There was no specific pattern of degeneration. For both groups, the subject’s age, gender, or putative contributing factors did not correlate with the histopathologic scores. Conclusions and RelevanceThese results support the hypothesis that “ICR” and TMJ-only JIA are distinct clinical entities and can be distinguished by histopathologic findings in the mandibular condyles and synovia.

Immunomodulatory Effect of Vitamin D3 in Rats with Induced Osteoarthritis

Background: The (OA) caused by imbalance between anabolic and catabolic processes within the cartilage ,one of the effects of increased catabolic changes is presence of products of extracellular matrix degradation in the synovial fluid which lead to the joint microenvironment alteration which attempt. Aim of study: Evaluate the influence of induce osteoarthritis (OA) on knee joint and looking on (OA) effect as local immune response in addition to the possible role of vitamin (D3) as protective and repairing agent against (OA) complications. Methods: Total number of rats male (89) were used and divided into three groups, first group (control group) (19) rats, second group (OA induced) (35) rats injected with papain enzyme at dose of (10 mg), treated group (35) rats which firstly injected with papain enzyme at dose (10 mg) then after (2) weeks of injection, treated the rats with vitamin D. Results and Dicussion: Macroscopic observations revealed to cartilage surface erosion , fibrillation , hypertrophied condyles, degeneration. The rats knee joints that treated (2) weeks with vitamin (D3) post (OA) induced showed smooth, intact cartilage surface. Radiographic images indicated to narrowing joints cavity (space) at knee joint of (OA) rat model, destruction of epiphyseal plate, while the results related to (OA) rats treated with vitamin (D3) showed no osteophyte growth , the synovial cavity nearest to the normal, no defect. Conclusion: Vitamin (D) prevent the stability and life of chondrocytes which lead to cartilage protection and synthesis of (ECM) , and inhibite the inflammation resulted from cartilage damaged.

The transepicondylar distance is a reliable and easily measured parameter for estimating femoral cartilage surface area using MRI.

Different cartilage repair techniques are widely used to regenerate cartilage, such as autologous chondrocyte implantation (ACI), osteochondral autograft transfer, microfracturing and minced cartilage. Defect size is a key parameter for selecting the best procedure to repair cartilage. However, the defect's size is not related to the patient's total cartilage surface. This is because assessing the femoral cartilage surface area is time-consuming and therefore unsuitable in the daily clinical routine. It has been proposed that the femur's total cartilage area correlates positively with the transepicondylar distance (TEA). The knees of 40 subjects were analysed. Their average age was 30.1 ± 8.6 years. Twenty-four female and 16 male subjects were examined. Their mean body height was 176.2 ± 8.8 cm. MRI scans were performed via 3-Tesla MRI. These data were postprocessed and quantified using the browser-based, customizable SATORI platform (Fraunhofer MEVIS). This software computed the femoral cartilage surface area (FeCA), the patella cartilage surface area (PCA), the TEA and the patella length. Body height reveals a good correlation (r = 0.722, p < 0.001) with the distal femur's cartilage area surface. However, regression analysis shows only moderate dependence (R2: 0.514). A very good correlation (r = 0.830, p < 0.001) was observed between the TEA distance and the total cartilage surface area of the distal femur. The regression analysis yields a good value (R2: 0.684). The cranio-caudal length of the patella was chosen as a suitably measurable two-dimensional parameter for correlation analysis with the patella's total cartilage surface area. Those results yield a poor correlation (r = 0.577, p < 0.001) between the two parameters, and regression analysis reveals a low value (R2: 0.384). The TEA is a reliable parameter for estimating the femur's cartilage area using MRI. A simple determination of this parameter allows the estimation of the femur's total cartilage area as well as the surface-corrected defect size (SCDS) in daily routine. Level II.

Assessment of whole cartilage surface damage in an osteoarthritis rat model: The Cartilage Roughness Score (CRS) utilizing microcomputed tomography

ObjectiveThis study aims to establish an accurate and robust imaging biomarker for pre-clinical osteoarthritis (OA) research, focusing on early detection of cartilage surface degeneration. MethodUsing 50 male Wistar rats, this study aims to observe Collagenase Induced Osteoarthritis (CIOA) progression through microcomputed x-ray tomography (µCT), histopathological analysis, and gait analysis. A novel parameter, Cartilage Roughness Score (CRS), was developed for assessing cartilage structural damage from µCT data and was compared with histological OARSI Cartilage Degeneration Score (OARSI CDS). Additionally, as CRS maps the full surface, it was used to simulate the level of uncertainty in histological sampling. ResultsCRS and OARSI CDS have a linear relationship. CRS for healthy cartilage is 2.75 (95% CI: 1.14-4.36) and with every 1 unit increase in OARSI, CRS is expected to increase by 0.64 (95% CI: 0.35-0.92). Cartilage degeneration due to CIOA was evident in both histopathological scoring and CRS. However, only CRS was sensitive enough to show consistent damage progression from day 10 to day 60. Furthermore, our simulation for histological sampling suggested that up to 16 coronal slices with 200µm spacing would be needed to accurately represent the full extent of cartilage surface degeneration in a slice wise manner. Gait analysis showed changes solely at eight days post-collagenase injection, normalizing by day 60. ConclusionThe CRS analysis method emerges as a robust tool for cartilage surface damage assessment. This study demonstrates the potential of automatic 3D analysis over the traditional 2D histological approach when evaluating cartilage surface damage. Data statementMicro-computed tomography data is available via ida.fairdata.fi46 (https://doi.org/10.23729/f33d3ba8-01b8-47af-90dd-94b7c7861247)

Promotion and Mechanism of Acupotomy on Chondrocyte Autophagy in Knee Osteoarthritis Rabbits.

To explore the effect of acupotomy intervention on autophagy of chondrocytes in rabbits with knee osteoarthritis (KOA), and to determine the possible mechanisms of acupotomy to alleviate cartilage degeneration. The modified Videman method was used to construct a KOA rabbit model. After modeling, 40 rabbits were randomly divided into 4 groups by a random number table: control; KOA (model); KOA + acupotomy (acupotomy), and KOA + sham acupotomy (sham), 10 in each group. After a 3-week treatment course, the knee joint activity was determined by the modified Lequesne MG index. Hematoxylin-eosin staining staining was used to examine the morphological changes of chondrocytes. Autophagy of chondrocytes was observed by transmission electron microscopy. The surface morphology of cartilage tissue was observed by scanning electron microscope. The mRNA and protein levels of AMP kinase/mammalian target of rapamycin/Unc-51 (AMPK/mTOR/ULK1) signal pathway key proteins, autophagy-related factor Beclin-1 and microtubule-associated protein 1A/1B light chain 3 (LC3) in rabbit knee cartilage were assessed by real-time fluorescence quantitative polymerase chain reaction and Western blot, respectively. The modified Lequesne MG score of acupotomy group was significantly lower than that of model group (P<0.05). Pathological results showed that chondrocyte autophagy decreased and cartilage surface was rough in the model group, which recovered after acupotomy treatment. The mRNA expressions of AMPK, ULK1, Beclin-1 and the protein levels of p-AMPK, p-ULK1, Beclin-1, and LC3 II/LC3 I were decreased in the model group, while the mRNA and protein expressions of mTOR were increased (P<0.01). However, acupotomy treatment reversed these abnormal changes (P<0.05). Acupotomy could effectively up-regulate the expressions of AMPK, ULK1 and Beclin1, reduce the expression of mTOR, promote autophagy, and alleviate joint degeneration. Acupotomy is a promising complementary and alternative therapy for KOA.

Effect of moxibustion on plasma amino acid metabolism in rats with knee osteoarthritis.

To observe the effect of moxibustion at "Zusanli "(ST36) on the plasma amino acid metabolism in rats with knee osteoarthritis (KOA), and to explore the amino acid metabolism mechanism of moxibustion in repairing cartilage injury in KOA. A total of 30 SD rats were randomly divided into normal, model and moxibustion groups, with 10 rats in each group. Rats in the model and moxibustion groups were injected with the mixture of L-cysteine and papain into bilateral knee joint cavity to make the KOA model. The moxibustion group received moxibustion at bilateral ST36 for 30 min, once daily for 30 days. At the end of the experiment, the swelling degree of knee joint was calculated, the mechanical pain threshold was measured by the Von Frey filament, the cartilage tissue injury was observed by HE staining, the matrix metalloproteinase-13 (MMP-13) content in the synovial tissue was detected by enzyme-linked immunosorbent assay (ELISA), and the differential amino acid metabolites in plasma were detected and screened by liquid chromatography-mass spectrometry (LC-MS). Compared with the normal group, the model group showed irregular cartilage surface, decreased number of chondrocytes, uneven distribution, and local clusters of chondrocytes；the contour of the tide line was blurred. The degree of joint swelling in the model group was higher than that in the normal group (P<0.01), the mechanical pain threshold was lower (P<0.01), and the content of MMP-13 in synovial tissue was higher (P<0.01). The contents of proline and tryptophan in the model group were down-regulated (P<0.01, P<0.05). Compared with the model group, the cartilage tissue damage and knee joint swelling were decreased(P<0.05), mechanical pain threshold was increased(P<0.05), MMP-13 content in synovial tissue and levels of glutamate and histidine expression were decreased (P<0.01, P<0.05). Moxibustion at ST36 significantly alleviated arthritis-related swelling and pain in KOA model rats, attenuated cartilage damage, and regulated levels of certain plasma amino acid metabolites. Moxibustion may regulate KOA cartilage synthesis and degradation through amino acid metabolic pathways such as proline, tryptophan, glutamate and histidine, exerting anti-inflammatory, analgesic, and protection of cartilage injury effects.

An in situ forming cartilage matrix mimetic hydrogel scavenges ROS and ameliorates osteoarthritis after superficial cartilage injury

Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in clinical settings, posing significant treatment challenges. Here, we fabricated a cartilage extracellular matrix mimic hydrogel (GHC, consisting of Gelatin, Hyaluronic acid, and Chondroitin sulfate) to avoid the exacerbation of cartilage deterioration, which is often driven by the accumulation of reactive oxygen species (ROS) and a pro-inflammatory microenvironment. The GHC hydrogel exhibited multifunctional properties, including in situ formation, tissue adhesiveness, anti-ROS capabilities, and the promotion of chondrogenesis. The enhancement of tissue adhesion was achieved by chemically modifying hyaluronic acid and chondroitin sulfate with o-nitrobenzene, enabling a covalent connection to the cartilage surface upon light irradiation. In vitro characterization revealed that GHC hydrogel facilitated chondrocyte adhesion, migration, and differentiation into cartilage. Additionally, GHC hydrogels demonstrated the ability to scavenge ROS in vitro and inhibit the production of inflammatory factors by chondrocytes. In the animal model of superficial cartilage injury, the hydrogel effectively promoted cartilage ECM regeneration and facilitated the interface integration between the host tissue and the material. These findings suggest that the multifunctional GHC hydrogels hold considerable promise as a strategy for cartilage defect repair. Statement of significanceSuperficial cartilage defects represent the most prevalent type of cartilage injury encountered in the clinic. Previous cartilage tissue engineering materials are only suitable for full-thickness cartilage defects or osteochondral defects. Here, we developed a multifunctional GHC hydrogel composed of gelatin, hyaluronic acid, and chondroitin sulfate, which are natural cartilage extracellular matrix components. The drug-free and cell-free hydrogel not only avoids immune rejection and drug toxicity, but also shows good mechanical properties and biocompatibility. More importantly, the GHC hydrogel could adhere tightly to the superficial cartilage defects and promote cartilage regeneration while protecting against oxidation. This natural ingredients and multifunctional hydrogel is a potential material for repairing superficial cartilage defects.

Midterm Clinical Outcomes of a Resurfacing Capitate Pyrocarbon Implant: A Case Series

Abstract Purpose Scaphoid nonunion advanced collapse (SNAC), scapholunate advanced collapse (SLAC), and Kienbock's disease are some of the most common pathologies to result in arthritis of the wrist in patients with a relatively high functional demand. An option for treatment where there are not two cartilage surfaces suitable for articulation to allow either a proximal row carpectomy (PRC) or partial fusion is to perform a PRC combined with resurfacing of the capitate using a pyrocarbon implant (RCPI). The purpose of this study was to examine the medium-term survivorship, clinical-, and patient-reported outcomes of the RCPI in a case series of patients. Methods Survivorship was assessed in 46 patients at approximately 21 months or greater (range = 21–144, median follow-up = 67). Of these, 36 patients completed patient-reported outcome measures (Visual Analogue Scales, Disabilities of the Arm, Shoulder and Hand–short form, Patient-Rated Wrist Evaluation, Global Rating of Change) at 21 months or greater. Patient population was 42% (n = 16) female, average age was 59 (range = 25–79), and majority had the operation on their right hand (78%, n = 35). Results Implant survival can be confirmed until most recent follow-up at a median of 60 months (range = 21–144), with Kaplan–Meier analysis indicating an 83% survival probability at 10 years. Complications at 21 months or greater were observed in 11 patients (24%), with 9 (20%) patients receiving further surgery (7 wrist fusions, 1 ulnar nerve decompression, and 1 distal radioulnar joint replacement [RCPI in situ]). Time to revision was a mean of 20 months (range = 4–39). Comparison between passive range of motion at 21 months to 4 years and &gt;5 years showed no significance (p &gt; 0.5), suggesting 2- to 4-year outcomes are maintained midterm. Conclusions The RCPI extends the indications for PRC where there is unsatisfactory cartilage on the proximal capitate, the lunate facet of the radius, or both. It provides a safe and effective treatment for pain relief and improved functional use of the hand for SLAC and SNAC arthritis without the increased morbidity of more complex arthroplasty or total wrist arthrodesis. Level of Evidence IV, case series