Cartilage Injury Research Articles

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.

Sports injury prevalence and associated factors in functional fitness: a cross-sectional study

PurposeWe investigated injury rates over the previous 12 months, associated factors, and injury characteristics in a cohort of recreational functional fitness training participants.MethodsA cross-sectional study was conducted with a convenience sample of 304 participants (175 females and 129 males; mean age: 32.6 ± 7.2 years; mean training experience: 27.6 ± 21.4 months) from three CrossFit™ affiliated gyms in Brazil. Data were collected via face-to-face interviews, using a questionnaire that focused on functional fitness-related injuries in the previous year and included data on participant demographics and training regimens.ResultsOut of all the participants, 82 (27.0%) experienced a functional fitness-related injury with an incidence rate of 1.22 injuries/1000 hours of participation. The practice of other sports activities and dissatisfaction with joint mobility of the shoulders increased the odds of being injured in the multivariate logistic regression. The shoulder was the most affected body part (26.6%). A gradual injury mechanism was the most commonly reported (36.2%), and joint sprain (18.1%), cartilage injury (11.7%), and tendinopathy (10.6%) were the most common pathology types. Concerning symptom severity, in most cases, participants referred to the injury as severe (36.2%), with a sporting time loss greater than 28 days (50%).ConclusionsInjury prevalence over the last 12 months was 27.0% (82/304), with an incidence of 1.22 injuries/1000 hours. The practice of other sports activities and dissatisfaction with joint mobility of the shoulders increased the odds of injury. Most injuries occurred in the shoulder, with a gradual injury mechanism, and participants classified symptoms as severe, leading to significant sporting time loss.

A dynamically loaded ex vivo model to study neocartilage and integration in human cartilage repair.

Articular cartilage injuries in the knee can lead to post-traumatic osteoarthritis if untreated, causing debilitating problems later in life. Standard surgical treatments fail to ensure long lasting repair of damaged cartilage, often resulting in fibrotic tissue. While there is a vast amount of research into cartilage regeneration, integrating engineered implants with cartilage remains a challenge. As cartilage is a load bearing tissue, it is imperative to evaluate tissue repair strategies and their ability to integrate under mechanical loading. This work established a dynamically loaded ex vivo model of cartilage repair using human cartilage explants. The model was used to assess the efficacy of a stem cell therapy delivered in a bioadhesive hydrogel comprised of photocrosslinkable gelatin methacryloyl (GelMA) and microbial transglutaminase to repair the model defect. Extensive neocartilage production and integration were observed via histology and immunohistochemistry after 28days chondrogenic culture. Analysis of culture media allowed monitoring of glycosaminoglycan and type II collagen production over time. A mechanical assessment of integration via a push out test showed a 15-fold increase in push out strength over the culture duration. The model was successful in exhibiting robust chondrogenesis with transglutaminase or without, and under both culture conditions. The work also highlights several limitations of ex vivo models and challenges of working with bioreactors that must be overcome to increase their utility. This ex vivo model has the potential to delay the need for costly pre-clinical studies and provide a more nuanced assessment of cartilage repair strategies than is possible in vivo.

Research Progress on the SDF-1/CXCR4 Axis in Cartilage Injury

The chemokine CXCL12, also known as stromal cell-derived factor 1 (SDF-1), is a small pro-inflammatory chemokine that primarily binds to CXC receptor 4 (CXCR4; CD184), serving as a major regulatory factor for cell transport and adhesion. When SDF-1 binds to CXCR4, it triggers intracellular signaling through several pathways that initiate processes such as chemotaxis, cell survival, proliferation, calcium influx, and gene transcription. The SDF-1/CXCR4 axis plays a crucial role in the development of bone marrow stem cells and the process of tissue regeneration. Repairing cartilage tissue necessitates a sufficient number of chondrocytes, making bone marrow mesenchymal stem cells particularly suitable for this purpose. This signaling pathway is essential for cartilage injury repair. It promotes stem cell migration and localization, regulates cell proliferation and differentiation, and inhibits inflammatory responses. This article reviews the current research advancements related to the SDF-1/CXCR4 axis in cartilage tissue repair.

Omega-3 fatty acids protect cartilage from acute injurie by reducing the mechanical sensitivity of chondrocytes

Acute cartilage injuries, such as intra-articular fractures and blunt impacts, frequently result in chondrocyte death and extracellular matrix (ECM) degradation, significantly elevating the risk of post-traumatic osteoarthritis (PTOA). Despite advances in treatment, no effective therapies currently exist to fully cure PTOA or halt its progression. This study explores the protective effects of the dietary fatty acid eicosapentaenoic acid (EPA) on human primary chondrocytes (HPCs) and cartilage explants exposed to mechanical overload and blunt trauma. HPCs were isolated and subjected to mechanical stretching using BioFlex six-well culture plates, while cartilage explants were subjected to impact loading via a customized drop tower. EPA was incorporated into the culture medium, followed by assays to evaluate cell viability, calcium (Ca²⁺) influx, apoptosis, reactive oxygen species (ROS) levels, and collagen type II alpha (Col-2a) expression. EPA treatment markedly decreased chondrocyte mechanical sensitivity, as demonstrated by enhanced cell viability and reduced lactate dehydrogenase (LDH) release. Furthermore, EPA inhibited Piezo1 activation, leading to lower intracellular Ca²⁺ concentrations, decreased apoptosis, and diminished ROS levels. In cartilage explants, EPA improved chondrocyte viability, minimized structural damage, and sustained higher Col-2a expression compared to the blunt trauma group. These results indicate that EPA effectively shields chondrocytes and cartilage explants from mechanical overload-induced damage by inhibiting Piezo1 activation and mitigating Ca²⁺ influx, apoptosis, and oxidative stress. The findings suggest that EPA supplementation could offer a promising strategy for preventing PTOA progression following acute cartilage injuries. Further research is warranted to assess the clinical applications of EPA and confirm its efficacy in larger animal models and human trials.

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

New perspectives on the role of platelet factors in enhancing wound regeneration

Aim. To analyze the use of biological factors in the stimulation of the wound healing process. In the course of the study, we analysed relevant domestic and foreign literature sources on the given topic.Methods. The literature was reviewed using the key query ‘the role of biological factors in wound healing stimulation’ through the eLIBRARY and PubMed databases.Results. Currently, the range of therapeutic approaches is broad and diverse, incorporating both traditional and experimental methods such as advanced dressings, tissue matrices, growth factors (GFs), cell therapy, and nanotechnology. The wound healing process is regulated by a complex interplay of intercellular, intracellular, and extracellular signalling mechanisms across various phases of healing.Conclusion. The application of platelet-based therapies in different medical fields has shown promising outcomes in certain conditions, such as acute and chronic injuries of bone and cartilage. However, platelet-based preparations have yet to gain widespread clinical use. Several studies have demonstrated the involvement of platelets and related products, such as platelet microparticles (PMPs) and exosomes, in multiple phases of wound healing. The presence of a substantial number of biologically active molecules within platelet granules—exhibiting anti-inflammatory, angiogenic, proliferative, and other properties—renders platelets particularly attractive for use in regenerative medicine, including the stimulation of wound healin

Metabolic modulation to improve MSC expansion and therapeutic potential for articular cartilage repair

BackgroundArticular cartilage degeneration can result from injury, age, or arthritis, causing significant joint pain and disability without surgical intervention. Currently, the only FDA cell-based therapy for articular cartilage injury is Autologous Chondrocyte Implantation (ACI); however, this procedure is costly, time-intensive, and requires multiple treatments. Mesenchymal stromal cells (MSCs) are an attractive alternative autologous therapy due to their availability and ability to robustly differentiate into chondrocytes for transplantation with good safety profiles. However, treatment outcomes are variable due to donor-to-donor variability as well as intrapopulation heterogeneity and unstandardized MSC manufacturing protocols. Process improvements that reduce cell heterogeneity while increasing donor cell numbers with improved chondrogenic potential during expansion culture are needed to realize the full potential of MSC therapy.MethodsIn this study, we investigated the potential of MSC metabolic modulation during expansion to enhance their chondrogenic commitment by varying the nutrient composition, including glucose, pyruvate, glutamine, and ascorbic acid in culture media. We tested the effect of metabolic modulation in short-term (one passage) and long-term (up to seven passages). We measured metabolic state, cell size, population doubling time, and senescence and employed novel tools including micro-magnetic resonance relaxometry (µMRR) relaxation time (T2) to characterize the effects of AA on improved MSC expansion and chondrogenic potential.ResultsOur data show that the addition of 1 mM L-ascorbic acid-2-phosphate (AA) to cultures for one passage during MSC expansion prior to initiation of differentiation improves chondrogenic differentiation. We further demonstrate that AA treatment reduced the proportion of senescent cells and cell heterogeneity also allowing for long-term expansion that led to a > 300-fold increase in yield of MSCs with enhanced chondrogenic potential compared to untreated cells. AA-treated MSCs with improved chondrogenic potential showed a robust shift in metabolic profile to OXPHOS and higher µMRR T2 values, identifying critical quality attributes that could be implemented in MSC manufacturing for articular cartilage repair.ConclusionsOur results suggest an improved MSC manufacturing process that can enhance chondrogenic potential by targeting MSC metabolism and integrating process analytic tools during expansion.

Injection therapy in professional footballers.

Injection therapy offers a minimally invasive approach for symptomatic relief that allows concurrent training, limiting time loss and providing a faster recovery. However, there is a lack of scientific evidence to support it, and there are controversies about its use. The present narrative review aims to present the available scientific literature on injection therapies in professional footballers (PF), highlighting the advantages and disadvantages of its use in the most common injuries. The authors searched and reviewed contemporary literature on injection therapies in PF in electronic databases, summarizing them in a narrative review. Injection therapies such as hyaluronic acid and PRP have shown an adequate safety profile that allows their use. Current evidence suggests that hyaluronic acid injections are a valid option for managing symptomatic cartilage injuries. At the same time, PRP injections have failed to prove beneficial in treating muscle injuries and should be avoided until further evidence proves the opposite. Yet, PRP may have potential use in partial ACL injuries, anterior inferior tibiofibular ligament injuries (ankle syndesmosis), and fifth metatarsal fractures and needs further study. Due to the long-term health repercussions, other injection therapies should be preferred over corticosteroids in PF. There is a paucity of evidence on the use and benefits of injection therapies in PF despite its extensive use among physicians. Viscosupplementation may have a role in improving symptomatic cartilage injuries. In contrast, PRP injection therapy needs further high-quality clinical trials to assess its role in PF sports injuries.

Hesperetin Attenuates T-2 Toxin-Induced Chondrocyte Injury by Inhibiting the p38 MAPK Signaling Pathway.

Hesperetin, a flavonoid derived from citrus fruits, exhibits potent antioxidant and anti-inflammatory activities and has been implicated in cartilage protection. However, its effectiveness against T-2 toxin-induced knee cartilage damage remains unclear. In this study, high-throughput sequencing analysis was employed to identify the key signaling pathways involved in T-2 toxin-induced articular cartilage damage in rats. Animal models were divided into the following groups: control, low-dose T-2 toxin, high-dose T-2 toxin, T-2 toxin + hesperetin, hesperetin, and vehicle. Pathological staining and immunohistochemistry were used to assess pathological changes, as well as the expression levels of the cartilage matrix-related proteins MMP13 and collagen II, along with the activation of the p38 MAPK signaling pathway. Additionally, primary rat chondrocytes were cultured to establish an in vitro model for investigating the underlying mechanism. High-throughput sequencing analysis revealed the involvement of the MAPK signaling pathway in T-2 toxin-induced articular cartilage damage in rats. Hesperetin intervention in T-2 toxin-exposed rats attenuated pathological cartilage damage. Immunohistochemistry results demonstrated a significant reduction in collagen II protein expression in the high-dose T-2 toxin group (p < 0.01), accompanied by a significant increase in MMP13 protein expression (p < 0.01). In both the articular cartilage and the epiphyseal plate, the T-2 toxin + hesperetin group exhibited significantly higher collagen II protein expression than the high-dose T-2 toxin group (p < 0.05), along with significantly lower MMP13 protein expression (p < 0.05). Hesperetin inhibited the over-activation of the p38/MEF2C signaling axis induced by T-2 toxin in primary rat chondrocytes. Compared to the T-2 toxin group, the T-2 toxin + hesperetin group showed significantly reduced phosphorylation levels of p38 and protein expression levels of MEF2C (p < 0.001 or p < 0.05). Moreover, the T-2 toxin + hesperetin group exhibited a significant decrease in MMP13 protein expression (p < 0.05) and a significant increase in collagen II protein expression (p < 0.01) compared to the T-2 toxin group. T-2 toxin activates the p38 MAPK signaling pathway, causing knee cartilage damage in rats. Treatment with hesperetin inhibits the p38/MEF2C signaling axis, regulates collagen II and MMP13 protein expression, and reduces cartilage injury significantly.

Application of adhesives in the treatment of cartilage repair

AbstractFrom degeneration causing intervertebral disc issues to trauma‐induced meniscus tears, diverse factors can injure the different types of cartilage. This review highlights adhesives as a promising and rapidly implemented repair strategy. Compared to traditional techniques such as sutures and wires, adhesives offer several advantages. Importantly, they seamlessly connect with the injured tissue, deliver bioactive substances directly to the repair site, and potentially alleviate secondary problems like inflammation or degeneration. This review delves into the cutting‐edge advancements in adhesive technology, specifically focusing on their effectiveness in cartilage injury treatment and their underlying mechanisms. We begin by exploring the material characteristics of adhesives used in cartilage tissue, focusing on essential aspects like adhesion, biocompatibility, and degradability. Subsequently, we investigate the various types of adhesives currently employed in this context. Our discussion then moves to the unique role adhesives play in addressing different cartilage injuries. Finally, we acknowledge the challenges currently faced by this promising technology.

Clinical study on improving the diagnostic accuracy of adult elbow joint cartilage injury by multisequence magnetic resonance imaging.

Due to frequent and high-risk sports activities, the elbow joint is susceptible to injury, especially to cartilage tissue, which can cause pain, limited movement and even loss of joint function. To evaluate magnetic resonance imaging (MRI) multisequence imaging for improving the diagnostic accuracy of adult elbow cartilage injury. A total of 60 patients diagnosed with elbow cartilage injury in our hospital from January 2020 to December 2021 were enrolled in this retrospective study. We analyzed the accuracy of conventional MRI sequences (T1-weighted imaging, T2-weighted imaging, proton density weighted imaging, and T2 star weighted image) and Three-Dimensional Coronary Imaging by Spiral Scanning (3D-CISS) in the diagnosis of elbow cartilage injury. Arthroscopy was used as the gold standard to evaluate the diagnostic effect of single and combination sequences in different injury degrees and the consistency with arthroscopy. The diagnostic accuracy of 3D-CISS sequence was 89.34% ± 4.98%, the sensitivity was 90%, and the specificity was 88.33%, which showed the best performance among all sequences (P < 0.05). The combined application of the whole sequence had the highest accuracy in all sequence combinations, the accuracy of mild injury was 91.30%, the accuracy of moderate injury was 96.15%, and the accuracy of severe injury was 93.33% (P < 0.05). Compared with arthroscopy, the combination of all MRI sequences had the highest consistency of 91.67%, and the kappa value reached 0.890 (P < 0.001). Combination of 3D-CISS and each sequence had significant advantages in improving MRI diagnostic accuracy of elbow cartilage injuries in adults. Multisequence MRI is recommended to ensure the best diagnosis and treatment.

Three-dimensional gas-foamed scaffolds decorated with metal phenolic networks for cartilage regeneration

Inflammation is a major impediment to the healing of cartilage injuries, yet bioactive scaffolds suitable for cartilage repair in inflammatory environments are extremely rare. Herein, we utilized electrospinning to fabricate a two-dimensional nanofiber scaffold (2DS), which was then subjected to gas foaming to obtain a three-dimensional scaffold (3DS). 3DS was modified with metal phenolic networks (MPNs) composed of epigallocatechin gallate (EGCG) and strontium ions (Sr2+) to afford a MPNs-modified 3D scaffold (3DS-E). Gas-foamed scaffold exhibited multilayered structure conducive to cellular infiltration and proliferation. Compared to other groups, 3DS-E better preserved chondrocytes under interleukin (IL)-1β induced inflammatory environment, showing less apoptosis of chondrocytes and higher expression of cartilage matrix. Additionally, 3DS-E facilitated the regeneration of more mature cartilage in vivo, reduced cell apoptosis, and decreased the expression of pro-inflammatory cytokines.Taken together, 3DS-E may offer an ideal candidate for cartilage regeneration.

Selenium deficiency and T-2 toxin trigger ferroptosis in cartilage from Kashin-Beck diseases

Kashin-Beck disease (KBD) is a prevalent, endemic, and degenerative cartilage injury disorder, characterized by high rates of teratogenicity and disability. The etiology and pathogenesis of KBD are not fully understood, although research suggests that selenium deficiency and exposure to T-2 toxin are significant environmental risk factors. The initial pathological changes of KBD manifest as necrosis of deep chondrocytes, dedifferentiation of chondrocytes, excessive apoptosis of chondrocytes, and subsequent disruption of extracellular matrix metabolism. However, the precise pathogenic mechanisms of chondrocyte damage in KBD remain incompletely understood. Ferroptosis is auniqueform of programmed cell death triggered byiron-dependent lipid peroxide accumulation. It has been shown to contribute to cartilage damage and chondrocyte death in various osteoarticular conditions, particularly osteoarthritis (OA). Notably, KBD not only exhibits clinical and pathologicalsimilarities with OA, but also indicates a potential association with ferroptosis in morphological and molecular similarities. Additionally, the environmental risk factors T-2 toxin exposure and selenium deficiency are also significant contributors toferroptosis. Consequently, it is plausible to postulate that environmental risk factors may trigger ferroptosis, leading to the initiation of cartilage damage in KBD. Our hypothesis can be verified through both in vitro and in vivo experiments. Chondrocyte injury induced by ferroptosis may be a novel finding in KBD, which is important for clarifying its etiology and developing effective therapeutic strategies.

Baicalin Ameliorates Cartilage Injury in Rats With Osteoarthritis via Modulating miR-766-3p/AIFM1 Axis

The study aims to elucidate the therapeutic mechanism of Baicalin (BAI) in alleviating cartilage injury in osteoarthritic (OA) rat models, concentrating on its regulation of the miR-766-3p/AIFM1 axis. An OA rat model was developed with unilateral anterior cruciate ligament transection (ACLT). Interventions comprised of BAI treatment and intra-articular administration of miR-766-3p inhibitor. For evaluation, histopathological staining was conducted to investigate the pathological severity of knee cartilage injury. The levels of oxidative stress (OS) indicators including MDA, SOD, and GSH-Px, were quantified using colorimetric assays. Inflammatory factors (IFs; TNF-α, IL-1β, and IL-6) in knee joint lavage fluids were assessed using ELISA, while RT-PCR was employed to quantify miR-766-3p expression. TUNEL apoptosis staining was utilized to detect chondrocyte apoptosis, and western blotting examined autophagy-related markers (LC3, Beclin, p62), extracellular matrix (ECM) synthesis-associated indices (COL2A, ACAN, MMP13), and apoptosis-inducing factor mitochondrion-associated 1 (AIFM1). Histological examination revealed a marked amelioration of cartilage injury in the BAI-treated OA rat models compared to controls. BAI treatment significantly reduced inflammation and OS of knee joint fluid, activated autophagy, and decreased chondrocyte apoptosis and ECM degradation. Interestingly, the inhibitory effects of BAI on these pathological markers were significantly decreased by the miR-766-3p inhibitor. Further assessment revealed that BAI efficiently promoted miR-766-3p expression while inhibiting AIFM1 protein expression. BAI potentially mitigates articular cartilage injury in OA rats, likely through modulation of miR-766-3p/AIFM1 axis.

External Focus of Attention Reduces Cartilage Load During Drop Landings.

The aim of the present study was to examine the effects of attentional focus instructions on acute changes in the transverse relaxation time (T2) of the femorotibial cartilage and in cartilage volume during repeated drop-jump landings. Ten healthy females (Mage = 20.4 ± 0.8 years) performed a drop landing task from a 50 cm high box over the course of 3 days (50 repetitions each day) across three attentional focus conditions: external focus (EF: focus on landing as soft as possible), internal focus (IF: focus on bending your knees when you land), and control (CON: no-focus instruction), which was counterbalanced across focus conditions. T2 mapping and the volume of femorotibial cartilage were determined from magnetic resonance imaging scans at 1.5 T for the dominant knee before and after completing the drop landings in each attentional focus condition per day. Results indicated a smaller change in cartilage T2 relaxation time and volumetry in the central load-bearing lateral cartilage under the EF, compared to IF and CON. Moreover, the change in T2 and cartilage volume was greater for lateral tibial cartilage as compared to femoral cartilage and was independent of attentional focus instructions. No significant acute quantitative changes were observed in the medial compartment. The peak vertical ground reaction force was found to be the lowest under the EF, compared to IF and CON. These findings suggest that external focus of attention may reduce cartilage load, potentially aiding in the control or management of cartilage injuries during landing in female athletes.

Novel injectable adhesive hydrogel loaded with exosomes for holistic repair of hemophilic articular cartilage defect

Hemophilic articular cartilage damage presents a significant challenge for surgeons, characterized by recurrent intraarticular bleeding, a severe inflammatory microenvironment, and limited self-repair capability of cartilage tissue. Currently, there is a lack of tissue engineering-based integrated therapies that address both early hemostasis, anti-inflammation, and long-lasting chondrogenesis for hemophilic articular cartilage defects. Herein, we developed an adhesive hydrogel using oxidized chondroitin sulfate and gelatin, loaded with exosomes derived from bone marrow stem cells (BMSCs) (Hydrogel-Exos). This hydrogel demonstrated favorable injectability, self-healing, biocompatibility, biodegradability, swelling, frictional and mechanical properties, providing a comprehensive approach to treating hemophilic articular cartilage defects. The adhesive hydrogel, featuring dynamic Schiff base bonds and hydrogen bonds, exhibited excellent wet tissue adhesiveness and hemostatic properties. In a pig model, the hydrogel could be smoothly injected into the knee joint cartilage defect site and gelled in situ under fluid-irrigated arthroscopic conditions. Our in vitro and in vivo experiments confirmed that the sustained release of exosomes yielded anti-inflammatory effects by modulating macrophage M2 polarization through the NF-κB pathway. This immunoregulatory effect, coupled with the extracellular matrix components provided by the adhesive hydrogel, enhanced chondrogenesis, promoted the cartilage repair and joint function restoration after hemophilic articular cartilage defects. In conclusion, our results highlight the significant application potential of Hydrogel-Exos for early hemostasis, immunoregulation, and long-term chondrogenesis in hemophilic patients with cartilage injuries. This innovative approach is well-suited for application during arthroscopic procedures, offering a promising solution for addressing the complex challenges associated with hemophilic articular cartilage damage.

After 40 days intra-articular injury, risk profile increases linearly with time to surgery in adolescent patients undergoing primary anterior cruciate ligament reconstruction.

Anterior cruciate ligament (ACL) injuries are becoming more common in youth athletes. Time-to-surgery has been shown to significantly affect the rates of concurrent injuries at the time of ACL reconstruction (ACLR). The purpose of this study was to evaluate if time-to-surgery in ACLR impacts observances of intra-articular injuries and to categorize injury profile in relation to time. An Institutional Review Board-approved retrospective cohort study was conducted. Included subjects were aged 21 and below and underwent primary ACLR within 6 months of injury between January 2012 and April 2020. Skeletal maturity was determined via imaging. Laterality, location and severity/pattern of meniscal and chondral injuries were recorded. Multivariate logistic regression was utilized to identify risk factors for intra-articular pathology. Cut-off analyses were added to regression models to identify trends of concurrent injuries. Eight hundred and fifty patients met the inclusion criteria. Patients with observed articular cartilage injuries had a significantly longer time-to-surgery of 66 days (p = 0.01). Risk factors for chondral injury were time-to-surgery (p = 0.01) and skeletal maturity (p = 0.01), while medial meniscal tears were prognosticated by time-to-surgery (p = 0.03), skeletal maturity (p = 0.01) and body mass index (p = 0.00). Cut-off analysis showed that after 40 days the proportion of patients with observed chondral injury increased with time to surgery and that there were significantly different observances of chondral (p = 0.00) and medial meniscal (p = 0.03) injuries in the 6-week model, as compared to the continuous time model. Longer time-to-surgery in ACLR is associated with higher rates of concomitant intra-articular pathology, especially chondral injuries. After 40 days, the observed rates of intra-articular injury increase proportionately with time from injury. A 6-week categorical model best stratifies intra-articular injury risk profile. Risk factor analysis identified skeletally mature patients with delayed surgery of >12 weeks to be at the highest risk for both chondral and medial meniscal injuries after an ACLR. Level III.

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.