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Osteoarthritis is a degenerative disease that affects articular cartilage, leading to changes on the macro and micro levels of this multi-component tissue. Understanding the processes underlying this pathology plays an important role in planning the following management tactics. Timely detection of the knee joint degradation at the level of tissue changes can prevent its progressive damage due to the early beginning of appropriate treatment. This study aimed to provide an overview of the current level of knowledge about the composition of cartilage and menisci using a wide range of different diagnostic methods. A systematic review of the literature published from 1978 to 2023 was conducted. Original studies of the knee joint cartilage (articular and meniscus) research, reporting content composition and mechanical properties, were included. Studies of the non-knee joint cartilage, tissue research other than cartilage and meniscus, or reporting treatment outcomes were excluded (n = 111). Thirty-one papers were included in this review, which reported on the composition of animal and human cartilage (articular and meniscus). The most frequently investigated parameters were quantitative proteoglycan determination and hydration level of the cartilage. Cartilage and meniscus degeneration, i.e., reduced collagen and proteoglycan content, reduced mechanical properties, and increased hydration level, was shown in every article about osteoarthritis. Among all diagnostic methods, laboratory methods (biochemical and histological analysis) are the most frequently used, compared to the instrumental ones (spectroscopy, MRI, and CT). At the same time, spectroscopy takes the lead and becomes the most common approach for determining cartilage composition (collagen and proteoglycans content). [ABSTRACT FROM AUTHOR]

Objectives: Microfracture (MFx) technique is the most commonly used first-line treatment for cartilage injuries; however, it has been shown to have inferior long-term clinical outcomes as the repaired tissue is predominantly fibrocartilage. Bone Marrow Aspirate Concentrate (BMAC) treatment has been shown to enhance the healing ability of cartilage repair, superior to MFx treatment alone, although chondral defect filling was achieved with fibrocartilage or "hyaline-like" cartilage. Therefore, new therapeutic strategies to further improve cartilage healing following defects are in need. Fisetin (FIS) is a compound with antioxidant, anti-inflammatory, and senolytic activity capable of eliminating senescent cells systemically. Previous studies have reported that FIS attenuates the progression of osteoarthritis and osteoporosis in aged mice, however, whether FIS treatment improves the quality of repaired cartilage in MFx-treated acute osteochondral defects augmented with BMAC has not yet been investigated. We hypothesized that FIS or autologous BMAC, or a combination of the two, would enhance MFx procedure both histologically and mechanically in the repair of osteochondral defects in a rabbit model. Methods: All surgical procedures were performed by an experienced orthopaedic surgeon and followed Institutional IACUC approved protocols. Sixty-four skeletally mature New Zealand White rabbits at seven months old were used in this study. Animal procedure: Before surgery, bone marrow aspirate was collected through the iliac crests in each rabbit under anesthesia and processed via a two-step centrifugation method to prepare BMAC. After exposing the bilateral knee joints through the medial parapatellar approach, osteochondral defects (diameter: 5 mm, depth: 2 mm) were created bilaterally in the patellar groove of each rabbit, followed by the MFx procedure (5 holes with 2 mm depth) to allow bleeding at each MFx hole as previously described (Fig.1). BMACs were injected into the left knee joint as an autograft immediately after closing the joint capsule in all rabbits, with the right knee as a control (no BMAC transplantation). Rabbits were then randomly divided into 4 groups (N=8/group): MFx alone, MFx+FIS, MFx+BMAC and MFx+FIS+BMAC. FIS-treated rabbits were given FIS orally via drinking water at a dose of 20 mg/kg/day daily from immediately after surgery until euthanasia. Rabbits were sacrificed at 6 and 12 weeks post-op. The macroscopic appearance was evaluated using the International Cartilage Repair Society (ICRS) macroscopic assessment grading. ΜicroCT and histology: Microcomputed tomography (μCT) was performed to evaluate subchondral bone healing. Cartilage healing was assessed histologically on de-calcified tissue at 6 and 12 weeks post-op (H&E, Safranin O, and Alcian blue) and with immunohistochemistry for collagen II and p16. Regenerated cartilage was scored using the Modified O'Driscoll ICRS grading system (max 27 points). Biomechanical tests: The strength of the regenerated cartilage was analyzed by measuring the instantaneous elastic modulus of the regenerated cartilage in each group of samples collected at 12 weeks. (N=6/group). Results: Macroscopic assessment and μCT : At both 6 and 12 weeks postoperatively, MFx+BMAC and MFx+FIS+BMAC groups scored significantly higher than MFx alone group in the ICRS macroscopic evaluation. (p < 0.01, Fig. 2 A, D and Fig. 3 A, D). At both 6- and 12-week time points after surgery, μCT showed favorable healing of the bone defect in MFx+FIS, MFx+BMAC, and MFx+FIS+BMAC groups compared to MFx alone group. (Fig. 2 B and Fig. 3 B). Histology : At both 6- and 12- week time points, the Modified O'Driscoll score was significantly higher in the MFx+BMAC and MFx+FIS+BMAC groups than in the MFx alone group (p <0.01), and at 12 weeks, the MFx+FIS group had a significantly higher score than the MFx alone group. (p <0.05, Fig. 2E and Fig. 3E). In addition, immunohistochemistry showed stronger staining of type II collagen (brown) in the MFx+FIS, MFx+BMAC, and MFx+FIS+BMAC groups than in the MFx alone group at both time points, with a stronger reduction in staining of the cellular senescence marker p16 (brown) in FIS-treated group compared to MFx alone or MFx+BMAC group. (Fig. 2C and Fig. 3C). Biomechanical analysis: The instantaneous elastic modulus (cartilage's strength) was significantly increased in the MFx+FIS+BMAC group compared to MFx alone group. (p < 0.05, Fig. 4). Gene expression analyses : qPCR showed the expression level of SOD1 in synovium was significantly higher in the MFx+FIS group at 6 weeks (p < 0.01) and in the MFx+FIS+BMAC group at 12 weeks (p < 0.05) compared to the MFx alone group. Conclusions: Our results showed that BMAC treatment enhanced the healing of MFx-treated osteochondral defects, macroscopically, biomechanically, and histologically, compared to MFx alone. Furthermore, FIS treatment improved MFx-treated cartilage repair, and its combined use with BMAC led to significantly higher quality cartilage regeneration with stronger mechanical properties. Oxidative stress, which is one of the inducers of cell senescence, has been noted as the primary factor contributing to age-related changes in cartilage homeostasis, function, and response to injury. Given the increase in SOD1 expression commensurate with p16 reduction in the FIS-treated group (Figs 2-3), our results suggest that FIS may improve cartilage healing via reducing cellular senescence. These results support the clinical use of FIS combined with BMAC to enhance the effect of MFx in the repair of osteochondral defects and highlight cellular senescence as a novel therapeutic target for cartilage repair following injury. Figure 1: Acute osteochondral defect microfracture rabbit model Figure 2: Macroscopy, MicroCT, and Histological findings at 6 weeks postoperatively A: Macroscopic findings. B: Micro CT showed better subchondral bone healing in the MFx+FIS, MFx+BMAC, and MFx+FIS+BMAC group. C: In the MFx+BMAC and MFx+FIS+BMAC groups, the ICRS macroscopic score was significantly increased compared to the MFx alone group. (D) In the MFx+BMAC and MFx+FIS+BMAC groups, the Modified O'Driscoll score increased significantly compared to the MFx alone group (E), indicating primarily hyaline-like cartilage regeneration. In addition, strong staining of type II collagen was observed in the MFx+FIS+BMAC groups, and there was a strong decrease in p16 (cellular senescence marker) staining in the FIS-treated group. * p <.05, ** p <.01. Figure 3: Macroscopy, MicroCT, and Histological findings at 12 weeks postoperatively A: Macroscopic findings. B: Micro CT showed better subchondral bone healing in the MFx+FIS, MFx+BMAC, and MFx+FIS+BMAC group. C: In the MFx+BMAC and MFx+FIS+BMAC groups, the ICRS macroscopic score was significantly increased compared to the MFx alone group. (D) In the MFx+FIS, MFx+BMAC, and MFx+FIS+BMAC groups, the Modified O'Driscoll score increased significantly compared to the MFx alone group (E), indicating primarily hyaline-like cartilage regeneration. In addition, strong staining of type II collagen was observed in the MFx+FIS, MFx+BMAC, and MFx+FIS+BMAC groups, and there was a strong decrease in p16 (cellular senescence marker) staining in the FIS-treated group. * p <.05, * * p <.01. Figure 4: Biomechanical findings at 12 weeks postoperatively Instantaneous elastic modulus (cartilage's strength) measurements for each group are shown, with a significant increase in the MFx+FIS+BMAC group compared to MFx alone group. * * P <.05 [ABSTRACT FROM AUTHOR]

Objectives: Patients with anterior cruciate ligament (ACL) injury are at high risk for the development of post-traumatic osteoarthritis (PTOA), despite ACL reconstruction (ACLR). ACL injuries are frequently associated with damage of other structures within the knee, such as the meniscus. The meniscus is an important structure that provides protection for articular cartilage and stabilization of the joint. Long-term studies of PTOA after ACLR mainly used radiographs. Conventional magnetic resonance imaging (MRI) has been used in a limited number of studies to evaluate structural damages, but this only provides information on morphologic changes that occur at relatively late stages of the disease. In this study, we aim to use quantitative MRI (qMRI) to evaluate cartilage and meniscus degeneration in patients at 10 years after ACLR. Methods: This is a multi-site multi-vendor study that involves three sites and two MR platforms (Siemens 3T and Philips 3T). MRI protocols have been harmonized between sites and cross validation data were collected using phantoms. The patients are from a nested cohort within Multicenter Orthopaedic Outcomes Network (MOON) Onsite Cohort at 10 years after ACLR. Inclusion/Exclusion criteria were: 22-50 years old; ACL tear during a sport; no previous knee injury; no graft rupture during follow-up. In this preliminary report, 51 patients (age 32.8 ± 6.4 years; 25 females; body mass index [BMI] 25.7 ± 5.7 kg/m2; 40 hamstring autograft, 9 bone-patellar tendon-bone autograft, and 2 allograft) and 17 healthy control participants (age 30.8 ± 7.8 years; 10 females; BMI 23.8 ± 5.6 kg/m2) were studied. The MRI protocol included high-resolution Dual-Echo Steady State (DESS), and combined gradient echo MAPSS T1ρ and T2 mapping. Cartilage and meniscus were automatically segmented on DESS images using an in-house developed deep-learning model into medial/lateral femoral condyle (MFC/LFC), medial/lateral tibia (MT/LT), trochlear (TRO), and patellar cartilage (PAT), and medial and lateral menisci (MM/LM). Each cartilage compartment was further divided into sub-regions based on a modified MRI Osteoarthritis Knee Score (MOAKS) definition: central and posterior for MFC/LMC (cMFC/cLMC, pMFC/pLMC); anterior, central, and posterior for MT/LT (aMT/aLT, cMT/cLT, pMT/pLT); medial, central, and lateral for PAT/TRO (mPAT/mTRO, cPAT/cTRO, lPAT/lTRO). Menisci were further divided into anterior horn (aMM, aLM), central (body) (cMM, cLM), and posterior horn (pMM, pLM) subregions. These cartilage and menisci subregions were then transformed and overlaid onto the T1ρ and T2 parameter maps after co-registering the DESS image to the first echo of the 3D MAPSS sequence using the Elastix toolbox. T1ρ and T2 parameter maps were obtained by a voxel-wise two-parameter monoexponential fitting. The mean and standard deviation for each subregion was recorded and compared between three knee groups: operated and contralateral knees from patients, and control knees from healthy controls, using a mixed-effects regression model, adjusted for age, sex, and BMI. Results: For cartilage, compared to contralateral knees, operated knees in patients had significantly higher T1ρ and T2 values in MFC, MT, and TRO compartments. Looking into subcompartments, for MFC, MT, and TRO, most of the subcompartments (cMFC, pMFC; cMT, pMT; mTRO, cTRO) showed significantly higher T1ρ and T2 values compared to contralateral knees. For LFC and LT, only the posterior subcompartments showed significantly higher T1ρ and T2 values compared to contralateral knees. For PAT, no significant differences were observed between operated and contralateral knees. Compared to healthy control knees, operated knees in patients had significantly higher T1ρ and T2 values in all the six compartments. Besides, contralateral knees also showed higher T1ρ and T2 values in LFC, LT and PAT compartments compared to healthy control knees (Figure 1 for T1ρ, T2 with similar trend was not shown). For meniscus, no significant differences in T1ρ and T2 values were observed between injured and contralateral knees. Compared to healthy control knees, both operated and contralateral knees in patients had significantly higher T1ρ values in LM and significantly higher T2 values in MM (Figure 2). Conclusions: Cartilage T1ρ and T2 values were higher in operated knees compared to contralateral knees at 10 years after ACLR, except for patellar compartment. In patellar cartilage, no significant differences were observed between sides in patients, but both sides were significantly higher than control knees. Our data showed that contralateral knees after ACLR may not represent 'healthy controls' as there might be compensatory changes and early degeneration in contralateral knees as a result of injury and surgery to their other knee. Although we observed this general trend of higher cartilage T1ρ and T2 values in the operated knees compared to contralateral knees, no significant differences were observed in meniscus T1ρ and T2 values between sides in patients, suggesting the timing of cartilage and meniscus degeneration may be different for patients after ACLR. Meniscus T1ρ and T2 values in both sides are higher than control knees, suggesting early degeneration in meniscus in patients in both sides. The results will be confirmed with more patient data being collected in the ongoing study. The relationship between qMRI, morphological tissue changes, and patient-reported outcomes after ACLR will also be evaluated in future work. Figure 1. T1p comparisons of cartilage among operated, contralateral, and healthy control knees. *P < 0.05, **P < 0.01. ***P < 0.001. Figure 2. T1p and T2 comparisons of menisci among operated, contralateral, and healthy control knees. *P < 0.05. **P < 0.01. ***P < 0.001. [ABSTRACT FROM AUTHOR]

Objectives: The goal of treatment of osteochondritis dissecans (OCD) is most commonly to preserve the native chondral surface to avoid long term development of osteoarthritis. However, some OCD lesions are not considered amenable to fixation and therefore deemed unsalvageable. Little is known about the OCD subpopulation presenting with such lesions or the detailed characteristics of unsalvageable lesions and their treatment. The purpose of this study is to investigate the characteristics of lesions and their treatment in a large volume of patients with OCD lesions that were determined to be unsalvageable upon presentation. Methods: A review of the ROCK (Research in Osteochondritis of the Knee) study group's prospective cohort database from 2014 to 2022 was performed to identify condylar lesions in patients <20 years old that were deemed unsalvageable, based on a cartilage resurfacing technique being preliminary treatment performed. Demographic data, radiographic descriptors, intraoperative lesion findings, and treatments performed were analyzed. Treatments for lesions considered unsalvageable were categorized as marrow stimulation (e.g. microfracture, McFx), osteochondral autograft transplantation surgery (e.g. OATS), osteochondral allograft transplantation (OCA), and cultured chondrocyte/cell-based therapy (e.g. MACI). Comparative analysis was performed between the cohort with unsalvageable lesions and those who underwent lesion preservation techniques associated with unstable lesions (ie fixation). Results: A total of 590 out of 1291 (45.7%) surgically treated OCDs (mean age 13.7 years old, 2:1 male: female) were included with 10.8% considered unsalvageable. The distribution of techniques for unsalvageable lesions was McFx (4.4%), OCA (2.9%), and MACI (2.0%). Compared to the lesion preservation cohort, the unsalvageable was older (15.9 vs. 14.6; p=-0.006), had a higher body mass index (24.2 vs. 22.7; p<0.001), and was more likely to have had prior surgery (33.3% vs. 10.3%; p<0.001). The presence of bone in the progeny, a linear signal on MRI, and bone edema were less common in unsalvageable lesions (p<0.05 for all). A multivariate analysis model resulted in significant associated in unsalvageable OCD lesions with prior surgery (p<0.001, OR 1.97, CI 2.736-19.929). Conclusions: OCD patients with unsalvageable lesions are more likely to be identified in those that have undergone prior surgical procedure, but MRI signs of instability still undergo preservation techniques. Given the implications of long-term joint health, comparative analyses of outcomes of the different cartilage resurfacing techniques for such lesions is of critical importance for future study. [ABSTRACT FROM AUTHOR]

Objectives: Sex mismatch between donor and recipient has been considered a potential contributor to adverse outcomes following solid organ transplantation. However, the influence of sex mismatching in osteochondral allograft (OCA) transplantation is yet to be determined. Therefore, the objective of this study was to evaluate whether donor-recipient sex mismatching impacts graft survival after OCA transplantation. Methods: In this review of prospectively collected data, patients who underwent OCA transplantation between November 2013 and November 2017 by a single surgeon were analyzed. Cumulative survival was performed through the Kaplan–Meier method using log-rank tests to compare patients with similar donor groups. Multivariable Cox regression analysis adjusted for patient age, graft size and body mass index (BMI) were used to evaluate the influence of donor–recipient sex on graft survival. Results: A total of 154 patients were included, 102 (66.2%) who received OCAs from a same sex donor, and 52 (33.8%) from a different sex donor. At 5 years follow-up, a significantly lower graft survival rate was observed for different sex donor transplantation in comparison to same sex donor (63% versus 92%, p = 0.01). (Figure 1.) When correcting for age, graft size and BMI, donor-recipient sex mismatching demonstrated a 2.9 times greater likelihood to fail at 5 years compared to donor-recipient same sex (p = 0.03). A subgroup analysis showed no significant difference in graft survival between female-to-female and female-to-male groups (91% and 84%, respectively). (Figure 2.) Conversely, male-to-male demonstrated a significant higher cumulative 5-year survival (94%, p = 0.04), whereas a lower survival was found in the male-to-female group (64%, p = 0.04). Multivariable Cox regression indicated a 2.6 times higher likelihood of failure for male-to-female in comparison with other groups (p = 0.04). Male-to-male had a tendency toward decreased likelihood of OCA failure (0.33 hazard ratio), although without statistical significance. Conclusions: Mismatch between donor and recipient sex has a negative effect on OCA survival following transplantation, particularly in those cases when male donor tissue was transplanted into a female recipient. [ABSTRACT FROM AUTHOR]

The article informs that research paper “Biphasic Creep and Stress-Relaxation of Articular-Cartilage in Confined Compression: Theory and Experiments" by V. C. Mow, S. C. Kuei, W. M. Lai, and C. G. Armstrong, has been named as the Legacy Paper 2016 by "Journal of Biomechanical Engineering."

Background: Articular cartilage is a vital component of the joint, as it is frequently exposed to trauma and is affected by several conditions and diseases such as osteoarthritis and hemophilic arthropathy. Therefore, its evaluation and assessment are crucial. Magnetic resonance imaging (MRI) plays a critical role in its evaluation. With the recent advances in MRI imaging, multiple techniques and modalities allow both morphological and physiological evaluation of articular cartilage. Morphological methods allow the evaluation of articular cartilage structural integrity, and physiological methods allow the evaluation of chemical changes in its components even prior to degeneration. This aids in the early detection and improved assessment of articular cartilage pathology. Therefore, it permits a more accurate evaluation of patients with articular cartilage issues and defects, allowing for prompt treatment and high better quality of life. This article reviews recent and innovative MRI techniques and sequences for morphological and functional evaluation of the cartilage. Methods: A broad-based internet search, utilizing multiple academic search engines, Google Scholar, and PubMed, using the keywords for title and abstract. We found 17500 results and excluded 1700 papers from the title and abstract. Furthermore, papers emphasizing the imaging of specific peripheral joints without discussing the main techniques were excluded. Finally, our search yielded 15 articles highlighting the most recent imaging and evaluation techniques for articular cartilage. Recent advancements and new MRI techniques aid in elucidating the anatomical and physiological details of articular cartilage, allowing for the early detection and treatment of the articular cartilage. Conclusions: Multiple recent advances and new MRI techniques help better delineate the anatomical and physiological details of the articular cartilage, so early interference and treatment of cartilage defects. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Multi-atlas based segmentation techniques constitute an effective approach in the automatic segmentation of medical images. Existing methods usually rely on single spectral descriptors extracted from a specific imaging modality. In this paper, we propose the Multi-View Knee Cartilage Segmentation (MV-KCS) approach, for segmenting the knee joint articular cartilage from MR images. Operating under the Semi-supervised learning framework, MV-KCS leverages spectral content from multiple feature spaces by constructing sparse graphs for each view individually, and aggregating them via optimisation to obtain a common data graph. In We consider two multi-view scenarios: in the former case views correspond to multiple feature descriptors, while on the latter, the views correspond to multiple image modalities. We propose two effective labelling schemes, implementing label propagation from the atlas library to the target image. The proposed methodology is applied to the publicly available Osteoarthritis Initiative repository. We devise a comprehensive experimental design to validate different test cases, comparing single-feature vs multi-features, multi-features vs feature stacking and multi-features vs multi-modalities. Comparative results and statistical analysis reveal that the proposed MV-KCS provides enhanced performance ($DSC = 92.56\% \left({FC} \right), 89.91\% \left({TC} \right)$ DSC = 92.56 % FC , 89.91 % TC ), outperforming a series of patch-based approaches, six recent state-of-the-art deep supervised models and three deep semi-supervised ones, in terms of both classification and volumetric measures. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic progressive disease of the joint. Although representing the most frequent cause of disability in the elderly, OA remains partly obscure in its pathogenic mechanisms and is still the orphan of resolutive therapies. The concept of what was once considered a "wear and tear" of articular cartilage is now that of an inflammation-related disease that affects over time the whole joint. The attention is increasingly focused on the synovium. Even from the earliest clinical stages, synovial inflammation (or synovitis) is a crucial factor involved in OA progression and a major player in pain onset. The release of inflammatory molecules in the synovium mediates disease progression and worsening of clinical features. The activation of synovial tissue-resident cells recalls innate immunity cells from the bloodstream, creating a proinflammatory milieu that fuels and maintains a damaging condition of low-grade inflammation in the joint. In such a context, cellular and molecular inflammatory behaviors in the synovium could be the primum movens of the structural and functional alterations of the whole joint. This paper focuses on and discusses the involvement of innate immunity cells in synovitis and their role in the progression of OA. [ABSTRACT FROM AUTHOR]

Polyvinyl alcohol (PVA), possessing a strong ability to form hydrogels, has been widely used for various pharmaceutical and biomedical applications. In particular, the use of PVA-PEG in the form of theta gels for altered cartilage treatment has attracted an enormous amount of attention in the last 20 years. In this paper, we prepared 42 PVA-PEG in the form of theta gels at room temperature in an aqueous environment, testing the crystallization occurrence at basic pH (10 or 12). Using a statistical approach, the effect of PEG molecular weight, PVA molecular weight and alkaline pH values on water content and mechanical performance was evaluated. The used procedure permitted the theta gels to maintain swelling properties comparable to those of human cartilage, from 60% to 85%, with both polymers having the same influence. PEG MW mainly affected the hydrophilic properties, whereas the thermal properties were mostly influenced by the PVA. The shear and compression mechanical behavior of the produced materials were affected by both the polymers' MWs. The sample obtained using PVA 125 kDa with PEG 20 kDa as a porogen appeared to be the most suitable one for cartilage disease treatment, as it had an equilibrium shear modulus in the range of 50–250 kPa, close to that of native articular cartilage, as well as optimal mechanical response under compression along the entire analyzed frequency range with a mean value of 0.12 MPa and a coefficient of friction (COF) which remained under 0.10 for all the tested sliding speeds (mm/s). [ABSTRACT FROM AUTHOR]

Articular cartilage has limited self-healing ability, resulting in injuries often evolving into osteoarthritis (OA), which poses a significant challenge in the medical field. Although some treatments exist to reduce pain and damage, there is a lack of effective means to promote cartilage regeneration. Reactive Oxygen Species (ROS) have been found to increase significantly in the OA micro-environment. They play a key role in biological systems by participating in cell signaling and maintaining cellular homeostasis. Abnormal ROS expression, caused by internal and external stimuli and tissue damage, leads to elevated levels of oxidative stress, inflammatory responses, cell damage, and impaired tissue repair. To prevent excessive ROS accumulation at injury sites, biological materials can be engineered to respond to the damaged microenvironment, release active components in an orderly manner, regulate ROS levels, reduce oxidative stress, and promote tissue regeneration. Hydrogels have garnered significant attention due to their excellent biocompatibility, tunable physicochemical properties, and drug delivery capabilities. Numerous antioxidant hydrogels have been developed and proven effective in alleviating oxidative stress. This paper discusses a comprehensive treatment strategy that combines antioxidant hydrogels with existing treatments for OA and explores the potential applications of antioxidant hydrogels in cartilage tissue engineering. [ABSTRACT FROM AUTHOR]

Objectives: While bone marrow aspirate concentrate (BMAC) and amniotic suspension allografts (ASA) have all garnered clinical interest for the treatment of osteoarthritis, basic science evidence supporting their use is lacking. Specifically, there is a paucity of literature on the in vitro effects of BMAC and ASA on inflammation and cartilage matrix metabolism in OA chondrocytes and synoviocytes. The purpose of this study was to evaluate the effect of BMAC and ASA on inflammation and cartilage metabolism in a model that mimics the OA intra-articular environment: a co-culture of OA cartilage explants and synoviocytes. Methods: After institutional IRB approval, 17 patients were enrolled at the time of total knee arthroplasty for donation of cartilage, synovium, and bone marrow aspirate tissue samples. All patients had Kellgren-Lawrence Stage 2 or 3. The aspirate was then be prepared and centrifuged using a standard commercially available BMAC centrifuge system, typically yielding up to 3mL of BMAC. Synoviocyte and cartilage explant co-culture systems were created using 24-well culture plates containing 0.4mm filtered inserts. Four co-culture systems were established per patient to accommodate the 2 biologic treatment groups (BMAC and ASA), one control group at 96 hours, and one baseline control cartilage group. Multiplex ELISA was used to measure concentrations of pro-inflammatory mediators interleukin – 1b (IL-1b), interleukin – 6 (IL-6), and tumor necrosis factor – alpha (TNF–a) at 96 hours. Each sample was measured in duplicate to ensure accuracy. Additionally, both chondrocyte and synoviocyte RNA were assayed for collagen type I a1 (COL1A1), collagen type II a1 (COL2A1), collagen type III a1 (COL3A1), aggrecan (ACAN), and cartilage oligomeric matrix protein (COMP). All statistical analyses were performed on STATA v16.1. Normality of data was determined by Shapiro-Wilk test, and non-parametric or parametric tests were utilized where appropriate. Results: There were no significant differences in cytokine concentration between the 96-hr control group and the BMAC co-culture for any cytokine, although IL-6 was trending towards significance (Control: 856.3 ± 346.2 vs BMAC: 662.3 ± 346.8, p=.08). There was a significantly lower concentration of IL-1B in the ASA group compared to the control group (ASA: 11.2 ± 13.9 vs Control: 20.2 ± 39.5, p=.04) (Table 1). No significant differences in expression were observed for Col1A1, Col2A1, Col3A1, COMP or ACAN in either cartilage or synovium samples across the three groups. Conclusions: The early results from this study suggest that ASA may have anti-inflammatory properties and promote the expression of major extracellular matrix genes in both osteoarthritic chondrocytes and synoviocytes involved in cartilage matrix metabolism. Specifically, ASA was associated with decreased concentrations of IL-1ß. The use of intra-articular therapies as sources of growth factors, anti-inflammatory mediators, and potentially mesenchymal stem cells (MSCs) for OA is rapidly evolving. MSCs have garnered significant interest due to their chondrogenic potential and promise for tissue regeneration. Two commercially available sources of MSCs are bone marrow aspirate concentrate (BMAC) and amniotic membrane. As biologics garner more attention in the clinical setting, their underlying mechanisms and efficacy in in-vitro models become important to elucidate. The results from this study provide basic science support for further clinical trials comparing ASA and BMAC to current standard of care corticosteroid injections for OA. Table 1. Luminex Assay for Cytokine Concentrations in Media [ABSTRACT FROM AUTHOR]