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Objective: Cartilage and meniscus are important structures that maintain the health of the knee joint. Early detection of changes in the internal components of cartilage and meniscus before morphological changes occur is essential to prevent and delay the development of osteoarthritis (OA). This study was designed to determine the changes in the matrix composition of morphologically intact cartilage and meniscus during the acute phase of an anterior cruciate ligament (ACL) rupture, as well as the effect of different states of meniscus (intact or tear) on adjacent cartilage during the acute phase. Methods: This cross‐sectional study compared and analyzed 50 patients in the acute phase of ACL rupture who underwent surgical treatment and 66 age‐, weight‐ and height‐matched healthy volunteers from May 2022 to May 2023 at our institution. Mean T2 relaxation times and effect sizes in different regions of tibiofemoral articular cartilage and meniscus were compared between the two groups using the Mann–Whitney nonparametric t‐test, and correlations between different meniscal states and adjacent cartilage were analyzed. Results: Both in the lateral and medial compartments of the knee, T2 relaxation times were significantly higher in all subregions of cartilage and meniscus in the ACL rupture group (p < 0.05), and the site of injury was predominantly centered in the medial compartment (femur, p = 0.000; tibia, p = 0.000; anterior horn, p = 0.000). In the respective compartments, the posterior horn of the lateral meniscus showed a significant positive correlation with the mid‐cartilage of the femoral and tibial (r = 0.566, p = 0.035; r = 0.611, p = 0.02); and the posterior horn of the medial meniscus showed a significant positive correlation with the posterior tibial cartilage (r = 0.668, p = 0.018). Conclusion: During the acute phase of ACL rupture, the internal composition of the cartilage and meniscus undergoes significant changes, even if the morphology is intact. More importantly, the state of the meniscus significantly affects the internal composition of the adjacent cartilage. This is an early warning sign of OA, which should be closely monitored and carefully managed in clinical practice. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) affects millions of people worldwide, but there are limited drugs available to treat it, so acquiring a more comprehensive comprehension of the underlying reasons and mechanisms behind inflammation is crucial, as well as developing novel therapeutic approaches to manage it and mitigate or forestall associated harm. It is evident that current in vitro models cannot faithfully replicate all aspects of joint diseases, which makes them ineffective as tools for disease research and drug testing. Organ-on-a-chip (OoC) technology is an innovative platform that can mimic the microenvironment and physiological state of living tissues more realistically than traditional methods by simulating the spatial arrangement of cells and interorgan communication. This technology allows for the precise control of fluid flow, nutrient exchange, and the transmission of physicochemical signals, such as bioelectrical, mechanical stimulation and shear force. In addition, the integration of cutting-edge technologies like sensors, 3D printing, and artificial intelligence enhances the capabilities of these models. Here, we delve into OoC models with a particular focus on Synovial Joints-on-a-Chip, where we outline their structure and function, highlighting the potential of the model to advance our understanding of RA. We integrate the actual evidence regarding various OoC models and their possible integration for multisystem disease study in RA research for the first time and introduce the prospects and opportunities of the chip in RA etiology and pathological mechanism research, drug research, disease prevention and human precision medicine. Although many challenges remain, OoC holds great promise as an in vitro model that approaches physiology and dynamics. [ABSTRACT FROM AUTHOR]

The squat and its variants can provide numerous benefits including positively affecting sports performance and injury prevention, injury severity reduction, and rehabilitation. The positive benefits of squat are likely the result of training-induced neural alterations and mechanical and morphological adaptations in tendons, skeletal muscles, and bones, resulting in increased tissue stiffness and cross-sectional area (CSA). Although direct evidence is lacking, structural adaptations can also be expected to occur in ligaments. These adaptations are thought to beneficially increase force transmission and mechanical resistance (e.g., resistance to mechanical strain) and reduce the likelihood and severity of injuries. Adaptations such as these, also likely play an important role in rehabilitation, particularly for injuries that require restricted use or immobilization of body parts and thus lead to a consequential reduction in the CSA and alterations in the mechanical properties of tendons, skeletal muscles, and ligaments. Both volume and particularly intensity (e.g., levels of loading used) of training seem to be important for the mechanical and morphological adaptations for at least skeletal muscles, tendons, and bones. Therefore, the training intensity and volume used for the squat and its variations should progressively become greater while adhering to the concept of periodization and recognized training principles. [ABSTRACT FROM AUTHOR]

Abstract: The superficial zone (SFZ) of articular cartilage is an important interface that isolates deeper zones from the microenvironment of the articular cavity and is directly exposed to various biological and mechanical stimuli. The SFZ is not only a crucial structure for maintaining the normal physiological function of articular cartilage but also the earliest site of osteoarthritis (OA) cartilage degeneration and a major site of cartilage progenitor cells, suggesting that the SFZ might represent a key target for the early diagnosis and treatment of OA. However, to date, SFZ research has not received sufficient attention, accounting for only about 0.58% of cartilage tissue research. The structure, biological composition, function, and related mechanisms of the SFZ in the physiological and pathological processes of articular cartilage remain unclear. This article reviews the key role of the SFZ in articular cartilage physiology and pathology and focuses on the characteristics of SFZ in articular cartilage degeneration and regeneration in OA, aiming to provide researchers with a systematic understanding of the current research status of the SFZ of articular cartilage, hoping that scholars will give more attention to the SFZ of articular cartilage in the future., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: In an earlier study, a scaffold-free tissue-engineered construct (TEC) derived from autologous synovial membrane mesenchymal stromal cells (MSCs) was developed and demonstrated to be safe and effective for cartilage repair at 2 years postoperatively. Purpose: To investigate clinical outcomes and magnetic resonance imaging (MRI) findings at 5 years after implantation. Study Design: Case series; Level of evidence, 4. Methods: This was an observational first-in-human study limited to 5 patients (age, 28-46 years) with symptomatic knee chondral lesions (size, 1.5-3.0 cm2) on the medial femoral condyle, lateral femoral condyle, or femoral groove. Synovial MSCs were isolated from arthroscopic biopsy specimens and cultured to develop a TEC that matched the lesion size. The TECs were then implanted into chondral defects without fixation and assessed at up to 5 years postoperatively. The patients were clinically evaluated using the visual analog scale for pain, Lysholm score, Tegner score, and Knee injury and Osteoarthritis Outcome Score. An MRI scan evaluation was also performed for morphologic and compositional quality of the repair tissue at both 2 and 5 years of follow-up. Results: All clinical scores were significantly improved from the preoperative evaluation to the 2- and 5-year follow-ups and the results were stable over time. The MRI scan evaluation showed cartilage defects filled with newly generated tissues with good tissue integration to adjacent host cartilage over time. The cartilage thickness and surface smoothness of the repair cartilage were maintained up to 5 years postoperatively. The MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 Knee Scores remained high at 5 years, although the total points decreased slightly. Conclusion: The results highlight the efficacy and feasibility of autologous scaffold-free TEC derived from synovial MSCs for regenerative cartilage repair via a sutureless and simple implantation procedure, showing good clinical outcomes and MRI findings with stable results at midterm follow-up. Further follow-up will be needed to assess the long-term quality of the repair tissue. [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) have gained popularity in recent years as biologic approaches to potentially augment healing after meniscus repair. There have been few studies comparing outcomes in patients undergoing meniscus repair with versus without biologic augmentation and, furthermore, little clarity on the role of biologic augmentation for meniscus repairs performed with concomitant anterior cruciate ligament reconstruction (ACLR). Purpose: To determine the association of BMAC or PRP augmentation with revision surgery after both isolated meniscus repair and meniscus repair performed concomitantly with ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: The PearlDiver Mariner dataset was queried to identify all patients who underwent primary meniscus repair, both with and without concomitant ACLR, and who received ipsilateral BMAC or PRP at the time of surgery. Patients who underwent similar surgery but without BMAC or PRP augmentation were then identified and matched in a 5:1 ratio according to age, sex, body mass index, and various comorbidities to 3 separate BMAC/PRP augmentation groups: overall cohort (with and without ACLR), repair with concomitant ACLR, and isolated repair. The primary outcome was revision meniscus surgery (meniscectomy or revision meniscus repair). Results: Overall, 3420 patients (570 with BMAC/PRP augmentation; 2850 matched controls without augmentation) were included. There were no significant differences in the reported demographics or comorbidities between any of the BMAC/PRP groups and their respective matched controls (P >.05 for all comparisons). There was no difference in revision rate between BMAC/PRP-augmented isolated meniscus repairs and matched controls (P =.235). Patients who underwent BMAC/PRP-augmented meniscus repair with concomitant ACLR experienced a significantly lower incidence of revision surgery compared with matched controls without BMAC/PRP augmentation (5.2% vs 7.9% respectively; odds ratio, 0.41; 95% CI, 0.27-0.63; P <.001), but the number of revisions was relatively small. Conclusion: There was no association between BMAC or PRP augmentation and the incidence of revision surgery after isolated primary meniscus repair. There was a statistically significant decrease in the rate of revision meniscus surgery when BMAC or PRP was used to augment meniscus repairs in the setting of concurrent ACLR; however, the overall revision rates were small. [ABSTRACT FROM AUTHOR]

Treatment of osteoarthritic patients requires the development of morphologically and mechanically complex hyaline cartilage at the injury site. A tissue engineering approach toward differentiating mesenchymal stem cells into articular chondrocytes has been developed to overcome the drawbacks of conventional therapeutic and surgical procedures. To imitate the native micro and macro environment of articular chondrocytes, cell culture parameters such as oxygen concentration, mechanical stress, scaffold design, and growth factor signalling cascade regulation must be addressed. This review aims to illuminate the path toward developing tissue engineering approaches, accommodating these various parameters and the role these parameters play in regulating chondrogenesis for better articular cartilage development to treat osteoarthritis effectively. Osteoarthritis is a common problem where the protective layer of cartilage on the joints wears away. It's difficult to treat with current methods. However, stem cell therapy is a promising alternative that has been researched a lot recently. Stem cells are special cells that can change into different types of tissue, including cartilage. Scientists are trying to figure out how to get these stem cells to grow into cartilage effectively. They are also trying to understand how stem cells find the right place in the body to go and do their job. By modifying the genes of stem cells and using special materials and growth factors, scientists hope to improve the effectiveness of stem cell therapy for osteoarthritis. To pave the way toward effectively treating damaged articular chondrocytes, this article reviews the various cell culture parameters required to develop an efficient tissue engineering protocol for differentiating autologous MSC in cartilaginous tissue. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic degenerative osteoarthropathy. Although it has been revealed that a variety of factors can cause or aggravate the symptoms of OA, the pathogenic mechanisms of OA remain unknown. Reliable OA models that accurately reflect human OA disease are crucial for studies on the pathogenic mechanism of OA and therapeutic drug evaluation. This review first demonstrated the importance of OA models by briefly introducing the OA pathological features and the current limitations in the pathogenesis and treatment of OA. Then, it mainly discusses the development of different OA models, including animal and engineered models, highlighting their advantages and disadvantages from the perspective of pathogenesis and pathology analysis. In particular, the state-of-the-art engineered models and their potential were emphasized, as they may represent the future direction in the development of OA models. Finally, the challenges in obtaining reliable OA models are also discussed, and possible future directions are outlined to shed some light on this area. [ABSTRACT FROM AUTHOR]

The current literature has mainly focused on the biology of tendons and on the characterization of the biological properties of tenocytes and tenoblasts. It is still not understood how these cells can work together in homeostatic equilibrium. We put forward the concept of the "tendon unit" as a morpho-functional unit that can be influenced by a variety of external stimuli such as mechanical stimuli, hormonal influence, or pathological states. We describe how this unit can modify itself to respond to such stimuli. We evidence the capability of the tendon unit of healing itself through the production of collagen following different mechanical stimuli and hypothesize that restoration of the homeostatic balance of the tendon unit should be a therapeutic target. [ABSTRACT FROM AUTHOR]

A characteristic feature of arthritic diseases is cartilage extracellular matrix (ECM) degradation, often orchestrated by the overexpression of matrix metalloproteinases (MMPs) and other proteases. The interplay between fibril level degradation and the tissue-level aggregate response to biomechanical loading was explored in this work by a computational multiscale cartilaginous model. We considered the relative abundance of collagenases (MMP-1) and gelatinases (MMP-9) in surrogate models, where the diffusion (spatial distribution) of these enzymes and the subsequent, co-localized fibrillar damage were spatially randomized with Latin Hypercube Sampling. The computational model was constructed by incorporating the results from prior molecular dynamics simulations (tensile test) of microfibril degradation into a hyper-elastoplastic fibril-reinforced cartilage model. Including MMPs-mediated collagen fibril-level degradation in computational models may help understand the ECM pathomechanics at the tissue level. The mechanics of cartilage tissue and fibril show variations in mechanical integrity depending on the different combinations of MMPs-1 and 9 with a concentration ratio of 1:1, 3:1, and 1:3 in simulated indentation tests. The fibril yield (local failure) was initiated at 20.2 ± 3.0 (%) and at 23.0 ± 2.8 (%) of bulk strain for col 1:gel 3 and col 3: gel 1, respectively. The reduction in failure stress (global response) was 39.8% for col 1:gel 3, 37.5% for col 1:gel 1, and 36.7% for col 3:gel 1 compared with the failure stress of the degradation free tissue. These findings indicate that cartilage's global and local mechanisms of failure largely depend on the relative abundance of the two key enzymes—collagenase (MMP-1) and gelatinase (MMP-9) and the spatial characteristics of diffusion across the layers of the cartilage ECM. [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.)

Currently, there are no effective clinical or experimental treatments to fully restore the function of the torn acetabular labrum. To fill the gap, here, we report the finding of progenitor cells in labral tissue, which can be recruited and stimulated to repair torn acetabular labral tissue. This study aimed to develop a biomolecule releasing bioadhesive which can speed up labral tissue healing by eliciting autologous labral progenitor cellular responses. A click chemistry‐based bioadhesive, capable of releasing biomolecules, was synthesized to exert ~3× adhesion strength compared with fibrin glue. Via the release of platelet‐derived growth factor (PDGF), the adhesive was shown to actively recruit and stimulate the proliferation of labral progenitor cells to the tear sites and within the adhesive. Finally, the ability of this biomolecules‐releasing adhesive designed to promote labral tissue regeneration was evaluated using discarded human acetabular labrum tissue compared with surgical suture ex vivo. Histological analysis shows that PDGF‐releasing bioadhesive yielded significantly more labrum cell responses and extracellular matrix protein (proteoglycan and collagen) production at the tear tissue site than surgical suture controls. The results confirm that the new PDGF‐releasing bioadhesive can activate the responses of autologous labral progenitor cells to significantly improve labral tissue regeneration. Clinical significance: These PDGF‐releasing bioadhesives may serve as a new and effective tool for repairing and regenerating acetabular labrum tears. [ABSTRACT FROM AUTHOR]

Abnormal loading of the knee due to injuries or obesity is thought to contribute to the development of osteoarthritis (OA). Small animal models have been used for studying OA progression mechanisms. However, numerical models to study cartilage responses under dynamic loading in preclinical animal models have not been developed. Here we present a musculoskeletal finite element model of a rat knee joint to evaluate cartilage biomechanical responses during a gait cycle. The rat knee joint geometries were obtained from a 3-D MRI dataset and the boundary conditions regarding loading in the joint were extracted from a musculoskeletal model of the rat hindlimb. The fibril-reinforced poroelastic (FRPE) properties of the rat cartilage were derived from data of mechanical indentation tests. Our numerical results showed the relevance of simulating anatomical and locomotion characteristics in the rat knee joint for estimating tissue responses such as contact pressures, stresses, strains, and fluid pressures. We found that the contact pressure and maximum principal strain were virtually constant in the medial compartment whereas they showed the highest values at the beginning of the gait cycle in the lateral compartment. Furthermore, we found that the maximum principal stress increased during the stance phase of gait, with the greatest values at midstance. We anticipate that our approach serves as a first step towards investigating the effects of gait abnormalities on the adaptation and degeneration of rat knee joint tissues and could be used to evaluate biomechanically-driven mechanisms of the progression of OA as a consequence of joint injury or obesity. Author summary: Osteoarthritis is a disease of the musculoskeletal system which is characterized by the degradation of articular cartilage. Changes in the knee loading after injuries or obesity contribute to the development of cartilage degeneration. Since injured cartilage cannot be reversed back to intact conditions, small animal models have been widely used for investigating osteoarthritis progression mechanisms. Moreover, experimental studies have been complemented with numerical models to overcome inherent limitations such as cost, difficulties to obtain accurate measures and replicate degenerative situations in the knee joint. However, computational models to study articular cartilage responses under dynamic loading in small animal models have not been developed. Thus, here we present a musculoskeletal finite element model (MSFE) of a rat knee joint to evaluate cartilage biomechanical responses during gait. Our computational model considers both the anatomical and locomotion characteristics of the rat knee joint for estimating mechanical responses in the articular cartilage. We suggest that our approach can be used to investigate tissue adaptations based on the mechanobiological responses of the cartilage to prevent the progression of osteoarthritis. [ABSTRACT FROM AUTHOR]

Background: Posttraumatic inflammation after joint injury, ranging from sprains to articular fracture, contributes to the development of arthritis, and the administration of interleukin 1 (IL-1) receptor antagonist (IL-1Ra) is a potential intervention to mitigate this response. Although IL-1Ra mitigates cartilage degenerative changes induced by IL-1, lidocaine is used for local pain management in acute joint injury. Intra-articular delivery of both drugs in combination would be a novel and possibly disease–modifying treatment. However, it is not known whether the interaction with lidocaine at clinical concentrations (1%) would alter the efficacy of IL-1Ra to protect cartilage from the catabolic effects of IL-1. Hypothesis: Treatment of articular cartilage with IL-1Ra in combination with a clinically relevant concentration of lidocaine (1%) will inhibit the catabolic effects of IL-1α in a manner similar to treatment with IL-1Ra alone. Study Design: Controlled laboratory study. Methods: Fresh porcine cartilage explants were harvested, challenged with IL-1α, and incubated for 72 hours with IL-1Ra or a combination of IL-1Ra and lidocaine. The primary outcome was total sulfated glycosaminoglycan (sGAG) release. Additional experiments assessed the effect of storage temperature and premixing of IL-1Ra and lidocaine on sGAG release. All explants were histologically assessed for cartilage degradation using a modified Mankin grading scale. Results: The combination of IL-1Ra and lidocaine, premixed at various time points and stored at room temperature or 4°C, was as effective as IL-1Ra alone at inhibiting IL-1α–mediated sGAG release. Mankin histopathology scores supported these findings. Conclusion: Our hypothesis was supported, and results indicated that the combination of IL-1Ra and lidocaine was as efficacious as IL-1Ra treatment alone in acutely mitigating biological cartilage injury due to IL-1α in an explant model. Clinical Significance: The combination of IL-1Ra and lidocaine is stable when reagents are stored in advance of administration at varying temperatures, providing clinically relevant information about storage of medications. The ability to premix and store this drug combination for intra–articular delivery may provide a novel treatment after joint injury to provide pain relief and block inflammation–induced catabolism of joint tissues. [ABSTRACT FROM AUTHOR]

Formalin‐fixed and paraffin‐embedded (FFPE) biospecimens are a valuable and widely‐available resource for diagnostic and research applications. With biobanks of tissue samples available in many institutions, FFPE tissues could prove to be a valuable resource for translational orthopaedic research. The purpose of this study was to characterize the molecular profiles and degree of histologic degeneration on archival fragments of FFPE human menisci obtained during arthroscopic partial meniscectomy. We used FFPE menisci for multiplexed gene expression analysis using the NanoString nCounter® platform, and for histological assessment using a quantitative scoring system. In total, 17 archival specimens were utilized for integrated histologic and molecular analyses. The median patient age was 22 years (range: 14–62). We found that the genes with the highest normalized counts were those typically expressed in meniscal fibrocartilage. Gene expression differences were identified in patient cohorts based on age (≤40 years), including genes associated with the extracellular matrix and tissue repair. The majority of samples showed mild to moderate histologic degeneration. Based on these data, we conclude that FFPE human menisci can be effectively utilized for molecular evaluation following a storage time as long as 11 years. Statement of Clinical Significance: The integration of histological and transcriptomic analyses described in this study will be useful for future studies investigating the basis for biological classification of meniscus specimens in patients. Further exploration into the genes and pathways uncovered by this study may suggest targets for biomarker discovery and identify patients at greater risk for osteoarthritis once the meniscus is torn. [ABSTRACT FROM AUTHOR]

The objective of the current study was to investigate the feasibility of quantitative 3D ultrashort echo time (UTE)‐based biomarkers in detecting proteoglycan (PG) loss and collagen degradation in human cartilage. A total of 104 cartilage samples were harvested for a trypsin digestion study (n = 44), and a sequential trypsin and collagenase digestion study (n = 60), respectively. Forty‐four cartilage samples were randomly divided into a trypsin digestion group (tryp group) and a control group (phosphate‐buffered saline [PBS] group) (n = 22 for each group) for the trypsin digestion experiment. The remaining 60 cartilage samples were divided equally into four groups (n = 15 for each group) for sequential trypsin and collagenase digestion, including PBS + Tris (incubated in PBS, then Tris buffer solution), PBS + 30 U col (incubated in PBS, then 30 U/ml collagenase [30 U col] with Tris buffer solution), tryp + 30 U col (incubated in trypsin solution, then 30 U/ml collagenase with Tris buffer solution), and tryp + Tris (incubated in trypsin solution, then Tris buffer solution). The 3D UTE‐based MRI biomarkers included T1, multiecho T2*, adiabatic T1ρ (AdiabT1ρ), magnetization transfer ratio (MTR), and modeling of macromolecular proton fraction (MMF). For each cartilage sample, UTE‐based biomarkers (T1, T2*, AdiabT1ρ, MTR, and MMF) and sample weight were evaluated before and after treatment. PG and hydroxyproline assays were performed. Differences between groups and correlations were assessed. All the evaluated biomarkers were able to differentiate between healthy and degenerated cartilage in the trypsin digestion experiment, but only T1 and AdiabT1ρ were significantly correlated with the PG concentration in the digestion solution (p = 0.004 and p = 0.0001, respectively). In the sequential digestion experiment, no significant differences were found for T1 and AdiabT1ρ values between the PBS + Tris and PBS + 30 U col groups (p = 0.627 and p = 0.877, respectively), but T1 and AdiabT1ρ values increased significantly in the tryp + Tris (p = 0.031 and p = 0.024, respectively) and tryp + 30 U col groups (both p < 0.0001). Significant decreases in MMF and MTR were found in the tryp + 30 U col group compared with the PBS + Tris group (p = 0.002 and p = 0.001, respectively). It was concluded that AdiabT1ρ and T1 have the potential for detecting PG loss, while MMF and MTR are promising for the detection of collagen degradation in articular cartilage, which could facilitate earlier, noninvasive diagnosis of osteoarthritis. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a painful and disabling musculoskeletal disorder, with a large impact on the global population, resulting in several limitations on daily activities. In OA, inflammation is frequent and mainly controlled through inflammatory cytokines released by immune cells. These outbalanced inflammatory cytokines cause cartilage extracellular matrix (ECM) degradation and possible growth of neuronal fibers into subchondral bone triggering pain. Even though pain is the major symptom of musculoskeletal diseases, there are still no effective treatments to counteract it and the mechanisms behind these pathologies are not fully understood. Thus, there is an urgent need to establish reliable models for assessing the molecular mechanisms and consequently new therapeutic targets. Models have been established to support this research field by providing reliable tools to replicate the joint tissue in vitro. Studies firstly started with simple 2D culture setups, followed by 3D culture focusing mainly on cell-cell interactions to mimic healthy and inflamed cartilage. Cellular approaches were improved by scaffold-based strategies to enhance cell-matrix interactions as well as contribute to developing mechanically more stable in vitro models. The progression of the cartilage tissue engineering would then profit from the integration of 3D bioprinting technologies as these provide 3D constructs with versatile structural arrangements of the 3D constructs. The upgrade of the available tools with dynamic conditions was then achieved using bioreactors and fluid systems. Finally, the organ-on-a-chip encloses all the state of the art on cartilage tissue engineering by incorporation of different microenvironments, cells and stimuli and pave the way to potentially simulate crucial biological, chemical, and mechanical features of arthritic joint. In this review, we describe the several available tools ranging from simple cartilage pellets to complex organ-on-a-chip platforms, including 3D tissue-engineered constructs and bioprinting tools. Moreover, we provide a fruitful discussion on the possible upgrades to enhance the in vitro systems making them more robust regarding the physiological and pathological modeling of the joint tissue/OA. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a progressive, chronic, debilitating autoimmune disease manifested clinically by polyarthralgia associated with joint dysfunction triggering the antibodies targeting against the self-neoepitopes determined by autoimmune responses associated with chronic arthritic attacks. Arthritis is not an inherited disease but caused by stimulation of some hidden arthritis susceptible genes lowering the quality of life throughout the world, particularly in developing countries. RA generally affects the joints like wrists, elbows, knees and ankles. Usually women are more affected by RA than men due to the prevalence of hormonal changes. Age is also an important factor that contributes for the development of RA. Several anti-inflammatory and disease-modifying drugs are available for RA therapy. However, the prolonged use of these drugs is associated with severe side effects. Furthermore, these drugs are effective only in a proportion of RA patients. Hence, there is a need to search for new therapeutic agents that are effective yet safe. Interestingly, a variety of herbs and other natural products offer a vast resource for such anti-arthritic agents. Nature has been a source of medicinal agents for more than thousands of years and herbal therapy predominates in traditional systems of medicine as well as in alternative medicine practiced in various cultures such as Indian system of medicine, Chinese Traditional Medicine, Unani classical literature. This review article presents about various polyherbal formulations (PHF) utilized in RA treatment. PHF has been used all around the earth due to its medicinal and therapeutic application. The present review deals with various commercial and non-commercial polyherbal formulation used by different countries of the world for the treatment of RA, their therapeutic potentials including clinical and preclinical results along with their safety and efficacy. This review will facilitate to gain all about the past scientific research and the necessary information about the anti-arthritic activities of polyherbal formulations which will insist the young researchers for future research to protect human beings from RA and may serves as a natural gold for the promotion of mankind. [ABSTRACT FROM AUTHOR]

Aim: To mimic the ultrastructural morphology of the meniscus with nanofiber scaffolds coupled with controlled growth factor delivery to modulate cellular performance for tissue engineering of menisci. Methods: The authors functionalized collagen nanofibers by conjugating heparin to the following growth factors for sustained release: PDGF-BB, TGF-β1 and CTGF. Results: Incorporating growth factors increased human meniscal and synovial cell viability, proliferation and infiltration in vitro, ex vivo and in vivo; upregulated key genes involved in meniscal extracellular matrix synthesis and enhanced generation of meniscus-like tissue. Conclusion: The authors' results indicate that functionalizing collagen nanofibers can create a cell-favorable micro- and nanoenvironment and can serve as a system for sustained release of bioactive factors. Meniscal tears are a common injury to the part of the knee called the meniscus. Loss of meniscal tissue can lead to arthritis. In this study, the authors aimed to recreate the structure of the human meniscus using very thin (nanometers in diameter) fibers made of collagen. The authors also attached proteins called growth factors to the fibers. The addition of these proteins increased the growth rate of cells collected from human knee tissue. The levels of important genes involved in meniscal tissue formation were increased in these cells. These results show that adding proteins such as growth factors to collagen nanofibers can create an environment beneficial to growing meniscal tissue. Successful development of this technology could help in repairing meniscal damage in people. [ABSTRACT FROM AUTHOR]

Purpose: Tendon overuse injuries are prevalent conditions with limited therapeutic options to halt disease progression. The specialized extracellular matrix (ECM) both enables joint function and mediates mechanical signals to tendon cells, driving biological responses to exercise or injury. With overuse, tendon ECM composition and structure changes at multiple scales, disrupting mechanotransduction and resulting in inadequate repair and disease progression. This review highlights the multiscale ECM changes that occur with tendon overuse and corresponding effects on cell-matrix interactions and cellular response to load.Results: Different functional joint requirements and tendon types experience a wide range of loading profiles, creating varied downstream mechanical stimuli. Distinct ECM structure and mechanical properties within the fascicle matrix, interfascicle matrix, and enthesis and their varied disruption with overuse are considered. The pericellular matrix (PCM) comprising the microscale tendon cell environment has a unique composition that changes with overuse injury and exercise, suggesting an important role in mechanotransduction and promoting repair. Cell-matrix interactions are mediated by structures including cilia, integrins, connexins and cytoskeleton that signal downstream homeostasis, adaptation, or repair. ECM disruption with tendon overuse may cause altered mechanical loading and cell-matrix interactions, resulting in mechanobiological understimulation, apoptosis, and ineffective repair. Current interventions to promote repair of tendon overuse injuries including exercise, targeting cell signaling, and modulating inflammation are considered.Conclusion: Future therapeutics should be assessed with regard of their effects on multiscale mechanotransduction in addition to joint function, with consideration of the central role of ECM. [ABSTRACT FROM AUTHOR]

Excessive pressure or overload induces and aggravates osteoarthritic changes in articular cartilage, but the underlying biomechanical forces are largely ignored in existing pharmacological in vitro models that are used to investigate drugs against osteoarthritis (OA). Here, we introduce a novel in vitro model to perform pathophysiological and pharmacological investigations, in which cartilage explants are subjected to intermittent cyclic pressure, and characterize its ability to mimic OA‐like tissue reactivity. Mechanical loading time‐dependently increased the biosynthesis, content and retention of fibronectin (Fn), whereas collagen metabolism remained unchanged. This protocol upregulated the production and release of proteoglycans (PGs). The release of PGs from explants was significantly inhibited by a matrix metalloproteinase (MMP) inhibitor, suggesting the involvement of such proteinases in the destruction of the model tissue, similar to what is observed in human OA cartilage. In conclusion, the metabolic alterations in our new biomechanical in vitro model are similar to those of early human OA cartilage, and our pharmacological prevalidation with an MMP‐inhibitor supports its value for further in vitro drug studies. [ABSTRACT FROM AUTHOR]

Copyright of Ataturk University Journal of Veterinary Sciences is the property of Ataturk University Coordinatorship of Scientific Journals 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.)

Background: The increasing incidence of anterior cruciate ligament (ACL) and meniscal injuries has led to strong interest in discovering new methods to enhance the biological healing response of these tissues. Platelet-rich plasma (PRP) contains various growth factors associated with a positive healing response, but few existing clinical studies are available to determine the risks and benefits of these therapies. Purpose: To determine the effects of intraoperative PRP on postoperative knee function and complications at 2 years after ACL reconstruction with meniscal repair. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective matched case-control study was conducted between 2013 and 2017 using a single surgeon database of 1014 patients undergoing primary ACL reconstruction with concomitant meniscal repair, resulting in 324 patients (162 PRP patients and 162 control patients) who met the study criteria. Patients were matched by age, sex, graft type, and meniscal injury. The Single Assessment Numeric Evaluation (SANE) was administered at 2 years, and injury surveillance was conducted. Secondary outcomes included the time to return to activity (months), self-reported knee function (International Knee Documentation Committee [IKDC] score), functional performance testing (knee range of motion, single-leg balance, single-leg hopping, agility testing), and postoperative complications (graft failure, infection, loss of motion [requiring repeat arthroscopy for lysis of adhesions], venous thrombosis, etc). Univariate models were used for between-group comparisons, and alpha was set at.05 for all analyses. Results: No differences were found in SANE knee function scores between the PRP and matched-control groups at 2 years (91.6 ± 11.2 vs 92.4 ± 10.6, respectively; P =.599). Additionally, no differences were reported between groups for self-reported function (IKDC score, 87.6 ± 13.3 vs 88.1 ± 12.6; P =.952), functional performance testing (P >.05), and timing of return to activity (7.8 ± 1.9 vs 8.0 ± 1.9 months; P =.765). The PRP group demonstrated a higher rate of postoperative knee motion loss compared with the control group (13.6% vs 4.6%; P <.001). No other differences were observed in postoperative complications (P >.05). Conclusion: The added use of intraoperative PRP did not improve self-reported knee function, functional performance, and timing of return to activity for patients undergoing ACL reconstruction with meniscal repair. Furthermore, the use of PRP may have negative consequences for regaining knee range of motion after surgery. On the basis of these data, surgeons should cautiously consider the application of PRP when planning surgery for intra-articular injuries of the knee. Registration: NCT03704376 (ClinicalTrials.gov identifier). [ABSTRACT FROM AUTHOR]