Treatment Of Articular Cartilage Injury Research Articles

A novel mesenchymal stem cell-targeting dual-miRNA delivery system based on aptamer-functionalized tetrahedral framework nucleic acids: Application to endogenous regeneration of articular cartilage

Articular cartilage injury (ACI) remains one of the key challenges in regenerative medicine, as current treatment strategies do not result in ideal regeneration of hyaline-like cartilage. Enhancing endogenous repair via microRNAs (miRNAs) shows promise as a regenerative therapy. miRNA-140 and miRNA-455 are two key and promising candidates for regulating the chondrogenic differentiation of mesenchymal stem cells (MSCs). In this study, we innovatively synthesized a multifunctional tetrahedral framework in which a nucleic acid (tFNA)-based targeting miRNA codelivery system, named A-T-M, was used. With tFNAs as vehicles, miR-140 and miR-455 were connected to and modified on tFNAs, while Apt19S (a DNA aptamer targeting MSCs) was directly integrated into the nanocomplex. The relevant results showed that A-T-M efficiently delivered miR-140 and miR-455 into MSCs and subsequently regulated MSC chondrogenic differentiation through corresponding mechanisms. Interestingly, a synergistic effect between miR-140 and miR-455 was revealed. Furthermore, A-T-M successfully enhanced the endogenous repair capacity of articular cartilage in vivo and effectively inhibited hypertrophic chondrocyte formation. A-T-M provides a new perspective and strategy for the regeneration of articular cartilage, showing strong clinical application value in the future treatment of ACI.

Catalpol promotes articular cartilage repair by enhancing the recruitment of endogenous mesenchymal stem cells.

Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (μCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.

Effects of Electrical Stimulation on Articular Cartilage Regeneration with a Focus on Piezoelectric Biomaterials for Articular Cartilage Tissue Repair and Engineering.

There is increasing evidence that chondrocytes within articular cartilage are affected by endogenous force-related electrical potentials. Furthermore, electrical stimulation (ES) promotes the proliferation of chondrocytes and the synthesis of extracellular matrix (ECM) molecules, which accelerate the healing of cartilage defects. These findings suggest the potential application of ES in cartilage repair. In this review, we summarize the pathogenesis of articular cartilage injuries and the current clinical strategies for the treatment of articular cartilage injuries. We then focus on the application of ES in the repair of articular cartilage in vivo. The ES-induced chondrogenic differentiation of mesenchymal stem cells (MSCs) and its potential regulatory mechanism are discussed in detail. In addition, we discuss the potential of applying piezoelectric materials in the process of constructing engineering articular cartilage, highlighting the important advances in the unique field of tissue engineering.

Platelet Rich Plasma in the Repair of Articular Cartilage Injury: A Narrative Review.

ObjectiveThis paper reviews the research of platelet-rich plasma (PRP) in articular cartilage injury repair, to assess the mechanism, utilization, and efficacy of PRP in the treatment of articular cartilage injury, hoping to provide a theoretical basis for the clinical application of PRP in the future.Materials and MethodsA comprehensive database search on PRP applications in cartilage repair was performed. Among them, the retrieval time range of PRP in clinical trials of repairing knee cartilage injury was from January 1, 2021 to January 1, 2022. Non-clinical trials and studies unrelated to cartilage injury were excluded.ResultPRP can affect inflammation, angiogenesis, cartilage protection, and cellular proliferation and differentiation after articular cartilage injury through different pathways. In all, 13 clinical trials were included in the analysis.ConclusionPRP is an emergent therapeutic approach in tissue engineering. Most studies reported that PRP has a positive effect on cartilage injury, improving the joint function, meanwhile there is a lack of standardized standards. The technology of PRP in the repair and treatment of articular cartilage injury is worthy of further research.

Deconstruction of Knee Cartilage Injury in Athletes Using MR Images Based on Artificial Intelligence Segmentation Algorithm.

The knee joint is the second largest joint in the human body, with a wide range of functional activities and strong support for the human body. Moreover, the cartilage of the knee joint is hyaline cartilage, which is relatively brittle, so it is most vulnerable to trauma. In clinical work, the damage of articular cartilage is a disease with a high rate of orthopedic visits. In this paper, all the experimental group cases included in the observation were patients with acute articular cartilage injury or OA diagnosed by knee arthroscopy. All experimental groups and control groups did not have any strenuous exercise one day before MRI (magnetic resonance imaging), and they sat for 30 minutes before the examination. Conventional scanning sagittal FSE-T1WI, FSE-T2WI, FS-FSE-T1WI, FS-FSE-T2WI, FS-PDWI, and coronal FS-PDWI sequence. In the normal control group, after the T2 color map was generated in the workstation, the articular cartilage was divided on the midsagittal plane, and the patellar cartilage and tibial plateau were roughly divided into upper, middle, lower and anterior, middle, and posterior thirds. In order to ensure the maximum comparability of the results, an artificial intelligence segmentation algorithm is used to divide the region of interest equally, and the central part of each partition is selected as much as possible for measurement. The T2 values of the three partitions of each cartilage were measured one by one and averaged. For the comparison results of T2 value of cartilage in the same part: according to patellar cartilage, femoral cartilage, and tibial cartilage, the P values are 0.973, 0.150, and 0.525, respectively. Therefore, early detection and early treatment of articular cartilage injury are of great significance to the performance of athletes' competition level and the extension of sports life.

Evaluating potential of tissue‐engineered cryogels and chondrocyte derived exosomes in articular cartilage repair

Treatment of articular cartilage injuries especially osteochondral tissue requires intervention of bioengineered scaffold. In this study, we investigated the potential of the tissue-engineered cryogel scaffold fabricated using cryogelation technology. Two types of cryogels viz. chitosan-gelatin-chondroitin sulfate (CGC) for articular cartilage and nano-hydroxyapatite-gelatin (HG) for subchondral bone were fabricated. Further, novel bilayer cryogel designed using single process fabrication of two layers (CGC as top layer and HG as the lower layer) was designed to mimic osteochondral unit. CGC cryogel was tested for their biocompatibility using the enzymatically isolated chondrcoytes from goat articular cartilage while HG cryogel was tested using pre-osteoblast cell line. Extracellular vesicles, specifically exosomes were isolated from the spent media of chondrocytes to validate their effect over cell proliferation and migration which are required for defect healing and infiltration respectively. These isolated exosomes were characterized and analyzed for confirming their size distribution profile and visualized morphologically using advanced microscopy techniques. For cartilage part, CGC cryogels were examined as delivery system for delivering exosomes at defect site, where 80% of release was observed in 72 h. Release of 18.7 µg chondroitin sulfate/mg cryogel was obtained in a period of one week from CGC cryogel (termed cryogel extract) which has chondroprotective effect. Further, effect of exosome concentration (10 and 20 µg/ml), CGC extract and combination of exosome and CGC extract (Exo-Ex) were assessed over the chondrocytes. In addition, in vitro scratch wound assay was performed to analyse the migration capacity over the micro-injury when treated with exosomes, cryogel extract and Exo-Ex. The overall results thus answer key questions of therapeutic potential of chondrocyte exosomes, cryogel extract in addition to potential of CGC and HG cryogel for osteochondral repair.

AN INTEGRATIVE REVIEW OF THE ADVANCES IN THE EXPANSION OF HUMAN CONDROCYTES FOR USE IN KNEE CARTILAGE REPAIR

<h3>Background</h3> Cell therapy, which involves the transplantation of stem cells, progenitor cells, primary cells and/or genetically modified, may facilitate the repair of damaged tissue and organs. In orthopedics, the use of chondrocytes to treat articular cartilage lesions is already present in clinical practice. However, there is a demand for the standardization of cells isolation, characterization and expansion. The aim of this study was to conduct an integrative literature review about the methods used, purposing at the development of a standardized research laboratory protocol. <h3>Methods</h3> Bardin's method (2011) was used to characterize in electronic spreadsheets the findings referring to the descriptors "Chondrocyte", "Chondrocyte isolation", "Chondrocyte cultivation" and "Chondrocyte characterization" on the ClinicalTrials, PubMed and Scopus platforms. Based on the methodological parameters, the efficiency of the techniques found in the literature review, a new protocol was developed for the isolation, characterization and expansion of chondrocytes obtained from the knee cartilage. <h3>Results</h3> The Scopus platform presented more studies available (62.3%). The chi-squared test showed statistical significance for the descriptor "Chondrocyte" in the number of results retrieved (p= 0.004) and useful (p=0.04). A total of 78.9% of the surgeries were performed in the knee region, mainly for the treatment of articular cartilage injuries (57.4%). The review identified few studies about the objective, even so it was possible to establish the proposed protocol. The knee cartilage was the region with the highest cells for isolation (31.4%) which we standardized in our study to 3 mm² biopsy dissociated enzymatically with type I collagenase. Expansion time was detailed in 30.8% of the studies, with two weeks being standardized for confluence at passage three. Chondrocyte characterization was not very explained or performed in the researched articles, however we established a protocol by flow cytometry with the following markers: anti-CD14, anti-CD45, anti-CD19, anti-CD44, anti-CD73, anti-CD90, anti-CD151, anti-CD49C, anti-HLA-DR, anti-CD34, anti-CD105, anti-CD29. <h3>Conclusion</h3> The integrative literature review was sufficient to demonstrate studies about the proposed aim, allowing the construction of a research protocol of isolation, expansion and characterization ready to be applied in laboratory research.

The treatment of articular cartilage injuries with mesenchymal stem cells in different animal species.

One of the major problems observed in veterinary practice is articular cartilage injuries in animals. In terms of agriculture, it leads to their culling from the herd, even if they are highly productive animals. With companion animals, owners usually have to decide between euthanasia or long-term sometimes lifelong treatment of the injury by a veterinarian. The use of mesenchymal stem cells (MSCs) for the treatment of cartilage injury in veterinary medicine is based on the good results observed in preclinical studies, where large animals have been used as experimental models to study the regenerative activity of MSCs. According to the literature, MSCs in veterinary medicine have been used to treat cartilage injury of dogs and horses, whereas sheep and goats are generally models for reproducing the disease in preclinical experimental studies.

Icariin inhibits the inflammation through down-regulating NF-κB/HIF-2α signal pathways in chondrocytes.

Articular cartilage injury or defect is a common disease and is mainly characterized by cartilage degradation because of chondrocyte inflammation. By now, there are no effective drugs and methods to protect articular cartilage from degradation. Icariin (ICA) is a typical flavonoid compound extracted from Epimedii Folium with anti-inflammatory and bone-protective effects. Our previous studies demonstrate that ICA up-regulates HIF-1α expression and glycolysis in chondrocytes and maintains chondrocyte phenotype. As another member of HIFs family, HIF-2α always plays a key role in inflammation. The effect of ICA on HIF-2α is unclear by now. In the present study, we confirmed the findings in our previous study that ICA promoted not only chondrocyte vitality and extracellular matrix (ECM) synthesis, but also the anti-inflammatory effect of ICA. In bone defect mice, ICA inhibited the expressions of NF-κB and HIF-2α. In TNF-α-treated ADTC5 chondrocytes, ICA neutralized the activation of IKK (IKK phosphorylation), the phosphorylation of IkB and NF-κB and the expression of HIF-2α. Furthermore, ICA inhibited the nucleus transfer of NF-κB and the expressions of MMP9 and ADAMTS5, two key targets of NF-κB/HIF-2α signal pathway. Taken together, the present study demonstrated that ICA may increase the vitality of chondrocytes by suppressing the inflammatory injury through the inhibition on NF-κB/HIF-2α signaling pathway. ICA is one effective candidate drug for the treatment of articular cartilage injury.

The time-dependent effects of bipolar radiofrequency energy on bovine articular cartilage

PurposeThe purpose of this study was to compare the effect of bipolar radiofrequency energy (bRFE) on chondroplasty at the different time durations in an in vitro experiment that simulated an arthroscopic procedure.MethodsSix fresh bovine knees were used in our study. Six squares were marked on both the medical and lateral femoral condyles of each femur. Each square was respectively treated with bRFE for 0 s, 10 s, 20 s, 30 s, 40 s and 50 s. Full-thickness articular cartilage specimens were harvested from the treatment areas. Each specimen was divided into three distinct parts: one for hematoxylin/eosin staining histology, another for cartilage surface contouring assessment via scanning electron microscopy (SEM), and the last one for glycosaminoglycan (GAG) content measurement.ResultsbRFE caused time-correlated damage to chondrocytes, and GAG content in the cartilage was negatively correlated to exposure time. bRFE caused time-correlated damage to chondrocytes. The GAG content in the cartilage negatively correlated with the exposure time. The sealing effect positively correlated with the exposure time. Additionally, it took at least 20 s of radiofrequency exposure to render a smooth cartilage surface and a score of 2 (normal) in the scoring system used.ConclusionbRFE usage in chondroplasty could effectively trim and polish the cartilage lesion area; however, it induces a dose-dependent detrimental effect on chondrocytes and metabolic activity that negatively correlated with the treatment time. Therefore, cautions should be taken in the use of bRFE for treatment of articular cartilage injury.

Регенеративные эффекты гидрогеля из биоматериала пуповины человека в восстановлении повреждений суставного хряща

Регенеративные эффекты гидрогеля из биоматериала пуповины человека в восстановлении повреждений суставного хряща

Understanding Articular Cartilage Injury and Potential Treatments.

The goals of all orthopaedic surgeons treating articular cartilage injuries have been anatomic reduction and stable fixation of the articular cartilage surface with restoration of limb alignment and/or reestablishment of the joint stability, all while minimizing the risk of surgical complications. Recent developments in the study of articular cartilage injury have shown that there is a robust cellular response to joint injury. This response has been shown to involve the synoviocytes, chondrocytes, and osteocytes in and around the injured joint and if these responses are left unchecked, they can lead to the development of posttraumatic osteoarthritis (PTOA). Therefore, to predictably and successfully treat articular cartilage injuries, it is not sufficient to just restore articular congruity, limb alignment, and joint stability, but we must also recognize and attempt to mitigate this associated cellular response. Understanding not only the mechanical aspects of these joint injuries but also the biological aspects is paramount to giving our patients the best opportunity to heal their injuries, recover full function, and avoid the potential devastating development of PTOA. Gone is the simplistic view that if one can achieve articular congruity after intraarticular fracture, as well as joint stability after ligamentous injury, that our patients will do just fine. This review sheds new light on the molecular response to cartilage injury, how residual joint incongruity and instability affect the joint's ability to recover from injury, and how chondrocyte apoptosis in response to injury can influence joint. This article then briefly reviews how cellular and growth factors may be beneficial to the treatment of articular cartilage injury and how ultimately cartilage regeneration may be used in the future to salvage the joints ravaged by PTOA in response to injury.

Platelet-Rich Plasma and Cartilage Repair

To assess the utilization and efficacy of platelet-rich plasma (PRP), for the treatment of articular cartilage injury, most commonly characterized by progressive pain and loss of joint function in the setting of osteoarthritis (OA). PRP modulates the inflammatory and catabolic environment through a locally applied concentrate of platelets, leukocytes, and growth factors. Clinically, PRP has been shown to be possibly a viable treatment adjuvant for a variety of inflammatory and degenerative conditions. Recent efforts have focused on optimizing delivery methods that enable platelets to slowly degranulate their biological constituents, which may promote healing and improve OA symptoms for a longer duration. There are various factors that affect the progression of OA within joints, including inhibition of inflammatory cytokines and altering the level of enzymatic expression. PRP therapy aims to mediate inflammatory and catabolic factors in a degenerative environment through the secretion of anti-inflammatory factors and chemotaxic effects. There are a growing number of studies that have demonstrated the clinical benefit of PRP for non-operative management of OA. Additional randomized controlled trials with long-term follow-up are needed in order to validate PRP's therapeutic efficacy in this setting. Additionally, continued basic research along with well-designed pre-clinical studies and reporting standards are necessary in order to clarify the effectiveness of PRP for cartilage repair and regeneration for future clinical applications.

Treatment of Articular Cartilage Injuries in the Glenohumeral Joint.

Articular cartilage injuries in the glenohumeral joint present a unique and difficult problem for the patient and surgeon alike. Various etiologies exist for the development of these cartilage lesions; therefore, treatment options are vast and must be chosen thoughtfully, especially in the young, active patient. Across all treatment modalities, the goal is for the patient to regain lasting function and mobility while decreasing pain.

Relationship Between Quantitative MRI Biomarkers and Patient-Reported Outcome Measures After Cartilage Repair Surgery: A Systematic Review

Background:Treatment of articular cartilage injuries remains a clinical challenge, and the optimal tools to monitor and predict clinical outcomes are unclear. Quantitative magnetic resonance imaging (qMRI) allows for a noninvasive biochemical evaluation of cartilage and may offer advantages in monitoring outcomes after cartilage repair surgery.Hypothesis:qMRI sequences will correlate with early pain and functional measures.Study Design:Systematic review; Level of evidence, 3.Methods:A PubMed search was performed with the following search terms: knee AND (cartilage repair OR cartilage restoration OR cartilage surgery) AND (delayed gadolinium-enhanced MRI OR t1-rho OR T2 mapping OR dgemric OR sodium imaging OR quantitative imaging). Studies were included if correlation data were included on quantitative imaging results and patient outcome scores.Results:Fourteen articles were included in the analysis. Eight studies showed a significant relationship between quantitative cartilage imaging and patient outcome scores, while 6 showed no relationship. T2 mapping was examined in 11 studies, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) in 4 studies, sodium imaging in 2 studies, glycosaminoglycan chemical exchange saturation transfer (gagCEST) in 1 study, and diffusion-weighted imaging in 1 study. Five studies on T2 mapping showed a correlation between T2 relaxation times and clinical outcome scores. Two dGEMRIC studies found a correlation between T1 relaxation times and clinical outcome scores.Conclusion:Multiple studies on T2 mapping, dGEMRIC, and diffusion-weighted imaging showed significant correlations with patient-reported outcome measures after cartilage repair surgery, although other studies showed no significant relationship. qMRI sequences may offer a noninvasive method to monitor cartilage repair tissue in a clinically meaningful way, but further refinements in imaging protocols and clinical interpretation are necessary to improve utility.

Clinical curative effect of repair surgery for treatment of articular cartilage injury

Objective: This study aims to determine the clinical efficacy of articular cartilage injury repair surgery. Methods: A total of 112 patients with knee articular cartilage injury who received treatment at our hospital from August 2015 to May 2017 were selected as research subjects. The patients were divided into control and experimental groups (56 patients in each group) through random even-odd number method and treated with arthroscopic joint debridement and arthroscopic microfracture repair surgery, respectively. Clinical treatment effect, HSS score, complication, and surgical result satisfaction were observed and compared between the two groups. Results: Patients in the experimental group exhibited significantly higher total effective rate than those in the control group (P<0.05). The HSS score in the experimental group was higher than that in the control group, and more patients in the former group showed HSS score higher than 85 or between 60-85 and less patients had HSS score less than 60 (P<0.05). Patients in the control group experienced less satisfaction on the result of surgery and higher complication incidence rate than those in the experimental group; the difference was statistically significant between the two groups (P<0.05). Conclusion: Arthroscopic microfracture surgery exerts satisfactory treatment effect for knee articular cartilage injury and can significantly improve patient satisfaction regarding surgery result, improve the articular function and physical action ability of patients, and reduce the incidence rate of complications. Hence, this technique is a feasible option and must be promoted for clinical application.

Joint Preservation Techniques in Orthopaedic Surgery.

Context:With increasing life expectancy, there is growing demand for preservation of native articular cartilage to delay joint arthroplasties, especially in younger, active patients. Damage to the hyaline cartilage of a joint has a limited intrinsic capacity to heal. This can lead to accelerated degeneration of the joint and early-onset osteoarthritis. Treatment in the past was limited, however, and surgical treatment options continue to evolve that may allow restoration of the natural biology of the articular cartilage. This article reviews the most current literature with regard to indications, techniques, and outcomes of these restorative procedures.Evidence Acquisition:MEDLINE and PubMed searches relevant to the topic were performed for articles published between 1995 and 2016. Older articles were used for historical reference. This paper places emphasis on evidence published within the past 5 years.Study Design:Clinical review.Level of Evidence:Level 4.Results:Autologous chondrocyte implantation and osteochondral allografts (OCAs) for the treatment of articular cartilage injury allow restoration of hyaline cartilage to the joint surface, which is advantageous over options such as microfracture, which heal with less favorable fibrocartilage. Studies show that these techniques are useful for larger chondral defects where there is no alternative. Additionally, meniscal transplantation can be a valuable isolated or adjunctive procedure to prolong the health of the articular surface.Conclusion:Newer techniques such as autologous chondrocyte implantation and OCAs may safely produce encouraging outcomes in joint preservation.

Articular cartilage: injury, healing, and regeneration

Treatment of large articular cartilage defects is technically demanding, and healing is a complicated process often associated with failure. The aim of treatment of articular cartilage injuries is to induce an acceptable healing process. Invasive and noninvasive treatments usually have good short- to mid-term outcomes; however, long-term results have been disappointing probably due to scar formation. Thus, current options are more palliative than curative. Tissue engineering and regenerative medicine (TERM) that includes scaffolds, healing factors, stem cells, and genetic engineering was introduced to orthopaedic research in the last 2 decades. Although TERM has demonstrated utility, the expected goals are not necessarily realistic. Despite advancements, several problems still exist and must be solved. This review discusses articular cartilage structure and function, injury types, the healing process, and factors that influence the healing response. Current treatment modalities, including TERM-based strategies, and their limitations are reviewed to provide future directions for treatment.

Osteochondral allograft transplantation in cartilage repair: Graft storage paradigm, translational models, and clinical applications.

The treatment of articular cartilage injury and disease has become an increasingly relevant part of orthopaedic care. Articular cartilage transplantation, in the form of osteochondral allografting, is one of the most established techniques for restoration of articular cartilage. Our research efforts over the last two decades have supported the transformation of this procedure from experimental "niche" status to a cornerstone of orthopaedic practice. In this Kappa Delta paper, we describe our translational and clinical science contributions to this transformation: (1) to enhance the ability of tissue banks to process and deliver viable tissue to surgeons and patients, (2) to improve the biological understanding of in vivo cartilage and bone remodeling following osteochondral allograft (OCA) transplantation in an animal model system, (3) to define effective surgical techniques and pitfalls, and (4) to identify and clarify clinical indications and outcomes. The combination of coordinated basic and clinical studies is part of our continuing comprehensive academic OCA transplant program. Taken together, the results have led to the current standards for OCA processing and storage prior to implantation and also novel observations and mechanisms of the biological and clinical behavior of OCA transplants in vivo. Thus, OCA transplantation is now a successful and increasingly available treatment for patients with disabling osteoarticular cartilage pathology.

Treatment for cartilage injuries of the knee with a new treatment algorithm.

Treatment of articular cartilage injuries to the knee remains a considerable challenge today. Current procedures succeed in providing relief of symptoms, however damaged articular tissue is not replaced with new tissue of the same biomechanical properties and long-term durability as normal hyaline cartilage. Despite many arthroscopic procedures that often manage to achieve these goals, results are far from perfect and there is no agreement on which of these procedures are appropriate, particularly when full-thickness chondral defects are considered.Therefore, the search for biological solution in long-term functional healing and increasing the quality of wounded cartilage has been continuing. For achieving this goal and apply in wide defects, scaffolds are developed.The rationale of using a scaffold is to create an environment with biodegradable polymers for the in vitro growth of living cells and their subsequent implantation into the lesion area. Previously a few numbers of surgical treatment algorithm was described in reports, however none of them contained one-step or two -steps scaffolds. The ultimate aim of this article was to review various arthroscopic treatment options for different stage lesions and develop a new treatment algorithm which included the scaffolds.