Purpose
Many studies have shown that local anesthetics may impede chondrocyte metabolism. However, the influence of a single-dose local anesthetics is controversial. The aim of this metaanalysis was ...to review the literature for studies investigating the cytotoxic effects of single-dose local anesthetics on chondrocytes and cartilage.
Methods
A comprehensive literature search was performed using established search engines (Medline, Embase) to identify studies, investigating the influence of single-dose local anesthetics on cartilage. The systematic analysis included the influence on histology, cell viability, morphology, and matrix production depending upon dose, exposure time, and type of local anesthetics.
Results
Twelve studies with four different local anesthetics were included in this metaanalysis. Bupivacaine and lidocaine were found to be more chondrotoxic than mepivacaine and ropivacaine. The amount of dead cells increased in a substance-, dose-, and time-dependent process. Osteoarthritic cartilage seems to be more vulnerable compared to intact cartilage. The toxic effects occur first in the superficial cartilage layers and include damage to membrane integrity, mitochondrial DNA, and nuclear changes. There is no study that could show a significant chondrotoxic effect with low concentrations of bupivacaine (0.0625%), ropivacaine (0.1 and 0.2%), and mepivacaine (0.5%).
Conclusions
The cytotoxicity of local anesthetics on chondrocytes is dependent on dose, time, and type of local anesthetics. Single-dose intra-articular administration of local anesthetics impede chondrocyte metabolism and should be performed only with low concentrations for selected diagnostic purposes and painful joints. The use of lidocaine should be avoided.
Level of evidence
II.
Articular cartilage covers the surface of synovial joints and enables joint movement. However, it is susceptible to progressive degeneration with age that can be accelerated by either previous joint ...injury or meniscectomy. This degenerative disease is known as osteoarthritis (OA) and it greatly affects the adult population. Cell-based tissue engineering provides a possible solution for treating OA at its earliest stages, particularly focal cartilage lesions. A candidate cell type for treating these focal defects are Mesenchymal Stem Cells (MSCs). However, present methods for differentiating these cells towards the chondrogenic lineage lead to hypertrophic chondrocytes and bone formation in vivo. Environmental stimuli that can stabilise the articular chondrocyte phenotype without compromising tissue formation have been extensively investigated. One factor that has generated intensive investigation in MSC chondrogenesis is low oxygen tension or physioxia (2⁻5% oxygen). In vivo articular cartilage resides at oxygen tensions between 1⁻4%, and in vitro results suggest that these conditions are beneficial for MSC expansion and chondrogenesis, particularly in suppressing the cartilage hypertrophy. This review will summarise the current literature regarding the effects of physioxia on MSC chondrogenesis with an emphasis on the pathways that control tissue formation and cartilage hypertrophy.
Intraarticular injections of local anesthetics are frequently used as part of multimodal pain regimens. However, recent data suggest that local anesthetics affect chondrocyte viability. In this ...study, we assessed the chondrotoxic effects of mepivacaine, ropivacaine, and bupivacaine. We hypothesized that specific cytotoxic potencies directly correlate with analgesic potencies, and that cytotoxic effects in intact cartilage are different than in osteoarthritic tissue.
Human articular chondrocytes were exposed to equal and equipotent concentrations of bupivacaine, ropivacaine, and mepivacaine for 1 hour. Cell viability, apoptosis, and necrosis were determined at predefined time points using flow cytometry, live-dead staining, and caspase detection. Intact and osteoarthritic human cartilage explants were treated with equipotent concentrations of named drugs to determine cell viability applying fluorescence microscopy.
Chondrotoxic effects increased from ropivacaine to mepivacaine to bupivacaine in a time-dependent and concentration-dependent manner. Compared with control, bupivacaine 0.5% decreased chondrocyte viability to 78% ± 9% (P = 0.0183) 1 hour and 16% ± 10% (P < 0.0001) 24 hours later, as determined by live-dead staining in monolayer cultures. Viability rates were reduced to 80% ± 7% (P = 0.0475) 1 hour and 80% ± 10% (P = 0.0095) 24 hours after treatment with ropivacaine 0.75%. After exposure to mepivacaine 2%, viable cells were scored 36% ± 6% (P < 0.0001) after 1 hour and 30% ± 11% (P < 0.0001) after 24 hours. Ropivacaine treatment was less chondrotoxic than bupivacaine (P = 0.0006) and mepivacaine exposure (P = 0.0059). Exposure to concentrations up to 0.25% of bupivacaine, 0.5% of ropivacaine, and 0.5% of mepivacaine did not reveal significant chondrotoxicity in flow cytometry. However, chondrotoxicity did not correlate with potency of local anesthetics. Immediate cell death was mainly due to necrosis followed by apoptosis. Cellular death rates were clearly higher in osteoarthritic compared with intact cartilage after bupivacaine, mepivacaine, and ropivacaine treatment in a decreasing order.
Bupivacaine, ropivacaine, and mepivacaine are chondrotoxic in a time-dependent, concentration-dependent, and drug-dependent manner. Chondrotoxic and analgesic potencies do not directly correlate. Cellular death rates were higher in osteoarthritic compared with intact cartilage after local anesthetic treatment.
Purpose The purpose of this study was to investigate the cytotoxic potency of local anesthetics on human mesenchymal stem cells (MSCs) before and after chondrogenic differentiation. Methods MSCs were ...exposed to equal and equipotent concentrations of bupivacaine, ropivacaine, and mepivacaine for 1 hour. Cell viability, apoptosis, and necrosis were determined using flow cytometry and live/dead staining. After chondrogenic differentiation, MSC viability was determined in aggregates exposed to equipotent concentrations of the named agents, applying fluorescence microscopy. Results All local anesthetics showed detrimental cytotoxic effects on MSC monolayer cultures in a concentration- and time-specific manner. Minimum viability rates were found 96 hours after a 1-hour exposure. Bupivacaine 0.5% caused a reduction of vital MSCs to 5% ± 1%. Sixteen percent ± 2% viable cells were detected after treatment with 0.75% ropivacaine. Exposure to 2% mepivacaine decreased vitality rates to 1% ± 0%. Ropivacaine was significantly less cytotoxic than were bupivacaine and mepivacaine. Immediate cell death was mainly caused by necrosis followed by apoptosis afterward. Viability rates of MSCs embedded in cartilaginous tissue after chondrogenic differentiation were not reduced by local anesthetic treatment. Conclusions Local anesthetics are cytotoxic to MSCs in a concentration-, time-, and agent-dependent manner in monolayer cultures but not in whole-tissue probes. Clinical Relevance MSCs are applied for treatment of cartilage defects. Intra-articular application of local anesthesia is a common procedure in pain management and has shown chondrotoxic effects. Therefore, it is crucial to evaluate the impact of local anesthetics on human MSCs and regenerative cartilage tissue engineering.
It is widely accepted that partial meniscectomy leads to early onset of osteoarthritis (OA). A strong correlation exists between the amount and location of the resected meniscus and the development ...of degenerative changes in the knee. On the other hand, osteoarthritic changes of the joint alter the structural and functional integrity of meniscal tissue. These alterations might additionally compromise the limited healing capacity of the meniscus. In young, active patients without cartilage damage, meniscus therapy including partial meniscectomy, meniscus suture, and meniscus replacement has proven beneficial effects in long-term studies. Even in an early osteoarthritic milieu, there is a relevant regenerative potential of the meniscus and the surrounding cartilage. This potential should be taken into account, and meniscal surgery can be performed with the correct timing and the proper indication even in the presence of early OA.
Level of evidence IV.
Background
The meniscus plays an important role in the integrity of the knee joint. Therefore, meniscus tissue preserving techniques for the therapy of meniscus injuries seem to be reasonable. One of ...the important questions is whether meniscal repair can prevent the knee joint from early onset of osteoarthritis.
Methods
According to the review of the current literature, the principles of a successful meniscal repair are explained and the functional outcome and its impact on the prevention of osteoarthritis are analyzed in this article.
Results
Current data show a positive impact of a successful meniscus repair on the functional outcome in long-term. By this a protective effect on the development of osteoarthritis via the repair of meniscus lesions to restore the meniscus integrity can be confirmed. However, higher rates of re-operations in context to meniscus suturing have to be considered.
Conclusion
Due to the improved functional outcomes as well as preventive effect on the development of osteoarthritis within the knee joint in long-term, it is of importance to preserve as much meniscus tissue as possible in meniscus therapy. Patients previously have to be informed about the higher revision rate in context to meniscus suturing.
Articular cartilage is crucial for joint function but its avascularity limits intrinsic repair, leading to conditions like osteoarthritis (OA). Chondromodulin-I (Cnmd) has emerged as a key molecule ...in cartilage biology, with potential implications for OA therapy. Cnmd is primarily expressed in cartilage and plays an important role in chondrocyte proliferation, cartilage homeostasis, and the blocking of angiogenesis. In vivo and in vitro studies on Cnmd, also suggest an involvement in bone repair and in delaying OA progression. Its downregulation correlates with OA severity, indicating its potential as a therapeutic target. Further research is needed to fully understand the mode of action of Cnmd and its beneficial implications for managing OA. This comprehensive review aims to elucidate the molecular characteristics of Cnmd, from its expression pattern, role in cartilage maintenance, callus formation during bone repair and association with OA.
Purpose
Injuries are a common occurrence in football. Sufficient epidemiological data are available in professional football but not in salaried semi-professional football. This study investigates ...the injury incidence at different levels of semi-professional football with focus on junior football.
Methods
The data were based on injury reports provided by players and medical staff over the 2015–2016 season, which corresponded to the consensus statement for data samples in football. This study investigated the injury incidence and prevalence of five skill levels of semi-professional football (the fourth to the seventh league and elite junior football).
Results
1130 players had sustained 2630 injuries over the 2015–2016 season. The overall injury incidence was 9.7 per 1000 h football exposure; prevalence with at least one injury was 79%. The highest overall injury incidence in elite junior football was 10.4 in 1000 h football exposure. The fifth league had the lowest incidence with 9.0 in 1000 h football (
p
< 0.05). Traumatic injuries most often occurred in the fourth league (3.9 in 1000 h football). The body areas most affected by traumatic injury were knees, ankles and thighs. Elite junior players had a significantly higher incidence of overuse complaints (7.4 in 1000 h football) than the fourth league (5.4,
p
= 0.005). The body areas most affected by overuse complaints were the lower back, thigh and groin. No differences were found between the different positions on field.
Conclusions
Salaried semi-professional football involves a high overall injury incidence. The highest incidence, particularly of overuse injuries, was seen in elite junior football. These findings should be incorporated in specific injury prevention training or screenings beginning in junior football.
Level of evidence
II.
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