An analytical model to predict interstitial lubrication of cartilage in migrating contact areas

For nearly a century, articular cartilage has been known for its exceptional tribological properties. For nearly as long, there have been research efforts to elucidate the responsible mechanisms for application toward biomimetic bearing applications. It is now widely accepted that interstitial fluid pressurization is the primary mechanism responsible for the unusual lubrication and load bearing properties of cartilage. Although the biomechanics community has developed elegant mathematical theories describing the coupling of solid and fluid (biphasic) mechanics and its role in interstitial lubrication, quantitative gaps in our understanding of cartilage tribology have inhibited our ability to predict how tribological conditions and material properties impact tissue function. This paper presents an analytical model of the interstitial lubrication of biphasic materials under migrating contact conditions. Although finite element and other numerical models of cartilage mechanics exist, they typically neglect the important role of the collagen network and are limited to a specific set of input conditions, which limits general applicability. The simplified approach taken in this work aims to capture the broader underlying physics as a starting point for further model development. In agreement with existing literature, the model indicates that a large Peclet number, Pe, is necessary for effective interstitial lubrication. It also predicts that the tensile modulus must be large relative to the compressive modulus. This explains why hydrogels and other biphasic materials do not provide significant interstitial pressure under high Pe conditions. The model quantitatively agrees with in-situ measurements of interstitial load support and the results have interesting implications for tissue engineering and osteoarthritis problems. This paper suggests that a low tensile modulus (from chondromalacia or local collagen rupture after impact, for example) may disrupt interstitial pressurization, increase shear stresses, and activate a condition of progressive surface damage as a potential precursor of osteoarthritis.     

Alterative effects of an oral alginate extract on experimental rabbit osteoarthritis

Background

Osteoarthritis (OA) is a common joint disease that causes disabilities in elderly. However, few agents with high efficacy and low side effects have been developed to treat OA. In this study, we evaluated the effects of the alginate extract named CTX in OA cell and rabbit models.

Results

CTX was formulated by hydrolyzing sodium alginate polymers with alginate lyase and then mixing with pectin. HPLC was used to analyze the CTX content. Human chondrosarcoma SW1353 cells treated with interleukin-1β were used as OA model cells to investigate the effects of CTX on chondrocyte inflammation and anabolism. CTX at concentrations up to 1000 μg/ml exerted low cytotoxicity. It inhibited the gene expression of proinflammatory matrix metalloproteinases (MMPs) including MMP1, MMP3 and MMP13 in a dose-dependent manner and increased the mRNA level of aggrecan, the major proteoglycan in articular cartilage, at 1000 μg/ml. Thirteen-week-old New Zealand White rabbits underwent a surgical anterior cruciate ligament transection and were orally treated with normal saline, glucosamine or CTX for up to 7 weeks. Examinations of the rabbit femur and tibia samples demonstrated that the rabbits taking oral CTX at a dosage of 30 mg/kg/day suffered lesser degrees of articular stiffness and histological cartilage damage than the control rabbits.

Conclusions

The gene expression profiles in the cell and the examinations done on the rabbit cartilage suggest that the alginate extract CTX is a pharmaco-therapeutic agent applicable for OA therapy.     

Effects of fatigue on lower limb,pelvis and trunk kinematics and muscle activation: Gender differences

Background: Muscle fatigue is associated with biomechanical changes that may lead to anterior cruciate ligament (ACL) injuries. Alterations in trunk and pelvis kinematics may also be involved in ACL injury. Although some studies have compared the effects of muscle fatigue on lower limb kinematics between men and women, little is known about its effects on pelvis and trunk kinematics. The aim of the study was to compare the effects of fatigue on lower limb, pelvis and trunk kinematics and muscle activation between men and women during landing. Methods: The participants included forty healthy subjects. We performed kinematic analysis of the trunk, pelvis, hip and knee and muscle activation analysis of the gluteal muscles, vastus lateralis and biceps femoris, during a single-leg landing before and after fatigue. Results: Men had greater trunk flexion than women after fatigue. After fatigue, a decrease in peak knee flexion and an increase in Gmax and BF activation were observed. Conclusion: The increase in the trunk flexion can decrease the anterior tibiofemoral shear force resulted from the lower knee flexion angle, thereby decreasing the stress on the ACL.     

Fatigue injury risk in anterior cruciate ligament of target side knee during golf swing

A golf-related ACL injury can be linked with excessive golf play or practice because such over-use by repetitive golf swing motions can increase damage accumulation to the ACL bundles. In this study, joint angular rotations, forces, and moments, as well as the forces and strains on the ACL of the target-side knee joint, were investigated for ten professional golfers using the multi-body lower extremity model. The fatigue life of the ACL was also predicted by assuming the estimated ACL force as a cyclic load. The ACL force and strain reached their maximum values within a short time just after ball-impact in the follow-through phase. The smaller knee flexion, higher internal tibial rotation, increase of the joint compressive force and knee abduction moment in the follow-through phase were shown as to lead an increased ACL loading. The number of cycles to fatigue failure (fatigue life) in the ACL might be several thousands. It is suggested that the excessive training or practice of swing motion without enough rest may be one of factors to lead to damage or injury in the ACL by the fatigue failure. The present technology can provide fundamental information to understand and prevent the ACL injury for golf players.     

Collagen synthesis of articular cartilage explants in response to frequency of cyclic mechanical loading

Articular cartilage in vivo experiences the effects of both cell-regulatory proteins and mechanical forces. This study has addressed the hypothesis that the frequency of intermittently or continuously applied mechanical loads is a critical parameter in the regulation of chondrocyte collagen biosynthesis. Cyclic compressive pressure was applied intermittently to bovine articular cartilage explants by using a sinusoidal waveform of 0.1–1.0 Hz frequency with a peak stress of 0.5 MPa for a period of 5–20 s followed by a load-free period of 10–1,000 s. These loading protocols were repeated for a total duration of 6 days. In separate experiments, cyclic loading was continuously applied by using a sinusoidal waveform of 0.001–0.5 Hz frequency and a peak stress of 1.0 MPa for a period of 3 days. Unloaded cartilage discs of the same condyle were cultured in identically constructed loading chambers and served as controls. We report quantitative data showing that (1) no correlation exists between the relative rate of collagen synthesis expressed as the proportion of newly synthesized collagen among newly made proteins and either the frequency of intermittently or continuously applied loads or the overall time cartilage is actively loaded, and (2) individual protocols of intermittently applied loads can reduce the relative rate of collagen synthesis and increase the water content, whereas (3) continuously applied cyclic loads always suppress the relative rate of collagen synthesis compared with that of unloaded control specimens. The results provide further experimental evidence that collagen metabolism is difficult to manipulate by mechanical stimuli. This is physiologically important for the maintainance of the material properties of collagen in view of the heavy mechanical demands made upon it. Moreover, the unaltered or reduced collagen synthesis of cartilage explants might reflect more closely the metabolism of normal or early human osteoarthritic cartilage.This work was supported by the Federal Ministry of Education and Research (BMBF no. 0311058) and by the foundation S.E.T.     

ACL对膝关节胫骨内、外旋转稳定性控制作用的初步研究

目的:研究正常人前交叉韧带(Anterior Cruciate Ligament,ACL)对膝关节内、外旋转稳定性的控制作用;探讨膝关节ACL多纤维束动态力学特性。方法:采集5例新鲜正常成年男性左侧膝关节标本,评估标本完整性后,向ACL胫骨止点中心做斜行骨隧道,游离ACL胫骨侧止点,以象限法平均分为4区:1.后内区、2.后外区、3.前外区、4.前内区;将4区的附着纤维束分别连接至自制膝关节交叉韧带测力计传感器上,并固定于自主发明的通用生物关节自由度动态应力加载系统。对股内侧、股中间肌股直肌联合肌腱、股外侧肌群分别施以1.25N:1.5N:1N的负荷。分别在膝关节屈曲0°、30°、60°、90°位将ACL各纤维束张紧并系统平衡后,利用扭距传感器测量胫骨做内、外旋转时ACL的受力情况。结果:膝关节屈伸过程中,1区纤维束对膝关节内、外旋转稳定性的控制作用较小。2区纤维胫骨外旋时受力最大,并在屈膝30°时达最大(16.97±1.45N)。3区纤维束时对胫骨内、外旋控制作用相当,并在屈膝60°时最大,分别为10.67 1.34N和16.45 1.34N。4区纤维束对胫骨内旋稳定的控制明显大于胫骨外旋,在屈膝90°时作用最大,为11.67 2.25N。结论:膝关节在屈膝不同角度内、外旋转时,每一纤维束的受力是不同的且不断变化的。膝关节屈伸过程中ACL控制胫骨内、外旋转稳定性的最重要作用纤维束集中在胫骨止点的前内侧和后外侧。ACL后外侧纤维束(2区)对膝关节外旋稳定性控制作用最为重要,且以屈膝30°时控制作用最强。前内侧纤维束(4区)对膝关节内旋稳定性的控制最为重要,并且以屈膝90°控制作用最强。前外侧纤维束(3区)对膝关节的内旋和外旋相当,并且在屈膝60°对膝关节内、外旋转稳定性控制最强。     

The mechanical environment of the chondrocyte: a biphasic finite element model of cell-matrix interactions in articular cartilage

Mechanical compression of the cartilage extracellular matrix has a significant effect on the metabolic activity of the chondrocytes. However, the relationship between the stress–strain and fluid-flow fields at the macroscopic “tissue” level and those at the microscopic “cellular” level are not fully understood. Based on the existing experimental data on the deformation behavior and biomechanical properties of articular cartilage and chondrocytes, a multi-scale biphasic finite element model was developed of the chondrocyte as a spheroidal inclusion embedded within the extracellular matrix of a cartilage explant. The mechanical environment at the cellular level was found to be time-varying and inhomogeneous, and the large difference (3 orders of magnitude) in the elastic properties of the chondrocyte and those of the extracellular matrix results in stress concentrations at the cell–matrix border and a nearly two-fold increase in strain and dilatation (volume change) at the cellular level, as compared to the macroscopic level. The presence of a narrow “pericellular matrix” with different properties than that of the chondrocyte or extracellular matrix significantly altered the principal stress and strain magnitudes within the chondrocyte, suggesting a functional biomechanical role for the pericellular matrix. These findings suggest that even under simple compressive loading conditions, chondrocytes are subjected to a complex local mechanical environment consisting of tension, compression, shear, and fluid pressure. Knowledge of the local stress and strain fields in the extracellular matrix is an important step in the interpretation of studies of mechanical signal transduction in cartilage explant culture models.     

Altered biomechanical strategies and medio-lateral control of the knee represent incomplete recovery of individuals with injury during single leg hop

Anterior cruciate ligament (ACL) injury can result in failure to return to pre-injury activity levels and future osteoarthritis predisposition. Single leg hop is used in late rehabilitation to evaluate recovery and inform treatment but biomechanical understanding of this activity is insufficient.     

前交叉韧带损伤后软骨退变和骨性关节炎发生的分子变化

为了探讨凋亡酶的半胱天冬酶3 (Caspase 3)、促炎细胞因子interleukin-1β(IL-1β)、白细胞介素-6(IL-6)和基质金属蛋白酶降解酶-13 (MMP-13)的表达水平,来说明前交叉韧带(anterior cruciate ligament,ACL)损伤后软骨细胞的软骨变性和骨性关节炎的发展情况,本研究通过探讨软骨降解程度与损伤时间或患者年龄之间的关系,应用实时聚合酶链反应检测正常人(n=5)和ACL破裂患者(n=42)软骨细胞中IL-1β、IL-6和MMP-13 mRNA的表达水平,采用Western blotting检测MMP-13和Caspase 3蛋白表达水平。通过趋势分析和相关系数分析,分别得出MMP-13、IL-6、IL-1β基因表达与软骨缺损分级,MMP-13、IL-6、IL-1β基因表达与患者年龄的关系。结果表明,软骨降解程度与损伤时间之间存在相关性。与正常相比,ACL损伤的软骨细胞中,MMP-13、IL-6、IL-1β和Caspase 3的表达水平有显著上调。在ACL缺陷患者中,与ACL缺陷未到18个月的患者相比,在超过18个月的患者中发现MMP-13明显上调,而超过10月的患者软骨细胞中IL-6和IL-1β表达水平要高于未到10个月的ACL缺陷患者。同时,IL-1β、IL-6和MMP-13表达水平和软骨损伤或病人的年龄之间没有关联。研究发现,软骨细胞凋亡、炎症和分解代谢因子水平的升高与损伤时间有关,并可能导致ACL损伤后软骨退变和骨性关节炎的发生。     

Evaluation of cartilage damage by measuring collagen degradation products in joint extracts in a traumatic model of osteoarthritis

The objective of this work was to investigate whether collagen degradation products in protein extract from joints could provide quantitative information on cartilage damage. Osteoarthritis (OA) was surgically induced in rat knee joints. Joints were isolated 7, 14 and 28 days after surgery for protein extraction and histology. C-terminal telopeptide of type II collagen (CTX-II), CTX-I and hydroxyproline were measured in protein extracts. Matrix metalloproteinase (MMP)-2 and -9 activity was evaluated by gelatinase zymography and joint pathology was visualized by histology and immunohistochemistry. The results showed that levels of CTX-II were significantly increased in anterior cruciate ligament transection (ACLT)-operated compared with sham-operated knee joints on days 7 and 28, whereas the levels of hydroxyproline and CTX-I epitopes showed no difference. MMP activity was slightly increased in ACLT-operated joints. The CTX-II epitope was highly expressed and co-localized to damaged articular cartilage in ACLT-operated joints. We have therefore demonstrated an increased type II collagen degradation in knees after surgical induction of OA, and propose assessment of collagen degradation epitopes as a quantitative measure of cartilage damage.     

Evaluation of cartilage damage by measuring collagen degradation products in joint extracts in a traumatic model of osteoarthritis

The objective of this work was to investigate whether collagen degradation products in protein extract from joints could provide quantitative information on cartilage damage. Osteoarthritis (OA) was surgically induced in rat knee joints. Joints were isolated 7, 14 and 28 days after surgery for protein extraction and histology. C-terminal telopeptide of type II collagen (CTX-II), CTX-I and hydroxyproline were measured in protein extracts. Matrix metalloproteinase (MMP)-2 and -9 activity was evaluated by gelatinase zymography and joint pathology was visualized by histology and immunohistochemistry. The results showed that levels of CTX-II were significantly increased in anterior cruciate ligament transection (ACLT)-operated compared with sham-operated knee joints on days 7 and 28, whereas the levels of hydroxyproline and CTX-I epitopes showed no difference. MMP activity was slightly increased in ACLT-operated joints. The CTX-II epitope was highly expressed and co-localized to damaged articular cartilage in ACLT-operated joints. We have therefore demonstrated an increased type II collagen degradation in knees after surgical induction of OA, and propose assessment of collagen degradation epitopes as a quantitative measure of cartilage damage.     

Changes in the chondroitin sulfate-rich region of articular cartilage proteoglycans in experimental osteoarthritis

The chondroitin sulfate-rich region was cleaved from cartilage proteoglycans of experimental osteoarthritic canine joints to establish whether changes in this region of the molecule contribute to the well-documented increase in the chondroitin sulfate to keratan sulfate ratio in osteoarthritis. Experimental osteoarthritis was induced in eight dogs by severance of the right anterior cruciate ligament, the left joint serving as a control. Proteoglycans were extracted from the femoral cartilage of both joints, isolated as A1 fractions by associative density gradient centrifugation and cleaved with hydroxylamine. The chondroitin sulfate-rich region was isolated by either gel chromatography or dissociative density gradient centrifugation. The chondroitin sulfate-rich region from the proteoglycans of the experimental osteoarthritic joints was slightly larger in hydrodynamic size and had both a higher uronate/protein weight ratio and galactosamine/glucosamine molar ratio than the corresponding control. We conclude that the chondroitin sulfate-rich region of proteoglycans in articular cartilage of experimental osteoarthritic joints is larger and has more chondroitin sulfate than that of proteoglycans of normal cartilage.     

A comparison of patellofemoral cartilage morphology and deformation in anterior cruciate ligament deficient versus uninjured knees

Anterior cruciate ligament (ACL) deficient patients have an increased rate of patellofemoral joint (PFJ) osteoarthritis (OA) as compared to the general population. Although the cause of post-injury OA is multi-factorial, alterations in joint biomechanics may predispose patients to cartilage degeneration. This study aimed to compare in vivo PFJ morphology and mechanics between ACL deficient and intact knees in subjects with unilateral ACL ruptures. Eight male subjects underwent baseline MRI scans of both knees. They then performed a series of 60 single-legged hops, followed by a post-exercise MRI scan. This process was repeated for the contralateral knee. The MR images were converted into three-dimensional surface models of cartilage and bone in order to assess cartilage thickness distributions and strain following exercise. Prior to exercise, patellar cartilage was significantly thicker in intact knees as compared to ACL deficient knees by 1.8%. In response to exercise, we observed average patellar cartilage strains of 5.4 ± 1.1% and 2.5 ± 1.4% in the ACL deficient and intact knees, respectively. Importantly, the magnitude of patellar cartilage strain in the ACL deficient knees was significantly higher than in the intact knees. However, while trochlear cartilage experienced a mean strain of 2.4 ± 1.6%, there was no difference in trochlear cartilage strain between the ACL deficient and uninjured knees. In summary, we found that ACL deficiency was associated with decreased patellar cartilage thickness and increased exercise-induced patellar cartilage strain when compared to the uninjured contralateral knees.     

An in vitro model for the pathological degradation of articular cartilage in osteoarthritis

The objective of this study was to develop an in vitro cartilage degradation model that emulates the damage seen in early-stage osteoarthritis. To this end, cartilage explants were collagenase-treated to induce enzymatic degradation of collagen fibers and proteoglycans at the articular surface. To assess changes in mechanical properties, intact and degraded cartilage explants were subjected to a series of confined compression creep tests. Changes in extracellular matrix structure and composition were determined using biochemical and histological approaches. Our results show that collagenase-induced degradation increased the amount of deformation experienced by the cartilage explants under compression. An increase in apparent permeability as well as a decrease in instantaneous and aggregate moduli was measured following collagenase treatment. Histological analysis of degraded explants revealed the presence of surface fibrillation, proteoglycan depletion in the superficial and intermediate zones and loss of the lamina splendens. Collagen cleavage was confirmed by the Col II–3/4C_short antibody. Degraded specimens experienced a significant decrease in proteoglycan content but maintained total collagen content. Repetitive testing of degraded samples resulted in the gradual collapse of the articular surface and the compaction of the superficial zone. Taken together, our data demonstrates that enzymatic degradation with collagenase can be used to emulate changes seen in early-stage osteoarthritis. Further, our in vitro model provides information on cartilage mechanics and insights on how matrix changes can affect cartilage's functional properties. More importantly, our model can be applied to develop and test treatment options for tissue repair.     

Small animal models to understand pathogenesis of osteoarthritis and use of stem cell in cartilage regeneration

Osteoarthritis (OA) is one of the most common diseases, which affect the correct functionality of synovial joints and is characterized by articular cartilage degradation. Limitation in the treatment of OA is mostly due to the very limited regenerative characteristic of articular cartilage once is damaged. Small animal models are of particular importance for mechanistic analysis to understand the processes that affect cartilage degradation. Combination of joint injury techniques with the use of stem cells has been shown to be an important tool for understanding the processes of cartilage degradation and regeneration. Implementation of stem cells and small animal models are important tools to help researchers to find a solution that could ameliorate and prevent the symptoms of OA.     

Three-dimensional in vivo kinematics and finite helical axis variables of the ovine stifle joint following partial anterior cruciate ligament transection

Partial anterior cruciate ligament (p-ACL) rupture is a common injury, but the impact of a p-ACL injury on in vivo joint kinematics has yet to be determined in an animal model. The in vivo kinematics of the ovine stifle joint were assessed during ‘normal’ gait, and at 20 and 40 weeks after p-ACL transection (Tx). Gross morphological scoring of the knee was conducted. p-ACL Tx creates significant progressive post-traumatic osteoarthritis (PTOA)-like damage by 40 weeks. Statistically significant increases for flexion angles at hoof-strike (HS) and mid-stance (MST) were seen at 20 weeks post p-ACL Tx and the HS and hoof-off (HO) points at 40 weeks post p-ACL-Tx, therefore increased flexion angles occurred during stance phase. Statistically significant increases in posterior tibial shift at the mid-flexion (MF) and mid-extension (ME) points were seen during the swing phase of the gait cycle at 40 weeks post p-ACL Tx. Correlation analysis showed a strong and significant correlation between kinematic changes (instabilities) and gross morphological score in the inferior-superior direction at 40 weeks post p-ACL Tx at MST, HO, and MF. Further, there was a significant correlation between change in gross morphological combined score (ΔGCS) and the change in location of the helical axis in the anterior direction (ΔsAP) after p-ACL Tx for all points analyzed through the gait cycle. This study quantified in vivo joint kinematics before and after p-ACL Tx knee injury during gait, and demonstrated that a p-ACL knee injury leads to both PTOA-like damage and kinematic changes.     

Effect of limb dominance and sex on neuromuscular activation patterns in athletes under 12 performing unanticipated side-cuts

Non-contact ACL injuries are one of the most common injuries to the knee joint among adolescent/collegiate athletes, with sex and limb dominance being identified as risk factors. In children under 12 years of age (U12), these injuries occur less often and there is no sex-bias present. This study set out to explore if sex and/or limb dominance differences exist in neuromuscular activations in U12 athletes. Thirty-four U12 males and females had six bilateral muscles analyzed during unanticipated side-cuts. Principal component analysis was performed, capturing differences in overall magnitudes and timing of peak magnitudes. Two-way mixed-model ANOVAs determined significant limb effects with both sexes displaying (i) greater magnitudes in the lateral gastrocnemius and both hamstrings in the dominant limb and (ii) earlier timing of peak magnitudes in both gastrocnemii, both hamstrings and vastus medialis in the non-dominant limb, while no sex differences were identified. This study demonstrated that limb dominance, not sex, affects neuromuscular activation strategies in U12 athletes during unanticipated side-cuts. When developing injury prevention programs for younger athletes, an increased focus on balancing neuromuscular activations in both limbs could be beneficial in reducing the likelihood of ACL injuries in these athletes as they mature through puberty.     

In vivo assessment of the interaction of patellar tendon tibial shaft angle and anterior cruciate ligament elongation during flexion

A potential cause of non-contact anterior cruciate ligament (ACL) injury is landing on an extended knee. In line with this hypothesis, studies have shown that the ACL is elongated with decreasing knee flexion angle. Furthermore, at low flexion angles the patellar tendon is oriented to increase the anterior shear component of force acting on the tibia. This indicates that knee extension represents a position in which the ACL is taut, and thus may have an increased propensity for injury, particularly in the presence of excessive force acting via the patellar tendon. However, there is very little in vivo data to describe how patellar tendon orientation and ACL elongation interact during flexion. Therefore, this study measured the patellar tendon tibial shaft angle (indicative of the relative magnitude of the shear component of force acting via the patellar tendon) and ACL length in vivo as subjects performed a quasi-static lunge at varying knee flexion angles. Spearman rho rank correlations within each individual revealed that flexion angles were inversely correlated to both ACL length (rho = −0.94 ± 0.07, mean ± standard deviation, p < 0.05) and patellar tendon tibial shaft angle (rho = −0.99 ± 0.01, p < 0.05). These findings indicate that when the knee is extended, the ACL is both elongated and the patellar tendon tibial shaft angle is increased, resulting in a relative increase in anterior shear force on the tibia acting via the patellar tendon. Therefore, these data support the hypothesis that landing with the knee in extension is a high risk scenario for ACL injury.