Effects of intermittently applied cyclic loading on proteoglycan metabolism and swelling behaviour of articular cartilage explants

Steinmeyer, Jürgen; Knue, Sabine; Raiss, R.; Pelzer, Ingeborg

doi:10.1053/joca.1998.0204

Cited by 36 publications

(34 citation statements)

References 31 publications

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“…This study demonstrated that the short-term (24 h) biosynthetic response of passaged adult articular chondrocytes seeded in porous type II collagen scaffolds was similar to that reported for primary chondrocytes in intact articular cartilage, 4,7,16,19,35,36 regardless of the age of the culture. Specifically, static compression generally down-regulated protein and proteoglycan biosynthesis in a time-(1 to 24 h) and dose-(0-50% strain) dependent manner (Figs.…”

Section: Discussionsupporting

confidence: 80%

Biosynthetic response of passaged chondrocytes in a type II collagen scaffold to mechanical compression

Lee

Grodzinsky

Spector

2003

J Biomedical Materials Res

111

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To investigate the potential utility of mechanical loading in articular cartilage tissue engineering, porous type II collagen scaffolds seeded with adult canine passaged chondrocytes were subjected to static and dynamic compressions of varying magnitudes (0-50% static strain) and durations (1-24 h), and at different times during culture (2-30 days postseeding). The effects of mechanical compression on the biosynthetic activity of the chondrocytes were evaluated by measuring the amount of (3)H-proline-labeled proteins and (35)S-sulfate-labeled proteoglycans that accumulated in the cell-scaffold construct and was released to the medium during the loading period. Similar to published results on loading of articular cartilage explants, static compression decreased protein and proteoglycan biosynthesis in a time- and dose-dependent manner (each p < 0.005), and selected dynamic compression protocols were able to increase rates of biosynthesis (p < 0.05). The main difference between the results seen for this tissue engineering system and cartilage explants was in the amount of newly synthesized matrix molecules that accumulated within the construct under dynamic loading, with less accumulating in the type II collagen scaffold. In summary, the general biosynthetic response of passaged chondrocytes in the porous type II collagen scaffolds is similar to that seen for chondrocytes in their native environment. Future work needs to be directed to modifications of the cell-seeded construct to allow for the capture of the newly synthesized matrix molecules by the scaffold.

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Section: Discussionsupporting

confidence: 80%

Biosynthetic response of passaged chondrocytes in a type II collagen scaffold to mechanical compression

Lee

Grodzinsky

Spector

2003

J Biomedical Materials Res

111

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“…Cartilage explant thickness was measured twice and averaged from perpendicular orientations across the center of the explant using a digital vernier caliper. 15 A magnet with a 4.3 mm-diameter hole was placed on top of the explant to secure the edges and help resist curling. The explant and fixture were then submerged into a room-temperature phosphate-buffered solution (pH 7.2).…”

Section: Methodsmentioning

confidence: 99%

High levels of glucosamine–chondroitin sulfate can alter the cyclic preload and acute overload responses of chondral explants

Wei

Haut

2009

Journal Orthopaedic Research

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A recent study by our laboratory showed that 14 days of low intensity, intermittent cyclic preloading of chondral explants elevated the concentration of proteoglycans (PGs) to cause a mechanical stiffening of the explants prior to an acute overload and limit the extent of tissue damage. Longer term loading to 21 days resulted in tissue degradation prior to the acute traumatic event and excessive damage from an acute overload. Previous studies by others showed that bathing chondral explants in a supplement of glucosaminechondroitin sulfate (glcN-CS) upregulated the synthesis of tissue PGs, particularly in stressed tissue, and the supplement served as an antiinflammatory agent. Our current hypothesis was that the supplementation of culture media with a high concentration of glcN-CS would upregulate the production of tissue PG and limit or mitigate long-term degradation of chondral explants under cyclic preloading and limit tissue damage in an acute overload. We showed that, in the presence of supplement, cyclic preloading significantly increased tissue PG content and matrix modulus by about 65 and 300%, respectively, at 21 days, resulting in a reduction of matrix damage and cell death following an acute overload. These data show a biological action of high concentrations of this supplement and its effect on the mechanical properties in this in vitro model. In vitro studies of impact loading 1,2 on cartilage show cell death and matrix damage. In contrast, in vitro and in vivo studies showed positive aspects of low intensity, intermittent compressive loading, such as increased biosynthesis of proteoglycans (PGs). [3][4][5] Changes in PG and collagen contents of cartilage significantly alter the mechanical properties of this tissue. 6 Thus, it is reasonable to assume that cyclic preloading of cartilage can alter its mechanical properties and help determine the extent of matrix damage and cell death that will occur due to the blunt force overloading of a joint, such as during an acute knee ligament rupture. 7 Recent studies in our laboratory show that low intensity, intermittent cyclic preloading of chondral explants prior to an acute overload yields an increase in the synthesis of tissue PGs, resulting in a less severe traumatic insult for an acute overload. 8 Between 14 and 21 days of cyclic preloading, the explants experience a significant PG loss that leads to a dramatic loss in mechanical properties. Acute overloading of the explanted tissue then yields matrix damage and cell death significantly greater than nonpreloaded controls. A recent study by others shows a significant loss of tissue PG and cell death with production of matrix metalloproteinase (MMP-3) adjacent to damaged collagen fibers under cyclic compression at 0.5 Hz for intensities of 1 and 5 MPa over 24 h. 9 Similarly, under 0.5 MPa of 1 Hz cyclic loading, a significant increase in the MMP-2 and -9 synthesis was found after 3 h. 10 The combination of glucosamine-chondroitin sulfate (glcN-CS) was shown in in vitro studies to function as a ''...

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“…Some studies indicate that longer term (6 days) unconfined, dynamic load applied to cartilage explant pieces, while resulting in an increased 35 S synthesis, did not increase GAG content within the disk (Sauerland et al, 2003;Steinmeyer et al, 1999). This is believed to be due to damage to the collagen fibrils and subsequent increased release of GAG molecules into the medium.…”

Section: Discussionmentioning

confidence: 99%

Enhanced matrix synthesis in de novo, scaffold free cartilage-like tissue subjected to compression and shear

Stoddart

Ettinger

Häuselmann

2006

Biotechnol. Bioeng.

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Production of a de novo cartilage-like tissue construct is a goal for the repair of traumatic chondral defects. We aimed to enhance the matrix synthesis within a scaffold free, de novo cartilage-like tissue construct by way of mechanical load. A novel loading machine that enables the application of shear, as well as compression, was used to subject tissue engineered cartilage-like tissue to mechanical stress. The machine, which applies the load through a roller mechanism, can load up to 20 constructs with four different loading patterns simultaneously. The expression of mRNA encoding matrix products, and subsequent changes in matrix protein content, were analyzed after various loading regimes. The force applied to the immature tissue had a direct bearing on the short-term (first 4 h) response. A load of 0.5 N caused an increase in collagen II and aggrecan mRNA within an hour, with a peak at 2 h. This increased mRNA expression was translated into an increase of up to 60% in the glycosaminoglycan content of the optimally loaded constructs after 4 days of intermittent cyclical loading. Introducing pauses between load cycles reproducibly lead to an increase in GAG/DNA. In contrast, constant cyclical load, with no pause, lead to a decrease in the final glycosaminoglycan content compared with unloaded controls. Our data suggest that a protocol of mechanical stimulation, simulating in vivo conditions and involving shear and compression, may be a useful mechanism to enhance the properties of tissue engineered tissue prior to implantation.

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Effects of intermittently applied cyclic loading on proteoglycan metabolism and swelling behaviour of articular cartilage explants

Abstract: Considering numerous reports of elevated PG levels synthesized as well as released from human and experimental osteoarthritic cartilage, our results implicate that degenerative processes can also be mimicked by applying well-defined mechanical conditions as described here.

Cited by 36 publications

References 31 publications

Biosynthetic response of passaged chondrocytes in a type II collagen scaffold to mechanical compression

Biosynthetic response of passaged chondrocytes in a type II collagen scaffold to mechanical compression

High levels of glucosamine–chondroitin sulfate can alter the cyclic preload and acute overload responses of chondral explants

Enhanced matrix synthesis in de novo, scaffold free cartilage-like tissue subjected to compression and shear

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