Contribution of Proteoglycan Osmotic Swelling Pressure to the Compressive Properties of Articular Cartilage

Han, EunHee; Chen, Silvia S.; Klisch, Stephen M.; Sah, Robert L.

doi:10.1016/j.bpj.2011.07.006

Cited by 123 publications

(93 citation statements)

References 48 publications

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“…Initial thickness can be controlled well due to low p PG with low GAG concentration, 4 which could be balanced by the restraining force of agarose, consistent with our previous study. 13 The swelling of the PG-containing constructs (Groups II and IV) beyond the thickness of agarose only or COL-containing constructs (Groups I and III) after compaction indicates the presence of swelling pressure exerted by PG that was restrained with the increased thickness in the agarose gel network.…”

Section: Han Et Alsupporting

confidence: 89%

“…3 The COL network aids in the retention and concentration of PG, providing the restraining force that counterbalances p PG at rest or in compression. 3,4 To treat damaged articular cartilage, several strategies, including tissue engineering approaches, have emerged aiming to repair cartilage and stimulate healing. 5 However, many cell-based tissue-engineered constructs for articular cartilage are mechanically soft and have an imbalance between its ECM components.…”

Section: Introductionmentioning

confidence: 99%

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Compaction Enhances Extracellular Matrix Content and Mechanical Properties of Tissue-Engineered Cartilaginous Constructs

Han

Ge²,

Chen³

et al. 2012

Tissue Engineering Part A

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Many cell-based tissue-engineered cartilaginous constructs are mechanically softer than native tissue and have low content and abnormal proportions of extracellular matrix (ECM) constituents. We hypothesized that the load-bearing mechanical properties of cartilaginous constructs improve with the inclusion of collagen (COL) and proteoglycan (PG) during assembly. The objectives of this work were to determine (1) the effect of addition of PG, COL, or COL + PG on compressive properties of 2% agarose constructs and (2) the ability of mechanical compaction to concentrate matrix content and improve the compressive properties of such constructs. The inclusion of COL + PG improved the compressive properties of hydrogel constructs compared with PG or COL alone. Mechanical compaction increased the PG and COL concentrations in and compressive stiffness of the constructs. Chondrocytes included in the constructs maintained high viability after compaction. These results support the concepts that the assembly of cartilaginous constructs with COL + PG and application of mechanical compaction enhance the ECM content and compressive properties of engineered cartilaginous constructs.

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Section: Han Et Alsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Compaction Enhances Extracellular Matrix Content and Mechanical Properties of Tissue-Engineered Cartilaginous Constructs

Han

Ge²,

Chen³

et al. 2012

Tissue Engineering Part A

Self Cite

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“…The negatively charged GAGs on the PGs influence the compressibility of the ground substance (10), tissue osmotic pressure (39,40), and tissue swelling (40,41). We found increased swelling by more water retention in the emphysematous lung.…”

Section: 33mentioning

confidence: 75%

Proteoglycans Maintain Lung Stability in an Elastase-Treated Mouse Model of Emphysema

Takahashi

Majumdar

Parameswaran

et al. 2014

Am J Respir Cell Mol Biol

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Extracellular matrix remodeling and tissue rupture contribute to the progression of emphysema. Lung tissue elasticity is governed by the tensile stiffness of fibers and the compressive stiffness of proteoglycans. It is not known how proteoglycan remodeling affects tissue stability and destruction in emphysema. The objective of this study was to characterize the role of remodeled proteoglycans in alveolar stability and tissue destruction in emphysema. At 30 days after treatment with porcine pancreatic elastase, mouse lung tissue stiffness and alveolar deformation were evaluated under varying tonicity conditions that affect the stiffness of proteoglycans. Proteoglycans were stained and measured in the alveolar walls. Computational models of alveolar stability and rupture incorporating the mechanical properties of fibers and proteoglycans were developed. Although absolute tissue stiffness was only 24% of normal, changes in relative stiffness and alveolar shape distortion due to changes in tonicity were increased in emphysema (P , 0.01 and P , 0.001). Glycosaminoglycan amount per unit alveolar wall length, which is responsible for proteoglycan stiffness, was higher in emphysema (P , 0.001). Versican expression increased in the tissue, but decorin decreased. Our network model predicted that the rate of tissue deterioration locally governed by mechanical forces was reduced when proteoglycan stiffness was increased. Consequently, this general network model explains why increasing proteoglycan deposition protects the alveolar walls from rupture in emphysema. Our results suggest that the loss of proteoglycans observed in human emphysema contributes to disease progression, whereas treatments that promote proteoglycan deposition in the extracellular matrix should slow the progression of emphysema.

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“…Only for constructs containing NCs, matrix components were significantly correlated to their biomechanical functionality. It is already known that GAGs and collagens, the main components of the ECM, are both associated with the biomechanical properties of native cartilage: (1) the negatively charged GAGs provide an osmotic pressure within the tissue; and (2) the architecture of the collagen network captures the GAGs and prevents them from leaking out of the tissue (Han et al, 2011). In contrast, the elastic fibre network in constructs containing ECs might have influenced the biomechanical properties in vivo as well, although the exact contribution of elastin to mechanical functionality is not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

The in vitro and in vivo capacity of culture-expanded human cells from several sources encapsulated in alginate to form cartilage

Pleumeekers

Nimeskern²,

Koevoet³

et al. 2014

eCM

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Cartilage has limited self-regenerative capacity. Tissue engineering can offer promising solutions for reconstruction of missing or damaged cartilage. A major challenge herein is to define an appropriate cell source that is capable of generating a stable and functional matrix. This study evaluated the performance of culture-expanded human chondrocytes from ear (EC), nose (NC) and articular joint (AC), as well as bone-marrow-derived and adipose-tissuederived mesenchymal stem cells both in vitro and in vivo. All cells (≥ 3 donors per source) were culture-expanded, encapsulated in alginate and cultured for 5 weeks. Subsequently, constructs were implanted subcutaneously for 8 additional weeks. Before and after implantation, glycosaminoglycan (GAG) and collagen content were measured using biochemical assays. Mechanical properties were determined using stress-strain-indentation tests. Hypertrophic differentiation was evaluated with qRT-PCR and subsequent endochondral ossification with histology. ACs had higher chondrogenic potential in vitro than the other cell sources, as assessed by gene expression and GAG content (p < 0.001). However, after implantation, ACs did not further increase their matrix. In contrast, ECs and NCs continued producing matrix in vivo leading to higher GAG content (p < 0.001) and elastic modulus. For NC-constructs, matrix-deposition was associated with the elastic modulus (R 2 = 0.477, p = 0.039). Although all cells -except ACsexpressed markers for hypertrophic differentiation in vitro, there was no bone formed in vivo. Our work shows that cartilage formation and functionality depends on the cell source used. ACs possess the highest chondrogenic capacity in vitro, while ECs and NCs are most potent in vivo, making them attractive cell sources for cartilage repair.

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Contribution of Proteoglycan Osmotic Swelling Pressure to the Compressive Properties of Articular Cartilage

Cited by 123 publications

References 48 publications

Compaction Enhances Extracellular Matrix Content and Mechanical Properties of Tissue-Engineered Cartilaginous Constructs

Compaction Enhances Extracellular Matrix Content and Mechanical Properties of Tissue-Engineered Cartilaginous Constructs

Proteoglycans Maintain Lung Stability in an Elastase-Treated Mouse Model of Emphysema

The in vitro and in vivo capacity of culture-expanded human cells from several sources encapsulated in alginate to form cartilage

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