ECM Scaffold

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Extra cellular matrix (ECM) providing the micro-environment for the cells is unique in each type of tissue. ECM of cartilage consists of 2% chondrocytes, 20-35% of polymeric components and 65-80% of water. The more specific ratio of polymeric component is about 60% collagen mainly type II and X, 30% proteoglycans [1,2].

Collagen II is the main type of collagen (90%) responsible for the tensile strength of the cartilaginous surface. To mimic this structure hydrogels, consisting of 70-90% of water, have been utilized widely in cartilage tissue engineering. However, the weight bearing properties and the mechanical stiffness of these materials have been the limiting factory in developing clinical applications.

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Figure 1 Schematic representation of the ECM based scaffold. A: Cartilage fragments and HA-tyr are mixed together to form “paste” that can be applied with a spatula to the cartilage defect; HA-tyr crosslinks to both cartilage defect surface and cartilage fragments. B: Sulfated GAG staining of the scaffold, scale bar 200 µm. C: Collagen 2 staining of the scaffold, scale bar 200 µm.

Articular cartilage has a very limited capacity to heal and cartilage injury is a frequent cause of disability and pain. The current surgical solutions include microfracture, mosaicplasty and autologous chondrocyte implantation (ACI). All of these techniques have limitations that include donor site morbidity, variable quality of repair tissue and high costs. As an alternative or as coadjutant to these techniques, cartilage fragments transplantation has been investigated since 1980’s. Cartilage fragments have been used to improve the tissue quality after bone marrow stimulation, to promote chondrogenesis of MSCs and as intraoperative source of chondrocytes. In addition to providing mechanical support, cartilage fragments contain the key components of cartilage, including proteoglycans, collagen type 2 and growth factors.

Thus far, the potential of cartilage fragments has only been investigated with fibrin glue as an adhesive. Fibrin glue however degrades rapidly in vivo and has relatively low mechanical properties. Our approach is to develop a scaffold for cartilage repair based on extracellular matrix fragments and tyramine modified hyaluronic acid (HA-tyr).

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Figure 2 HA-tyr mediates the adhesion of two cartilage cylinders to each other.

HA-tyr is an injectable hydrogel that can be crosslinked in situ with horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The crosslinking reaction is based on the formation of covalent bonds between hydroxyphenyl groups that are present both in HA-tyr and in tyrosine residues of cartilage proteins. Hence, the HA-tyr can be enzymatically crosslinked to both the cartilage fragments and to the cartilage defect promoting initial adhesion and integration of the scaffold.

Contact

ETH Zurich

Gewebetechnol. und Biofabrikation

Emma Cavalli

HPL J 12

Otto-Stern-Weg 7

8093 Zürich

Switzerland

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Wed Jun 28 22:47:32 CEST 2017
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