ECM Particle Bioprinting

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Extra cellular matrix (ECM) providing the micro-environment for the cells is unique in each type of tissue.

In craniofacial cartilage tissue, specifically nasal and auricular cartilage tissues consist of high concentration of elastin, glycosaminoglycans and collagen type II. Collagen type II is the main type of collagen (90%) responsible for the tensile strength of the tissue while combination of GAGs and elastin are responsible of the elastic properties.

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.

New Nose  
Figure 1. Three-dimensional nose model and the process of creating de novo nasal cartilage graft. Scale increments representing 1mm.

Partly in response to the limitations of pure hydrogel approach and partly due to the need for large quantities of strong biocompatible material, increasing focus has been directed towards the use of cartilage itself as a structural component of the scaffold and in the biomaterial used in the three-dimensional bioprinting.

Bioprinting materials, also known as bioinks, are required to be shear thinning and spontaneously thickening after extrusion to maintain the resolution. Our ECM paste bioinks are designed based on natural polysaccharides as carrier and support materials for decellularized cartilage particles. In the decellularization procedure the α-gal epitopes, any possible DNA residue and other immunogenic molecules are removed from the cartilage ECM to provide non-immunogenic matrix.

Decellularization protocols are optimized to preserve the functional GAGs, elastin and cell stimulating growth factors during the decellularization treatment. This ECM paste bioink is further mixed with chondrocytes or other chondrogenesis supporting cell types and biological crosslinker molecules to allow the cellular tissue construct bioprinting.

Layer-by-layer manufactured extrusion printed structures replicate the patient specific shape to customize the tissue graft manufacturing process. Furthermore, developing of layer specific bioinks gives us the possibility to produce high resolution cartilage structures together with surrounding soft tissues.

Designing the architectural support and engineered porosity enhance the cell survival in large structures without sacrificing the mechanical properties. The end goal of this project is to develop a biomimetic, patient specific tissue constructs for the craniofacial cartilage reconstructions.


ETH Zurich

Matti Jaakko Johannes Kesti

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Wed Jul 26 18:39:18 CEST 2017
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