Bioprinting the multiscale extracellular matrix (ECM) environment for Articular Cartilage repair

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Articular cartilage (AC) defects are one of the major causes of immobility and poor quality of life for millions of individuals worldwide. Current medical therapies have proven to be insufficient for the long-term regeneration of AC defects. Alternatively, the integration of Bioprinting in Tissue Engineering opens the possibility of generating complex 3D AC implants via the precise spatial deposition of multiple cells and biomaterials. Despite providing an adequate mechanical support for adhering cells, these constructs have largely failed in mimicking the native Extracellular Matrix (ECM) microenvironment. The ECM, dominated by collagen proteins, is a complex 3D microenvironment with specific biophysical and chemical properties responsible for coordinating intracellular signalling and triggering downstream biological responses which regulate cell function. Whilst significant advances have been made in the development of scaffolds capable of mimicking the zonal macro-organization of AC tissues, very little attention has been dedicated on replicating the nano-structure organization of collagen fibrils in vitro. This is due to chemical complexity of the ECM and expression of various chaperons (e.g. SPARC) playing critical role in supramolecular assembly of the collagen fibres. Interestingly, celluloses (i.e. plant analogues of the collagens),with architectures assembled and controlled by the cell, when broken down to its crystalline building blocks, can self-assemble themselves in much similar ways to plant architecture. Therefore we aim to explore the use of cellulose as a structural directing agent for the collagen fibrils to create intricate, multi-scale, zonal self-assemblies in AC bioprinted tissue implants.