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

关节软骨（AC）缺陷是全球数百万人的不动和生活质量差的主要原因之一。目前的医学疗法已被证明不足以长期再生AC缺陷。或者，生物打印在组织工程中的集成开辟了通过多个细胞和生物材料的精确空间沉积生成复杂3D AC植入物的可能性。尽管为粘附细胞提供了足够的机械支撑，但这些构建体在模拟天然细胞外基质（ECM）微环境方面基本上失败。ECM由胶原蛋白主导，是一种复杂的3D微环境，具有特定的生物物理和化学特性，负责协调细胞内信号传导并触发调节细胞功能的下游生物反应。虽然在开发能够模拟AC组织的带状宏观组织的支架方面已经取得了显著进展，但是很少有人关注体外复制胶原纤维的纳米结构组织。这是由于ECM的化学复杂性和在胶原纤维的超分子组装中起关键作用的各种伴侣（例如，β-D）的表达。有趣的是，具有由细胞组装和控制的结构的纤维素（即胶原蛋白的植物类似物），当分解成其晶体结构单元时，可以以与植物结构非常相似的方式自组装。因此，我们的目标是探索使用纤维素作为胶原纤维的结构导向剂，以在AC生物打印的组织植入物中产生复杂的、多尺度的、区域性的自组装。

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.