New High Performance Bioinks for 3D Extrusion Bioprinting

3D Biopprint已经成为设计结构复杂的生物组织的首选方法，用于再生医学，并作为癌症研究和药物开发的模型。3D Biopprint从结构的计算机模型开始，然后打印机使用生物墨水逐层重建结构，生物墨水由生物材料基质中支撑的活细胞组成。这一方法大大受益于打印机技术的改进和打印机的日益负担，然而，为了真正发挥3D生物打印的潜力，现在迫切需要对生物墨水进行重大改进。生物墨水必须是可打印的，并具有足够的机械性能以在打印后保持其形状，从而允许细胞沉积成定义明确的高保真多层形状，以获得结构复杂的3D打印组织。它们还必须模拟自然的细胞微环境，以确保所需的印刷后细胞行为，例如细胞黏附、增殖和分化，这是印刷构件要实现其预期应用所必需的。因此，可打印性和仿生性对于3D打印结构在其期望的应用中都是有用的。目前的水凝胶以仿生学为代价重视可打印性，在3D生物打印方面做了大量工作，使用了基于几种坚固和众所周知的基本水凝胶的经过试验和测试的生物墨水，例如明胶、透明质酸和海藻酸盐。尽管它们具有良好的印刷性，但它们并不是细胞的理想选择，因为它们不提供许多细胞系所需的生化线索，以鼓励所需的打印后细胞行为，这些行为是生产具有高应用要求的复杂程度的组织所必需的。在这个项目中，我们将开发新的高性能生物油墨，既可印刷又可仿生。我们的生物墨水将基于由工程菌产生的囊膜抗原片段1(CAF1)，由&gt；1000蛋白质单体亚基组成的长(&gt；1微米)薄聚合物。我们以前已经学会了将CAF1设计成一种无与伦比的天然细胞外基质的模拟物，我们实验室的初步工作表明，CAF1水凝胶具有令人鼓舞的印刷性能。我们预计，我们基于CAF1的生物墨水将显示出与藻酸盐等常见生物墨水相匹配的印刷水平，我们将展示如何利用其优越的生物仿生性来制备使用常用的水凝胶生物墨水无法制备的复杂组织结构。

3D Bioprinting has emerged as the approach of choice to engineer structurally complex living tissues for use in regenerative medicine and as models for cancer studies and drug development. 3D Bioprinting starts with a computer model of a structure, which is then recreated by the printer layer-by-layer using a bioink, which consists of live cells supported within a biomaterial matrix. The approach has benefited greatly from improvements in printer technology and printers are increasingly affordable, however, for 3D bioprinting to truly fulfil its potential, significant improvements to bioinks are now urgently required. Bioinks must be printable and possess sufficient mechanical properties to hold their shape after printing, allowing the deposition of the cells into well-defined high-fidelity multilayer shapes required to obtain structurally-complex 3D printed tissues. They must also mimic natural cellular microenvironments to ensure desired post-printing cell behaviours e.g. cell adhesion, proliferation and differentiation, which are required if the printed construct is to fulfil its intended application. Thus, BOTH printability and biomimicry are important for a 3D printed construct to be useful in its desired application. Current hydrogels prize printability at the expense of biomimicry, with much work in 3D bioprinting utilizing tried-and-tested bioinks based upon a handful of robust and well-known basic hydrogels e.g. gelatine, hyaluronic acid and alginate. Although these have good printability, they are not, however, ideal for cells as they do not present the biochemical cues required by many cell lines to encourage desired post-printing cell behaviours that are required to produce tissues with the high levels of complexity demanded in applications. In this project we will develop new high performance bioinks that present BOTH printability and biomimicry. We will base our bioink upon Capsular antigen fragment 1 (Caf1), long (>1 micrometre) thin polymers composed of >1000 protein monomer subunits that are produced by engineered bacteria. We have previously learned to engineer Caf1 to become an unrivalled mimic of natural extracellular matrix, and preliminary work from our lab indicates that Caf1 hydrogels possess encouraging levels of printability. We anticipate that our Caf1-based bioinks will display levels of printability which match those of common bioinks such as alginate, and we will show how its superior biomimicry can be harnessed to prepare complex tissue constructs which cannot be prepared using commonly used hydrogel-based bioinks.