New High Performance Bioinks for 3D Extrusion Bioprinting

用于 3D 挤出生物打印的新型高性能生物墨水

• 批准号: EP/X01990X/1
• 负责人: David Fulton
• 金额: $ 58.96万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX01990X%2F1
• 关键词: New; Performance; Bioinks; 3D; Extrusion

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.

3D生物打印已经成为设计结构复杂的活组织的首选方法，用于再生医学，作为癌症研究和药物开发的模型。3D生物打印从一个结构的计算机模型开始，然后由打印机使用生物墨水逐层重建，生物墨水由生物材料基质内支持的活细胞组成。这种方法从打印机技术的改进中受益匪浅，打印机越来越便宜，然而，为了使3D生物打印真正发挥其潜力，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，并且具有足够的机械性能以在打印后保持其形状，允许细胞沉积成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细胞微环境，以确保所需的打印后细胞行为，例如细胞粘附、增殖和分化，如果打印结构要实现其预期应用，这些都是必需的。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有用是很重要的。目前的水凝胶以牺牲仿生学为代价获得可打印性，在3D生物打印中，利用基于少量强大且众所周知的基本水凝胶（如明胶、透明质酸和海藻酸盐）的经过验证的生物墨水进行了大量工作。尽管这些材料具有良好的可打印性，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，以促进所需的打印后细胞行为，而这些行为是生产应用中所需的高水平复杂性组织所必需的。在这个项目中，我们将开发新的高性能生物墨水，同时具有可打印性和仿生性。我们将把我们的生物链接建立在荚膜抗原片段1 （Caf1）上，这是一种由工程细菌产生的由>1000个蛋白质单体亚基组成的长（>1微米）薄聚合物。我们之前已经学会了设计Caf1，使其成为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可打印性。我们预计我们的基于caf1的生物墨水将显示出与普通生物墨水（如海藻酸盐）相匹配的可打印性水平，并且我们将展示如何利用其优越的仿生学来制备复杂的组织结构，这是使用常用的基于水凝胶的生物墨水无法制备的。