Development of Engineered Living Materials using 3D Bioprinting

在改变其机械性能的同时，将生物系统添加到合成材料中可以为封装材料提供额外的功能维度。这些生物复合材料被称为工程生物材料，为开发利用活细胞的功能多样性、自我修复特性和适应性的复杂结构提供了机会。3D生物打印是制造这些材料的一条途径。在再生医学领域使用这项技术创造器官和组织替代物方面取得了重大进展，有可能在未来消除对器官捐赠者的需求。这一过程包括将干细胞包裹到剪切变稀水凝胶中，使其能够以3D结构的形式沉积。然后，细胞可以分化成各种组织，而对打印过程中细胞活性的影响最小。这些富含细胞的凝胶被称为生物墨水。细菌也被成功地印刷在类似的材料上。细菌所显示的广泛功能为创造能够对其环境或随时间变化做出反应的4D材料提供了巨大的空间。例如，细菌细胞外基质的产生可能会导致凝胶硬度的增加。还可以选择胶囊化细菌来提供生物反应器功能，要么生产天然产品，要么分解底物。材料对环境的响应性可以通过使用响应性聚合物或基因表达调控来实现。该项目旨在通过3D打印将细菌加入水凝胶中来探索生物材料的设计。假设油墨成分会影响油墨中细菌的生存能力，可能会提供一个环境，保护细胞免受外界压力，如温度、pH或渗透梯度、紫外线暴露和机械变形。辅助墨水也可能是细菌种群的长期营养来源。本项目将研究生物墨水的组成，以实现凝胶的最佳机械性能(可印刷性、形状保真度、韧性、弹性)，同时保持其中的活细菌种群。这将涉及使用各种聚合物体系，以及相关的交联剂机制，如离子或紫外线引发的交联剂，以及可能在油墨中添加二次组分，包括粘合剂，如粘土纳米片。该项目属于EPSRC‘制造未来’研究领域，主要从事生物材料和复合材料工程方面的工作。

Along with modifying its mechanical properties, the addition of biological systems to synthetic materials can provide an extra dimension of functionality to the encapsulating material. These biological composites are referred to as engineered living materials and present an opportunity for the development of complex structures that utilise the diversity of function, self-healing characteristics and adaptability of living cells. 3D bioprinting is a route towards the fabrication of these materials. Major progress has been made towards using this technology in the regenerative medicine field to create organ and tissue replacements, potentially eliminating the need for organ donors in the future. This process involves the encapsulation of stem cells into shear thinning hydrogels to enable their deposition as 3D structures. The cells can then be differentiated to form various tissues with minimal impact on cell viability associated with the printing process. These cell laden gels are known as bioinks. Bacteria have also been successfully printed in similar materials. The wide range of functions displayed by bacteria offer great scope for the creation of 4D materials that could respond to their environment or change over time. For example, the production of bacterial extracellular matrices could cause an increase in gel stiffness. Encapsulated bacteria could also be chosen to provide a bioreactor function, either producing natural products or breaking down substrates. Responsivity of the material to its environment could be realised by either the use of responsive polymers or gene expression regulation. This project aims to explore the design of living materials by the incorporation of bacteria into hydrogels using 3D printing. Ink composition is hypothesised to affect the viability of bacteria within the ink, with the potential for it to provide an environment that shelters cells from external stressors such as temperature, pH or osmotic gradients, UV exposure and mechanical deformation. The supporting ink could also be a long-term source of nutrients for the bacterial population. Bioink composition will be investigated in this project with an aim of achieving the best mechanical properties for the gel (printability, shape fidelity, toughness, elasticity) whilst sustaining a living bacterial population within. This will involve the use of various polymer systems, with associated crosslinking mechanisms such as ionic or UV initiated crosslinking, and the potential addition of secondary components to the ink, including viscosifiers, such as clay nanosheets. This project falls within the EPSRC 'Manufacturing the Future' research area as work on biomaterials and composite engineering.