Development of Engineered Living Materials using 3D Bioprinting

沿着改变其机械性能，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活材料，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种途径。在再生医学领域使用这项技术来创造器官和组织替代品方面取得了重大进展，可能会在未来消除对器官捐赠者的需求。该过程涉及将干细胞封装到剪切稀化水凝胶中，以使其沉积为3D结构。然后，细胞可以分化形成各种组织，对与打印过程相关的细胞活力的影响最小。这些载有细胞的凝胶被称为生物墨水。细菌也被成功地打印在类似的材料中。细菌所显示的广泛功能为创造4D材料提供了很大的空间，这些材料可以对其环境做出反应或随时间变化。例如，细菌细胞外基质的产生可能导致凝胶硬度的增加。也可以选择包封的细菌以提供生物反应器功能，或者生产天然产物或者分解底物。材料对其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。该项目旨在通过使用3D打印将细菌掺入水凝胶中来探索生物材料的设计。假设油墨组合物影响油墨内细菌的生存力，其可能提供保护细胞免受外部应激因素如温度、pH或渗透梯度、UV暴露和机械变形影响的环境。支持墨水也可以是细菌种群的长期营养来源。生物墨水组合物将在该项目中进行研究，目的是实现凝胶的最佳机械性能（可印刷性，形状保真度，韧性，弹性），同时维持内部的活细菌种群。这将涉及使用各种聚合物体系，其具有相关的交联机制，例如离子或UV引发的交联，以及可能向油墨中添加次要组分，包括增粘剂，例如粘土纳米片。该项目属于EPSRC“制造未来”研究领域的生物材料和复合材料工程工作的福尔斯。

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.