New High Performance Bioinks for 3D Extrusion Bioprinting

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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.