Biomimetic dense collagen gel bioinks for automated biofabrication and 3D bioprinting

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Additive manufacturing and three-dimensional bioprinting technologies have recently generated much interest in developing biomaterials, such as in biofabricating tissue engineering scaffolds, medical devices, and in vitro tissue-like structures that model both healthy and diseased conditions, thus enabling high-throughput drug screening and diagnostic tools. 3D bioprinting relies on the layer-by-layer deposition of tissue specific cells incorporated into hydrogels (called bioinks) to form complex hierarchical structures that mimic the body's natural extracellular matrix. Therefore, the composition, 3D bioprintability, as well as resulting bioink structure and mechanical properties are all critical to success, and ideally these would mimic, as best as possible, the natural tissue extracellular matrix. The fibre-forming collagen type I molecule is the natural scaffolding material that exists in our body. It provides many key biological and mechanical properties to numerous tissues. When extracted from the native environment, these can form hydrogels that are able to incorporate cells and be used as scaffolds for tissue engineering. However, the printing of cell-seeded collagen-based bioinks with controlled structure and mechanical properties is challenging. Collagen-based hydrogel bioinks are restricted by their narrow printability range, where the protein structure, seeded cell viability, and bioactivity of incorporated biomolecules, all need to be tightly controlled. Also, when these collagen molecules assemble into hydrogels, they suffer from low fibrillar content and have low mechanical stiffness and strength properties, all impacting our ability to engineer stable hierarchical structures. In order to overcome these challenges, we have developed a novel approach to bioprint collagen structures through our automated gel aspiration-ejection technique. By using this process, we can generate biomimetic, dense, tissue-like collagenous matrices, which can be used as in vitro models, and as scaffolds for the potential regeneration of hard and soft tissues. The technique is also ideal for producing functionalized scaffolds by incorporating other biopolymers or bioactive glasses. We will also use our in-lab developed low temperature sol-gel processing route to synthesize a novel range of borate-based glasses and to functionalize the dense collagen bioinks. Through this, we can identify the biochemical factors that drive tissue regeneration, and to continue to develop novel technologies for biomaterials development. Therefore, the knowledge gained from this Discovery Grant Program will significantly contribute to a number of fields, such as 3D bioprinting, biofabrication and tissue engineering. It will also continue to provide a rich and diverse environment for its trainees, while serving as a platform for innovative technologies.