Unlocking the potential of bio-inspired bioinks: A collective breakthrough in mammalian tissue bioprinting

Abstract The composition of soft tissues in mammals can be simplified as approximately 60–65% water, 16% protein, 16% fat, 1% carbohydrate, and trillions of cells. This report brings together the collaborative efforts of 10 research groups over the past five years, all dedicated to producing mammalian tissues through extrusion-based bioprinting. What unified these studies was a common approach, with a shared bioink composition consisting of gelatin, alginate, and fibrinogen, and a post-printing consolidation strategy involving transglutaminase crosslinking, calcium chelation, and thrombin-mediated fibrin production. By consolidating the findings of these studies, it was conclusively demonstrated that bioprinting and culturing all 19 cells tested from 14 different organs was indeed achievable. These remarkable outcomes were attributed not only to the bio-inspired nature of the common bioink but also to its unique rheological properties, such as significant shear-thinning and a sufficiently high static yield stress. The majority of these cells exhibited behaviours consistent with their natural in vivo environments. Clearly identifiable microstructures and organizations showcased intricate morphogenesis mechanisms resulting in the formation of micro-tubules, micro-vessels, and micro-acini. It is now evident that microextrusion bioprinting, especially when using bio-inspired bioink formulations, represents a promising avenue for generating a wide range of mammalian soft tissues.