Clinically Relevant and Precisely Printable Live Adipose Tissue–Based Bio‐Ink for Volumetric Soft Tissue Reconstruction

Abstract Autologous fat is widely used in soft tissue reconstruction; however, significant volume reduction owing to necrosis and degradation of the transplanted adipose tissue (AT) remains a major challenge. To address this issue, a novel live AT micro‐fragment–based bio‐ink (ATmf bio‐ink) compatible with precision 3D printing, is developed. Live AT micro‐fragments of ≈280 µm in size are prepared using a custom tissue micronizer and they are incorporated into a fibrinogen/gelatin mixture to create the ATmf bio‐ink. AT micro‐fragments exhibit high viability and preserve the heterogeneous cell population and extracellular matrix of the native AT. The developed bio‐ink enables precise micropatterning and provides an excellent adipo‐inductive microenvironment. AT grafts produced by co‐printing the bio‐ink with polycaprolactone demonstrate a 500% improvement in volume retention and a 300% increase in blood vessel infiltration in vivo compared with conventional microfat grafts. In vivo engraftment of AT grafts is further enhanced by using a stem cell–laden ATmf bio‐ink. Last, it is successfully demonstrated that the bio‐ink is enabled for the creation of clinically relevant and patient‐specific AT grafts for patients undergoing partial mastectomy. This novel ATmf bio‐ink for volumetric soft tissue reconstruction offers a pioneering solution for addressing the limitations of existing clinical techniques.