Light-based multi-material bioprinting of vascularised adipose tissue for breast fatty tissue engineering

Abstract

Reconstructive surgery following breast cancer ablation is a surgical gold standard, but current options comprising autologous fatty tissue transfer and artificial soft tissue implants are inferior. With the advent of powerful biofabrication technologies, researchers for the first time have the tools to engineer life-like tissues with the ultimate goal of clinical application. Here, we apply multi-material stereolithographic bioprinting together with a novel sacrificial biomaterial system to engineer complex fatty tissue constructs. Biomaterials, cellular composition and cultivation conditions of these constructs were designed to enable in vitro creation of vascularised fatty tissue. Cells within the constructs showed an overall good survival (>93%), indicated by live-dead cell staining, over the entire cultivation period of 27 d. Adipose-derived stem cells were successfully differentiated in situ, forming fat vesicles and expressing adipocyte markers PPARγ, FAPB4 and S100B. Additionally, secretion of adipokines leptin and adiponectin into culture supernatants increased significantly. Endothelial cells vascularised the constructs, creating macro- and microvascular structures within the printed channels and extending beyond with culture time. Moreover, cells invaded into the surrounding hydrogel. The engineered fatty tissue constructs could serve as a base to develop patient-specific tissue building blocks with the final goal to achieve an all-natural reconstruction of the breast.