H. Cui, T. Esworthy, L.G. Zhang
The George Washington University,
Keywords: nanomedicine, 3D bioprinting, tissue regeneration
Summary:The repair of damaged tissues and organs presents a significant clinical problem worldwide. As a promising technique for tissue engineering, 3D bioprinting offers greater precision to control the internal and external structure of a tissue scaffold and cell distribution to better replicate the structural and functional complexity of native tissues. However, one critical challenge in 3D bioprinting tissues and organs is the need to create a highly efficient and perfusable 3D vascular network. In addition, cells within the human body are in intimate contact with a 3D nanostructured extracellular matrix composed of numerous organic and inorganic components. It is desirable to create a biomimetic nano environment to regulate cell behaviors. Therefore, the main objective of this research is to integrate advanced 3D bioprinting techniques and biologically inspired nanomaterials to fabricate the next generation of complex vascularized tissue constructs. Under this objective, an engineered vascularized tissue construct was developed for the first time by integrating biomimetic 3D bioprinted fluid perfused microstructure with biologically inspired smart release nanocoating. Angiogenesis and osteogenesis were successively induced through a matrix metalloprotease 2 regulative mechanism by delivering dual growth factors with a sequential release in spatiotemporal coordination for the microvascularized bone formation. In addition, we successfully created sophisticated 3D bioprinted microvascular networks with biomimetic smooth muscle and endothelium. The novel small-diameter vascular networks possess similar flow characteristics to native blood vessels under pulsatile arterial flow. Our vasculoactivity and extracellular matrix deposition results demonstrated physiologically relevant reactions such as endothelium-dependent vasodilation and improved extracellular matrix deposition. Furthermore, we implanted our 3D bioprinting vascular construct into mice in vivo. Histological analysis showed that the bioprinting material has excellent biocompatibility and a suitable degradation rate for various biomedical applications. The results also demonstrated the bioprinted vascular construct has excellent in vivo autonomous connection (~2 weeks) as well as vascular remodeling (~6 weeks).