Embedded bioprinting for designer 3D tissue constructs with complex structural organization

3D bioprinting has been developed as an effective and powerful technique for the fabrication of living tissue constructs in a well-controlled manner. However, most existing 3D bioprinting strategies face substantial challenges in replicating delicate and intricate tissue-specific structural organizations using mechanically weak biomaterials such as hydrogels. Embedded bioprinting is an emerging bioprinting strategy that can directly fabricate complex structures derived from soft biomaterials within a supporting matrix, which shows great promise in printing large vascularized tissues and organs. Here, we provide a state-of-the-art review on the development of embedded bioprinting including extrusion-based and light-based processes to manufacture complex tissue constructs with biomimetic architectures. The working principles, bioinks, and supporting matrices of embedded printing processes are introduced. The effect of key processing parameters on the printing resolution, shape fidelity, and biological functions of the printed tissue constructs are discussed. Recent innovations in the processes and applications of embedded bioprinting are highlighted, such as light-based volumetric bioprinting and printing of functional vascularized organ constructs. Challenges and future perspectives with regard to translating embedded bioprinting into an effective strategy for the fabrication of functional biological constructs with biomimetic structural organizations are finally discussed. STATEMENT OF SIGNIFICANCE: It is still challenging to replicate delicate and intricate tissue-specific structural organizations using mechanically-weak hydrogels for the fabrication of functional living tissue constructs. Embedded bioprinting is an emerging 3D printing strategy that enables to produce complex tissue structures directly inside a reservoir filled with supporting matrix, which largely widens the choice of bioprinting inks to ECM-like hydrogels. Here we aim to provide a comprehensive review on various embedded bioprinting techniques mainly including extrusion-based and light-based processes. Various bioinks, supporting matrices, key processing parameters as well as their effects on the structures and biological functions of resultant living tissue constructs are discussed. We expect that it can provide an important reference and generate new insights for the bioprinting of large vascularized tissues and organs with biological functions.