Microfluidic fiber spinning for 3D bioprinting: Harnessing microchannels to build macrotissues

Microfluidics is rapidly revolutionizing the scientific panorama, providing unmatched high-throughput platforms that find application in numerous areas of physics, chemistry, biology, and materials science. Recently, microfluidic chips have been proposed, in combination with bioactive materials, as promising tools for spinning cell-laden fibers with on-demand characteristics. However, cells encapsulated in filaments produced via microfluidic spinning technology are confined in a quasi-three-dimensional (3D) environment that fails to replicate the intricate 3D architecture of biological tissues. Thanks to the recent synergistic combination of microfluidic devices with 3D bioprinting technologies that enable the production of sophisticated microfibers serving as the backbone of 3D structures, a new age of tissue engineering is emerging. This review looks at how combining microfluidics with 3D printing is contributing to the biofabrication of relevant human substitutes and implants. This paper also describes the whole manufacturing process from the production of the microfluidic tool to the printing of tissue models, focusing on cutting-edge fabrication technologies and emphasizing the most noticeable achievements for microfluidic spinning technology. A theoretical insight for thixotropic hydrogels is also proposed to predict the fiber size and shear stress developing within microfluidic channels. The potential of using microfluidic chips as bio-printheads for multi-material and multi-cellular bioprinting is discussed, highlighting the challenges that microfluidic bioprinting still faces in advancing the field of biofabrication for tissue engineering and regenerative medicine purposes.