Abstract
Engineering three-dimensional (3D) scaffolds with in vivo like architecture and function has shown great potential for tissue regeneration. Here we developed a facile microfluidic-based strategy for the continuous fabrication of cell-laden microfibers with hierarchically organized architecture. We show that photolithographically fabricated microfluidic devices offer a simple and reliable way to create anatomically inspired complex structures. Furthermore, the use of photo-cross-linkable methacrylated alginate allows modulation of both the mechanical properties and biological activity of the hydrogels for targeted applications. Via this approach, multilayered hollow microfibers were continuously fabricated, which can be easily assembled in situ, using 3D printing, into a larger, tissue-like construct. Importantly, this biomimetic approach promoted the development of phenotypical functions of the target tissue. As a model to engineer a complex tissue construct, osteon-like fiber was biomimetically engineered, and enhanced vasculogenic and osteogenic expression were observed in the encapsulated human umbilical cord vein endothelial cells and osteoblast-like MG63 cells respectively within the osteon fibers. The capability of this approach to create functional building blocks will be advantageous for bottom-up regeneration of complex, large tissue defects and, more broadly, will benefit a variety of applications in tissue engineering and biomedical research.
Highlights
The regeneration of functional tissues depends on the capability of controlling biocompatible extracellular matrix (ECM) complexities at the nano/microscale and requires the ability of the components to assemble into larger length scales
A facile method has been developed for the continuous fabrication of a variety of functional cell-laden microfibers that can be assembled into large tissue constructs
The innovative integration of microfluidics and functional biomaterials significantly enhanced our capability of creating large functional tissues of complex structure
Summary
The fabrication of three-dimensional (3D) scaffolds with in vivo like architecture and function has shown great potential for tissue regeneration.[1−4] in the body, tissues comprise multiple cell types that are hierarchically organized within a complex extracellular matrix (ECM).[5,6] the regeneration of functional tissues depends on the capability of controlling biocompatible ECM complexities at the nano/microscale and requires the ability of the components to assemble into larger length scales. Alginate can disintegrate in a common culture medium at a low Ca2+ concentration.[34] As a consequence, most previous work has only reported the viability of cells encapsulated within alginate-based microfibers, rarely involving the considerable spreading and function enchantment of cells.[20,21,23,35] In contrast, hydrogels from natural ECM such as gelatin and collagen can provide cells with a more biomimetic microenvironment Their gelation takes hours, which is too slow to match the rapidity of the microfluidic spinning process, which is a matter of seconds. The outer calcium alginate shell provided temporary mechanical support for the microfibers, whereas the subsequently formed cell-containing ECM microfibers induced a certain level of physiological function of the encapsulated cells This approach is viable for creating simple doublelayered microfibers, the fabrication of more complex structures would require many stages of assembly of glass capillaries, which is not technically practical. These functional building blocks will be advantageous for the bottom-up regeneration of complex, large tissue defects
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