Much effort has been made to engineer artificial fiber‐shaped cellular constructs that can be potentially used as muscle fibers or blood vessels. However, existing microfiber‐based approaches for culturing cells are still limited to 2D systems, compatible with a restricted number of polymers (e.g., alginate) and always lacking in situ mechanical stimulation. Here, a simple, facile, and high‐throughput technique is reported to fabricate 3D cell‐laden hydrogel microfibers (named hydrogel noodles), inspired by the fabrication approach for Chinese Hele noodle. A magnetically actuated and noncontact method to apply tensile stretch on hydrogel noodles has also been developed. With this method, it is found that cellular strain‐threshold and saturation behaviors in hydrogel noodles differ substantially from their 2D analogs, including proliferation, spreading, and alignment. Moreover, it is shown that these cell‐laden microfibers can induce muscle myofiber formation by tensile stretching alone. This easily adaptable platform holds great potential for the creation of functional tissue constructs and probing mechanobiology in three dimensions.

Adipose tissue-derived stromal cells (ASCs) natively reside in a relatively low-oxygen tension (i.e., hypoxic) microenvironment in human body. Low oxygen tension (i.e., in situ normoxia), has been known to enhance the growth and survival rate of ASCs, which, however, may lead to the risk of tumourigenesis. Here, we investigated the tumourigenic potential of ASCs under their physiological condition to ensure their safe use in regenerative therapy. Human ASCs isolated from subcutaneous fat were cultured in atmospheric O2 concentration (21% O2) or in situ normoxia (2% O2). We found that ASCs retained their surface markers, tri-lineage differentiation potential, and self-renewal properties under in situ normoxia without altering their morphology. In situ normoxia displayed a higher proliferation and viability of ASCs with less DNA damage as compared to atmospheric O2 concentration. Moreover, low oxygen tension significantly up-regulated VEGF and bFGF mRNA expression and protein secretion while reducing the expression level of tumour suppressor genes p16, p21, p53, and pRb. However, there were no significant differences in ASCs telomere length and their relative telomerase activity when cultured at different oxygen concentrations. Collectively, even with high proliferation and survival rate, ASCs have a low tendency of developing tumour under in situ normoxia. These results suggest 2% O2 as an ideal culture condition for expanding ASCs efficiently while maintaining their characteristics.

F. Xu and co‐workers successfully fabricate cell‐laden hydrogel fibers on page 5999, using a simple, facile, high‐throughput, and mechanical‐based method, inspired by fabrication process of Chinese noodles. Muscle myotubes are generated in 3D hydrogel fibers under mechanical strain. Such an approach holds the potential to create functional tissue constructs and help in understand the mechanobiological responses of cells in 3D.