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Engineered, centimeter-scale skeletal muscle tissue (SMT) can mimic muscle pathophysiology to study development, disease, regeneration, drug response, and motion. Macroscale SMT requires perfusable channels to guarantee cell survival and support elements to enable mechanical cell stimulation and uniaxial myofiber formation. Here, stable biohybrid designs of centimeter-scale SMT are realized via extrusion-based bioprinting of an optimized polymeric blend based on gelatin methacryloyl and sodium alginate, which can be accurately co-printed with other inks. A perfusable microchannel network is designed to functionally integrate with perfusable anchors for insertion into a maturation culture template. The results demonstrate that (i) co-printed synthetic structures display highly coherent interfaces with the living tissue; (ii) perfusable designs preserve cells from hypoxia all over the scaffold volume; and (iii) constructs can undergo passive mechanical tension during matrix remodeling. Extrusion-based multimaterial bioprinting with our inks and design realizesin vitromatured biohybrid SMT for biomedical, nutritional, and robotic applications.

Miniaturization of interventional medical devices can leverage minimally invasive technologies by enabling operational resolution at cellular length scales with high precision and repeatability. Untethered micron-scale mobile robots can realize this by navigating and performing in hard-to-reach, confined and delicate inner body sites. However, such a complex task requires an integrated design and engineering strategy, where powering, control, environmental sensing, medical functionality and biodegradability need to be considered altogether. The present study reports a hydrogel-based, biodegradable microrobotic swimmer, which is responsive to the changes in its microenvironment for theranostic cargo delivery and release tasks. We design a double-helical magnetic microswimmer of 20 μm length, which is 3D-printed with complex geometrical and compositional features. At normal physiological concentrations, matrix metalloproteinase-2 (MMP-2) enzyme can entirely degrade the microswimmer body in 118 h to solubilized non-toxic products. The microswimmer can respond to the pathological concentrations of MMP-2 by swelling and thereby accelerating the release kinetics of the drug payload. Anti-ErbB 2 antibody-tagged magnetic nanoparticles released from the degraded microswimmers serve for targeted labeling of SKBR3 breast cancer cells to realize the potential of medical imaging of local tissue sites following the therapeutic intervention. These results represent a leap forward toward clinical medical microrobots that are capable of sensing, responding to the local pathological information, and performing specific therapeutic and diagnostic tasks as orderly executed operations using their smart composite material architectures.