Untethered mini‐robots can move single cells or aggregates to build complex constructs in confined spaces and may enable various biomedical applications such as regenerative repair in medicine and biosensing in bioengineering. However, a significant challenge is the ability to control multiple microrobots simultaneously in the same space to operate toward a common goal in a distributed operation. A locomotion strategy that can simultaneously guide the formation and operation of multiple robots in response to a common acoustic stimulus is developed. The scaffold‐free cellu‐robots comprise only highly packed cells and eliminate the influence of supportive materials, making them less cumbersome during locomotion. The ring shape of the cellu‐robot contributes to anisotropic cellular interactions which induce radial cellular orientation. Under a single stimulus, several cellu‐robots form predetermined complex structures such as bracelet‐like ring‐chains which transform into a single new living entity through cell–cell interactions, migration or cellular extensions between cellu‐robots.
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Canadas, Raphaël F. ; Ren, Tanchen ; Marques, Alexandra P. ; Oliveira, Joaquim M. ; Reis, Rui L. ; Demirci, Utkan ( , Advanced Functional Materials)
Abstract Anisotropic 3D tissue interfaces with functional gradients found in nature are replicated in vitro for drug development and tissue engineering. Even though different fabrication techniques, based on material science engineering and microfluidics, are used to generate such microenvironments, mimicking the native tissue gradient is still a challenge. Here, the fabrication of 3D structures are described with linear/random porosity and gradient distribution of hydroxyapatite microparticles which are combined with a gradient of growth factors generated by a dual chamber for the development of heterotypic‐like tissues. The hydroxyapatite gradient is formed by applying a thermal ramp from the first to the second gel layer, and the porous architecture is controlled through ice templating. A 3D osteochondral (OC) tissue model is developed by codifferentiating fat pad adipose‐derived stem cells. Osteogenic and chondrogenic markers expression is spatially controlled, as it occurs in the native osteochondral unit. Additionally, a prevasculature is spatially induced by the perfusion of proangiogenic medium in the bone‐like region, as observed in the native subchondral bone. Thus, in this study, precise spatial control is developed over cell/tissue phenotype and formation of prevasculature which opens up possibilities for the study of complex tissues interfaces, with broader applications in drug testing and regenerative medicine.