Recreating the extracellular matrix organization and cellular patterns of anisotropic tissues in bioengineered constructs remains a significant biofabrication challenge. Magnetically‐assisted 3D bioprinting strategies can be exploited to fabricate biomimetic scaffolding systems, but they fail to provide control over the distribution of magnetic materials incorporated in the bioinks while preserving the fidelity of the designed composites. To overcome this dichotomy, the concepts of magnetically‐ and matrix‐assisted 3D bioprinting are combined here. By allowing low viscosity bioinks to remain uncrosslinked after printing, this approach enables the arrangement of incorporated magnetically‐responsive microfibers without compromising the resolution of printed structures before inducing their solidification. Moreover, the fine design of these magnetic microfillers allows the use of low inorganic contents and weak magnetic field strengths, minimizing the potentially associated risks. This strategy is evaluated for tendon tissue engineering purposes, demonstrating that the synergy between the biochemical and biophysical cues stemming from a tendon‐like anisotropic fibrous microstructure, combined with remote magneto‐mechanical stimulation during in vitro maturation, is effective on directing the fate of the encapsulated human adipose‐derived stem cells toward tenogenic phenotype. In summary, the developed strategy allows the fabrication of anisotropic high‐resolution magnetic composites with remote stimulation functionalities, opening new horizons for tissue engineering applications.

Designing functional, vascularized, human scale in vitro models with biomimetic architectures and multiple cell types is a highly promising strategy for both a better understanding of natural tissue/organ development stages...

Tendinopathies are poorly understood diseases for which treatment remains challenging. Relevant in vitro models to study human tendon physiology and pathophysiology are therefore highly needed. Here we propose the automated 3D writing of tendon microphysiological systems (MPSs) embedded in a biomimetic fibrillar support platform based on cellulose nanocrystals (CNCs) self-assembly. Tendon decellularized extracellular matrix (dECM) was used to formulate bioinks that closely recapitulate the biochemical signature of tendon niche. A monoculture system recreating the cellular patterns and phenotype of the tendon core was first developed and characterized. This system was then incorporated with a vascular compartment to study the crosstalk between the two cell populations. The combined biophysical and biochemical cues of the printed pattern and dECM hydrogel were revealed to be effective in inducing human-adipose-derived stem cells (hASCs) differentiation toward the tenogenic lineage. In the multicellular system, chemotactic effects promoted endothelial cells migration toward the direction of the tendon core compartment, while the established cellular crosstalk boosted hASCs tenogenesis, emulating the tendon development stages. Overall, the proposed concept is a promising strategy for the automated fabrication of humanized organotypic tendon-on-chip models that will be a valuable new tool for the study of tendon physiology and pathogenesis mechanisms and for testing new tendinopathy treatments.