Hydrogels are excellent mimetics of mammalian extracellular matrices and have found widespread use in tissue engineering. Nanoporosity of monolithic bulk hydrogels, however, limits mass transport of key biomolecules. Microgels used in 3D bioprinting achieve both custom shape and vastly improved permissivity to an array of cell functions, however spherical‐microbead‐based bioinks are challenging to upscale, are inherently isotropic, and require secondary crosslinking. Here, bioinks based on high‐aspect‐ratio hydrogel microstrands are introduced to overcome these limitations. Pre‐crosslinked, bulk hydrogels are deconstructed into microstrands by sizing through a grid with apertures of 40–100 µm. The microstrands are moldable and form a porous, entangled structure, stable in aqueous medium without further crosslinking. Entangled microstrands have rheological properties characteristic of excellent bioinks for extrusion bioprinting. Furthermore, individual microstrands align during extrusion and facilitate the alignment of myotubes. Cells can be placed either inside or outside the hydrogel phase with >90% viability. Chondrocytes co‐printed with the microstrands deposit abundant extracellular matrix, resulting in a modulus increase from 2.7 to 780.2 kPa after 6 weeks of culture. This powerful approach to deconstruct bulk hydrogels into advanced bioinks is both scalable and versatile, representing an important toolbox for 3D bioprinting of architected hydrogels.

Hydrogels that provide mechanical support and sustainedly release therapeutics have been used to treat tendon injuries. However, most hydrogels are insufficiently tough, release drugs in bursts, and require cell infiltration or suturing to integrate with surrounding tissue. Here, we report that a hydrogel serving as a high-capacity drug depot and combining a dissipative tough matrix on one side and a chitosan adhesive surface on the other side supports tendon gliding and strong adhesion (larger than 1,000 J/m2) to tendon on opposite surfaces of the hydrogel, as we show with porcine and human tendon preparations during cyclic-friction loadings. The hydrogel is biocompatible, strongly adheres to patellar, supraspinatus and Achilles tendons of live rats, boosted healing and reduced scar formation in a rat model of Achilles-tendon rupture, and sustainedly released the corticosteroid triamcinolone acetonide in a rat model of patellar tendon injury, reducing inflammation, modulating chemokine secretion, recruiting tendon stem and progenitor cells, and promoting macrophage polarization to the M2 phenotype. Hydrogels with ‘Janus’ surfaces and sustained-drug-release functionality could be designed for a range of biomedical applications.

31Hydrogels are an excellent biomimetic of the extracellular matrix and have found great 32 use in tissue engineering. Nanoporous monolithic hydrogels have limited mass transport, 33 restricting diffusion of key biomolecules. Structured microbead-hydrogels overcome some 34 of these limitations, but suffer from lack of controlled anisotropy. Here we introduce a 35 novel method for producing architected hydrogels based on entanglement of microstrands. 36 The microstrands are mouldable and form a porous structure which is stable in water. 37 Entangled microstrands are useable as bioinks for 3D bioprinting, where they align during 38 the extrusion process. Cells co-printed with the microstrands show excellent viability and 39 augmented matrix deposition resulting in a modulus increase from 2.7 kPa to 780.2 kPa 40 after 6 weeks of culture. Entangled microstands are a new class of bioinks with 41 unprecedented advantages in terms of scalability, material versatility, mass transport, 42 showing foremost outstanding properties as a bioink for 3D printed tissue grafts. 43 44 45 46 47 48 49 50 129 130 131 Results 132 133 Entangled Microstrand Materials are Mouldable, Stable in Water and Macroporous 134 135Here we report on a robust and versatile method for preparing 'entangled' microstrands. 136 Bulk hyaluronan-methacrylate (HA-MA) hydrogels were mechanically pressed through a 137

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