,Electric field-driven building blocks for introducing multiple gradients to hydrogels

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Gradient biomaterials are considered as preferable matrices for tissue engineering due to better simulation of native tissues.The introduction of gradient cues usually needs special equipment and complex process but is only effective to limited biomaterials.Incorporation of multiple gradients in the hydrogels remains challenges.Here,betasheet rich silk nanofibers (BSNF) were used as building blocks to introduce multiple gradients into different hydrogel systems through the joint action of crosslinking and electric field.The blocks migrated to the anode along the electric field and gradually stagnated due to the solutton-hydrogel transition of the systems,finally achieving gradient distribution of the blocks in the formed hydrogele.The gradient distribution of the blocks could be tuned easily through changing different factors such as solution viscosity,which resulted in highly tunable gradient of mechanical cues.The blocks were also aligned under the electric field,endowing orientation gradient slmultaneously.Different cargos could be loaded on the blocks and form gradient cues through the same crosslinklng-electric field strategy.The building blocks could be Introduced to various hydrogels such as Gelatin and NIPAM,indicating the universality.Complex niches with multiple gradient cues could be achieved through the strategy.Silk-based hydrogels with suitable mechanical gradients were fabricated to control the osteogenesis and chondrogenesis.Chondrogenic-osteogenic gradient transition was obtained,which stimulated the ectopic osteochondral tissue regeneration in vivo.The versatility and highly controllability of the strategy as well as multifunctlon of the building blocks reveal the applicability in complex tissue enginesring and various interfacial tissues.
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