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

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 solution-hydrogel transition of the systems,finally achieving gradient distribution of the blocks in the formed hydrogels.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 simultaneously.Different cargos could be loaded on the blocks and form gradient cues through the same crosslinking-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 multifunction of the building blocks reveal the applicability in complex tissue engineering and various interfacial tissues.

Injectable silk/hydroxyapatite nanocomposite hydrogels with vascularization capacity for bone regeneration

Localized and sustained osteogenic-angiogenic stimulation to bone defects is critical for effective bone repair.Here,desferrioxamine(DFO)was loaded on silk fibroin nanofibers and blended with hydroxyapatite nanorods(HA),forming injectable DFO-loaded silk fibroin-HA nanocomposite hydrogels.The composite hydrogels remained homogeneous distribution of HA with high ratio(60%)and also higher stiffness than that of pure silk fibroin nanofiber hydrogels,which provided stable osteogenic stimulation niches for tissue regeneration.Without the scarify of injectability,the hydrogels achieved slow delivery of DFO for above 60 days,resulting in suitable angiogenesis in vitro and in vivo and better osteogenesis than DFO-free systems.Compared to previous injectable silk fibroin-HA hydrogels,the introduction of vascularization capacity further stimulated the osteogenic differentiation of stem cells and accelerated new bone formation.Quicker and better bone healing were detected at defect sites after the injection of DFO-loaded nanocomposite hydrogels,indicating the effective synergistic effect of osteogenic and angiogenic cues.This work provides a simple and effective strategy of introducing angiogenic cues to bone matrices.We believe that the injectable nanocomposite hydrogels are suitable for the regeneration of bone tissues.