Hydrogels that can respond to dynamic forces either from endogenous biological activities or from external mechanical stimuli show great promise as novel drug delivery systems (DDS). However, it remains challenging to engineer hydrogels that specifically respond to externally applied mechanical forces with minimal basal drug leakage under normal stressful physiological conditions. Here we present an ultrasound responsive hydrogel-based DDS with special dual-crosslinked nanoscale network architecture. The covalent crosslinks endow the hydrogel high mechanical stability and greatly suppress deformation-triggered drug release. Meanwhile, the dynamic covalent boronate ester linkages between hydrogel backbone and the anti-inflammation compound, tannic acid (TA), allow effective ultrasound-triggered pulsatile release of TA. As such, the hydrogel shows distinct drug release profiles under compression and ultrasound. A proof-of-principle demonstration of the suppression of inflammation activation of macrophage upon ultrasound-triggered release of TA was also illustrated. We anticipate that this novel hydrogel-based drug delivery system can be used for the treatment of inflammatory diseases on load-bearing tissues, such as muscle and cartilage.

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可以响应来自内源性生物活性或来自外部机械刺激的动力的水凝胶作为新型药物递送系统（DDS）具有广阔的前景。然而，设计在正常压力生理条件下以最小的基础药物渗漏对外部施加的机械力作出特殊反应的水凝胶仍然具有挑战性。在这里，我们介绍具有特殊的双交联纳米级网络体系结构的超声响应水凝胶基DDS。共价交联赋予水凝胶很高的机械稳定性，并大大抑制了变形触发的药物释放。同时，水凝胶骨架与抗炎化合物鞣酸（TA）之间的动态共价硼酸酯键可有效触发超声触发的TA搏动释放。因此，水凝胶在压缩和超声作用下显示出独特的药物释放曲线。还举例说明了超声触发释放TA后巨噬细胞炎症激活受到抑制的原理性证明。我们预计，这种新颖的基于水凝胶的药物递送系统可用于治疗承重组织（例如肌肉和软骨）上的炎性疾病。

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