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Photothermal Microneedle Hydrogel Patch for Refractory Soft Tissue Injuries through Thermosensitized Anti-Inflammaging Modulation

Wanbo Zhu,Quan Liu,Ziheng Zhang,Yingjie Wang,Jiawei Mei,Dongdong Xu,Jun Zhou,Zheng Su,Xianzuo Zhang,Chen Zhu,Jiaxing Wang,Junchen Zhu,Xiaochun Peng,Xianlong Zhang

Soft tissue injuries (STIs) are the most common cause of extremity pain and motion dysfunction. Persistent inflammatory activation of immune cells characterized by senescence-associated secretory phenotype (SASP) and mitochondrial stress are considered the primary causes of STIs, a pathological process also termed inflammaging. Meanwhile, scavenging excessive “cellular waste” in the inflammaging microenvironment and further activating tissue repair processes remain elusive. Herein, an anti-inflammaging photothermal hydrogel microneedle patch for treating STIs is developed. Taurine-loaded Prussian blue nanoparticles (Taurine@PB) are encapsulated in a methacrylate-based hyaluronic acid hydrogel (HAMA) and further fabricated into taurine@PB@HAMA@microneedles (TPH@MN) patches. The acidic microenvironment of chronic inflammation and mild photothermal effects promote taurine release and anti-inflammaging immunomodulation, inhibiting mitochondrial stress via the SIRT3-NF-κB axis to promote glycolytic metabolic microenvironment of neutrophils reprogramming toward oxidative phosphorylation metabolism. Furthermore, TPH@MN activates macrophage efferocytosis and initiates the process of tissue repair. In mouse models of chronic diabetic wounds and tibialis anterior (TA) muscle injury, TPH@MN inhibits SASP expression and promotes STIs healing through thermosensitized anti-inflammaging immunomodulation. In summary, TPH@MN circumvents the side effects of systemic administration, providing new translatable options in the treatment modalities for patients suffering from STIs worldwide.