Jie Li, Z Wang, Wenjing Yang, Yuchen Zhang, Yuchen Zhang, Yanjun Wang, Hongrui Wang, Hongrui Wang, Yang Xie, Shuogui Xu, Yan Shang, Chunyu Xue, Yuntong Zhang, Yuntong Zhang, Shuo Fang
The healing of infected tendons is hindered by mechanical dysfunction, tissue adhesion, bacterial colonization, and immune imbalance. Inspired by the biphasic “adhesion-lubrication” structure of tendon sheaths, we developed a Janus hydrogel, named HAPP@H-EXO, for spatiotemporal repair. The material exhibits antifatigue properties and redistributes mechanical stress through a dynamic network formed by norbornylated PVA and boronic acid-modified hyaluronic acid-PVA. Its high-adhesion side integrates tissue via borate and hydrogen bonds, whereas the lotus leaf-induced low-adhesion side prevents postsurgical adhesion. The incorporation of oligo-polyethyleneimine and phenylboronic acid groups traps and kills bacteria, overcoming resistance. The pH-responsive release of hypoxic tendon stem cell exosomes reprogrammes macrophages via inhibition of the NF-κB pathway, reducing inflammation and promoting regeneration. In an infected Achilles tendon model, HAPP@H-EXO eliminated MRSA, suppressed early inflammation, and enhanced regeneration. Within 8 weeks, it significantly improved biomechanical strength, prevented adhesion, and restored motor function, establishing a mechanoimmunotherapeutic strategy for infected tissue regeneration. Healing of infected tendons is hindered by mechanical dysfunction, tissue adhesion, and immune imbalance. Here, Li et al. develop a multifunctional Janus hydrogel with asymmetric adhesion, antibacterial properties, and pH-responsive release of tendon stem cell-derived exosomes for infected tendon repair.