Bionic Janus hydrogel drives infected Achilles tendon regeneration via mechano-immune spatiotemporal steering

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.