Dual Dynamic Crosslinked Hydrogel Patch Embodied with Anti‐Bacterial and Macrophage Regulatory Properties for Synergistic Prevention of Peritendinous Adhesion

Abstract The occurrence of peritendinous adhesion, which hampers the quality and function of the healed tendon, is strongly linked to oxidative stress, inflammatory, and infection that occur after surgery. Tendon damage and repair provide a considerable obstacle for regenerative medicine owing to the absence of patches that possess comprehensive functionality, including self‐healing capacity, anti‐inflammatory and anti‐bacterial properties, as well as tissue repair guidance. A dual dynamic crosslinked network is created by coordination bonds between catechol groups in protocatechuic aldehyde (PA) and Fe 3+ , as well as a dynamic Schiff base reaction between amino groups in hyaluronic acid‐adipic acid dihydrazide (HA‐ADH) and aldehyde groups in PA. The HA‐ADH@PA/Fe hydrogel exhibits self‐healing ability, tissue adhesion, anti‐bacterial activity, regulation of macrophage polarization via the NF‐κB signaling, oxidative stress elimination, and anti‐inflammation. In addition, a dual‐layer Janus patch is created, taking inspiration from the anatomy and disease progression of tendon adhesion. The inner layer of the patch, which is in direct contact with the operated tendon, is a multifunctional HA‐ADH@PA/Fe hydrogel, encircled further by a poly(ɛ‐caprolactone) (PCL) electrospinning membrane outer layer facing the surrounding tissue. The PCL@HA‐ADH@PA/Fe hydrogel patch reduced tendon adhesion and supported tissue regeneration by stimulating macrophages polarization into an anti‐inflammatory phenotype and resolving both local and systemic inflammation. This research showcased the PCL@HA‐ADH@PA/Fe hydrogel patch as an alternative therapeutic method for preventing the development of adhesions around tendons.