Abstract
Abstract Tissue repair is challenged by inefficient cellular infiltration and prolonged inflammation. Herein, the mesoporous polydopamine nanoparticles were loaded with spermidine and then encapsulated in agarose, which were incorporated into the oxidized hyaluronic acid crosslinked collagen matrix to fabricate NIR-activated hydrogel (DOCH@P) by the directional freeze-thaw process. DOCH@P hydrogel had obvious oriented microchannel structure due to the extrusion of directional ice crystals and the chemical crosslinking during the directional freeze-thaw process, besides enhanced mechanical properties, viscoelasticity and favorable tissue adhesive strength. DOCH@P hydrogel with photothermal performance promoted the melting of the agarose in the shell of nanoparticles under NIR-activation, thus achieving NIR-responsive spermidine release behavior. NIR-activated DOCH@P hydrogel exhibited significantly robust broad-spectrum antibacterial activity and antioxidative activity. Significantly, DOCH@P hydrogel demonstrated superior capabilities in inducing directional migration and infiltration of fibroblasts through the synergistic integration of the oriented microchannels physical contact guidance and spermidine bioactivity. Based on the multi-layered spermidine-mediated immunoregulation, NIR-activated DOCH@P hydrogel ultimately drove macrophages towards anti-inflammatory M2 phenotype to alleviate excessive inflammation and remold immune homeostasis. Overall, the NIR-activated collagen-based hydrogel with oriented microchannel structure provides a promising scaffold foundation for guiding tissue regeneration through physical contact-guided cellular infiltration and anti-inflammation. Graphical Abstract