Microenvironment self-adaptive multifunctional hydrogels elicit immunomodulation mediated wound healing.

Herein, we report a microenvironment self-adaptive multifunctional hydrogel (GBOD-PF) dressing with intrinsic hemostasis, antimicrobial and anti-inflammatory properties that promotes collagen deposition, activates the immune response, and angiogenesis, accelerates large-scale chronic wound healing. To address these needs, aldehyde-functionalized dextran (ODT) was first synthesized through oxidation, and an injectable hydrogel was prepared by mixing Gel and ODT solutions in the presence of borax and paeoniflorin (PF) through the formation of dynamic Schiff base bonds (GBOD-PF). This multifunctional hydrogel exhibits remodeling and self-healing properties, enhanced adhesion strength and biocompatibility. Moreover, it possesses broad-spectrum antibacterial activity and superior hemostasis, providing early-stage protection for complex wounds. Notably, GBOD-PF targets the TLR4/NF-κB signaling pathway, a core mediator of inflammation, thereby dampening the inflammatory cascade. The results demonstrate the application of the GBOD-PF hydrogel in an infection wound and diabetic model wound healing model, which enhanced immune response, induced M1-to-M2 macrophage repolarization to establish anti-inflammatory microenvironment, regulated MMP-9, promoted angiogenesis, thereby inducing a pro-regenerative response. Therefore, this work provides an effective strategy for the treatment of chronic wound repair and tissue regeneration.