Effective strategies for managing chronic wounds include rapid hemostasis, infection control, and excessive infiltration of inflammatory factors. Herein, we report a microenvironment self-adaptive multifunctional hydrogel dressing with intrinsic antimicrobial and anti-inflammatory properties that promotes collagen deposition and angiogenesis and accelerates large-scale chronic wound healing. This hydrogel, synthesized based on the gelatin (Gel) and dextran (DT) backbone, adapts to irregular wound shapes and accelerates coagulation by promoting rapid platelet aggregation and activation of the coagulation cascade, offering early-stage protection for complex wounds. Incorporating paeoniflorin (PF), a Traditional Chinese Medicine monomer with anti-inflammatory properties, into the GBOD hydrogel (GBOD-PF), establishes an anti-inflammatory microenvironment by inducing M1-to-M2 macrophage repolarization. Thus, the microenvironment self-adaptive multifunctional hydrogel was found to play a role in drug delivery and promoting chronic wound (infected wound and diabetic wound) healing by exerting hemostatic, antibacterial, and anti-inflammatory effects simultaneously.

Postoperative adhesions (PAs) are a common complication after intraperitoneal surgery. Hydrogels are a physical barrier that prevents peritoneal adhesions, but their efficacy is still controversial. In this study, Laponites, a layered two-dimensional nanoscale, is incorporated into zwitterionic hydrogel (pSBLA) to enhanced biocompatibility and bioactivity to develop a nanocomposite for rapid prevention of postoperative and recurrent adhesion. The anisotropic distribution of charges in laponites results in strong electrostatic repulsion in aqueous solutions and enables electrostatic interactions between amphiphilic ions, thereby enhancing the mechanical properties of hydrogels. The pSBLA hydrogels also possess a series of characters for an ideal anti-adhesion material, including resistance to adhesion against fibrinogen, proteins, bacteria as well as cells. The mechanism underlying the extraordinary hydration of pSBLA is elucidated in this study using molecular dynamic simulations. In addition, pSBLA hydrogel is shown to represent a major advancement in anti-adhesion efficacy by completely and reliably preventing postoperative and recurrent adhesions after adhesiolysis in rat models. Furthermore, mechanistic explorations revealed that pSBLA hydrogel inhibits inflammatory responses and resists fibrosis by regulating the transforming growth factor-β/Smad signal pathway. Above results have therefore provided a facile but effective strategy to improve postoperative and recurrent adhesion.