VR-23

The rising threat of multidrug-resistant bacterial infections demands innovative antimicrobial strategies that combine rapid bactericidal action with minimized resistance development. Despite the promising prospects of antimicrobial peptides (AMPs) due to their rapid bactericidal effect and unique membrane disruption mechanism, toxicity and stability issues have hindered their clinical application. Here, we designed a gelatinase-responsive self-assembled AMP (PEG-PR-26) to overcome the limitations of natural AMPs and to combat methicillin-resistantStaphylococcus aureus (MRSA). Upon exposure to gelatinase at infection sites, PEG-PR-26 releases VR-23 nanoparticles, which disrupt bacterial membranes via rapid complete depolarization and content leakage. The PEGylation strategy enhances serum stability (half-life >24 h vs 9 h for FR-13) and biocompatibility (hemolysis rates <5% at 64 μM). In vivo studies showed that PEG-PR-26 had no obvious toxicity and effectively reduced the extent of lung bacterial infection in mice. Notably, PEG-PR-26 synergizes with antibiotics (Min_FICI = 0.18) and exhibits low resistance development after a 15 day exposure. Overall, this research provides a viable antimicrobial alternative to combat bacterial resistant infections by effectively killing drug-resistant bacteria in mice infected with pneumonia.

Chronic wounds pose a significant clinical challenge worldwide, which is characterized by impaired tissue regeneration and excessive scar formation due to over‐repair. Most studies have focused on developing wound repair materials that either facilitate the healing process or control hyperplastic scars caused by over‐repair, respectively. However, there are limited reports on wound materials that can both promote wound healing and prevent scar hyperplasia at the same time. In this study, VR23‐loaded dendritic mesoporous bioglass nanoparticles (dMBG) are synthesized and electrospun in poly(ester‐curcumin‐urethane)urea (PECUU) random composite nanofibers (PCVM) through the synergistic effects of physical adsorption, hydrogen bond, and electrospinning. The physicochemical characterization reveals that PCVM presented matched mechanical properties, suitable porosity, and wettability, and enabled sustained and temporal release of VR23 and BDC with the degradation of PCVM. In vitro experiments demonstrated that PCVM can modulate the functions and polarization of macrophages under an inflammatory environment, and possess effective anti‐scarring potential and reliable cytocompatibility. Animal studies further confirmed that PCVM can efficiently promote re‐epithelialization and angiogenesis and reduce excessive inflammation, thereby remarkably accelerating wound healing while preventing potential scarring. These findings suggest that the prepared PCVM holds promise as a bidirectional regulatory dressing for effectively promoting scar‐free healing of chronic wounds.