Thermosensitive in situ Hydrogel Based on Benzalkonium Chloride-Loaded Selenium-Doped Mesoporous Silica Nanoparticles for Diabetic Chronic Wound Treatment

Background: Diabetic chronic wounds are characterized by persistent infection, excessive oxidative stress, impaired angiogenesis, and prolonged inflammation, resulting in delayed healing. Current wound dressings lack the ability to simultaneously regulate these pathological processes. Methods: A multifunctional composite hydrogel was developed by incorporating benzalkonium chloride (BAC)-loaded selenium-doped mesoporous silica nanoparticles (Se-MSNs) into a PF127 matrix. In this system, BAC provides antibacterial activity, Se-MSNs enable redox regulation and immunomodulation, and PF127 serves as a delivery platform for localized retention and sustained release. The physicochemical properties, antibacterial activity, antioxidant capacity, pro-angiogenic effects, and anti-inflammatory performance were evaluated in vitro, followed by therapeutic assessment in a diabetic mouse wound model. Results: The composite hydrogel exhibited effective antibacterial activity against Staphylococcus aureus and Escherichia coli, reduced intracellular reactive oxygen species, promoted endothelial cell migration and tube formation, and modulated inflammatory cytokine expression in vitro. In vivo, the hydrogel significantly accelerated wound closure, enhanced collagen deposition and angiogenesis, and alleviated excessive inflammation in diabetic wounds. Conclusion: The therapeutic effects of the composite hydrogel are attributed to the restoration of redox homeostasis and the coordinated regulation of inflammation resolution and vascular regeneration. This study presents a multifunctional biomaterial strategy for improving the healing of diabetic chronic wounds. Illustration of BAC@Se-MSN@PF127 preparation and application in wound healing.The illustration shows the preparation and application of BAC at Se-MSN at PF127. The top section depicts the process starting with Se-MSN, which is combined with benzalkonium chloride (BAC) to form BAC at Se-MSN. This mixture is then processed at 4 degrees Celsius with PF-127 to create BAC at Se-MSN at PF127, which is stable at temperatures greater than or equal to 37 degrees Celsius. The bottom section illustrates the application of this compound in wound healing. A diagram shows the compound being applied to a wound on a mouse, highlighting its antibacterial, anti-inflammation, antioxidation, immune regulation and proliferation-promoting properties. The wound healing process is depicted with arrows indicating antibacterial action, anti-inflammation and antioxidation, immune regulation through M0 and M2 and promotion of proliferation, enhancing tissue repair and regeneration.