Spider-inspired nanohunter in ultrafast hydrogel enables spatiotemporal targeted delivery for enhanced healing of methicillin-resistant Staphylococcus aureus infected wounds.

Persistent drug-resistant bacterial infections and chronic inflammation severely hinder wound healing, highlighting the need for multifunctional therapies with spatiotemporal control. Herein, inspired by the bolas spider's three-stage predatory mechanism, we developed an "attract-penetrate-kill" bactericidal strategy by engineering a chitooligosaccharide-octyl gallate (COS-OG) nanohunter via ultrasound-assisted Fenton grafting. Notably, COS-OG selectively "attracted" bacteria while remaining non-toxic to mammalian cells. Molecular dynamics simulations further reveal its efficient "penetration" into bacterial membranes, followed by the "kill" phase under blue-light (BL, 54.24 J/cm2) irradiation, achieving 99.99% MRSA inhibition and vastly outperforming vancomycin (67.63%). To further enable spatiotemporally targeted delivery, COS-OG was encapsulated in a green hydrogel formed by carboxymethyl chitosan (CMCS) and oxidized tannic acid (OTA). OTA underwent auto-oxidation to crosslink CMCS through Schiff base and hydrogen bonds, enabling ultrafast gelation (within 20 s) with only 20% wt (CMCS dry weight) TA. This ingenious design not only imparted the hydrogel outstanding injectable properties and in situ moldability but also enabled sequential antibacterial and anti-inflammatory functions. Specifically, the system rapidly cleared bacteria by mimicking the bolas spider hunting mechanism (BL on, 162.72 J/cm2) and subsequently exerted an immunomodulatory function by inhibiting the IL17 signaling pathway (BL off) executed by TA and COS-OG, while enhancing collagen deposition and angiogenesis. In vivo, the hydrogel accelerated MRSA-infected wound healing, achieving 92.63% wound closure compared to only 67.18% for commercial 3 M dressings. Collectively, this system integrates biomimetic design, ultrafast gelation, and spatiotemporal control into a green platform, offering a simple, safe, low cost, and translatable therapeutic solution for bacterial infected wounds.