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AggreArch: A Programmable Nano-to-Micro Assembly Platform for Redox-Active Metal Microarchitectures in Infected Wound
Xuanshuo Zhang1, Jie Zhao1, Zhengyu Xu1
1The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital of Wannan Medical University), Zheshan West Road, Wuhu, Anhui241001, China.
None:
Chronic infected wounds, particularly under diabetic conditions, require antimicrobial biomaterials that combine potent bacterial suppression with host-tissue compatibility. Here, we report AggreArch, a tunable aqueous nano-to-micro assembly platform for constructing hierarchical metal-based microarchitectures with programmable composition, morphology, and biological activity. Using this strategy, we generated Ag-, Cu-, and Mn-based AggreArch variants to demonstrate the compositional extensibility of the platform. Among these variants, the dendritic silver architecture AAAg4 was identified as a representative lead candidate, achieving 99.7% inhibition against multidrug-resistant Escherichia coli (E. coli) at 30 μg mL-1 and 99.8% inhibition against methicillin-resistant Staphylococcus aureus (S. aureus) at 100 μg mL-1, while maintaining >85% cell viability and favorable short-term biosafety. Comparative release studies showed that AAAg4 released only 1-2% of total silver in PBS over 7 days vs ∼7% for conventional AgNPs, confirming architecture-regulated silver availability. Integrated transcriptomic and biochemical analyses indicated that AAAg4 induced a coordinated redox-metabolic stress program involving oxidative imbalance, Fe-S-dependent functions, and respiratory electron-transfer-related processes, while imposing a lower oxidative burden on host cells than freely available Ag+. In diabetic infected wound models, AAAg4 accelerated wound closure (approximately 92% by day 12), markedly reduced bacterial burden, and enhanced collagen deposition to 83.1% vs 36.1% in controls. Similar repair-promoting trends were observed in rabbit ear wounds. Collectively, these findings establish AAAg4 as a representative lead architecture within the AggreArch platform and demonstrate that hierarchical microarchitecture engineering can expand the antibacterial-biosafety window of metal-based wound-facing antimicrobial materials.
