Engineering hybrid hydrogels from sticker–spacer peptide and molybdenum disulfide (MoS₂) for advanced antimicrobial therapy

The rapid escalation of antibiotic-resistant bacterial infections poses a severe global health threat, demanding next-generation antimicrobial strategies beyond conventional antibiotics. Herein, we report the development of a hybrid hydrogel constructed through weak intermolecular interactions between a sticker-spacer peptide derivative and molybdenum disulfide (MoS₂) nanosheets. The incorporation of MoS₂ within the peptide hydrogel results in nanosheets embedded within a nanofibrous network and intercalation of nanofibers between the nanosheets. This hybrid architecture maintains the mechanical properties while conferring intrinsic, broad-spectrum antibacterial activity against Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus, primarily through mechanisms involving oxidative stress and membrane disruption. Furthermore, in vivo bacterial wound healing studies demonstrated that the hybrid hydrogel remarkably accelerated tissue regeneration, achieving complete wound closure. The histological and quantitative analysis further confirm enhanced re-epithelialization, collagen deposition, and reduced inflammation after the treatment. Overall, this work presents a multifunctional, biocompatible hybrid hydrogel platform that combines antimicrobial activity with regenerative capability, offering a promising strategy for next-generation wound dressings and a potential alternative to traditional antibiotics.