Engineering a Cell Wall–Deficient Protoplast-Incorporated Hydrogel for Infected Wound Healing

Bacteria-infected wounds remain a major clinical challenge due to persistent infection, impaired tissue regeneration, and the increasing prevalence of antibiotic resistance. Conventional antibiotic therapies primarily rely on biochemical bactericidal mechanisms and often fail to effectively modulate the wound-healing microenvironment. Here, we report the engineering of a protoplast-incorporated hydrogel for infected wound treatment, in which cell wall–deficient protoplasts derived from Rhodopseudomonas palustris (R. palustris) serve as a photothermally active antibacterial component. We demonstrate that these protoplasts retain the near-infrared (NIR) photothermal properties of the parent bacteria, enabling localized, non-antibiotic bacterial eradication upon NIR irradiation. Importantly, removal of the bacterial cell wall substantially reduces endotoxin burden, thereby mitigating inflammation-associated risks compared with intact bacteria. To enable localized delivery and retention, the protoplasts are uniformly encapsulated within a sodium alginate hydrogel, which prevents leakage and maintains a moist wound microenvironment. This protoplast-incorporated hydrogel not only achieves effective antibacterial activity but also exhibits a favorable safety profile. Beyond its photothermal bactericidal function, the system promotes cell migration, collagen deposition, and angiogenesis, while reducing pro-inflammatory cytokine levels, collectively accelerating wound closure. Overall, this work presents a hydrogel-based, photothermal, non-antibiotic antibacterial platform that integrates endotoxin-reduced bacterial derivatives with microenvironmental modulation, offering a promising strategy for the treatment of bacteria-infected wounds.