"Hot spring"-mimetic microneedle patches delivering probiotics to accelerate infected wound healing via antibacterial, anti-inflammatory, and angiogenesis.

Arginine facilitates the degradation of CuS NPs, leading to sustained release of Cu2+ ions from the microneedle system.

• The combination of arginine and CuS NPs was described as a novel discovery within this study.
• Cu2+ ion release combined with mild photothermal heating was designed to emulate a 'hot spring-like' ion bath.
• This sustained ion release mechanism provided synergistic antibacterial and pro-angiogenic effects.

The microneedle patch physically penetrates biofilms and delivers therapeutic agents efficiently into the wound bed.

• The MN system was designed to address persistent biofilm formation, which is described as a key pathological factor hindering wound healing.
• Physical biofilm penetration was combined with chemical/biological therapeutic delivery as a dual-mode approach.
• The patch was loaded with three distinct therapeutic components: inactivated Akkermansia muciniphila (Akk), CuS NPs, and arginine (Arg).

CuS nanoparticles generate mild photothermal heating under near-infrared laser irradiation, mimicking the thermal component of hot spring therapy.

• Near-infrared (NIR) laser irradiation was used to activate the photothermal component of the system.
• The photothermal effect was described as 'mild,' intentionally designed to mimic therapeutic hot spring temperatures rather than ablative hyperthermia.
• Photothermal therapy contributed to the antibacterial activity of the overall platform.

Inactivated Akkermansia muciniphila polarizes macrophages toward an anti-inflammatory phenotype, alleviating chronic inflammation in infected wounds.

• Inactivated (non-live) Akk was used, indicating viable bacteria were not required for the immunomodulatory effect.
• The mechanism involved macrophage polarization toward an anti-inflammatory phenotype.
• This immunomodulatory action was identified as addressing the 'prolonged inflammation' component of infected wound pathology.

The multifunctional microneedle platform resulted in accelerated wound closure in an infected mouse model.

• The study used an infected wound mouse model to evaluate in vivo efficacy.
• The platform combined photothermal therapy, antibacterial action, angiogenesis promotion, and anti-inflammatory modulation as cooperative mechanisms.
• The system addressed four intertwined pathological factors: persistent bacterial infection, prolonged inflammation, impaired angiogenesis, and biofilm formation.

The combined system provided synergistic pro-angiogenic effects through the copper ion release and photothermal components.

• Cu2+ ion release from degraded CuS NPs was identified as contributing to angiogenesis promotion.
• Impaired angiogenesis was identified as one of the key clinical challenges in infected wounds that conventional monotherapies fail to address.
• Angiogenesis promotion was listed as one of four cooperative therapeutic mechanisms of the platform.