A H₂S-Evolving Alternately-Catalytic Enzyme Bio-Heterojunction with Antibacterial and Macrophage-Reprogramming...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Regenerative Medicine

Background:

• Pathogenic infections in deep wounds cause macrophage dysfunction and lactate buildup, hindering skin regeneration.
• Hypoxic conditions exacerbate these issues, leading to stagnant wound healing.

Purpose of the Study:

• To develop a novel hydrogen sulfide (H2S)-evolving alternately catalytic bio-heterojunction enzyme (AC-BioHJzyme) for treating deep infectious wounds.
• To investigate the enzyme's ability to exhibit circular enzyme-mimetic antibacterial (EMA) activity and macrophage re-rousing capability activated by near-infrared-II (NIR-II) light.

Main Methods:

• Fabrication of CuFe2S3@LOD AC-BioHJzyme, combining CuFe2S3 and lactate oxidase (LOD).
• Utilized LOD to deplete lactate and generate H2O2, which was then converted to germicidal •OH via peroxidase-mimetic activity.
• Employed GPx-mimetic and CAT-mimetic activities for bacterial antioxidant system disruption and singlet oxygen generation, respectively.
• Leveraged H2S release from CuFe2S3@LOD to sustain EMA activity under infectious conditions.
• Performed in vitro and in vivo assays to evaluate efficacy in infectious cutaneous regeneration.

Main Results:

• CuFe2S3@LOD demonstrated circular EMA activity and macrophage re-rousing capability upon NIR-II light activation.
• The system effectively killed bacteria, facilitated epithelialization and collagen deposition, promoted angiogenesis, and reprogrammed macrophages.
• Significant facilitation of infectious cutaneous regeneration was observed in both in vitro and in vivo models.

Conclusions:

• The developed CuFe2S3@LOD AC-BioHJzyme offers a promising countermeasure for deep infectious wound healing.
• The strategy of circular enzyme-mimetic antibiosis and macrophage re-rousing presents a novel approach for regenerative medicine.