Programmed microalgae-gel promotes chronic wound healing in diabetes

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Microbiology

Background:

• Chronic diabetic wounds, particularly diabetic foot ulcers, face challenges like hypoxia, oxidative stress, inflammation, and infection.
• Existing treatments often struggle to address the multifaceted nature of these complex wounds.
• A need exists for innovative therapeutic strategies that can simultaneously manage multiple pathological factors.

Purpose of the Study:

• To develop a programmed therapeutic strategy using live Haematococcus (HEA) for treating chronic diabetic wounds.
• To investigate the multifaceted functions of HEA under varying light conditions for wound healing applications.
• To evaluate the efficacy of HEA-based therapy in a preclinical model of infected diabetic wounds.

Main Methods:

• Utilized live Haematococcus (HEA) cells and modulated light intensity (658 nm, 0.5 W/cm² and 0.1 W/cm²) to trigger specific functions.
• Assessed antibacterial activity, oxygen production via photosynthesis, and reactive oxygen species (ROS) scavenging capabilities.
• Investigated the transformation of green HEA (GHEA) to red HEA (RHEA) induced by light, leading to astaxanthin (AST) accumulation.
• Evaluated the immunomodulatory effects of RHEA, including ROS scavenging and macrophage polarization.
• Assessed the therapeutic potential of HEA hydrogel in promoting cell proliferation, migration, and neoangiogenesis in infected diabetic wounds in female mice.

Main Results:

• High light intensity activated GHEA for photothermal disinfection, while lower intensity enabled oxygen production, combating hypoxia and promoting vascular regeneration.
• Continuous light irradiation induced RHEA formation, which effectively scavenged ROS and enhanced antioxidant enzyme expression.
• RHEA, via exosome-mediated secretion of AST, promoted M2 macrophage polarization, indicating an anti-inflammatory and pro-regenerative immune response.
• The HEA hydrogel demonstrated significant improvements in wound sterilization, cell proliferation, migration, and neoangiogenesis.
• Successful improvement in infected diabetic wound healing was observed in female mice treated with the HEA hydrogel.

Conclusions:

• Live Haematococcus (HEA) can be programmed via light modulation to perform diverse therapeutic functions, including disinfection, oxygenation, ROS scavenging, and immune regulation.
• This HEA-based programmed therapy effectively addresses key pathological factors in chronic diabetic wounds.
• The findings suggest that HEA hydrogel holds significant potential as an innovative therapeutic agent for improving infected diabetic wound healing.