Ranya M Ibrahim, Nicolette N Houreld
Chronic wounds, such as diabetic ulcers, represent a substantial clinical difficulty because of impaired healing, often resulting from vascular and nerve damage associated with hyperglycemia. Traditional treatments primarily offer supportive care but frequently fail to fully restore tissue function, highlighting the urgent need for advanced regenerative strategies. Stem cell-based therapies, especially those leveraging secretome and exosomes, have gained attention as effective alternatives to direct stem cell transplantation. These cell-free approaches offer several advantages, including low immunogenicity, reduced risk of tumour formation, and greater ease of production, handling, and storage. Secretome and exosomes facilitate wound healing by modulating inflammation, promoting angiogenesis, aiding extracellular matrix remodelling, and stimulating the migration and proliferation of skin cells. Exosomes are vital for intercellular communication, delivering key regenerative signals that trigger anti-inflammatory responses and neovascularisation. Photobiomodulation (PBM), a non-invasive technique using specific light wavelengths, further enhances stem cell function and boosts the therapeutic impact of their secretome by influencing gene and protein expression. When combined, PBM and stem cell-derived secretome or exosomes offer a powerful treatment approach for chronic wound repair by activating critical biological pathways involved in regeneration of damaged tissue. This review highlights the current research on the roles of stem cell secretome, exosomes, and PBM in chronic wound treatment, with a focus on their synergistic mechanisms and promising therapeutic potential.