Oxygen carriers: core strategies for modulating hypoxic microenvironments and promoting healing in chronic wounds

Chronic wounds have emerged as a major healthcare challenge due to their prolonged healing cycle. A key feature of chronic wounds is local tissue hypoxia, resulting in insufficient oxygenation of the wound microenvironment. While traditional therapies like hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT) alleviate wound hypoxia by oxygen supplementation, they are limited by high costs, uncertainty in sustained efficacy, and complications, restricting clinical use. Oxygen carriers, such as perfluorocarbons (PFCs) and hemoglobin (Hb), exhibit high-efficiency oxygen delivery capacity, excellent biocompatibility and cost-effectiveness. They hold enormous potential for clinical applications. This review focuses on the application of PFCs and Hb-based oxygen carriers in chronic wound therapy. It systematically elaborates on the diversified oxygen delivery strategies based on PFCs and Hb. It also quantitatively compares their oxygen delivery capabilities and analyzes their multiple synergistic biological effects. Meanwhile the review also describes the difficulties and challenges in precise delivery and clinical translation.