In orchestrating the wound healing process, the immune system plays a critical role. Hence, controlling the immune system to repair skin defects is an attractive approach. The highly complex immune system includes the coordinated actions of several immune cells, which can produce various inflammatory and anti-inflammatory cytokines and affect the healing of skin wounds. This process can be optimized using biomaterials, bioactive molecules, and cell delivery. The present review discusses various immunomodulation strategies for supporting the healing of chronic wounds. In this regard, following the evolution of the immune system and its role in the wound healing mechanism, the interaction between the extracellular mechanism and immune cells for acceleration wound healing will be firstly investigated. Consequently, the immune-based chronic wounds will be briefly examined and the mechanism of progression, and conventional methods of their treatment are evaluated. In the following, various biomaterials-based immunomodulation strategies are introduced to stimulate and control the immune system to treat and regenerate skin defects. Other effective methods of controlling the immune system in wound healing which is the release of bioactive agents (such as anti-inflammatory, antigens, and immunomodulators) and stem cell therapy at the site of injury are reviewed.
