Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process

Abstract

Reactive oxygen species (ROS) play a pivotal role in the orchestration of the normal wound-healing response. They act as secondary messengers to many immunocytes and non-lymphoid cells, which are involved in the repair process, and appear to be important in coordinating the recruitment of lymphoid cells to the wound site and effective tissue repair. ROS also possess the ability to regulate the formation of blood vessels (angiogenesis) at the wound site and the optimal perfusion of blood into the wound-healing area. ROS act in the host's defence through phagocytes that induce an ROS burst onto the pathogens present in wounds, leading to their destruction, and during this period, excess ROS leakage into the surrounding environment has further bacteriostatic effects. In light of these important roles of ROS in wound healing and the continued quest for therapeutic strategies to treat wounds in general and chronic wounds, such as diabetic foot ulcers, venous and arterial leg ulcers and pressure ulcers in particular, the manipulation of ROS represents a promising avenue for improving wound-healing responses when they are stalled. This article presents a review of the evidence supporting the critical role of ROS in wound healing and infection control at the wound site, and some of the new emerging concepts associated with ROS modulation and its potential in improving wound healing are discussed.

Keywords: Host defence; Reactive oxygen species; Wound healing; Wound infection.

Figure 1

Reactive oxygen species (ROS) and its role in wound healing. The schematic diagram depicts the multiple roles of ROS during acute wound healing (note that this refers to homeostatic, not excessive, levels of ROS). (i) ROS are important in initial wound protection by reducing blood flow and local cell signalling for thrombus formation; (ii) local ROS release attracts blood vessel‐bound local neutrophils to the wound site for bacterial protection; (iii) phagocytosis releases ROS to stunt bacterial growth and provide further signals supporting the wound response; (iv) other immunocytes, including monocytes, migrate towards the wound site to help attack invading pathogens; (v) wound edge and general release of ROS stimulates endothelial cell division and migration for blood vessel reformation, fibroblast division and migration for new ECM formation (including collagen synthesis) and promote keratinocyte proliferation and migration.