Optimizing skin wound healing: The crucial role of the innate immune system and inflammatory microenvironment

Skin, as a part of the innate immune system, represents the first line of defense against pathogens. Each mechanical damage to the skin surface disrupts its homeostasis, thus rapidly inducing the cascade of repair processes. Wound healing comprises 4 subsequent and overlapping steps: hemostasis, inflammation, proliferation, and remodeling. The interplay of the abovementioned phases results in successful cell restoration and tissue repair. The efficiency of wound healing depends on numerous internal and external factors. The proper recruitment of immune cells, such as neutrophils and macrophages, and their interactions with keratinocytes, fibroblasts, and extracellular matrix (ECM) accounts for one of the most significant elements affecting this process. Despite the interaction of the immune cells, the development of a highly favorable microenvironment surrounding the damaged area also constitutes a vital component of successful healing. These optimal conditions combined with the inflow of stimuli, such as cytokines and growth factors, lead to complete wound closure and skin surface restoration. Nevertheless, in order to increase the efficiency of wound healing treatment and improve existing technologies, it is essential to gain a deeper understanding of the healing steps’ complexity. In this work, we elucidated basic mechanisms regarding skin injury sealing with a focus on the creation of a highly beneficial inflammatory microenvironment. The presented paper outlines current approaches to managing the excessive inflammation of the skin wound microenvironment to improve the treatment of chronic wounds. The most important perspectives in immunology phase modulation include the use of pharmaceuticals, natural bioactive compounds, immunomodulatory scaffolds, skin substitutes, cell-based therapies, and growth factors or cytokines injections.