From Inflammation to Current and Alternative Therapies Involved in Wound Healing

Abstract

Wound healing is a complex event that develops in three overlapping phases: inflammatory, proliferative, and remodeling. These phases are distinct in function and histological characteristics. However, they depend on the interaction of cytokines, growth factors, chemokines, and chemical mediators from cells to perform regulatory events. In this article, we will review the pathway in the skin healing cascade, relating the major chemical inflammatory mediators, cellular and molecular, as well as demonstrating the local and systemic factors that interfere in healing and disorders associated with tissue repair deficiency. Finally, we will discuss the current therapeutic interventions in the wounds treatment, and the alternative therapies used as promising results in the development of new products with healing potential.

Figure 1

Progression and overlap of the phases involved in the physiological wound healing process: (a) inflammation begins with (1) coagulation, platelet aggregation, and fibrin clot formation; (2) then inflammatory events occur through neutrophils and macrophages infiltration and phagocytosis of debris, apoptotic cells, and pathogens; anti-inflammatory events occur through inhibition of destructive inflammatory process and proliferation promotion. (b) In the proliferation occurs (3) angiogenesis; (4) reepithelization (epithelial cell mitosis and fibroblasts transformation into myofibroblasts), and granulation tissue formation (EMC composed of collagen, glycoprotein, proteoglycan, fibroblasts, and keratinocytes, under modulation of MMP-9). (c) Remodeling is marked by the (5) EMC reorganization: cells apoptosis and angiogenesis regression; and (6) type III collagen replaced by type I.