Thus, activated macrophages work in the wound environment and play a major role in the transition between the phases of inflammation and recovery. Macrophage growth factors promote the proliferation of new tissue cells, including fibroplasia and angiogenesis. Macrophages also release lactate into the wound environment, which stimulates connective tissue growth and collagen production. Macrophages, fibroblasts and young blood cells migrate into the wound as a single or a single wound module. Polymorphonuclear neutrophils and macrophages perform an important function of rejection of non-viable tissue and wound cleaning, regulated by cytokines and growth factors.The inflammatory phase in experimental wounds lasts approximately 5 days. The classic signs of this phase are redness, swelling, soreness, increased local temperature, and dysfunction. The environment of such wounds is ideal for bacterial infection, and rough handling of these tissues can maintain tissue necrosis with subsequent infection.
This tissue is called granulation because it is located on the surface of the wound and has a granular (granular) appearance. It is characterized by the proliferation of newly formed small blood vessels and fibroblasts. The multiple bends of small vessels macroscopically create the impression of grayish grains (granules) (Fig. 1). The newly formed vessels have permeable interendothelial contacts, allowing the release of proteins and erythrocytes from the vascular bed, therefore, the granulation tissue is often edematous. It is a very fragile tissue, but important because of its function as a barrier to infection.To accelerate this phase of wound healing, an innovative product Mirragen has been developed, which is a biologically active borate glass fiber. It serves as a matrix of fibers and beads based on boron and other inorganic trace elements.
The formation of a healthy bed of granulation tissue serves not only as a barrier to external contamination, but also as a scaffold for migrating epithelial cells. Collagen is directly responsible for the strength of the connection of the edges of the wound. Lack of collagen or improper formation of collagen can lead to a gaping wound. Collagen is the deposition of fibroblasts and associated fibrin filaments.
1–2 days after injury, epithelial cells begin to proliferate in the basal zone and the overlying spiny layer of cells (along the viable border of the skin defect) using pseudopodia. Epithelial cells damage the formed clot in the wound and the stroma secreting proteolytic enzymes (collagenases, plasminogen activators), and try to replace the coating with viable tissue. In the process of migration, epithelial cells can increase in size and "flatten" over the vascular wound bed (Fig. 2).The activity of epithelial cells leads to inhibition of granulation tissue to prevent the formation of excess amounts of this tissue.The total duration of epithelialization can vary from several days to several weeks (depending on the size of the wound and the state of the granulation tissue).
Figure: 2 Epithelialization. Drawing by Kip Carter © 2016, University of Georgia Research Foundation, Inc.
In wounds with minimal dermal rupture, closed with sutures, epithelial cells can form bridges within 48 hours. In wounds with damage to the entire thickness of the tissue, epithelial cells are formed only after the appearance of granulation tissue (on the 4-5th day after injury). In wounds small in width, epithelial migration may last for weeks or may not end with complete wound closure. Thus, the epithelialization process can take a time interval from the proliferation phase to the maturation phase.
Wound compression is a process in which peripheral skin with a full-thickness defect, thanks to a centripetal mechanism, gradually closes the wound, spreading towards the center. Compression of the wound encompasses both phases - proliferation and maturation.Starting from 5–9 days after injury, fibroblasts turn into smooth muscle contractile proteins, due to which the edges of the wound are pulled from the periphery to the center. If the contraction of the wound is excessive, contracture of the wound may occur, which is a pathological process leading to a restriction of the mobility of the underlying structures.Interestingly, square and rectangular wounds heal more effectively than circular skin defects. Linear margins contribute to the force of linear contraction of the myofibroblasts.
The transition from extracellular matrix to scar tissue requires connective tissue remodeling. During the transition from granulation tissue to cicatricial maturation, collagen remodeling occurs with a balance between its formation and destruction. Collagen formation is directly related to the tensile strength of the wound edges. So, after 3 weeks after injury, scar tissue is 20% of the final strength. Thereafter, the increase in elasticity occurs at a slower rate. In the next few weeks, the scar reaches only 70–80% of the strength of normal tissue.
At the end of the healing process, there is less collagen tissue (compared to its original content in the wound), but with a better structural configuration.The post-injury maturation and remodeling phase generally lasts approximately 20 days to 1 year. Using the Mirragen product for healing wound surfaces, you can speed up this process by 25-40%.