Mechanism of action of collagen
1. The repair effect of collagen on the wound surface
As the main component of extracellular matrix, collagen not only plays a weak role, but also can realize signal transmission between cells and extracellular matrix receptor molecules and participate in the regulation of cell behavior. Collagen can bind to cell surface receptors and participate in cell surface receptor recognition and signal transduction. Collagen plays a very important role in cell proliferation, migration, differentiation and other cell activities, such as tissue reconstruction, including morphology and wound healing. Collagen also plays an important role in the regulation of the immune system as well as in hemostasis and thrombosis.
Collagen can promote cell growth, the horniness cells in collagen, gelatin and collagen hydrolysate on the substrate culture, microscope observation training with cell proliferation after 16 hours, the results showed that contain collagen culture cell density was significantly greater than in the other samples, suggesting that the role of collagen has obviously improve the cutin cell growth. Collagen can not only promote cell division and proliferation, but also be effective in maintaining cell division function. Therefore, it can be made into various wound repair dressings. Collagen dressings come in many forms, such as diaphragms, sponges, granules, and gels. Collagen dressings can be dissolved in whole or in part and interact with host extracellular matrix to promote the adhesion, movement, growth and deposition of cells on new connective tissue. In addition, collagen can also induce the differentiation of wound cells and the chemotaxis of fibroblasts, thus achieving the effect of accelerating wound repair and improving wound healing quality.
2. Wet environment is conducive to wound healing
Moist Wound Healing refers to maintaining a Moist environment close to the physiological state for the Wound, which is conducive to accelerating the re-epithelialization of the Wound and reducing the risk of infection, so as to promote Wound Healing.
In 1962, zoologist George Winter confirmed in animal experiments that compared with exposure to air, the re-epithelialization rate of wound surface under wet environment was significantly accelerated [1]. This experiment laid the theoretical foundation for the application of wet dressing in wound care. Up to now, wet wound healing theory has been widely accepted as the standard in most kinds of wound treatment [2].
Wound healing in a wet environment has the following characteristics [3] :
1) Speed up epithelialization and wound healing;
2) Reduce inflammatory response to reduce the formation of crusts;
3) Reduce excessive exudate and toxic substances, and send back the important role of exudate;
4) Promote the release of various growth factors;
5) Keep the wound moist environment and maintain a constant temperature;
6) Promote the growth of granulation tissue;
7) Reduce fibrosis;
8) Reduce the risk of infection;
9) Autolytic debridement;
10) Reduce the frequency of dressing change and the pain caused by dressing change.
As a kind of hydrophilic macromolecular structural protein, wet or hydrophilic wound dressings with different structures and forms made by collagen, among which gel, adhesive dressing and other wet dressings form a wet environment for the wound. After absorbing exudate, hydrophilic dressings such as sponges, films and particles can also effectively maintain a moist environment close to physiological state locally on the wound. This is helpful to improve the speed and quality of wound healing.
3. Benefits of low pH microenvironment on wound healing [4]
PH is one of the key factors involved in wound healing in acute and chronic wounds. It affects matrix metalloproteinase activity, fibroblast activity, keratinocyte proliferation, microbial proliferation, biofilm formation and immune response. Different stages of the wound healing process may require different pH environments to recover from skin injury and infection, a more acidic environment may increase fibroblast proliferation, and neutral and alkaline environments ranging from 7.21 to 8.34 are suitable for re-epithelialization. The imbalance of pH value of the wound can lead to severe chronic wound.
Low pH helps to inhibit protease activity and prevent excessive protease activity from affecting wound healing. Matrix metalloproteinases (MMPs) are a family of more than 20 proteases. They can degrade extracellular components and facilitate the removal of damaged tissue, but excessive proteases can also cause endothelial cell damage and degrade epidermal - dermal connections, interrupting wound healing. Figure 1 describes the activity of four proteases, including MMP2, which are important for wound healing, under different pH environments. It can be seen that the activity of these four proteases can be very low or even inactivated under acidic environment (pH<5). In fact, the activity of most proteases is inhibited in an acidic environment, so lowering the pH of the wound site may be an effective treatment for chronic wounds.
FIG. 1 Activity of four proteases at different pH values during wound healing
Low pH can also affect bacterial growth and the toxins they produce. On the one hand, an acidic environment helps inhibit microbial growth (such as staphylococcus aureus with an optimal pH of 7.0 to 7.5) and neutralizes microbial metabolism of ammonia. On the other hand, studies have shown that low pH can alter the structure of Staphylococcus aureus endotoxin C2 (SEC2), making it less toxic. Maintaining the acidic environment in the wound area can inhibit the proliferation and toxicity of bacteria, thus playing a positive role in promoting the wound healing and preventing the acute wound from facing chronic transformation.
The solution and leachate of collagen prepared by Xanor biological are both weak acid, and the dressing prepared by Xanor biological contributes to the formation of a low pH environment locally on the wound, which is beneficial to the wound healing in the early stage (inflammatory reaction stage, granulation tissue hyperplasia stage) or the healing of chronic wounds that are difficult to heal.
[1] G. D. Winter, Nature 193(4812):293-294 (1962)
[2] G. A. Kannon, et al., Dermatologic Surgery 21(7):583-590 (1995)
[3] Zhang Yanhui et al. Chinese Journal of Modern Nursing 14(13):1528-1530. (2008)
[4] 1. S.-H. Kuo, et al., Diagnostics 10(2), 107-134 (2020).
