Genetic Factors in Wound Healing

Introduction

The process of healing a wound involves four physiological stages. They include homeostasis, inflammation, proliferation, and remodeling. A wound will heal properly when these processes follow a predetermined schedule. Many factors can interfere with these processes, which, in turn, can affect the whole wound-healing process. Age and sex hormones, stress, diabetes, obesity, drugs, alcoholism, smoking, oxygenation, and nutrition can be the factors that can influence the process.

How Does Wound Healing Occur?

Wound healing can occur in different stages. A wound will heal faster if it is smaller in size. A deep wound or a larger wound might take a longer time to heal. The steps involved in wound healing can include:

1. Homeostasis: Homeostasis, in simple terms, refers to stopping bleeding. When there is a cut in the body, it will begin to bleed. However, in an average human, blood cells join within minutes or even seconds to arrest the bleeding and prevent further blood loss. These are formed by a type of blood cell called platelets, which become a scab as they dry. Another protein called fibrin helps to hold the clot in place.

2. Inflammation: The blood vessels can slightly dilate to let new nutrients and oxygen into the wound to aid in healing after the wound has formed a clot. An appropriate amount of oxygen in the blood is necessary for wound healing. A lesser or a higher amount of oxygen may hinder the wound healing. Another type of blood cell called the macrophage protects the wound. These cells help to prevent any infection and promote wound healing. Macrophages produce chemical messengers that promote wound healing.

3. Proliferation: New tissue formation occurs at this stage. Blood cells, which contain good oxygen, also help in this. Chemical cues tell cells to start producing collagen and other tissues to start the healing process. This is the reason that the scar becomes red and then, later on, color changes.

4. Remodeling: The new tissue that is formed over the wound becomes strong over time. The wound can stretch, causing an itching or a feeling of scratching. The wound will be as strong as before within three months. Depending upon its severity, it might even take a few years to heal.

What Are the Factors That Affect Wound Healing?

There can be many factors that can affect the whole process of wound healing. The factors can be categorized as local and general. The factors that directly influence the wound-healing process are called local factors, while those that affect the whole body and in turn, the wound-healing process are called general factors.

Local Factors:

1. Oxygenation: Oxygen is an essential component of wound healing. It stops wounds from getting infected, stimulates the growth of new blood vessels, raises the differentiation, migration, and re-epithelialization of keratinocytes, increases the production of collagen and fibroblasts, and encourages wound contraction.

2. Infection: When a wound or a tear in the skin, microorganisms get easy access to the underlying tissue. The state of infection and the rate of infection's progression determines the wound's contamination status.

3. Inflammation: It is a normal part of the process. In addition, it helps to keep away the microorganisms that contaminate the wound. However, inflammation can last longer if the microorganisms are not effectively put out.

Systemic Factors:

1. Age: Increasing age can be a hindering factor in wound healing. Aging has the impact of causing a temporal delay in wound healing in healthy older persons but not a reduction in the quality of healing.

2. Sex Hormones: Age-associated deficiencies in wound healing are related to sex hormones. It has been observed that elderly males heal acute wounds more slowly than elderly ladies.

3. Stress: Stress has a significant effect on social behavior and individual health. Research on humans and animals has shown that psychological stress significantly slows down the healing of wounds.

4. Diabetes: Over 300 million people worldwide have diabetes. There is evidence that the ability to heal acute wounds is compromised in diabetics. This group is also more likely to get diabetic foot ulcers that are chronic and non-healing.

How Does Genetics Affect Wound Healing?

It has been discovered that the protein ‘MG53’ heals wounds without leaving scars. This protein circulates throughout the bloodstream, assisting the body in healing wounds to the kidneys, lungs, heart, and skin without leaving scars. Moreover, this may speed up the healing of open wounds, shorten the recovery period following surgery, and stop the spread of infections. Simple activities like walking, running, or cycling may cause injuries to the body. However, the protein MG53 prevents them from turning out to be very evident ones.

Bacterial infections significantly impede the healing process in chronic wounds. Chronic wounds are known to harbor a variety of bacterial species, while it is unclear why certain wound infections harbor certain species while others do not. In particular, it was shown that genetic diversity in the TLN2 and ZNF521 genes was connected to the number of common pathogens (mostly Pseudomonas aeruginosa and Staphylococcus epidermidis) as well as the number of bacteria found in wounds. In addition, it was observed that wounds infected with Pseudomonas had fewer species and healed more slowly. In addition, researchers noted that by identifying individuals susceptible to certain kinds of persistent infections, the biomarkers for chronic wound microbiomes can help direct treatment. These biomarkers may be utilized to determine which patients need early and focused treatment, as persistent wounds are linked to the emergence of multidrug-resistant bacteria.

Genes that expressed late included progranulin, a crucial growth factor for wound healing. Also referred to as acrogranin, PC-derived growth factor, granulin or epithelin precursor, and progranulin. A pluripotent growth factor called progranulin encourages tissue granulation and neovascularization. It activates extracellular kinases. Another late-expressed genes included MMP-9. VEGF's (vascular endothelial growth factor) receptor is more likely to bind to MMP-9, a metalloproteinase (an enzyme whose action involves a metal) that indirectly stimulates angiogenesis or the formation of new blood vessels. Angiogenesis in malignancies has been demonstrated to be promoted by MMP-9. The integrins alpha and beta five were among the other wound-healing genes whose expression rose later. Integrin αv is crucial in wound closure, fibroblast migration, and angiogenesis.

Conclusion

Wound healing is a complex process that is affected by many factors. These can be systemic or local factors. The effects of these elements do not preclude one another. Any individual phases may be influenced by one or more factors, which will ultimately determine how the healing process turns out. Genetics is one of the many factors that can affect wound healing.