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The Most Important Factors Affecting Wound Healing

Chronic non-healing wounds are those that do not follow a timely or predictable sequence of repair, usually with a prolonged inflammatory response. When this occurs, it places a severe burden on healthcare resources and also lowers the quality of life of patients. This article discusses the local and systemic factors that affect the rate of wound healing in patients.

Local Factors Affecting Wound Healing

These factors affect the rate of healing by directly affecting the nature of the wound. Examples include venous insufficiency, poor oxygenation, infection, and the presence of foreign bodies. 

Venous Insufficiency

This occurs when there is low perfusion to various parts of the body (including the limbs) due to an obstruction in the arteries carrying blood to the heart. Common causes include blood clots and varicose veins. This insufficiency results in edema, stasis dermatitis, and ulcerations with delayed wound healing. Risk factors for venous insufficiency in patients include diabetes mellitus, deep-vein thrombosis (DVT), congestive heart failure, obesity, pregnancy, and peripheral vascular disease. 

Poor Oxygenation

Oxygenation is critical for all phases of wound healing. It facilitates angiogenesis, keratinocyte differentiation, fibroblast proliferation, migration, wound contraction, collagen synthesis, and re-epithelialization. Low tissue oxygenation (hypoxia) due to systemic factors, such as diabetes and aging, can result in a decreased vascular flow, which impairs wound healing. 

Infection/Foreign Bodies

The presence of foreign bodies in the wound bed can result in localized infections that can impair the wound healing processes. Tears in the skin allow harmful micro-organisms at the skin surface to penetrate. Infected wounds left untreated can result in widespread tissue necrosis, complications that may necessitate limb amputation, and in severe cases, sepsis. 

Systemic Factors Affecting Wound Healing

Systemic factors refer to the overall state of health of patients, including underlying conditions that can impact wound healing. They include age, sex hormones, diabetes, stress, obesity, medications, and smoking or alcohol usage. 

Age and Sex

Patients aged 60 years and older (seniors) are at a higher risk for delayed wound healing. Factors associated with old age, including psychological, stress, malnutrition, use of medication, immobilization, and comorbidities (e.g., diabetes and peripheral artery disease), can slow the rate of wound healing in older patients. According to research, age impacts every phase of wound healing, including delayed angiogenesis and re-epithelialization, decreased wound strength, and impaired macrophage function. Also, male and female sex hormones have been found to have an impact on wound healing. Estrogen, the female hormone, has been found to improve age-related impairment in wound healing in elderly patients. Based on results from clinical studies involving randomized male and female participants with a mean age of 70.7 years, the application of exogenous estrogen improved the rate of wound healing in both sexes. Also, androgen, a male hormone, has been shown to enhance the inflammatory response.


Diabetes Mellitus, an abnormal increase in the level of blood sugar is a significant contributor to wound chronicity. According to data from the United States CDC, 34.2 million Americans are diabetic, and 88 million more are currently in the early stages of the disease (pre-diabetes). The CDC also notes that minority populations in the U.S., such as African Americans and Hispanics are at an increasing and disproportionate risk of diabetes. Diabetic patients have a higher risk of developing chronic, non-healing diabetic foot ulcers (DFUs) in the lower extremities, a leading cause of limb amputations in the U.S. One of the underlying causes of delayed healing in DFUs is hypoxia, which limits fibroblast proliferation, angiogenesis, and collagen synthesis. Another contributor is neuropathy, which causes a loss of sensation in the limbs. Sensory nerves have been found to play a crucial role in the homeostatic phase of wound healing. 


Stressors, such as anxiety and depression can impair wound healing by deregulation of the immune system. Psychological stress has been found to have profound effects on the hypothalamus, psychological responses (health-damaging behaviors), and autonomic nervous system. Cortisol, a stress-induced hormone can also impair wound healing by interfering with the production of pro-inflammatory cytokines. 


The accumulation of fatty or adipose tissue in obese persons can impair the rate of wound healing. According to data from the CDC, obesity had a prevalence of 42.2% among adults in the United States between 2017 and 2018. It is known to increase the risk of many health conditions, including coronary heart disease, hypertension, and cancer, and also contributes to diabetes. Higher levels of glucose in the blood promote vasoconstriction, which results in low perfusion to the lower extremities. 


use of certain medications, such as chemotherapy drugs and Non-steroidal Anti-inflammatory Drugs (NSAIDs) may interfere with wound healing processes, such as platelet formation or inflammatory responses. Chemotherapy drugs, used for the treatment of cancer, can cause venous irritation, delayed cellular migration, and lower collagen synthesis and fibroblast proliferation. Moreover, research suggests that NSAIDs like aspirin and Ibuprofen commonly used for pain relief can have a negative effect on wound healing.

Smoking and Alcohol Consumption

Smoking of substances, such as nicotine and tobacco are widely known to increase the likelihood of cardiovascular disease, heart disease, lung disease, and several cancers. However, these substances can also have adverse effects on wound healing as they contain thousands of toxic compounds. For example, nicotine usage can delay wound healing by lowering wound tensile strength and increasing the likelihood of wound infection. Smoking also induces ischemia which results in a decrease in the oxygen supply in chronic wounds along with vasoconstrictive effects. Carbon monoxide from nicotine and tobacco smoke has combinative effects with hemoglobin in the blood, which causes reduced oxygen levels. Alcohol use impairs wound healing due to reduced angiogenesis, a higher incidence of infections, and an increased risk of bleeding. 

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