The Most Common Causes of Wound Chronicity
Given the grave risks posed by chronic wounds, proper wound care and comprehensive assessment by a wound care specialist is essential for tissue preservation. Various factors can contribute to wound chronicity. These factors can be better understood by considering normal wound healing physiology.
What are Chronic Wounds?
Wounds that take longer than four weeks to heal are termed as 'chronic wounds'. Unlike in an acute wound, the wound healing stages in chronic wounds do not progress as they normally would and tissue integrity is not timely established.  If left untreated, this delayed wound healing can lead to loss of tissue, limb(s), and in severe cases, death.Moreover, chronic wounds also have psychological and economic implications for the patients. People with chronic wounds tend to have a poorer quality of life compared to the normal population and are more likely to struggle financially. An estimated 6.5 million Americans suffer from chronic wounds - and the prevalence is estimated to only increase in the coming years. 
Normal Wound Healing Stages
There are four main stages involved in a normal wound healing process:
All of these stages overlap and are a continuous process. In the first stage - 'homeostasis' - tissue injury leads to a fibrin mesh formation through the activation of a coagulation cascade. Inflammation, which begins soon after tissue injury, is characterized by an influx of neutrophils at the wound site for the removal of dead bacteria and necrotic tissue. This stage clinically appears as swelling and redness which is a normal physiological response.
In the third stage of wound healing, the injured tissue is rebuilt with collagen and extracellular matrix. Myofibroblasts migrate to the wound site and approximate the wound edges. This leads to wound contraction and formation of the granulation tissue.New blood vessel formation - called angiogenesis - occurs simultaneously which facilitates the transport of oxygen and nutrients to the newly formed tissue.In the final stage, type III collagen is remodeled and replaced with type Icollagen which has more tensile strength. 
Common Causes of Delayed Wound Healing
Any factor or disease that can disrupt the normal stages of wound healing can lead to delayed wound healing. Some of the factors are described below:
A common cause of delayed wound healing is infection. At the time of injury, microorganisms can enter the tissue. These microbes can delay wound healing by further prolonging the inflammatory process. Bacteria cause the release of pro-inflammatory cytokines which can inadvertently raise the levels of MMPs (matrix metalloproteases), which are a family of enzymes that degrade the extracellular matrix. This enzyme degrades the granulation tissue at the wound site, hence contributing to a delayed wound closure.
The commonly associated bacteria with delayed wound healing are P.aeruginosa and Staph Aureus. These bacteria tend to form 'biofilms' which are complex structures that resist antibiotics and degradation by the neutrophils. Without adequate wound care and decontamination, healing is extensively delayed in the setting of bacterial superinfection. 
Collagen is an important constituent of granulation tissue and any nutritional deficiency that can affect its synthesis will lead to delayed wound healing. Vitamin C, which is a cofactor required for collagen synthesis, and protein deficiency can negatively affect the wound healing process. When assessing chronic wounds, wound care specialists need to consider the nutritional status of their patients. Addressing these deficiencies can help improve wound healing. 
Steroids are known for their potent anti-inflammatory effect and unfortunately, this effect can be destructive for wound healing.Inflammation is an essential step in wound healing. As steroids inhibit the inflammatory process, they can halt normal wound repair. As a result, an inadequate amount of granulation tissue is produced. Steroids are also known to increase the risk of wound infections which leads to impaired wound healing.
Patients on long-term steroid use are also at an increased risk of developing diabetes, a metabolic syndrome that can further complicate the wound healing process. 
Globally, 422 million people are suffering from diabetes.  In America alone, 10.5% of the population was diagnosed with diabetes in 2018. The prevalence of diabetes is steadily rising, and diabetes-related complications are also expected to see an increase.  Patients with diabetes report a significant delay in wound healing and are more likely to suffer from chronic non-healing ulcers.
Diabetes contributes to wound chronicity through multiple mechanisms. Patients with diabetes experience low tissue blood supply which affects the oxygen and nutrient supply to the wound site. As a consequence,wounds heal slowly. Moreover, diabetes also predisposes individuals to neuropathy or nerve damage which means that diabetic patients aren't always aware of any trauma they experience. Decreased tissue perfusion combined with neuropathic changes puts diabetic patients at an increased risk of developing chronic ulcers and wounds. Diabetes is the single most likely cause of lower-limb amputations in the United States.
60% of all lower-limb amputations occur in diabetic individuals. To minimize these grim statistics, initial screening and management by podiatristsis vital. Podiatrists are well trained in the lower limb anatomy and are often the first to detect any initial ischemic or neuropathic changes. They can formulate a comprehensive foot care plan, treatment, and follow-up for diabetic patients. Diabetic foot ulcers are complex and often require a multidisciplinary management approach. A comprehensive treatment plan led by vascular surgeons, podiatrists and endocrinologists can help significantly reduce the rate of amputations in diabetic patients. 
Peripheral Vascular Disease
Wounds require oxygen, nutrients, and proper blood supply for optimum healing. An adequate blood supply to the tissues is therefore essential. Peripheral vascular disease affects the blood supply to the extremities and is linked with the development of chronic wounds. Peripheral Arterial Disease may be asymptomatic at first, later progressing to intermittent claudication and ischemic ulcers. The risk of peripheral vascular disease is four times higher in smokers. Smoking cessation is hence an important part of chronic wound management.
Like with diabetic foot ulcers, a comprehensive lower limb assessment by a podiatrist can help detect the presence of peripheral vascular disease in its initial stages. Incidence of foot amputations can be reduced by 45% to 85% with timely interventions.
Chronic wounds represent a significant burden to the patients, healthcare system, and economy. With an annual treatment cost of $25 billion and an ever-increasing rate of amputations, the need for screening and prevention of chronic wounds is now significantly more important.  A thorough understanding of the causes of chronic wounds can help physicians better address the risk factors.
- Siddiqui AR, Bernstein JM. Chronic wound infection: facts and controversies. Clin Dermatol. 2010;28(5):519–26.
- Fearns N, Heller-Murphy S, Kelly J, Harbour J. Placing the patient at the centre of chronic wound care: A qualitative evidence synthesis. J Tissue Viability. 2017;26(4):254–9.
- Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17(6):763–71.
- Wound healing and repair [Internet]. Medscape.com. 2021 Available from: https://emedicine.medscape.com/article/1298129-overview
- Bjarnsholt T, Kirketerp-Møller K, Jensen PØ, Madsen KG, Phipps R, Krogfelt K, et al. Why chronic wounds will not heal: a novel hypothesis. Wound Repair Regen. 2008;16(1):2–10.
- Elsevier. Robbins & Cotran Pathologic Basis of Disease [Internet]. Available from: https://www.elsevier.com/books/robbins-and-cotran-pathologic-basis-of-disease/kumar/978-0-323-53113-9
- Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res. 2010;89(3):219–29.
- Diabetes [Internet]. Who.int. Available from: https://www.who.int/news-room/fact-sheets/detail/diabetes
- National Diabetes Statistics Report, 2020 [Internet]. Cdc.gov. 2020 Available from: https://www.cdc.gov/diabetes/data/statistics-report/index.html
- Bell DP Jr. The role of podiatry in wound management. J Am Col Certif Wound Spec. 2009;1(3):78–9.
- Sen CK, Gordillo GM, Roy S, Kirsner R, LambertL, Hunt TK, et al. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17(6):763–71.