Chronic wounds, also known as skin ulcers and refractory wounds, are any wounds that fail to heal in an orderly and expected time according to the normal trauma healing process; wounds that fail to heal for more than 3 months can be referred to as chronic wounds. Typically, skin wound healing is a dynamic process that can be artificially divided into three or four overlapping processes: a hemostatic/inflammatory response phase, a proliferative phase, and a tissue remodeling phase. The chronic wound healing process is often blocked in one or several phases of the healing process, for example, there is usually a significantly prolonged inflammatory response phase. In acute wounds, there is a precise balance between the production and degradation of molecular products associated with wound repair, such as collagen; in chronic wounds, this balance is disrupted and a stronger degradation response is exhibited. Chronic wounds may remain unhealed for years or even a lifetime, causing severe psychological and physical stress and consequently a huge economic burden on the patient and the entire health care system. The number of people with chronic wounds has increased significantly with an aging population, weight gain, and increasing complications secondary to diseases such as diabetes and venous insufficiency. It is estimated that approximately 1% of the population may develop leg ulcers during their lifetime. In the United States alone, 3 to 6 million people suffer from chronic trauma each year, and the cost of treating these traumas is nearly $5 to $10 billion. In China, the rate of chronic trauma among surgical inpatients is approximately 1.5% to 20.3%, based on epidemiological studies. As a result, chronic trauma has become a heavy burden for patients, healthcare professionals and even the entire healthcare system. To effectively address this problem, it is important to gain a deeper understanding of the pathophysiology of chronic wounds and to further improve the ability to apply appropriate therapeutic measures including growth factors, cell therapy, gene therapy, and tissue-engineered skin.