Psychological Stress and Wound Healing in Humans

What We Know

Valentina S. Lucas, RN, MS, ANP-BC


Wounds. 2011;22(4):76-83. 

In This Article

How Wounds Heal

A wound can be defined "a disruption of the integrity and function of tissues in the body"[18] and can be further described according to its etiology (surgical, venous, neuropathic etc.), location (lower extremity, abdominal, foot, etc.) or by the duration (acute versus chronic).[19] Normal cutaneous wound healing is a complex process that occurs in overlapping phases and depends upon interactions not only between the person and environment, but on multiple interactions among a large number of cells and chemical mediators including cytokines, hormones, and neurotransmitters. These phases do not occur in isolation, but are dynamic and overlapping. Even so, wound healing can be characterized by three phases: inflammatory, proliferative, and remodeling. The inflammatory phase begins within seconds of injury and lasts anywhere from 2–5 days. Blood vessel disruption activates platelets and triggers the release of clotting factors. The occurrence of vasoconstriction and platelet aggregation stops bleeding and provides a provisional matrix for cellular migration into the injured area.[20–22] The large number of platelets in the clot will degranulate and release numerous growth factors and cytokines.

Approximately 24 hours after injury, neutrophils and macrophages begin to remove nonviable tissue, debris, and bacteria from the wound through the release of enzymes and phagocytosis.[23] In addition to cleaning up the wound bed of nonviable tissue, macrophages and neurtrophils have been shown to express several proinflammatory cytokines. Proinflammatory cytokines are some of the earliest signals to activate and recruit inflammatory cells and fibroblasts to the injury site causing inflammation and vasodilatation, which increases blood vessel permeability and allows easy passage of fluid and phagocytes. Platelet derived growth factor (PDGF) is released by the platelets, stimulating the growth of blood vessels and new structural tissue.[20,24,25] Cytokines are also responsible for activation of keratinocytes found at wound edges, hair follicles, sebaceous and sweat glands. Keratinocytes are the most prevalent cell type of epithelium and begin to migrate and proliferate within 24 hours after injury, paving the way for the formation of new epithelium.[26–28] This process continues on into the proliferative phase of wound healing.

Over the next 2 days to 3 weeks, the proliferative phase begins. Fibroblasts and other cell types begin to lay down the ground substances and collagen fibers in the site of injury. Various chemical mediators such as PDGF stimulate angiogenesis, which is marked by the formation of granulation tissue consisting of new capillary loops in a matrix of collagen and ground substance. Keratinocytes are actively carrying out re-epithelialization. Wound contraction is accomplished by the work of the myofibroblasts. The wound is considered closed with the establishment of a new epidermal covering.[29] The basement membrane, between the epidermis and the dermis, is typically repaired 7–9 days after re-epithelialization and is essential for the restoration of skin integrity and function.[22]

Over the next 3 weeks to 2 years, the final phase of wound healing takes place. In the maturation or remodeling phase, type III collagen is gradually replaced with type I. Tensile strength increases as the collagen fibers reorganize. Healed wounds result in a scar, which differs somewhat from the original tissue, and has approximately 70%–80% of its original tensile strength.[25]


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