Wound healing occurs through a similar process in most tissues in the body. It consists of three major stages: inflammatory, proliferative, and remodeling.
Inflammatory Stage of Wound Healing in Small Animals
The inflammatory stage of wound healing can be divided into several phases.
The inflammatory stage of wound healing begins with hemostasis. Hemorrhage is controlled with vasoconstriction, followed within minutes by vasodilation.
The next phase of the inflammatory stage of wound healing is chemotaxis, wherein cells adhere to the vascular endothelium. To resolve infection, leukocytes migrate through the vascular basement membrane into the newly created wound within 30 minutes. Initially, neutrophils predominate (as in the peripheral blood); later, the neutrophils die off and monocytes become the predominant cell type in the wound.
In the debridement phase, damaged cells, pathogens, and debris are removed from the wound area. Although neutrophils phagocytose bacteria, monocytes, rather than neutrophils, are considered essential for wound healing. Monocytes have several functions, including secreting a number of growth factors required for wound healing and attracting mesenchymal cells in addition to the phagocytizing necrotic debris.
Monocytes are considered macrophages after migration out of the blood vessels. Finally, mononuclear cells may coalesce to form multinucleated giant cells found in chronic inflammation.
Lymphocytes may also be present in the wound and contribute to the immunologic response to foreign debris.
Proliferative Stage in Wound Healing in Small Animals
The proliferative (repair) stage of wound healing does not occur at a discrete time but is ongoing. It consists of fibroblast, capillary, and epithelial proliferation phases.
During the proliferation stage, mesenchymal cells transform into fibroblasts, which lay fibrin strands to act as a framework for cellular migration. In a healthy wound, fibroblasts begin to appear ~3 days after the initial injury. These fibroblasts initially secrete ground substance and later, collagen.
The early collagen secretion allows an initial rapid increase in wound strength, which continues to increase more slowly as the collagen fibers reorganize according to the stress on the wound.
Migrating capillaries deliver a blood supply to the wound. The center of the wound is an area of low oxygen tension that attracts capillaries following the oxygen gradient. Because of the need for oxygen, fibroblast activity depends on the rate of capillary development.
As capillaries and fibroblasts proliferate, granulation tissue is produced. Because of the extensive capillary invasion, granulation tissue tends to be both very friable and resistant to infection.
Epithelial cell migration begins within hours after the initial wound. Basal epithelial cells flatten and migrate across the open wound. The epithelial cells may slide across the defect in small groups or “leapfrog” across one another to cover the defect. Migrating epithelial cells secrete mediators, such as transforming growth factors alpha and beta, which enhance wound closure.
Although epithelial cells migrate in random directions, migration stops when contact is made with other epithelial cells on all sides (ie, contact inhibition). Epithelial cells migrate across the open wound and can cover a properly closed surgical incision within 48 hours. However, in an open wound, epithelial cells must have a healthy bed of granulation tissue to cross. Epithelialization is delayed in desiccated wounds.
Remodeling in Wound Healing in Small Animals
Remodeling (or maturation) is the final stage of wound healing. During this period, the newly laid collagen fibers and fibroblasts reorganize along lines of tension. Fibers in a nonfunctional orientation are replaced by functional fibers. This process allows wound strength to continue to increase slowly over a long period (up to 2 years).
Most healed wounds remain 15%–20% weaker than the original tissue. However, the urinary bladder and bone regain their original strength after wounding and repair.