Wound Repair

Epithelialization

Injured epithelium has a genetically programmed regenerative ability that allows it to reestablish its integrity through proliferation, migration, and a process known as contact inhibition . In general, any edge of normal epithelium will begin and continue to migrate (by proliferation of germinal epithelial cells that advance the free edge forward) until it comes into contact with another free edge of epithelium, where it is signaled to stop growing laterally. Note that the other epithelium can be a different type of epithelium.

Although it is theorized that chemical mediators (released from epithelial cells that have lost contact with other epithelial cells circumferentially) regulate this process, no definitive evidence for this is yet available. Wounds in which only the surface epithelium is injured (i.e., abrasions) heal by proliferation of epithelium across the wound bed from the epithelium contained in rete pegs and adnexal tissues. Because epithelium does not normally contain blood vessels, the epithelium in wounds in which the subepithelial tissue is also damaged proliferates across whatever vascularized tissue bed is available and stays under the portion of the superficial blood clot that desiccates (i.e., forms a scab) until it reaches another epithelial margin. Once the wound is fully epithelialized, the scab loosens and eventually dislodges.

An example of the sometimes detrimental effect of the process of contact inhibition controlling epithelialization occurs when an opening is accidentally made into a maxillary sinus during tooth extraction (see Chapter 11 ). If the epithelium of both the sinus wall and the oral mucosa is injured, it begins to proliferate in both areas. In this case, the first free epithelial edge the sinus epithelium may contact is oral mucosa, thereby creating an oroantral fistula (i.e., an epithelialized tract between the oral cavity and the maxillary sinus).

The process of reepithelialization (i.e., secondary epithelialization) is sometimes used therapeutically by oral-maxillofacial surgeons during certain preprosthetic surgical procedures in which an area of oral mucosa is denuded of epithelium (i.e., unattached gingiva) and then left to epithelialize by adjacent epithelium (i.e., attached gingiva) creeping over the wound bed.

Stages of Wound Healing

Regardless of the cause of nonepithelial tissue injury, a stereotypical process is initiated and, if able to proceed unimpeded, works to restore tissue integrity. This process is called wound healing . The process has been divided into basic stages that, although not mutually exclusive, take place in this sequence. These three basic stages are (1) inflammatory, (2) fibroplastic, and (3) remodeling.

Inflammatory Stage

The inflammatory stage begins the moment tissue injury occurs and, in the absence of factors that prolong inflammation, lasts 3 to 5 days. The inflammatory stage has two phases: (1) vascular and (2) cellular. The vascular events set in motion during inflammation begin with an initial vasoconstriction of disrupted vessels as a result of normal vascular tone. The vasoconstriction slows blood flow into the area of injury, promoting blood coagulation. Within minutes, histamine and prostaglandins E ₁ and E ₂ , elaborated by white blood cells, cause vasodilation and open small spaces between endothelial cells, which allows plasma to leak and leukocytes to migrate into interstitial tissues. Fibrin from the transudated plasma causes lymphatic obstruction, and the transudated plasma—aided by obstructed lymphatic vessels—accumulates in the area of injury, functioning to dilute contaminants. This fluid collection is called edema ( Fig. 4.1 ).

The cardinal signs of inflammation are redness (i.e., erythema) and swelling (i.e., edema), with warmth and pain— rubor et tumour cum calore et dolore (Celsius, 30 bc – ad 38)—and loss of function— functio laesa (Virchow, 1821–1902). Warmth and erythema are caused by vasodilation; swelling is caused by transudation of fluid; and pain and loss of function are caused by histamine, kinins, and prostaglandins released by leukocytes, as well as by pressure from edema.

The cellular phase of inflammation is triggered by the activation of serum complement by tissue trauma. Complement-split products, particularly C _3a and C _5a , act as chemotactic factors and cause polymorphonuclear leukocytes (neutrophils) to stick to the side of blood vessels (margination) and then migrate through the vessel walls (diapedesis). Once in contact with foreign materials (e.g., bacteria), the neutrophils release the contents of their lysosomes (degranulation). The lysosomal enzymes (consisting primarily of proteases) work to destroy bacteria and other foreign materials and to digest necrotic tissue. Clearance of debris is also aided by monocytes such as macrophages, which phagocytize foreign and necrotic materials. With time, lymphocytes accumulate at the site of tissue injury.

The inflammatory stage is sometimes referred to as the lag phase , because this is the period during which no significant gain in wound strength occurs (because little collagen deposition is taking place). The principal material holding a wound together during the inflammatory stage is fibrin, which possesses little tensile strength ( Fig. 4.2 ).