Stages of Wound Healing
Regardless of the cause of nonepithelial tissue .injury, a stereotyptc process is initiated that, if able’ to proceed unimpeded, works to restore tissue integrity. This process 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 beginsis called wound healing.
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. It has two phases: vascular and 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 E1 and E2, 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 lymphatics-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 (t.e. erythema) and swelling (i.e., edema), with warmth and pain-mbor et tumour cum calore et dolore (Celsius, 30 Be to 38 AD) and loss of function-fimctio laesa. (Virchow, 1821
to 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 activatiorr of serum complement’ by tissue trauma.’ Complement-split products, particularly C3a and CSa, 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 neutrophtlsrelease the contents of their lysosomes (degranulation). ‘The lysosomal enzymes
· (consisting primarily of proteases) work to destroy bacte- • ria 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 accuinulate at the site •
· of tissue injury. The lymphocytes are in the B or T groups: ,B lymphocytes are able to recognize antigenic material, produce antibodies that assist the remainder of the immune system in identifying. foreign materials, and
interact-with complement to lyse foreign cells. T lympho- · cytes are divided into three principal subgroups: (1) helper : ,T cells, which stimulate B cell proliferation and differenti- ,atian;. (2) suppressor T cells, which work to regulate the tuncti~n of helper T cells; and (3) cytotoxic (killer) T cells,
which Secells bearing foreign antigens.
,i!te 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 is fibrin, which possesses little tensile strength (Fig. 4-2).
Fibroplastic- stage, The strands of fibrin, which are derived from the blood coagulation, crisscross wounds to
FIG. 4-1 Early vascular responses to injury. Initial transient vasoconstriction (A) is soon followed by
vasodilation (B). Vasodilation is caused by the actions of histamine, prostaglandins, and other vasodilatory
substances. Dilation causes intercellular gaps to occur, which allows egress of plasma and emigration
of leukocytes. (Copyright 1977 and 1981. /can Learning Systems, Reprinted with permission from
the Clinical Symposia, vol. 29/3 illustrated by John A. Craig, MD, and’ val 22/2 illustrated by Frank H.
Netter, MD. All rights reserved
form a latticework on which fibroblasts can begin laying down ground substance and tropocollagen. This is the ftbroplastic stage of wound repair. The ground substance consists of several mucopolysaccharides, which act to cement collagen fibers together. The fibroblasts transform
local and circulating pluripotential mesenchymal cells hat begin tropocollagen production on the third or ourth day after tissue injury. Fibroblasts also secrete fibronectin, a protein that performs several functions. Fibronectin helps stabilize fibrin, assists in recognizing
foreign material that should be removed by the immune system, acts as a chemotactic factor for fibroblasts, and helps to guide macrophages along fibrin strands for evenual phagocytosis of fibrin by macrophages.
The fibrin network is also used by new capillaries, .hich bud from existing vessels along the margins of the round and run along fibrin strands to cross the wound. ibroplasia continues, with Increasing ingrowth of new
. fihrinolysis occurs, which is caused by plasmin uhht in by the new capillaries to remove the fibrin and that have become unnecessary (Fig. 4-3).
Fibroblasts deposit tropocollagen, which undergoes cross-linking to produce collagen. Initially collagen is produced in excessive amounts and is laid down in a haphazard manner. The poor orientation of fibers
decreases the effectiveness of a given amount of collagen to produce wound strength, so an overabundance of collagen is necessary to strengthen the healing w0!lnd initially. Despite the poor organization of collagen,
wound strength rapidly increases during the fibroplastic stage, which normally lasts 2 to 3 weeks. If a wound is placed under tension at the beginning of fibroplasia, it tends to pull apart along the initial line of injury. However, if the wound were to be placed under tension near the end of fibroplasia, it would open along the. junction between old collagen previously on the edges of the wound and newly deposited collagen. Clinically, the wound at the end of the fibroplastic stage will be stiff
because of the excessive amount of collagen, erythemataus
because of the high degree of vascularization, and able to withstand 70’MI to 80% as much tension as uninjured tissue (Fig. 4-4).
FIG. 4-2 I~mmatory (lag) stage of wound repair. Wound fills with clotted blood,
inflammatory cells, and plasma. Adjacent epithelium begins to migrate into wound, and
undifferentiated mesenchymal cells begin to transform into fibrobla~ts. (Copyright 7977
and J 987. Icon Learning Systems. Reprinted with permission from the Oinical Symposia, vol.
2~/3 illustrated by John A Craig, 1.40, and vol 22/2 illustrated by Frank H. Netter, MD. All
FIG. 4-3 Migratory phase of fibroplastic stage of wound repair. Continued epithelial
migration occurs, leukocytes dispose of foreign and necrotic materials, capillary ingrowth
begins, and fibroblasts migrate into wound along fibrin strands. (Copyright 7977 and
7987. Icon Learning Systems.Reprinted with permission from the Clinical Symposia, vol. 29/3
illustrated by John A Craig, 1.40, and vOl 22/2 illustrated by Frank H. Netter, MD. All rights
FIG. 4-4 Proliferative phase ot’ fibroplastic ‘stage of wound repair. Proliferation increases
epithelial thickness, collagen fibers are haphaurdly laid down by fibroblasts, and budding capillaries
begin to establish contact ‘with their counterparts from other sites in wound. (Copyright
7977 and 7987. Icon ‘Learning Systems. Reprinted with pmnission from the Qinicol Symposia, vol.
29/3 illustrated by John A. Craig, MD, and vol 22/2 illustrated by Frank H. Netter, MD.”AlI rights
Remodeling stage. ‘The final stage of wound repair, which continues ‘indefinitely, is known as the remodeling stage, although some use the term wound maturation. During this stage many of the previous randomly laid collagen fibers are destroyed as they are replaced by new collagen
fibers, which are oriented to better resist tensile forces on the wound. In addition, wound strength increases slowly but not’ with the same magnitude of increase seen during the fibroplastic stage. Wound
strength never reaches more than 80% to 85% of the strength of uninjured tissue. Because of the collagen fibers’ more efficient orientation, fewer of them are necessary; the excess is removed, which allows the scar to
soften. As wound metabolism lessens, vascularity is decreased, which diminishes wound erythema. Elastin found in normal skin and ligaments is not replaced during wound healing,’ so injuries in those tissues cause a
loss of flexibility along the scarred area (Fig. 4-5}.
A final process, which begins near the end of fibroplasia and continues during the early portion of remodeling, is wound contraction. In most cases woufid contraction plays a beneficial role in wound repair, although the exact mechanism that contracts’ a wound is still unclear. During
wound contraction the edges of a wound migrate toward each other. In a wound in which the edges are not or will , not be placed in apposition, wound contraction diminishes the size of the wound. However, contraction can cause problems, such as those seen in victims of third-degree
(full-thickness) burns of skin, who develop deforming and debilitating contractures if wounds are not covered withskin grafts and aggressive physical therapy is not performed .Another example of detrimental contraction is seen in individuals suffering sharply curved lacerations,
who frequently are left with a mound of tissue on the concave side of the scar because of wound contraction, even when the edges are well readapted. Contraction can be lessened by placement of a layer of epithelium between the free edges of a wound. Surgeons use this phenomenon when they place skin grafts on the bared periosteum during
a vestibuloplasty or on full-thickness burn wounds.