Pathophysiology of acute wound healing
Introduction
Wound healing is a complex process that can be roughly divided into 3 overlapping phases of inflammatory reaction, proliferation, and remodeling. The inflammatory phase involves vascular responses characterized by blood coagulation and hemostasis as well as cellular events, including infiltration of leukocytes with varied functions in antimicrobial and cytokine release, which initiates the proliferative response for wound repair. Some authors have divided wound healing into 4 stages, with the first stage being hemostasis, highlighting the importance of vascular responses. During the proliferative phase, there is formation of the epithelium to cover the wound surface with concomitant growth of granulation tissue to fill the wound space. Granulation tissue formation involves proliferation of fibroblasts, deposition of collagens and other extracellular matrices, and development of new blood vessels. Once the new tissue within the wound is formed, the remodeling phase begins to restore tissue structural integrity and functional competence. The 3 phases of wound repair are however not simple linear events but rather overlapping in time (Fig. 1).
Acute wounds refer to those wounds, such as burns, other traumatic injuries, and surgically created wounds, that heal in a timely fashion. An example of a common acute wound is a clean and uninfected surgical incisional wound approximated by surgical sutures. Although the desirable final result of coordinated healing would be the formation of tissue with a similar structure and comparable functions as with intact skin, regeneration is uncommon (with notable exceptions such as early fetal healing); healing however results in a structurally and functionally satisfactory but not identical outcome. Wound healing processes seem to be strictly regulated by multiple growth factors and cytokines released at the wound site. Alterations that disrupt controlled timely healing processes would extend tissue damage and prolong repair.
Section snippets
Inflammatory phase
Inflammation is a highly effective component of the innate initial reaction of the body to injury. It is an important consequence of injury and one that normally leads to tissue repair and restoration of function. The inflammatory response can be subdivided into vascular and cellular responses. Early in the wounding process, local vasodilatation, blood and fluid extravasation into the extravascular space, and blocking of lymphatic drainage can produce cardinal signs of inflammation, including
Proliferative phase
The initial inflammatory responses to injury provide the necessary framework to the subsequent production of a new functional barrier. In this phase of healing, cellular activity predominates. The major events during this phase are the creation of a permeability barrier (ie, reepithelialization), the establishment of appropriate blood supply (ie, angiogenesis), and reinforcement of the injured dermal tissue (ie, fibroplasia).
Remodeling phase
Remodeling consists of the deposition of the matrix and its subsequent changes over time. It occurs throughout the entire wound repair process as fibrin clot formed in the early inflammatory phase is replaced by the granulation tissue that is rich in type III collagen and blood vessels during the proliferative phase and subsequently replaced by a collagenous scar predominantly of type I collagen predominant with much less mature blood vessels.30 One of the characteristics of wound remodeling is
Acknowledgment
This work was supported partially by grants from the Dermatology Foundation of South Florida (awarded to Jie Li) and the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant no. R03 AR048648; also awarded to Jie Li).
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