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Author: Michael Mercandetti, MD, MBA, FACS; Chief Editor: Joseph A Molnar, MD, PhD, FACS more... Updated: Apr 3, 2013
Overview
Wound healing is a complex and dynamic process of replacing devitalized and missing cellular structures and tissue layers. The human adult wound healing process can be divided into 3 or 4 distinct phases. Earlier authors referred to 3 phases: inflammatory, fibroblastic, and maturation,[1] which had been denoted in earlier versions as inflammatory, proliferative, and remodeling and this is maintained by some authors.[2] In the 4-phases concept, there are the hemostasis phase, the inflammatory phase, the proliferative phase, and the remodeling phase. In the 3-phases approach, the hemostasis phase is contained within the inflammatory phase. Not only do authors vary the number of phases, but authors also denote differences in the phase descriptors used as: hemostasis phase, inflammatory phase, proliferative phase, and remodeling phase[3] or hemostasis phase, inflammatory phase, proliferative phase, and maturation phase.[4] Therefore, certain phases have more than one name, such as remodeling or maturation and proliferation or granulation.[5] A recent query for phases of wound healing in PubMed retrieved 1011 records. Under the search query, wound healing and repair, 1 article was identified in PubMed in 1899. In 1989, there were 101 articles and in 2011 there were 1600 related articles. As our understanding of wound healing progresses, further phases and subphases may well be delineated. Within these broad phases are a complex and coordinated series of events that includes chemotaxis, phagocytosis, neocollagenesis, collagen degradation, and collagen remodeling. In addition, angiogenesis, epithelization, and the production of new glycosaminoglycans (GAGs) and proteoglycans are vital to the wound healing milieu. The culmination of these biological processes results in the replacement of normal skin structures with fibroblastic mediated scar tissue. For more information on wound healing, visit Medscapes Wound Management Resource Center. This process can go awry and produce an exuberance of fibroblastic proliferation with a resultant hypertrophic scar, which by definition is confined to the wound site. Further exuberance can result in keloid formation (see image below), in which scar production extends beyond the area of the original insult. The collagen is thicker, more irregularly arranged, and more often causes pain. In a hypertrophic scar, the collagen is thinner and arranged more parallel to the wound. Furthermore, hypertrophic scars occur in all races, although less so in young and elderly persons. Hormonal changes may have an impact. Keloid scarring is more often seen in nonwhite persons.[6]
A patient referred for keloid formation after excision of facial cancer and reconstruction.
Conversely, insufficient healing can result in a hypotrophic or atrophic scar formation (see image below). All wounds in adult skin heal with a scar. The degree of inflammation has a direct impact on the ultimate scar formation.[7]
Category 2
If the wound edges are not reapproximated immediately, delayed primary wound healing transpires. This type of healing may be desired in the case of contaminated wounds. By the fourth day, phagocytosis of contaminated tissues is well underway, and the processes of epithelization, collagen deposition, and maturation are occurring. Foreign materials are walled off by macrophages that may metamorphose into epithelioid cells, which are encircled by mononuclear leukocytes, forming granulomas. Usually the wound is closed surgically at this juncture, and if the "cleansing" of the wound is incomplete, chronic inflammation can ensue, resulting in prominent scarring.
Category 3
A third type of healing is known as secondary healing or healing by secondary intention. In this type of healing, a full-thickness wound is allowed to close and heal. Secondary healing results in an inflammatory response that is more intense than with primary wound healing. In addition, a larger quantity of granulomatous tissue is fabricated because of the need for wound closure. Secondary healing results in pronounced contraction of wounds. Fibroblastic differentiation into myofibroblasts, which resemble contractile smooth muscle, is believed to contribute to wound contraction. These myofibroblasts are maximally present in the wound from the 10th-21st days.
Category 4
Epithelialization is the process by which epithelial cells migrate and replicate via mitosis and traverse the wound. This occurs as part of the phases of wound healing, which are discussed in Sequence of Events in Wound Healing. In wounds that are partial thickness, involving only the epidermis and superficial dermis, epithelization is the predominant method by which healing occurs. Wound contracture is not a common component of this process if only the epidermis or epidermis and superficial dermis are involved.
coagulation commences with clotted blood immediately impregnating the wound, leading to hemostasis, and with dehydration, a scab forms. An influx of inflammatory cells follows, with the release of cellular substances and mediators. Angiogenesis and re-epithelialization occur and the deposition of new cellular and extracellular components ensues.
Summary
The process of trying to understand wound healing traces back to ancient times[6] and has continued to be investigated. Interest grew in the 1900s, and, by 1960, it was understood that wound healing time could be decreased up to 50% if appropriate dose-dependent settings are created.[13] Continuing from that time, there has been an ongoing expansion to not only understand the vast array of intrinsic and extrinsic factors of wound healing, but also the intracellular, extracellular, molecular, and biochemical processes and interactions that facilitate healing. The process of wound healing constitutes an array of interrelated and concomitant events. Understanding of these processes and effectors on these processes continues to expand.
Reparative strategies involving engineered tissue matrices, either exogenous or endogenous, have also been used.[21] Stem cells continue to be a new frontier of research in the armamentarium of wound healing strategies.[30] There still exists controversies with the use of fetal stem cells. Stem cells, in particular adipose-derived stem cells, have been shown to ameliorate wound healing, and continued research in these areas appears promising.[31, 32] Exogenous mesenchymalderived stem cells, commonly obtained from bone marrow, but available from other sources, are being used in the setting of nonhealing inflammatory wounds.[2] Third trimester human fetal placental chorionic stem cells did not compare favorably with first semester ones in promoting wound healing.[33] . However, first-,[34] and more recently mid-,[35] trimester amniotic stem cells, when treated using valproic acid, obtained pluripotentialism.
References
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