The Basic Science of Wound Healing

Abstract

Understanding wound healing today involves much more than simply stating that there are three phases: "inflammation, proliferation, and maturation." Wound healing is a complex series of reactions and interactions among cells and "mediators." Each year, new mediators are discovered and our understanding of inflammatory mediators and cellular interactions grows. This article will attempt to provide a concise report of the current literature on wound healing by first reviewing the phases of wound healing followed by "the players" of wound healing: inflammatory mediators (cytokines, growth factors, proteases, eicosanoids, kinins, and more), nitric oxide, and the cellular elements. The discussion will end with a pictorial essay summarizing the wound-healing process.

Autacoid 14S,21R-Dihydroxy-Docosahexaenoic Acid Counteracts Diabetic Impairment of Macrophage Prohealing Functions

“…2 We have observed that wounded skin can generate 14S,21R-diHDHA. 8,16 Several kinds of cells contribute to wound healing.…”

“…These data suggest that macrophages produce 14S,21R-diHDHA in wounds, especially at days 2 to 4 after wounding, when macrophages are the major leukocytes in wounds. 2 These results motivated us to further study the relation of decreased generation of 14S,21R-diHDHA to impaired prohealing functions of diabetic macrophages.…”

“…1,2,38 We postulated, therefore, that 14S,21R-diHDHA enhances the functions of db/db macrophages in angiogenesis, in part, by increasing their angiogenic cytokine production. The results demonstrated that lesser amounts of VEGF and PDGF-BB were released by db/db macrophages than by db/ϩ macrophages ( Figure 3, E and F), consistent with impaired functions of db/db macrophages.…”

“…8 We studied the 14S,21R-diHDHA biosynthesis in selected typical types of cells that are known to participate in wound healing. 2 The results from our chiral LC-MS/MS analysis show that PMNs, platelets, and skin cells (including fibroblasts and DMVECs) did not produce 14S,21R-diHDHA; whereas lymphocytes (T cells and B cells) produced a much lesser amount of 14S,21R-diHDHA, compared with macrophages, and platelets produced the intermediate 14S-HDHA for the biosynthesis of 14S,21R-diHDHA ( Figure 1A; see also Supplemental Figure S3 at http://ajp.amjpathol.org). These data suggest that macrophages produce 14S,21R-diHDHA in wounds, especially at days 2 to 4 after wounding, when macrophages are the major leukocytes in wounds.…”

“…Macrophages play critical roles in wound healing: they engulf apoptotic polymorphonuclear leukocytes (PMNs), tissue debris, and infectious microorganisms; they promote wound healing, including accelerating re-epithelialization by promoting keratinocyte migration from the wound edge to decrease the epithelial gap and increasing the formation of granulation tissue by promoting fibroblasts and endothelial cells moving into wounds to cover the wound bed 2 ; and they enhance angiogenesis, to repair damaged blood vessels and thus to supply sufficient oxygen and nutrients during healing. 2 Macrophage prohealing functions have been confirmed: macrophage transplantation into wounds promotes healing, 3,4 and macrophage depletion results in delayed wound healing. 5,6 The presence of diabetes, however, compromises macrophage functions and so contributes to disrupted wound healing.…”