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p.4-5 The healing of soft or hard tissues involves a sequence of events that begin at the moment of injury and continue for several subsequent months and can be divided into three stages: inflammation, proliferation and remodeling (Pietrzak and Eppley 2005; Marx 1999; Clark 1996).
The first, or inflammatory, phase involves platelet activation and aggregation and the formation of the fibrin matrix. During degranulation the platelets begin the coagulation cascade and release cytokines, which orchestrate the healing process (Fig. 2). The cytokines attract white blood cells (WBC) by chemotaxis, which begin to migrate to the injured area. The neutrophils are the first WBC to be recruited and are responsible for the initial local cleansing by removing bacteria and cellular debris (Clark 1996; Lorenz and Longaker 2001).
Over the next few days, a proliferative phase occurs in which monocytes migrate to the injured area, attracted by chemical signals from the growth factors. The circulating monocytes are differentiated into macrophages and begin to perform the signaling and modulation function that to this point had been performed by the platelets, which begin to vacate the area. The macrophages debride the area through phagocytosis and secrete factors responsible for initiating new healing events such as the formation of granulation tissue through fibroblasts. Angiogenesis then begins, due especially to the action of growth factors and thrombin. Neocapilary development depends on the recruitment of vascular endothelial cells and their activation by thrombin, which also provides negative feedback that limits the intensity of neovascular formation (Minami et al. 2004). The arrival of mesenchymal stem cells and their differentiation into specific tissues such as bone, cartilaginous and vascular tissue (Fig. 3) begins in this phase and depends on chemical signals (Clark 1996; Lorenz and Longaker 2001).
During the final, or remodeling, phase, the collagen contracts and the edges of the injury are drawn together. Cell density and vascularization decrease, excess repair matrix is removed and the collagen fibers are aligned along the stress lines, which increases the strength of the newly formed tissue (Pietrzak and Eppley 2005). Granulation tissue accumulates and either slowly remodels the scar tissue or is transformed into specific tissues such as skin and bone (Clark 1996; Lorenz and Longaker 2001).
p.40 the healing process of wounds involves a complex and dynamic cascade of events
p.226 platelets are responsible for activating the wound healing cascade and for releasing many of the growth factors
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