Wound healing cascade

Granulation tissue Classical wound healing cascade ... 

In vitro duplication of the FBR with much physiological fidelity is seemingly complicated by its relative simplicity compared to the in vivo implant wound healing scenario. Full cascades of cell-cell signaling responses, multiple cell types, and the phased kinetics of various cell-based inflammatory responses are completely missing from most models reported to date. Therefore, in vivo animal implant healing models have been developed in attempts to get more accurate information closer to the actual situation in human FBR. 

It is recognized that both the acellular and cellular activities involved in the healing cascade are optimized by a wound microenvironment that allows the free movement of cells and effective response to bioactive compounds. This optimal response can be expected where environmental factors such as temperature and humidity are at subdermal levels. 

As a result of the contact of blood with none-ndothelial surfaces, several humoral and cellular systems can be activated. Exposure of blood proteins and cells to blood contacting medical devices can activate plasma proteolytic systems (coagulation (blood clotting system), fibrinolysis (process by which clot is broken down), complement cascade (a system of soluble proteins involved in microbiocidal activity and the release of inflammatory components), Kallekrein-kinin and contact systems) and at least three cellular elements (leukocytes, endothelial cells, and platelets). Contrary to the normal situations whereby these mechanisms are localized and intended to promote wound healing, activation of these systems by medical devices can result in nonlocalized systemic reactions. The preclinical and clinical assessments of hemocompatibility are designed to minimize modification of these systems. 

As wounds heal, clots must be removed. The principal agent for dissolving clots is an enzyme called plasmin, which is synthesized as the inactive zymogen called plasminogen. Plasminogen is activated by a number of proteases, the most important of which is tissue-type plasminogen activator (t-PA). t-PA can be extremely effective in initiating the cascade to dissolve the unwanted blood clot involved in stroke or heart attack. 

Sharma GD, He J, Bazan HE (2003) p38 and ERKl/2 coordinate cellular migration and proliferation in epithelial wound healing evidence of cross-talk activation between MAP kinase cascades. J Biol Chem 278(24) 21989-21997... 

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