Wound healing and fibrosis

Intravascular (blood) cells Blood plasma proteins 

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The dermis provides a base for the epidermis and contains fibroblasts that elaborate proteins, such as collagens and elastin, which are crucial for the skin s structural integrity. In addition, mast cells, enriched in a variety of proinflammatory substances, play an important role in tissue remodeling, wound healing, and fibrosis. 

Taken together, the identification of mast cell hyperplasia and mediator release at sites of tissue fibrosis and wound healing, observations in animal models, and study of the actions of mast cell products, has provided much circumstantial evidence that mast cells are involved in tissue remodelling, healing and fibrosis. It is unlikely that mast cells are essential in these responses, but more likely that they augment them. Complex interactions between different connective tissue components, mast cells and other inflammatory cells are likely to operate, and are unlikely to be fully delineated in humans in vivo. It seems reasonable to hypothesize however that initial mast cell mediator release has the potential to activate fibroblasts, which may then promote the recruitment at d proliferation of further mast cells, explaining the mast cell hyperplasia often witnessed at sites of chronic inflammation. 

The implants reported in these series are representative of how the normal events of wound healing and the end result of the inflammatory response, i.e. fibrosis, may lead to implant failure. It is obvious that new methods and techniques of artificial joint fixation or stabilization are necessary if these joints are to be used in more active individuals for extended periods. It is hoped that investigators working in this area will take advantage of the healing response and incorporate the healing response into the stabilization technique. 

Recently, the notion that the chronicity of inflammation may not actually drive the fibrogenic process has been widely appreciated (Tables 1, 2, and 3). Some propose that it is indeed the alteration of the mesenchymal cell phenotypes that disrupts the balance between collagen synthesis and degradation in the wound-healing process, highlighted by clinical evidence that shows unsuccessful treatment of fibrosis with anti-inflammatory or immunosuppressive drugs (18,19). One scenario is that mesenchymal cells (myofibroblasts and fibroblasts) are phenotypically altered and thus do not undergo apoptosis after resolution. 

Fibrosis is a dynamic progression of dysregulated wound healing that results from chronic inflammation. It is a common pathology regardless of the tissue involved, and therefore, the mechanisms that progress to fibrosis can be widely applied. The recruitment, activation, and proliferation of inflammatory cells and their cooperation with resident cells appears to rely on the action of chemokines and the differential expression of the chemokine receptors by these cells. Thus, chemokine receptors make particularly attractive therapeutic targets. 

Fibrosis resulting in the loss of normal organ structures is the hallmark of chronic rejection. The fibrosis may be due to wound healing, which is then followed by the cellular necrosis of acute rejection. However, it must be pointed out that chronic rejection develops many times in the absence of acute rejection. Fibrosis may be a result of several diverse factors such as equation of chronic rejection with chronic delayed-type hypersensitivity reaction, injury to blood vessels and resulting response to chronic ischemia, the proliferation of smooth muscle cells in the intima of arterial walls producing vascular occlusion, or persistent viral infections that will induce cellular immune response. 

TGF-P — Fibrosis and wound healing in vivo, influences integrin expression and differentiation — Macrophages, T cells, B cells, epithelial cells... 

Hepatic fibrosis is seen with chronic exposure to hepatoxicants that cause increasing damage to hepatocytes and is part of the wound healing response. Chronic fibrosis leads to severe disruption of the liver architecture by the deposition of extracellular matrix (ECM). Advanced fibrosis disrupts the proper blood flow and results in scarring of the liver that can lead to irreversible liver damage known as cirrhosis. Chronic exposure to the hepatoxins CCI4, monocrotaline, and alcohol are examples of compounds that cause excessive fibrosis. 

In addition to finding mast cell infiltration and mediator release at sites of wound healing, tissue repair and fibrosis, studies of the effects of mast cell products on the cells involved in these processes, notably fibroblasts and endothelial cells, have supported the hypothesis that mast cells play an active role. 

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