Fibrin structure and wound healing

Abstract

To cite this article: Laurens N, Koolwijk P, de Maat MPM. Fibrin structure and wound healing. J Thromb Haemost 2006; 4: 932-9.Summary Fibrinogen and fibrin play an important role in blood clotting, fibrinolysis, cellular and matrix interactions, inflammation, wound healing, angiogenesis, and neoplasia. The contribution of fibrin(ogen) to these processes largely depends not only on the characteristics of the fibrin(ogen) itself, but also on interactions between specific-binding sites on fibrin(ogen), pro-enzymes, clotting factors, enzyme inhibitors, and cell receptors. In this review, the molecular and cellular biology of fibrin(ogen) is reviewed in the context of cutaneous wound repair. The outcome of wound healing depends largely on the fibrin structure, such as the thickness of the fibers, the number of branch points, the porosity, and the permeability. The binding of fibrin(ogen) to hemostasis proteins and platelets as well as to several different cells such as endothelial cells, smooth muscle cells, fibroblasts, leukocytes, and keratinocytes is indispensable during the process of wound repair. High-molecular-weight and low-molecular-weight fibrinogen, two naturally occurring variants of fibrin, are important determinants of angiogenesis and differ in their cell growth stimulation, clotting rate, and fibrin polymerization characteristics. Fibrin sealants have been investigated as matrices to promote wound healing. These sealants may also be an ideal delivery vehicle to deliver extra cells for the treatment of chronic wounds.

Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix

“…By binding the newly secreted GFs, fibrin could act as a GF reservoir while also creating biochemical gradients required for appropriate cell infiltration into the lesion. In addition, other ECM proteins present in the fibrin clot, such as fibronectin and vitronectin, bind GFs and act as bridging molecules between cells and fibrin by binding to the integrins on endothelial cells, smooth muscle cells, and other cell types (28). Moreover, GFs critical for angiogenesis during wound healing, such as FGF-2, bind fibrin(ogen) and fibronectin (3).…”

Experimental and theoretical modelling of blind-ended vessels within a developing angiogenic plexus

“…adjacent to the injury contains exudated fibrin (Laurens et al, 2006) and other filamentous proteins which form an early scaffold for angiogenic sprouts. In addition, matrix metalloproteases are released which loosen extracellular matrix interconnections (Roy et al, 2006) permitting the invasion of new blood vessels and other cell types involved in the wound healing response.…”

“…New vessels, including BEVs, which have yet to form functional basement membranes or attract peri-vascular support cells, are characteristically leaky, allowing large molecular-weight proteins access to the interstitium. These proteins include platelet degranulation products (Italiano, 2008), matrix-degrading enzymes (Roy et al, 2006) and components of the haemostatic cascade, which serve as a scaffold for blood vessel ingress and wound healing (Laurens et al, 2006).…”

Fatigue Life Estimation Models: A State of the Art

“…Many scientific centers and researchers are dealing with this issue, conducting new tests and developing models for the description of fatigue phenomena; however, no universal solution has yet been found (Papuga, 2011). In this paper, two recently proposed models have been studied, the first being the modified Wöhler curve method (MWCM) (Susmel & Taylor, 2008) in conjunction with the theory of critical distances (TCD) used in the form of the point method (Laurens, Koolwijk, & De Maat, 2006;Susmel, 2010). To apply MWCM, the critical plane is determined by the maximum variance method (MVM) (Susmel, 2010;Susmel & Taylor, 2008).…”