There are alpha and beta receptors for these three isoforms. They are essential for the embryological development and for regenerating processes. Both receptors have similar structures; they have an extra cellular segment formed by 5 domains, a transmembrane section and an intra cellular section that has only one domain. The alpha receptor can join A and B chains, beta receptor joins only B chains. (Fig 215-1)

Once the PDGF joins the extra cellular domain of its receptor, signal transduction begins. The tyrosine kinase domain is activated. Tirosin kinase causes cytoplasmic protein phosphorylation sending signals to the nucleus and the cell grows and divides.

All three isoforms of PDGF are mitogenic for connective tissue cells. They stimulate fibroblast´s, neutrophyl´s and macrophage´s migration. PDGF induces extra cellular matrix production in some types of cells. It also stimulates neutrophil´s phagocitosis as well as the function and the secretion of the collagenase.

By growing cells studies, it was discovered that GF are carried by serum. They are produced by many numerous cells their requirements are very different between the different cells. For cells to grow, it is necessary for the serum to provide GF as well as adhesive molecules (such as fibronectin, vitronectin), nutritional molecules (lipoproteins, transferrin) and nutriments: amino acids, energetic molecules and ions.

GF are normally released during the different stages of a normal cicatrisation process.

GF are released from the platelet’s alpha granules during the haemostasis stage. Platelets attach to the sub endothelium that was exposed during the injury. Later, a conformational platelet change takes place (activation), the platelet now ahs pseudopods. This allows a much better contact between platelets (aggregation) as well as the release of the alpha granules that contain the GF. (Fig. 215-2)

This process leads to the formation of a primary clot. Its function is to attract fibrin as a consequence of the activation of the Coagulation Cascade. Fibrin then forms the final clot with the primary clot. It is the final clot the one that captures the red cells. (Fig 215-3)

GF that were rapidly released, diffuse to the surrounding tissues and stimulate several cells to stimulate cicatrisation. Tissue harm generates Alpha Tumor Necrosis Factor (TNF-α) that combined with the Beta Transformed Growth Factor (TGF-β) lead inflammatory cells to the harmed area .

Fig. 215-2.  Platelet Activation and GF release.

Fig 215-3.  Clot Formation

After hemostasia, secondary vasodilatation takes place. This leads to an increase capillary permeability and to leucocyte’s migration and activation. This is the beginning of an Inflammatory Process. The first type of leucocytes to arrive is neutrophyles. By producing cytokines and interleukins they amplify the response. With phagocitosis, they control local bacteria contamination preventing infection. Neutrophyles also produce proteases to remove damaged compounds of the extra cellular matrix. Monocytes are attracted by some bacteria components, C5a (a bio-product of the complement cascade), by degradation products of the extra cellular matrix (TGB and fibronectin). Monocytes amplify and control the inflammatory response. Once they are in the injured area, they activate becoming macrophages to continue with bacteria destruction. They also produce cytokines and Growth Factors such as TGFp. TGFp is a fibroblast mutagenic factor that increases the total amount of collagen by stimulating its production and inhibiting its degradation. It also stimulates the production of some other factors such as TGF-α, EGF, LDGF (Leucocytes Derived Growth Factor) and bFGF (Basic Fibroblastic Growth Factor) All of them stimulate keratinocytes for epithelization; fibroblasts to produce extra cellular matrix and endothelial cells for the angiogenic process. Monocytes are also in charge of producing TNF-α and IL-1 to control the inflammatory response; they modify collagen´s structure by producing collagenase.

After the haemostasia phase and the inflammatory phase, the proliferating phase starts in which fibroflasts and endothelial cells migrate to the temporary matrix of the harmed area to establish again tissue´s integrity. During this phase the number of macrophages decreases, while the number of fibroblasts, keratinocytes and endothelial cells increases. Fibroblasts produce IGF-I. bFGF, TGF-p, PDGF, and KGF. Endothelial cells, VEGF, bFGF, PDGF and KDAF (Keratinocytes Derived Autocrine Factor)

Neo-vascularization is crucial to provide oxygen and nutrients to the harmed area. Proliferation and endothelial cell migration from pre-existing capillaries are the bases of angiogenesis. Many cells that were attracted by hypoxia participate during this stage.

Vascular reconstruction starts from unharmed vessels that are located in the edges of the injury. Because of Growth Factors stimulation, endothelial cells are able to degrade basement membrane. This way they are able to move and migrate to the harmed area. After many divisions a tubular structure is produced. Then it divides itself again adopting the shape of a button. These individual vascular buttons grow one on top of the other creating vascular loops. These loops will also divide until they reach a larger vessel where they can flow into.

Between day 6 or 10 collagen fibres start to mature. The wound contracts, vascular and water presence reduces every minute in the granular tissue that changes its consistency and will later become cicatricial tissue. Epithelization is the final step of the tissue healing process. This process includes epidermic cell reconstruction, achieved by migration and proliferation .

Main Growth Factors

Their common names reflect either their activity or their original source (Table 215-1).

There have been described many different functions for some GF for the regenerating process. It is important to keep in mind that they don´t act individually or in a specific amount of time. They act as a team to regenerate tissue.