Introduction: Fat grafting is not new in plastic surgery. There have been many studies performed about it. Techniques and ideas about fat grafting can be divided in three periods:

Abel Chajchir

“Open Surgery”, fat tissue is obtained by exceresis. Fat tissue is obtained by liposuction and re-injected with no previous refine. The last period has been influenced by the developing of molecular biology knowledge, providing new and more refined techniques to obtain the grafts and re-placing them. After 20 years of experience we have developed a technique that combines fat grafting and growth factors.

Nowadays, discovering the capacity of developing different types of cells from a stem cell as well as the cultivation of these cells, takes us to improve and complement these technique. Starting in 2005, a side from using growth factors, we started using stem cells to support different surgical techniques, opening a new investigation perspective and clinical applications with a promising future.

During this chapter we will describe the different growth factors, their mechanisms and their usage in the different plastic surgeries scenarios; using updated information from medical bibliography and emphasising on the growth factors obtained from the patient’s own plasma. We will later comment on the different types of stem cells, their applications and the way they are combined to improve graft implantation and cicatrization and to delay aging process .

Growth Factors

When tissues are damaged, their recovery takes place because of two processes: reparation and regeneration. The first one is the substitution of the tissue to connecting tissue, the original structure is modified and there is a functional loss. Regeneration substitutes the damaged tissue by parenchymal cells of the same type with no functional loss. The new tissue has the same characteristics as the one that was damaged in the first place.

The balance between reparation and regeneration as an answer to harm is different in between the different tissues. This is why in some cases; the reparation a tissue leads the organ to a functional loss. This is why, molecular biology advances have developed bio or artificial substances to cause cells to migrate, difference and proliferate, causing a the best regeneration possible. There are many reasons why a tissue may scar instead of regenerating: it may not have the necessary cells to do it or, it may have them but there is a lack of stimulating signals, these signals are in charge of regulating proliferation and cellular differentiation.

Many growth factors have been identified, knowing their exact function during a normal cicatrization process. Many of them have been used in plastic surgery.

Growth factors are polypeptides whose main role takes place during the cell’s differentiation, maturing, and metabolism. They are produced by different cells. One of their functions is to act as chemotactic for neutrophyles and monocytes. They stimulate fibroblasts migration and proliferation allowing collagen production and deposit. They also act as mitogens and chemotactics of epithelial and endothelial cells .

HISTORICAL REFERENCE

Franklin and Lynch were the first scientists to prove that repeated topical applications of Epithelial Growth Factor (EGF) accelerate the healing process of deep wounds. They performed a study in which, using animal models, experimenting on rabbit’s ears. Brown, Et al2 reported an increased in the stretching capacity of healed skin after the wound was treated with EGF on a regular bases schedule. Knighton, et al3 were the first to stimulate cicatrization after treating the patient with Cicatrization Factor, obtained from platelet.

Many random and controlled clinical essays have been performed to evaluate the clinical efficiency of some specific products that contain recombinant growth factors. An increased healing speed was observed when comparing to control groups.

During the 80´s, Matras developed a technique able to accelerate cicatrisation processes. During the 90´s the Spanish scientist Eduardo Anitua, used plasmatic proteins form the same patient, autologous plasma combined with growth factors.

The first filed in which this technique was applied, was in oral surgery. Scars took much less time to heal, and infection risk for smokers was reduced. It was also used to correct bone defects in dental implants.

Anitua´s technique starts with the extraction of 20cc of the patient’s blood; this blood sample is then centrifuged to differentiate the different plasma fractions and to separate the portion that contains the most growth factors, the one that accumulates an amount that is four or five times larger than normal.

Once selected, that portion is treated with calcium, to stimulate the coagulation process, and thrombin. Stimulated by calcium, thrombin initiates the transformation of fibrinogen to fibrin. Thrombin also activates factor XIII that cooperates in the formation of the clot.

The result of this process is an autologous fibrin combined with growth factors, which will stimulate the organism to substitute old tissues. This fibrin is used as a haemostatic agent or surgical adhesive, it also cooperates with tissue reparation and cicatrisation processes.

We have developed some variants to Anitua´s original method to adapt it to plastic surgery’s needs. We work with liquid autologous growth factors. This way they can be distributed or injected more easily, being able to stimulate large areas to obtain the best answer with the smallest amounts of GF.

On the other hand, we add neither calcium nor thrombin because this will activate premature GF release and our objective is for them to be released where they are needed during the haemostatic phase, as an answer to injuries.

We have been using this method since 2004 in different plastic surgery procedures to improve the healing quality, especially in face surgeries, tummy tucks and breast surgery. A combined method of fat grafting and GF, is used to improve the adaptation of the graft to its new location and to extend fat tissue’s survival time as long as possible.

Growth Factors. Functions

Growth factors are a group of substances, proteins most of them, that along with hormones and neurotransmitters are crucial to cell’s communication. Their most important function is to be the external control of the cell cycle. They regulate the ending of the cell’s quiescence (G0) and the beginning of G1 phase.

GF not only stimulate cellular proliferation by regulating the cell cycle; they also keep the cell’s survival time as long as possible, they stimulate migration, differentiation and apoptosis too. They act through cell receptors located on the cell’s membrane that transmit the signal from the outside to the inside. This signal activates a series of protein kinases that ends up in the activation of genes (signal transduction) (215-1 Picture)

GF function is regulated by different mechanisms that are in charge of controlling genetic activation:

1) Transcription of the GF gene.
2) Receptor’s signal regulation.
3) Answer control by molecules that have the opposite effect from the original answer.
4) Extra cellular control of the availability of the GF that is caught in the extra cellular matrix.

In the picture we can see the Signal Transduction Mechanism. We used as an example the connection of the Platelet Derived Growth Factor (PDGF). PDGF is a polypeptide that is kept in alpha granules in the Platelet and it is released during platelet aggregation.

Its molecular structure has two amino acid chains (A & B). Chain A has 121 amino acids; it is encoded by a gene located in chromosome 7. Chain B has 125 amino acids and is encoded by a gene in chromosome 22. the combination of these two chains creates three isoforms .

Fig. 215-1. Signal transduction. GF join to the extra cellular domain of the receptor. Tirosin-kinase domain activation. Cytoplasmic protein phosphorylation. Nucleus receives signals and the cell grows and divides.