Friday, February 22, 2008

1st Day-2nd Talk: “Neovascularization-The X Factor in Free Grafts for Reconstructive and Cosmetic Surgery” by Chris Moore, M.D.

Dr. Moore joins us from the Associated Head & Neck Surgeons of Greater Orange County, and his presentation discussed neovascularization and the use of growth factors in free grafts for reconstructive and cosmetic surgery. Autologous free grafts in facial plastic surgery can be skin, fat, bone, or composite. Skin grafts tend to be used to reconstruct patients with cancer or severe burns. Skin grafts develop a blood supply within 3-5 days and they produce predictable results. Bone graft success is size dependent (i.e. smaller grafts are better). The blood supply to bone grafts is variable and there tends to be an issue with donor site morbidity. Composite grafts consist of fat/dermis or skin/cartilage. The survival of these grafts is dependent upon the size (≤ 1 cm) and they have limited applications. Dr. Moore suggests the hot spot in this area of regenerative medical research is in fat grafts. These grafts provide the ideal facial volume replacement and there is an unlimited supply. It is much easier to find donor sites for fat, it is comparatively inexpensive, and the application is much easier in comparison. Some of the disadvantages to using fat grafts are that they require processing, there is variable resorption (20-80%), and they usually require several ‘tune-ups’.
Fat grafts contrast with modern facial plastic surgery (lifting and filling) in that fat is used as a filler, but the overall look of the face is not being completely changed by removing anything. Volume replacement fillers include: collagen, artecoll, restylane, goretex, fascian, sculptra, silicone, radiance, and fat. The ideal filler should be easy to use, inexpensive, permanent, safe, and versatile. To simplify, Dr. Moore states that the ideal volume replacement filler is one that replaces the volume with the same material.

Fat graft survival tends to be variable. Only 20-80% of the fat is retained and the rest is replaced with fibrous tissue. Fat is not static tissue; adipogenesis can occur at grafting sites. Proper technique and neovascularization to the site of the graft are two keys to graft survival. FGF (Fibroblast Growth Factor) will facilitates ingrowth of new blood supply (capillaries first, arterials later) and promote adipogenesis. When pre-adipocytes are exposed to FGF, they will mature into mature fat cells. FGF also enables pre-adipocytes to differentiate to various cell lines (i.e. the stem cell effect- differentiate & advance), and it is more effective in hypoxic conditions.

Recent studies done with FGF2 in rats confer adipocyte survival. The cells were harvested using liposuction and administered to rats via subcutaneous injection. FGF2 were injected in dextran beads subcutaneously with the fat. These beads are positively charged and have a diameter of 10-30μm. The fat was harvested in 1 and 12 months in each experimental group of 25 rats. In the 1 month group, only a slight difference was observed from the controls; however, at 12 months, significant differences in volume and morphology were observed. Treated sites also showed an increase in collagen.

What are some of the benefits of treatments with FGF1 versus FGF2? FGF2 provides a shorter duration of action, whereas FGF1 potentiates all FGF receptors and acts as an inhibitor for morbid obesity. FGF1 is very active and the inhibitor is equally as negatively active. This may have profound implications to fight morbid obesity. Although clinical trials are needed to verify these hypotheses in humans, Dr. Moore discussed FGF as the future of growth hormone research.

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