1, 2, 3, s-t-r-e-t-c-h; vacuum enhances wound closure
Stretching is good for muscles, and can help cells
By Liza G. Ovington, PhD, CWS
President, Ovington & Associates
Dania, FL
Applying an external vacuum to an open wound to assist in its closure may sound strange at first, but there is a significant body of research evidence that indicates it is not a far-fetched idea.
San Antonio-based Kinetic Concepts is marketing its Vacuum Assisted Closure (VAC) device as "applying localized negative pressure to draw the edges of the wound to the center." Actually the story may be much more exciting - and technical - than that.
Researchers have noted for decades that there is a relationship between the physical shape of a cell and many of its activities. For example, it has been empirically observed that in many types of cells, growth rates were highest when they were flattened out and attached to a surface, as opposed to when they were in suspension and spherical. As so often occurs in research, the observation of a naturally occurring effect leads to attempts to manipulate that effect for medical intervention. So it was that researchers thought to apply external mechanical forces to cells and tissues and measure their effects in vitro and in vivo.
In 1978, Folkman1 performed experiments where he quantitatively controlled the shape of different types of cells by varying the coating on their tissue culture surfaces, which affected the cells' ability to attach and flatten out. He then measured their uptake of tritiated thymidine (a way of labeling DNA in dividing cells) as an indicator of cell proliferation. He found that DNA synthesis was highly correlated to cell shape, with the highest rates of synthesis (or cell growth) occurring in cells that were flattened and the lowest rates occurring in cells that were rounded.
In 1984, Brunette2 subjected epithelial cells to mechanical stretching and found significant increases in the numbers of cells synthesizing DNA after only 30 minutes of stretching. He also found that the increased proliferative effect persisted after stretching was stopped.
Remember good old traction?
The concept of applying external forces to generate effects on cells and tissues is not a new one. In 1951, Ilizarov3 studied the effects of gradual traction on hard tissue, finding that bone subjected to gradual traction became metabolically activated. He called the effect the Law of Tension-Stress. The application of these findings for lengthening or straightening bones is well-known in orthopedics as the Ilizarov procedure/apparatus. It is also well-established that mechanically stretching intact skin results in an increase in basal cell proliferation and epidermal thickness, and that tendons and ligaments increase in tensile strength and mass when subjected to mechanical stress and motion.
By 1988, the effects of mechanical stresses on soft-tissue healing applications were becoming well-characterized. For example, it was known that tensile stresses applied to cells in culture result in increased DNA synthesis, increased protein synthesis (including collagen), and increased synthesis of metalloproteinases and proteoglycans (matrix molecules). A growing body of evidence from animal studies suggest that tensile or stretching forces could be beneficial for increasing wound strength. However, the mechanism of this beneficial effect is still under study. Some theories suggest that the stretching forces alter cell membrane permeabilities, change ion channels, and change the shape or expression of growth factor receptors to enhance binding and subsequent cellular responses.
With this very brief overview, let us now fast-forward to research undertaken in 1996 by researchers at the Bowman Gray School of Medicine at Wake Forest University in Winston-Salem, NC. They believed application of controlled negative pressures (i.e., external mechanical forces or stretching) to wounds would expedite closure or healing by secondary intention. Based on the evidence presented above, it seems reasonable to theorize that wounds treated in such a way may experience increased proliferation of wound-healing cells, resulting in increased deposition of granulation tissue.
Morykwas, Argenta, and colleagues tested their theory in a swine model using full-thickness wounds.4 They created their stretching forces by:
· placing a sterile, open-cell foam into the wounds (foam is cut to wound size);
· embedding an evacuation tube into the foam such that it exits the foam and is attached to an adjustable vacuum pump and fluid-collection canister;
· sealing the foam to the periwound skin with an adhesive transparent film to create a closed system;
· applying negative pressure or a vacuum that essentially "pulls" uniformly on the inner surface of the wound.
Based on their experimental design, they found that this application of negative pressure did indeed increase the rate of granulation tissue formation by an average of 63% as compared to control wounds. It was determined that intermittent negative pressure as opposed to continuous pressure resulted in significantly greater increases in granulation. The optimal cycle was five minutes on, two minutes off.
They also found that 125 mm Hg was the optimal amount of negative pressure, resulting in a fourfold increase in local blood flow. At higher negative pressures, blood flow declined below normal. This finding has implications for the utility of vacuum therapy in flap and graft survival. It is believed that the increase in local blood flow may be due to the reduction in local edema that can compress small vessels. A related effect of the increased blood flow was a measured significant decrease in tissue bacteria levels (one set of wounds was inoculated with known amounts of bacteria).
The one potential negative effect of the vacuum therapy was the observation of tissue ingrowth into the foam in several wounds, such that removal of the foam also removed the tissue. Manipulation of foam cell size could address this effect. Hypergranulation also was noticed in one wound, and could potentially be addressed by adjusting the duration of therapy.
This particular study did not attempt to examine epithelial cell response. There was a final arm to the study that examined the effect of vacuum therapy on flap survival and found that treated flaps had greater survival than untreated flaps, an effect believed to be related to increased nutrient blood flow.
The system of open-cell foam sealed with a transparent drape and connected to a vacuum pump is now known as the VAC device. It is currently in use in a variety of patient populations.
For more information on the indications and use of the VAC device, contact Kinetic Concepts at (800) 531-5346.
References
1. Folkman J, Moscana A. Role of cell shape in growth control. Nature 1978; 273:345-349.
2. Brunette DM. Mechanical stretching increases the number of epithelial cells synthesizing DNA in culture. J Cell Science 1984; 69:35-45.
3. Ilizarov GA. The tension-stress effect on the genesis and growth of tissues. Part I. The influence of stability of fixation and soft-tissue preservation. Clin Orthop 1989; 238:249-281.
4. Morykwas MJ, Argenta LC, et al. Vacuum-assisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg 1997; 38(6):553-562.
Selected readings
Urschel JD, Scott PG, Williams TG. The effect of mechanical stress on soft and hard tissue repair: a review. Br J Surg 1988; 41:182-186.
Vandenburgh HH. Mechanical forces and their second messengers in stimulating cell growth in vitro. Am J Physiol 1992; 262:R350-355.
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