The Effect of Intermittent Radiant Warming on the Contraction of
The Effect of Intermittent Radiant Warming on the Contraction of
In recent years, a novel dressing applying radiant warming to wounds has shown promising results in the clinic and has been shown to stimulate cell proliferation in vitro. This study aimed to investigate the effects of the dressing on the contraction of fibroblast-populated collagen lattices and on cell proliferation within the lattice. Normal human fibroblasts from a 54-year-old subject and normal and ulcer fibroblasts from an 87-year-old subject were used. Control lattices were maintained in culture at 33°C, and test lattices were warmed using the radiant heat-producing dressings with designated temperatures of 38°C and 42°C. These raised the temperature in the medium from 33.2°C to maxima 36.2°C and 38.1°C, respectively. Test lattices were warmed daily for seven days with three one-hour cycles with 1.5-hour intervals, and lattice areas were determined at intervals up to Day 7. By Day 7, lattice contraction by normal fibroblasts from the 54-year-old was enhanced to 45.4 percent and 30.5 percent of initial area under the 38°C and 42°C dressings, respectively, compared to 51.3 percent for the control at 33°C (p<0.005 and p<0.001, respectively). Cell numbers in the lattices from the 54-year-old subject had increased by 28 percent in controls, relative to Day 0, but by 62 percent and 86 percent under the 38°C and 42°C dressings, respectively (p<0.005). A similar increase in proliferation was observed for ulcer fibroblasts growing in monolayer. In conclusion, both lattice contraction and fibroblast proliferation in the lattices were stimulated by intermittent radiant warming.
In recent years, a novel practical method of providing therapeutic radiant heat to clinical wounds has become available through the development of a warming device, the Warm-Up dressing (Augustine Medical Inc. Eden Prairie, Minnesota, USA). This device applies safe, precisely controlled heat to the wound while maintaining a moist environment. Several clinical studies using the warming system on various kinds of chronic wounds have shown improved healing. A further benefit to the improved or complete healing with this treatment regimen was that patients frequently remarked on a decrease in the pain associated with their ulcers.
In the warming system, the infrared warming card is inserted into the plastic pocket attached to the top of the foam collar, which is sealed to the periwound skin by an adhesive (Figure 1). The dressing protects the wound without disrupting healing tissue. Any exudate is absorbed by the foam and a moist but not a wet environment is maintained. The temperature of the card is set to 38°C and regulated by a temperature control unit powered by the battery or electrical power.
(Enlarge Image)
Components of the warming device: a) clinical use; b) in laboratory. The warming cards are controlled to exact temperatures by the control units attached by the cables seen in the top right hand corner of b.
The system is based on the fundamental physiological premise that most cellular physiological functions, enzymatic reactions, and biochemical reactions in the human body are optimized at 37°C. Baseline skin and wound temperatures, however, are lower than core temperature. In our clinic, measurements of wound surface temperature, made with an infrared thermometer (ETI Ltd., Worthing, Sussex, United Kingdom) in 16 leg ulcer patients indicated an average ulcer surface temperature of 32.3°C (range 28.8°C-35.1°C). Application of the radiant warming raises the temperature of the periwound skin by about 2.4°C in one hour.
Application of noncontact radiant heat has been shown to improve tissue oxygen in normal volunteers, and this has been suggested as a possible mechanism contributing to improved healing. In patients with venous ulcers, raised oxygen tension and improved blood supply to the wound edge and surrounding skin have been demonstrated. Another possible contributing mechanism to its efficacy is the stimulation of cell proliferation, which is important in several stages of wound healing. In-vitro studies have shown that intermittent radiant warming for seven days, following a protocol similar to that used in the clinic, stimulates the proliferation of human fibroblasts, keratinocytes [unpublished], and dermal microvascular endothelial cells. All these in-vitro studies used cells grown in monolayer, but in-vivo fibroblasts are in a three-dimensional matrix. The contraction of a wound, part of the normal healing process for an open wound, is the result of dynamic cell-matrix interactions principally between fibroblasts and collagen but also involving fibronectin and other proteins. These interactions can be influenced by a number of factors including the matrix substrate, cell-surface receptors, and the presence of cytokines. Investigation of these interactions, which are involved in wound contraction in vivo, has been facilitated by the development of fibroblast-populated collagen lattices (FPCLs) in which cells are suspended in a polymerized three-dimensional collagen matrix. When cast in the lattice, the fibroblasts, which initially are spherical after trypsinization, become elongated. As the fibroblast moves through the collagen matrix, it becomes intimately linked with the fibrils and pulls on them, resulting in contraction. The ability of the lattices to contract can be affected by several factors, such as the concentration of collagen, the density of fibroblasts, and also the source of the fibroblasts. To our knowledge, no research has focused primarily on the effects of temperature on the contraction of FPCLs, although Nishiyama, et al., included temperature in their extensive analysis of a number of factors influencing gel contraction.
The study reported here aimed to investigate whether the intermittent use of the warming device, following a protocol similar to that used in the clinic, could have a direct effect on the contraction of collagen lattices and on the proliferation of fibroblasts within a three-dimensional matrix.
In recent years, a novel dressing applying radiant warming to wounds has shown promising results in the clinic and has been shown to stimulate cell proliferation in vitro. This study aimed to investigate the effects of the dressing on the contraction of fibroblast-populated collagen lattices and on cell proliferation within the lattice. Normal human fibroblasts from a 54-year-old subject and normal and ulcer fibroblasts from an 87-year-old subject were used. Control lattices were maintained in culture at 33°C, and test lattices were warmed using the radiant heat-producing dressings with designated temperatures of 38°C and 42°C. These raised the temperature in the medium from 33.2°C to maxima 36.2°C and 38.1°C, respectively. Test lattices were warmed daily for seven days with three one-hour cycles with 1.5-hour intervals, and lattice areas were determined at intervals up to Day 7. By Day 7, lattice contraction by normal fibroblasts from the 54-year-old was enhanced to 45.4 percent and 30.5 percent of initial area under the 38°C and 42°C dressings, respectively, compared to 51.3 percent for the control at 33°C (p<0.005 and p<0.001, respectively). Cell numbers in the lattices from the 54-year-old subject had increased by 28 percent in controls, relative to Day 0, but by 62 percent and 86 percent under the 38°C and 42°C dressings, respectively (p<0.005). A similar increase in proliferation was observed for ulcer fibroblasts growing in monolayer. In conclusion, both lattice contraction and fibroblast proliferation in the lattices were stimulated by intermittent radiant warming.
In recent years, a novel practical method of providing therapeutic radiant heat to clinical wounds has become available through the development of a warming device, the Warm-Up dressing (Augustine Medical Inc. Eden Prairie, Minnesota, USA). This device applies safe, precisely controlled heat to the wound while maintaining a moist environment. Several clinical studies using the warming system on various kinds of chronic wounds have shown improved healing. A further benefit to the improved or complete healing with this treatment regimen was that patients frequently remarked on a decrease in the pain associated with their ulcers.
In the warming system, the infrared warming card is inserted into the plastic pocket attached to the top of the foam collar, which is sealed to the periwound skin by an adhesive (Figure 1). The dressing protects the wound without disrupting healing tissue. Any exudate is absorbed by the foam and a moist but not a wet environment is maintained. The temperature of the card is set to 38°C and regulated by a temperature control unit powered by the battery or electrical power.
(Enlarge Image)
Components of the warming device: a) clinical use; b) in laboratory. The warming cards are controlled to exact temperatures by the control units attached by the cables seen in the top right hand corner of b.
The system is based on the fundamental physiological premise that most cellular physiological functions, enzymatic reactions, and biochemical reactions in the human body are optimized at 37°C. Baseline skin and wound temperatures, however, are lower than core temperature. In our clinic, measurements of wound surface temperature, made with an infrared thermometer (ETI Ltd., Worthing, Sussex, United Kingdom) in 16 leg ulcer patients indicated an average ulcer surface temperature of 32.3°C (range 28.8°C-35.1°C). Application of the radiant warming raises the temperature of the periwound skin by about 2.4°C in one hour.
Application of noncontact radiant heat has been shown to improve tissue oxygen in normal volunteers, and this has been suggested as a possible mechanism contributing to improved healing. In patients with venous ulcers, raised oxygen tension and improved blood supply to the wound edge and surrounding skin have been demonstrated. Another possible contributing mechanism to its efficacy is the stimulation of cell proliferation, which is important in several stages of wound healing. In-vitro studies have shown that intermittent radiant warming for seven days, following a protocol similar to that used in the clinic, stimulates the proliferation of human fibroblasts, keratinocytes [unpublished], and dermal microvascular endothelial cells. All these in-vitro studies used cells grown in monolayer, but in-vivo fibroblasts are in a three-dimensional matrix. The contraction of a wound, part of the normal healing process for an open wound, is the result of dynamic cell-matrix interactions principally between fibroblasts and collagen but also involving fibronectin and other proteins. These interactions can be influenced by a number of factors including the matrix substrate, cell-surface receptors, and the presence of cytokines. Investigation of these interactions, which are involved in wound contraction in vivo, has been facilitated by the development of fibroblast-populated collagen lattices (FPCLs) in which cells are suspended in a polymerized three-dimensional collagen matrix. When cast in the lattice, the fibroblasts, which initially are spherical after trypsinization, become elongated. As the fibroblast moves through the collagen matrix, it becomes intimately linked with the fibrils and pulls on them, resulting in contraction. The ability of the lattices to contract can be affected by several factors, such as the concentration of collagen, the density of fibroblasts, and also the source of the fibroblasts. To our knowledge, no research has focused primarily on the effects of temperature on the contraction of FPCLs, although Nishiyama, et al., included temperature in their extensive analysis of a number of factors influencing gel contraction.
The study reported here aimed to investigate whether the intermittent use of the warming device, following a protocol similar to that used in the clinic, could have a direct effect on the contraction of collagen lattices and on the proliferation of fibroblasts within a three-dimensional matrix.
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