Wound Bed Preparation and the Role of Enzymes
Wound bed preparation as a concept is revolutionizing the way we approach chronic wounds. We define it as the global management of wounds to accelerate endogenous healing or to facilitate the effectiveness of therapeutic products. As a result of this more encompassing way of approaching wounds, a number of new concepts are emerging. We now talk about the possibility that a cellular burden, comprising phenotypically abnormal cells, exists in chronic wounds and needs to be removed or corrected. We have come to recognize the deleterious effects of excessive exudate, which breaks down extracellular matrix material and blocks the effectiveness of new forms of therapy, including growth factors and bioengineered skin. We are becoming more cognizant of the pathophysiologic abnormalities of chronic wounds and of ways to correct them. We have also come to recognize that chronic wounds may be in need of constant or more steady-state debridement. Hence, the concept of maintenance debridement may need to be tested. In this review of wound bed preparation, we now propose that this more comprehensive approach to wounds will allow us to explore new therapeutic benefits of existing treatment modalities. As a proof of principle, we have examined the potential role of enzymatic debridement in other aspects of wound bed preparation. The hope is that in the context of wound bed preparation we will begin to reevaluate commonly used treatments for opportunities to explore their other properties and therapeutic benefits.
We are presently in an exciting period of time in the approach to chronic wounds. One can probably identify three distinct phases or revolutions in our therapeutic strategies over the years. The first revolution began almost two decades ago with the realization that moist wound healing principles were applicable to the treatment of chronic wounds. Since then, we have developed a variety of dressings capable of providing optimal coverage for wounds in different situations and actually stimulating wound repair. The second revolution, still ongoing, began about ten years ago with the successful testing of advanced technological products, such as topically applied growth factors and bioengineered skin. Finally, the third revolution began a few years ago with the introduction of the concept of wound bed preparation, which allows us to break down into individual components the critical steps involved in optimizing the clinical aspects and the microenvironment of chronic wounds. This review will discuss wound bed preparation with an emphasis on the principle that certain therapeutic agents, some long established, have more than one critical role in the repair process.
It might be worthwhile to first provide some perspective on the topic of chronic wounds. From an evolutionary standpoint, humans and other organisms were not destined to have chronic wounds. There are many responses to acute injury that are a product of evolutionary forces. These responses range from the relatively simple, i.e., coagulation to limit blood loss, to the very complex, i.e., regeneration of a limb in some animals. However, as far as we can tell, there are no known evolutionary steps that have evolved to handle chronic wounds. Humans were not supposed to live long enough to develop venous ulcers, pressure ulcers, or wounds that become chronic after complex surgical procedures. Simply stated, there has never been a survival advantage for handling chronic wounds. It is partly for these reasons that much of what we have learned about acute injury does not apply to chronic wounds from both a physiologic/pathogenic standpoint as well as from the therapeutic approach.
With increasing realization that the approach to chronic wounds should be more "tailor made" for the wounds and not rely entirely on what we know about acute wounds, a new frame of reference has emerged in the last two or three years. The term "wound bed preparation" refers to this new frame of reference, and this concept is having a very dramatic impact on how we approach chronic wounds and how we view new and established therapies. Cynically, some would argue that the concept of wound bed preparation is too simple, that there is nothing new about it, or that what we are preparing for is unclear. However, this term is being successful in altering the way we manage chronic wounds and in giving chronic wounds the independence they have long needed from models of acute injury. Wound bed preparation as a strategy is allowing us to break into individual components various aspects of wound care, while at the same time maintaining a global view of what we wish to achieve. In this focused review on certain aspects of wound bed preparation, we will first briefly discuss wound bed preparation in general and its main components. We will then address a class of therapeutic agents, in this case enzymes, as a case study for how this novel approach to chronic wounds introduces new elements in our view of established treatments. We do so because we see a number of opportunities in redefining therapies in the context of wound bed preparation. The emphasis on wound bed preparation allows us to better define the steps involved in the management of chronic wounds and in doing so it sheds additional light on what the clinical problems are and on their basic science underpinning. Therapeutic agents that were mainly thought to accomplish debridement may now also be viewed as needed in inducing a targeted and beneficial inflammatory response, in facilitating angiogenesis, or in aiding keratinocyte migration.
Abstract
Wound bed preparation as a concept is revolutionizing the way we approach chronic wounds. We define it as the global management of wounds to accelerate endogenous healing or to facilitate the effectiveness of therapeutic products. As a result of this more encompassing way of approaching wounds, a number of new concepts are emerging. We now talk about the possibility that a cellular burden, comprising phenotypically abnormal cells, exists in chronic wounds and needs to be removed or corrected. We have come to recognize the deleterious effects of excessive exudate, which breaks down extracellular matrix material and blocks the effectiveness of new forms of therapy, including growth factors and bioengineered skin. We are becoming more cognizant of the pathophysiologic abnormalities of chronic wounds and of ways to correct them. We have also come to recognize that chronic wounds may be in need of constant or more steady-state debridement. Hence, the concept of maintenance debridement may need to be tested. In this review of wound bed preparation, we now propose that this more comprehensive approach to wounds will allow us to explore new therapeutic benefits of existing treatment modalities. As a proof of principle, we have examined the potential role of enzymatic debridement in other aspects of wound bed preparation. The hope is that in the context of wound bed preparation we will begin to reevaluate commonly used treatments for opportunities to explore their other properties and therapeutic benefits.
Introduction
We are presently in an exciting period of time in the approach to chronic wounds. One can probably identify three distinct phases or revolutions in our therapeutic strategies over the years. The first revolution began almost two decades ago with the realization that moist wound healing principles were applicable to the treatment of chronic wounds. Since then, we have developed a variety of dressings capable of providing optimal coverage for wounds in different situations and actually stimulating wound repair. The second revolution, still ongoing, began about ten years ago with the successful testing of advanced technological products, such as topically applied growth factors and bioengineered skin. Finally, the third revolution began a few years ago with the introduction of the concept of wound bed preparation, which allows us to break down into individual components the critical steps involved in optimizing the clinical aspects and the microenvironment of chronic wounds. This review will discuss wound bed preparation with an emphasis on the principle that certain therapeutic agents, some long established, have more than one critical role in the repair process.
It might be worthwhile to first provide some perspective on the topic of chronic wounds. From an evolutionary standpoint, humans and other organisms were not destined to have chronic wounds. There are many responses to acute injury that are a product of evolutionary forces. These responses range from the relatively simple, i.e., coagulation to limit blood loss, to the very complex, i.e., regeneration of a limb in some animals. However, as far as we can tell, there are no known evolutionary steps that have evolved to handle chronic wounds. Humans were not supposed to live long enough to develop venous ulcers, pressure ulcers, or wounds that become chronic after complex surgical procedures. Simply stated, there has never been a survival advantage for handling chronic wounds. It is partly for these reasons that much of what we have learned about acute injury does not apply to chronic wounds from both a physiologic/pathogenic standpoint as well as from the therapeutic approach.
With increasing realization that the approach to chronic wounds should be more "tailor made" for the wounds and not rely entirely on what we know about acute wounds, a new frame of reference has emerged in the last two or three years. The term "wound bed preparation" refers to this new frame of reference, and this concept is having a very dramatic impact on how we approach chronic wounds and how we view new and established therapies. Cynically, some would argue that the concept of wound bed preparation is too simple, that there is nothing new about it, or that what we are preparing for is unclear. However, this term is being successful in altering the way we manage chronic wounds and in giving chronic wounds the independence they have long needed from models of acute injury. Wound bed preparation as a strategy is allowing us to break into individual components various aspects of wound care, while at the same time maintaining a global view of what we wish to achieve. In this focused review on certain aspects of wound bed preparation, we will first briefly discuss wound bed preparation in general and its main components. We will then address a class of therapeutic agents, in this case enzymes, as a case study for how this novel approach to chronic wounds introduces new elements in our view of established treatments. We do so because we see a number of opportunities in redefining therapies in the context of wound bed preparation. The emphasis on wound bed preparation allows us to better define the steps involved in the management of chronic wounds and in doing so it sheds additional light on what the clinical problems are and on their basic science underpinning. Therapeutic agents that were mainly thought to accomplish debridement may now also be viewed as needed in inducing a targeted and beneficial inflammatory response, in facilitating angiogenesis, or in aiding keratinocyte migration.