C linicians want to increase their understanding of which ulcers are not likely to heal with standard therapy and why.1-3 Several factors associated with an abnormal wound bed have been implicated in delayed healing; a multistep process to improve the wound bed termed wound bed preparation has been proposed.4,5 Certainly, any patient with a chronic wound can be helped using enhanced wound bed preparation strategy, but for patients who fail to heal, wound bed preparation is especially critical. Wound bed preparation is also important for patients who may receive advanced wound healing therapies, as cost of therapy requires that clinicians optimize chances for success.
Although debridement is often a critical aspect of wound bed preparation, it is only part of continual concerted effort to improve the wound bed. The overall goals are to remove necrotic and/or fibrinous tissue from the wound bed, increase the amount of granulation tissue, reduce the number of abnormal or senescent cells within the wound or at the wound edge, decrease exudate and edema, and decrease bacterial burden.
Removing necrotic/fibrinous wound tissue. This is a fundamental aspect of wound care. A wound is not likely to heal when covered by necrotic tissue. Debridement is commonly defined as the process of removing necrotic, devitalized tissue and foreign material from a wound.6 The presence of necrotic tissue within a wound may impair wound repair processes by stimulating inflammation and delaying granulation and epithelialization.7 However, the above definition of debridement may be limited. Debridement may additionally remove senescent cells in the wound bed and nonmigratory cells from the ulcer edge,8,9 allow for improved availability of growth factors, and remove excessive or abnormal bacteria. Several methods for debridement exist, including surgical, enzymatic, mechanical, autolytic, and biosurgical.
In diabetic ulcers, more aggressive surgical debridement leads to improved results when a topically applied growth factor (PDGF) is used.10 Clinicians generally accept that pressure (decubitus) ulcers need to be extensively debrided and their undermined edges removed. How aggressive surgical debridement should be in wounds such as venous ulcers, which are often covered by fibrinous material and can be intensely fibrotic, is a matter for debate. For example, many clinicians feel that venous ulcers do not need to be aggressively debrided surgically. However, it may be worthwhile to remove the lipodermatosclerotic tissue in circumstances where there is failure to heal.11
Edema control. Edema interferes with healing, probably because of a combination of impaired blood flow and increased bacterial colonization due to the accumulation of interstitial and other fluids. Leg elevation and compression therapy (ie, for venous ulcers) are the mainstays of edema control. Lymphatic compression pumps and pharmacologic agents such as aescin may have a therapeutic role as well.12
Bacterial wound colonization. Chronic wounds inevitably are colonized with bacterial organisms. The role bacteria play in a wound?s failure to heal remains unclear, but bringing bacterial colonization to a minimum is thought to be advantageous. High tissue bacterial counts are known to interfere with graft take13; the significance of high bacterial counts in tissue, their correlation with failure to heal, and the contribution of specific micro-organisms requires further definition. Specific bacteria also may impair healing even when they are present in small amounts.14 Additionally, speculation is emerging that biofilms develop within chronic wounds, making bacterial organisms difficult to eradicate with presently available antimicrobial approaches.15
In simple terms, bacterial colonization often can be handled by the fundamental procedure of surgical debridement. Some topical therapies available are useful in decreasing the bacterial load, containing wound exudate, and improving the appearance of the granulation tissue. Cadexomer iodine, an iodine-releasing agent, has the ability to absorb wound exudate and release iodine slowly into the wound,16 providing antiseptic and antimicrobial properties. Dressings capable of delivering silver ions as the antiseptic agents also may be applied. Given the increasing problem of bacterial resistance to traditional antibiotics, it is likely that additional products capable of delivering antiseptics slowly into wounds will become available. The slow-release feature of these products is a major advantage because it decreases the chance of cellular and tissue toxicity.
Wound exudates/inflammation. In contrast to acute wound fluid, chronic wound fluid blocks the proliferation and activity of certain cell types,17,18 including fibroblasts and keratinocytes. Optimal ways to deal with wound exudate are evolving. These include the use of compression bandages, highly absorbent dressings, or mechanical systems (vacuum-based). Metalloproteinases (MMPs) and other proteases, abundant in chronic wound fluid, can break down extracellular matrix materials as well as growth factors.19 Proteases may be related, in part, to a chronic state of inflammation that also may be seen in patients with refractory ulcers. Elevated pro-inflammatory cytokines have been associated with nonhealing ulcers.20 These pro-inflammatory cytokines can increase the amount of matrix MMPs and decrease the amount of tissue inhibitors of metalloproteinases (TIMP) in wounds.21 This imbalance also may decrease growth factor levels and activity. This alteration in MMPs and their inhibitors has been associated with impaired healing in chronic wounds. Recently, the ratio of MMP 9 to TIMP 1 has been found to be predictive of healing in some chronic wounds.22
Cellular senescence. Cellular senescence is the aging of cells that results in reduced growth capacity of cells, morphologic changes, and over-expression of certain matrix proteins such as cellular fibronectin. It can be detected by enhanced activity of beta-galactosidase at a pH of 6.0 (senescence-associated beta-Gal, or SA-beta-Gal).23 Cellular senescence may be induced (in addition to aging of cells) by the presence of chronic wound fluid. Cells that are senescent are less responsive to growth factor stimuli.24 Ulcers of longer duration are less likely to heal, perhaps due to the increased presence of senescent cells, which may be predictive of healing as well. It would seem logical to remove, eliminate, or otherwise reverse the number or presence of these cells.

Conclusions
Optimization of the wound bed and removal of exudate are important. Increased emphasis on wound bed preparation should result in better overall wound care.