Elsevier

Clinics in Dermatology

Volume 25, Issue 1, January–February 2007, Pages 19-25
Clinics in Dermatology

Impaired wound healing

https://doi.org/10.1016/j.clindermatol.2006.12.005Get rights and content

Abstract

Nonhealing wounds represent a significant cause of morbidity and mortality for a large portion of the population. One of the underlying mechanisms responsible for the failure of chronic wounds to heal is an out-of-control inflammatory response that is self-sustaining. Underappreciation of the inherent complexity of the healing wound has led to the failure of monotherapies, with no significant reduction in wound healing times. A model of the inflammatory profile of a nonhealing wound is one in which the equilibrium between synthesis and degradation has been shifted toward degradation. This review summarizes the current information regarding acute wound healing responses as contrasted to the delayed response characteristic of chronic wounds. In addition, some initial complexity theoretical models are proposed to define and explain the underlying pathophysiology.

Introduction

Chronic wounds are, by definition, wounds that have failed to progress through the normal stages of healing and therefore enter a state of pathologic inflammation. As a result, the healing process is delayed, incomplete, and does not proceed in a coordinated manner, subsequently resulting in poor anatomical and functional outcome.1 These wounds cause a major disability and are characterized by chronicity and frequent relapse. The differential diagnosis of the underlying etiology of a nonhealing wound is large (Table 1), but most (∼70%) ulcers are caused by ischemia, secondary to diabetes mellitus, venous stasis, and pressure.2

There are no large-scale, population-based studies that examine the prevalence and economic cost of chronic wounds in the United States. The prevalence of the 3 major types of nonhealing wounds is estimated to be between 3 and 6 million in the United States,3 with patients 65 years and older accounting for 85%.4 Nonhealing wounds result in enormous health care expenditures with the total cost being estimated at more than $3 billion per year.2 None of the financial estimates take into account the amount of lost work time, decreased productivity, disability payments, nor the cost of rehabilitation.

In addition, the resultant psychosocial damage incurred by patients and their significant others, friends, and families is incalculable. Unfortunately, nonhealing wounds are prone to complications that not only effect the time to healing completion but also have a negative impact on the patients themselves. The complications of chronic wounds include functional limitations, infections, and malignant transformation. Functional limitations include gait changes and difficulty ambulating. Many patients have chronic pain that decreases their quality of life. Another large category of complications is related to infections. Cellulitis, abscess formation, osteomyelitis, gangrene, and even sepsis all may occur as a result of an infected wound. Furthermore, chronic wounds have the potential for malignant transformation (ie, Marjolin's ulcer).5, 6 Lastly, foot ulcers are one of the most common causes of nontraumatic amputation.7

Section snippets

Acute vs chronic inflammation

The inflammatory reaction of a chronic wound differs markedly from that of an acute healing wound. The normal function of inflammation in an acute wound is to prepare the wound bed for healing by removing necrotic tissue, debris, and bacterial contaminates as well as recruiting and activating fibroblasts. Under normal conditions, inflammation is a self-limiting process. In contrast, the inflammation in a chronic wound serves only to cause further injury and promote inflammation. In an acute

Treatment modalities

Because excessive inflammation is the ultimate cause of the poor healing found in chronic wounds, most treatments are aimed at reducing inflammation. Surgical debridement and wound care methods are aimed at decreasing the necrotic tissue and protease burden, thus providing a virtual resetting of the wound back into the acute healing phase. If the inflammation level is subsequently kept low, the wound is then able to progress forward and begin to heal.

Another method for altering the inflammatory

Complexity constructs

The complex, multiscale, multitemporal, hierarchical nature of the chronic wound has, thus far, been underappreciated. Historically, research scientists and clinicians have focused on the study of individual cytokines and growth factors and how they affect the individual cells in vitro, out of context of the injury and the organism. The relationships among the various cell types and how they affect the dynamics of the wound healing process has not been properly studied to date. As a result,

Modeling

The previous description of complex nonlinear systems, as applied to wound healing, is highly attractive in attempting to explain our failure in creating successful monotarget therapies. New understandings tell us that the cells involved in wound healing and the cytokines and growth factors used to transmit signals could be better categorized as highly complex, layered, modular networks with stochastic dynamics at risk for dysfunction. The extent to which acute and chronic soft tissue wounds

Conclusions

The problem of chronic wounds is large in scope as well as in psychosocioeconomic cost. There are many causes of chronic wounds, with diabetes, pressure ulcers, and venous stasis as the 3 most common causes. Chronic wounds are associated with many complications that can further impair the healing process.

The inflammatory profile of a chronic nonhealing wound is much different than that of an acute wound. The balance between tissue degradation and synthesis is shifted toward degradation,

References (45)

  • G.S. Lazarus et al.

    Definitions and guidelines for assessment of wounds and evaluation of healing

    Arch Dermatol

    (1994)
  • H. Brem et al.

    Healing of diabetic foot ulcers and pressure ulcers with human skin equivalents

    Arch Surg

    (2000)
  • O. Nelzen et al.

    Chronic leg ulcers: an underestimated problem in primary health care among elderly patients

    Epidemiol Community Health

    (1991)
  • I.M. Eltorai et al.

    Marjolin's ulcer in patients with spinal cord injury

    J Spinal Cord Med

    (2002)
  • H. Chraibi et al.

    The diagnosis and treatment of carcinomas occurring at the sites of chronic pressure ulcers

    J Wound Care

    (2004)
  • CDC, National Diabetes Fact Sheet: National Estimates and General Information on Diabetes in the United States. 1998,...
  • R.F. Diegelmann

    Excessive neutrophils characterize chronic pressure ulcers

    Wound Repair Regen

    (2003)
  • M. Palolahti et al.

    Proteolytic activity in leg ulcer exudate

    Exp Dermatol

    (1993)
  • A. Piaggesi et al.

    Semiquantitative analysis of the histopathological features of the neuropathic foot ulcer: effects of pressure relief

    Diabetes Care

    (2003)
  • R. Lobmann et al.

    Proteases and the diabetic foot syndrome: mechanisms and therapeutic implications

    Diabetes Care

    (2005)
  • B.C. Nwomeh et al.

    Dynamics of the matrix metalloproteinases MMP-1 and MMP-8 in acute open human dermal wounds

    Wound Repair Regen

    (1998)
  • R. Lobmann et al.

    Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients

    Diabetologia

    (2002)
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