Challenges in the Treatment of Chronic Wounds

Abstract

Significance: Chronic wounds include, but are not limited, to diabetic foot ulcers, venous leg ulcers, and pressure ulcers. They are a challenge to wound care professionals and consume a great deal of healthcare resources around the globe. This review discusses the pathophysiology of complex chronic wounds and the means and modalities currently available to achieve healing in such patients. Recent Advances: Although often difficult to treat, an understanding of the underlying pathophysiology and specific attention toward managing these perturbations can often lead to successful healing. Critical Issues: Overcoming the factors that contribute to delayed healing are key components of a comprehensive approach to wound care and present the primary challenges to the treatment of chronic wounds. When wounds fail to achieve sufficient healing after 4 weeks of standard care, reassessment of underlying pathology and consideration of the need for advanced therapeutic agents should be undertaken. However, selection of an appropriate therapy is often not evidence based. Future Directions: Basic tenets of care need to be routinely followed, and a systematic evaluation of patients and their wounds will also facilitate appropriate care. Underlying pathologies, which result in the failure of these wounds to heal, differ among various types of chronic wounds. A better understanding of the differences between various types of chronic wounds at the molecular and cellular levels should improve our treatment approaches, leading to better healing rates, and facilitate the development of new more effective therapies. More evidence for the efficacy of current and future advanced wound therapies is required for their appropriate use.

Robert G. Frykberg, DPM, MPH

Figure 1.

Molecular and cellular deficiencies in chronic wounds (red circles) and factors required to overcome them (green rectangles). Nonhealing ulcers and wounds represent a failure to achieve complete reepithelialization in the appropriate temporal sequence of tissue repair. Such wounds are characterized by excessive inflammation (including elevated levels of proteases, ROS, and inflammatory cytokines), by senescent cell populations with impaired proliferative and secretory capacities, and by defective MSCs. Excessive inflammation leads to degradation of newly synthesized growth factors and ECM. There is a need to restore the proper balance of cytokines, growth factors, and proteases, to recruit functional cells (epithelial cells, fibroblasts, and endothelial cells) to the wound area, and to deliver healthy functional MSCs directly to the wound to compensate for the patient's own dysfunctional stem cells. ECM, extracellular matrix; MSCs, mesenchymal stem cells; ROS, reactive oxygen species.

Figure 2.

(A) Recurrent plantar ulcer not responsive to offloading. Biopsy revealed amelanotic melanoma. The clinician must be diligent in taking care to rule out the presence of malignancy in the wound either secondarily due to malignant degeneration as in the case of squamous cell carcinoma or as a primary lesion. (B) Cellulitis from infected digital wound with associated ischemia. Significant erythema can indicate cellulitis or infection requiring immediate hospitalization or might be an indicator of significant ischemia (dependent rubor). (C) Probe-to-bone test. If the bone is directly appreciated at the base of a wound, osteomyelitis is likely. A positive probe-to-bone test has a high predictive value for underlying osteomyelitis, even in the absence of acute signs of deep infection.

Figure 3.

Simplified algorithm for diabetic foot ulcer (DFU) treatment.

Figure 4.

Simplified algorithm for venous leg ulcer (VLU) treatment. ABI, ankle–brachial indices.