Elsevier

The Lancet

Volume 366, Issue 9498, 12–18 November 2005, Pages 1736-1743
The Lancet

Review
Wound healing and its impairment in the diabetic foot

https://doi.org/10.1016/S0140-6736(05)67700-8Get rights and content

Summary

Optimum healing of a cutaneous wound requires a well-orchestrated integration of the complex biological and molecular events of cell migration and proliferation, and of extracellular matrix deposition and remodelling. Cellular responses to inflammatory mediators, growth factors, and cytokines, and to mechanical forces, must be appropriate and precise. However, this orderly progression of the healing process is impaired in chronic wounds, including those due to diabetes. Several pathogenic abnormalities, ranging from disease-specific intrinsic flaws in blood supply, angiogenesis, and matrix turnover to extrinsic factors due to infection and continued trauma, contribute to failure to heal. Yet, despite these obstacles, there is increasing cause for optimism in the treatment of diabetic and other chronic wounds. Enhanced understanding and correction of pathogenic factors, combined with stricter adherence to standards of care and with technological breakthroughs in biological agents, is giving new hope to the problem of impaired healing.

Section snippets

Basic aspects of normal wound healing

The type, size, and depth of cutaneous injury have important implications for events at the cellular and molecular level. Scalpel injury (ie, after surgical procedures) causes less overall and diffuse tissue damage than burns or radiation, can be primarily closed (by suture), and generally results in less scarring. Small and superficial cutaneous defects can resurface mainly by epidermal migration, and do not have to rely on actual keratinocyte proliferation and its more substantial lag time

Impaired healing: the diabetic ulcer

The linear progression paradigm for normal wound healing shown in figure 1 has been highly valuable in understanding the basic biology of tissue repair. However, one should not oversimplify. Even during the normal process of wound healing complications can occur, including infection, thrombosis, and ischaemia. Also, lessons learned from experimental models, on which figure 1 and the previous discussion are based, cannot be completely extrapolated to the situation encountered in diabetic wounds.

Search strategy and selection criteria

I searched PubMed by matching “wound healing” and “wounds” with the search terms “keratinocytes”, “diabetes”, “hemidesmosomes”, “integrins”, “MMPs”, “contraction”, “neuropathic ulcers”, “gene therapy”, “stem cell therapy”, “growth factors”, “tissue engineering”. I mainly selected publications from the past 6 years. Relevant articles and book chapters were also included. No restriction was applied on language of publication.

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