EUROPEAN  TISSUE  REPAIR  SOCIETY

Dr David Thomas
Senior Lecturer & Consultant, Oral Surgery, Dental School,
University of Wales College of Medicine, Heath Park,
Cardiff, CF14 4XY, Wales.

Chronic leg wounds are characterised by defective remodelling of the extracellular matrix (ECM), failure of re-epithelialisation and prolonged inflammation (Cook, et al. J. Invest. Dermatol. 2000; 115: 225–233). The metallopro-teinases are part of a large superfamily (of over forty enzymes) which catabolise the ECM and currently include: collagenases, gelatinases, stromelysisns the Membrane-Type Matrix Metalloproteinases (MT-MMPs) and the ADAM’s family of enzymes. Matrix Metalloproteinase activity plays an important role in the regulation of cellular migration and ECM remodelling following injury and is partly regulated by the Tissue Inhibitors of Metallopro-teinases (TIMPs) and proteinases including MT-MMP’s. The balance of MMP’s and TMP’s following wounding appears crucial in directing successful wound repair. ECM catabolism is known to be altered with cellular ageing; increases in MMP’s, Plasminogen Activator Inhibitor (PAI)–1 and TIMPs production have previously been demonstrated in normal aged fibroblasts (Ashcroft et al., Cell Tissue Res. 290: 581–591 and J. Pathol. 183: 169–176, 1997b). The hypothesis that altered cellular responses are associated with phenotypic differences in the activity of the Matrix Metalloproteinases (MMP’s) and Tissue Inhibitors of Metalloproteinases (TIMPs) in elderly patients with chronic leg wounds, has been widely proposed and extensively studied. Previous studies showing generalised increases in MMP activity within chronic wound fluid have led to the concept that inhibition of MMP’s may stimulate chronic healing (Myers & Wolowacz, Advances in Dental research 12: 86–93, 1998). Interestingly, the role of the ADAM’s gene family has to date, received no attention in chronic wounds.

New data (from human chronic wounds, the diabetic mouse (C57BL/KSJ–db/db) model and a reversible model of cellular senescence) which challenged the conventional wisdom will be discussed. The human wound data suggest that the impaired cellular responses of chronic wound fibroblasts may be related to decreased levels of active MMP–2 and MMP–1 in the tissues resulting from increased TIMP–1 and TIMP–2 production by chronic wound fibroblasts. These findings provide a mechanism to explain the impaired cellular responses and ECM reorganisation observed in chronic leg wounds in vivo.

Dr Raj Mani
Principal Clinical Scientist and Senior Lecturer, Peripheral Vascular Group,
Southampton University Hospitals Trust, Southampton SO16 6YD, England

The importance of wound bed preparation, an essential step in acute wound management, has largely been un-discussed in the context of chronic wounds. In venous leg ulcer management, wound debridement is considered important and different methods exist by which this objective may be achieved. Surgically cutting back wound edges is rarely offered in venous leg ulcers. In diabetic foot ulcer management, surgery would be offered, unless blood flow was compromised. Adequate tissue nutrition is essential for healing – how can we ascertain these endpoints?

Blood flow may be measured by laser Doppler imaging. Laser imaging techniques have been valuable in studying wounds resulting form burns. Skin surface pH studies reveal that acidity and healing are associated. Venous ulcers are hypoxic; tissue oxygen is inversely correlated with wound surface pH. Video-recording techniques measure changes in wound colour reliably, offering thereby an estimate of wound bio-burden. The inter-relationships between infection and physiological variables are unknown.

Recent evidence suggests that the control of pain is directly correlated with infection, in an acute wound model. This may be relevant in chronic wound management with implications on the methods used for wound bed preparation.

Dr R Gary Sibbald
Associate Professor and Director of Continuing Education,
Dept of Medicine, University of Toronto, Canada

All chronic wounds are contaminated with bacteria. Colonisation or attachment of bacteria to the wound surface can result in the formation of bacterial biofilms^1,2, These biofilms are composed of non-motile micro-colonies of single or multiple species embedded in a glycocalyx. Periodic release of motile organisms may cause surrounding infection. Can these biofilms be responsible for non-healing and what is the best strategy for treatment? The chronic wound has superficial and deep compartments for bacterial-tissue interaction. The gold standard for the assessment of bacterial numbers in the deep compartment is the quantitative biopsy. Organism number ^> 1.0 x 10⁶ colony-forming units per gram of tissue can cause significant tissue damage, but the virulence of the organism and host factors must be considered before treating with systemic antimicrobials. Not all wounds with critical colonisation (increased bacterial burden) have the clinical signs of infection. What criteria should we use for antimicrobial treatment and when can topical and or oral agents be used most effectively?

References:

1. Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: A common cause of persistent infections. Science; Washington; May 21, 1999.
2. Potera C. Forging a link between biolfilm and disease. Science; Washington; Mar 19, 1999.