Considerations for the Use of Clostridial Collagenase in Clinical Practice

Abstract

Mammalian collagenases belong to the family of metalloproteinases. They specifically cleave collagen and thus play an important role in the metabolism of collagen in mammalian tissues. Since a very high proportion of the skin (70 to 80% of its dry weight) consists of collagen, the action of collagenases during the repair of damaged skin is of major importance. Collagenases are produced by different cells involved in the wound-healing process, e.g. macrophages, fibroblasts and keratinocytes. Their synthesis and activity are finely regulated. In healthy subjects, where wounds normally heal by primary intention, the amount and activity of endogenous collagenases are sufficient for the removal of dead tissue from the wound. In patients presenting with chronic nonhealing wounds such as pressure sores, venous leg ulcers and diabetic ulcers, the underlying disease, nutritional state, drug treatment or aged skin may cause an impairment of endogenous collagenase production and activity, and thus lead to insufficient removal of dead tissue. In such cases, supplementation with bacterial collagenase helps to clean the wound so that the healing process can start. This has been demonstrated in clinical trials and is also known from long-term clinical experience. In addition to the debriding effect, collagenase may contribute to the wound-healing process itself. Experimental findings suggest that cleavage products of collagen after treatment with bacterial collagenase and collagenase itself may contribute to the migration and activity of important cells such as wound macrophages, fibroblasts and keratinocytes. Experimental findings indicate the involvement of cell-matrix interactions in the expression of collagenase in keratinocytes and fibroblasts. The localisation of the enzyme in burn wounds —within cells as well as within the wound site —suggests that the enzyme directly takes part in the healing mechanisms.