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Protease modulators

VIEW PRODUCTS: Protease modulators

Protease-modulating dressings have been developed to reduce the levels of activity of harmful proteases (proteinases), in particular matrix metalloproteinases (MMPs), in the wound fluid (exudate) of chronic wounds. This is achieved either by absorbing exudate, removing cofactors, or releasing inhibitors.

By actively interacting with the wound, protease modulators influence the wound-healing environment so that it is more conducive to healing.

How do protease-modulating dressings work?

Proteases are needed for wound healing to occur, as they naturally debride the wound (Gibson et al, 2009). The two main ones in wound healing are MMPs and serine proteases, e.g. elastin. However, in chronic/complex wounds, their activity rises above normal levels and gets out of control, prolonging the inflammatory phase of healing and thus delaying healing.

Protease modulators are a new range of interactive dressings that not only create a moist wound-healing environment, but also control/modulate protease activity to promote wound healing.

The technology and modality of dressings in this category varies. For example, there is one that has a starch-based matrix and modulates the wound pH. Other dressings are fibrous and have a gel-blocking action, or consist of superabsorbent polymers or oxidised regenerated cellulose (ORC)/collagen, which creates a soft gel when in contact with exudate.

It is always important to regulate and monitor the length of time that protease-modulating dressings are applied, with the proposed duration of treatment being clearly documented with a review date. 

There are different protease-modulating dressings available, how do I select the right one?

Each patient has different needs that should be considered when choosing the correct product. The following questions can help with dressing selection.

How much exudate is the wound producing?

If a chronic wound is producing moderate-to-high volumes of exudate, a protease-modulating dressing may be required. Moisture management is essential to maintain a moist wound-healing environment and to control wound proteases so that they do not exceed their required levels of activity and prolong the inflammatory phase of healing (Derbyshire, 2003).

Methods for assessing exudate have been suggested by Falanga (2000), Bates-Jensen (wound assessment tool) (2007); and a proposed national wound assessment form (Fletcher, 2010). The latter uses the term ‘wound moisture level’ rather than exudate, and is based on the World Union of Wound Healing Societies (WUWHS) document on exudate (WUWHS, 2007; Clinicians should also refer to their local policy on exudate assessment.

What types of wounds can protease-modulating dressings be used on?

These dressings can be used on any wound that is failing to heal over a period of time. Some authors have defined this as an eight-week period without evidence of healing (Lazarus et al, 1994); whereas others have put this time as nearer 12 weeks (Mustoe et al, 2006).

Wounds that are particularly prone to poor healing include:

  • Pressure ulcers
  • Venous leg ulcers
  • Diabetic foot ulcers.

Does the patient have fragile skin?

Research has shown that an elevated level of MMPs on the surface of the wound and in wound exudate, can damage the periwound skin (Wolcott et al, 2009). Therefore, protease-modulating dressings can help to combat maceration in the fragile periwound skin by reducing the level of MMPS present in the exudate. 

Is the dressing going to be used under compression?

Applying compression can be a problem for wounds that produce heavy volumes of exudate, which is often where protease-modulating dressings are used in order to absorb protease-rich wound fluid. Some protease-modulating dressings can be used under compression bandaging, but it is important to check the manufacturer’s instructions to make sure that the dressing is suitable for use in this instance.

Is antimicrobial action needed?

Studies have suggested that protease-modulating dressings are able to control the levels of bacterial load within a wound (Cullen et al, 2002; Hart et al, 2002). Indeed, some protease-modulators are specifically designed for this role, with the addition of antimicrobial properties, such as silver.

Where is the wound? Is it in a place that is difficult to dress?

Some wound sites can be difficult to dress areas, or wounds may have developed in unusual configurations. Some protease-modulating dressings are manufactured with a gelling component, which can swell to conform to different sizes and shapes of wound, while others are supplied as a ribbon, which can be used to fill cavities.

Selecting a protease-modulating dressing

Selection of a protease-modulating dressing should be guided by:

  • Volume of exudate
  • Condition of periwound skin
  • Presence of infection.


Although cost-effectiveness is important, choosing the cheapest protease-modulating dressing is not necessarily the best thing to do, as dressing choice should always be guided by the patient’s needs. If a dressing fails to perform well, more frequent dressing changes will be needed incurring greater nursing time.

Performance indictors

  • Fluid-handling capacity
  • Prolongs inflammatory phase of healing
  • Modulates wound proteases
  • Antimicrobial
  • Can be used under compression.


Bates-Jensen B (1997) The pressure sore status tool a few thousand assessments later. Adv Wound Care 10(5): 65–73

Fletcher J (2010) Development of a new wound assessment form. Wounds UK 6(1): 92–9

Cullen B, Watt PW, Lundqvist C, et al (2002) The role of oxidised regenerated cellulose/collagen in chronic wound repair and its potential mechanism of action. Int J Biochem Cell Biol 34(12): 1544–56

Derbyshire A (2003) A case study to demonstrate the role of proteases in wound healing. Nursing Times. Read online at:

Falanga V (2000) Classifications for wound bed preparation and stimulation of chronic wounds. Wound Rep Regen 8(5): 347–52

Gibson D, Cullen B, Legerstee R, et al (2009) MMPs Made Easy. Wounds International 1(1). Available online at:

Hart J, Silcock D, Gunnigle S, et al (2002) The role of oxidized regenerated cellulose/collagen in wound repair: effects in vitro on fibroblast biology and in vivo in a model of compromised healing. Int J Biochem Cell Biol 34(12): 1557–70

Lazarus GS, Cooper DM, Knighton DR, et al (1994) Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol 130(4): 489–93

Mustoe TA, O’Shaughnessy K, Kloeters O (2006) Chronic wound pathogenesis and current treatment strategies: a unifying hypothesis. Plast Reconstr Surg 117(7 Suppl): S35S–41

Wolcott RD, Kennedy JP, Dowd SE (2009) Regular debridement is the main tool for maintaining a healthy wound bed in most chronic wounds. J Wound Care 18(2): 54–6