The Potential Use of Proteases in Wound Care Diagnostics

By Laurie Swezey RN, BSN, CWOCN, CWS, FACCWS

There is more to wound care diagnostics than swabbing a wound to determine whether infection is present. Advances in science and knowledge in wound care have led to new ways of assessing wound healing.

What are Proteases?

Proteases (or proteinases) are enzymes that break down proteins into amino acids and peptides. There are several proteases that influence wound healing, including matrix metalloproteinases (MMPs) and serine proteases, i.e. elastase. Different proteases exert their effect on distinct proteins, such as elastin, collagen, extracellular matrix (ECM), proteoglycans and gelatin.

How do Proteases Affect Wound Healing?

When wound healing progresses normally, proteases break down damaged ECM, as well as foreign material, allowing new tissue to form and the wound to close. However, there is such a thing as "too much of a good thing"- when protease activity is excessive, the balance between tissue repair and tissue breakdown is upset.

When there is excessive protease activity, receptors, growth factors, newly formed ECM and other necessary components for wound healing are broken down, thus wound healing is impaired. Wounds can become 'stuck' in the inflammatory stage of healing, failing to progress to proliferation.

Where do Proteases Come From?

Proteases are secreted by cells involved in the process of wound repair (i.e. endothelial cells, fibroblasts). They are also manufactured by immune cells, which are stimulated by infection or inflammation. Some bacteria actually produce proteases, but the impact of proteases derived from wound bacteria on wound healing is yet to be determined.

Can Proteases be used as Biomarkers for Non-Healing Wounds?

Initially, in normal wounds protease activity rapidly increases until about the third day and begins to slowly decrease by day five. In non-healing wounds, however, proteases reach much higher levels, and protease levels remain high well beyond the time when they should be decreasing. This creates a very destructive wound environment. Foreign material, damaged tissue, bacteria and the presence of biofilm may act as stimuli that prolong protease activity at higher than normal levels.

Since studies show that protease activity is elevated in wounds that have stalled in the inflammatory phase, researchers believe that proteases show great promise as biomarkers that could be used to assess wound healing. In particular, proteases could be used early on in the healing process to predict which wounds might require advanced interventions, as well as wounds that are likely to be slow to heal.

How Can We Assess Protease Activity?

The technology is currently available to measure protease activity. However, the technology is very advanced and it is not feasible for most labs to evaluate this activity. Studies have shown that even skilled clinicians have difficulty accurately predicting wounds that have high protease levels based on signs of chronic inflammation. Clinical signs are not reliable to predict protease levels.

Point-of-Care Protease Testing

It is hoped that one day there will be a widely available point-of-care test for protease levels and activity. Such a test would allow clinicians to make decisions regarding the appropriateness of expensive treatments. In addition, point-of-care testing could result in:

• Reduced nursing time
• Reduced need for frequent dressing changes
• Fewer clinic visits
• Earlier recognition of complications
• Faster healing
• Improved quality of life
• Decreased pain
• Decreased duration of treatment time
• Avoidance of unnecessary treatments
• Earlier return to work
• Cost savings

Thus it seems clear that the ability to easily test for elevated protease levels (preferably at the bedside) should continue to be a focus of continued research and development, as it will be of immense value to clinicians in decision-making regarding non-healing wounds. Several companies are currently working on developing such a test.

Source

International Consensus. The Role of Proteases in Wound Diagnostics. An expert working group review. London: Wounds International, 2011. http://www.woundsinternational.com/pdf/content_9869.pdf

About The Author
Laurie Swezey RN, BSN, CWOCN, CWS, FACCWS is a Certified Wound Therapist and enterostomal therapist, founder and president of WoundEducators.com, and advocate of incorporating digital and computer technology into the field of wound care.

The views and opinions expressed in this blog are solely those of the author, and do not represent the views of WoundSource, Kestrel Health Information, Inc., its affiliates, or subsidiary companies.