A Historical Review of Enzymatic Debridement

A Historical Review of Enzymatic Debridement

Author(s): David W Brett*

Affiliation(s): Medical Education Manager, Advance Wound Care| Wound Management Division, Smith & Nephew, Fort Worth, TX, USA

Subject Category: Biotechnology and Biomedicine

About this Book

The following is an update to a book entitled, “A Historical Review of Enzymatic Debridement”, which I wrote in 2003. Since its publication, while the relevant clinical evidence has remained consistent, the amount of biochemical research and knowledge gained has been impressive. In the first chapter a sampling of the typical topical enzymatic debriding agents that have been used in wound care are reviewed and interestingly enough only one remains on the market. The FDA has removed all others from the marketplace and an explanation is provided in chapter one along with descriptions of the use and mode of action (MoA) of these agents. Chapter two is a review of the many different types of collagen found in the body, including their structure, form, and function as so much additional insight into this molecule has been gained since 2003. In chapter three we see an account depicting the many advances in understanding matrix metalloproteinases (MMPs) reviewed in detail. Form, function, tissue orientation and preferred substrates are addressed. Finally, in chapter four we see the history of the MoA of MMPs as compared to bacterial collagenase starting in the early ‘80s to the time of this current publication. In addition we see the level of complexity of bacterial collagenases compared to MMPs, helping us to better understand why bacterial collagenase is much more efficient at removing necrotic tissue from wounds than are our own (endogenous) MMPs. I hope the reader finds this review useful from an academic standpoint, but more importantly from a clinical framework helping to understand the role of these types of therapies in wound care.

Table of Contents (4 Chapters)

Chapter 1: Types of Enzymes Pages: 003-008

The recognition of the importance of enzymes in biological phenomena has been a prominent feature of the current surge in scientific progress. Proteolytic enzymes have been used therapeutically in various areas [1]:

  1. as oral agents for specific gastrointestinal disorders;
  2. as local agents to debride or solubilize collections of proteinaceous material, which either cause or foster disease;
  3. as anti-inflammatory agents;
  4. as thrombolytic agents in the treatment of thromboembolic disorders;
  5. as a treatment for specific connective tissue disorders, such as Dupuytren’s Contracture and Peyronie’s Disease.


Chapter 2: Technical Review of Collagen Pages: 009-015

Proteins are natural polymers, which make up about 15% of our bodies (dry weight). The building blocks of all proteins are α-amino acids. The alpha (α) is derived from the fact that the amino group (–NH2) is always attached to the α-carbon, which is bonded to the carboxyl group (–CO2H). Amino acids are joined together into proteins via condensation reactions in which the amine group of one amino acid reacts with the carbonyl group of another amino acid. In this reaction, a peptide bond is formed and a molecule of water is liberated (condensation). As the reaction proceeds repetitively, a polypeptide is produced and, eventually, a protein.


Chapter 3: Endogenous CollagenasePages: 016-032

The serine proteinases comprise the largest family of extracellular enzymes and include plasmin, plasminogen activators, and leukocyte elastase, as well as the coagulation and digestive proteinases. Generally, these are potent enzymes with broad catalytic specificity and are readily available when needed. Plasminogen, the inactive form of plasmin, is present in high concentrations in blood and tissue. Neutrophils store an abundance of leukocyte elastase. In contrast, the metalloproteinases in wounded tissues have more defined substrate specificity and are generally produced on demand.


Chapter 4: Modes of Action of Enzymatic DébridementPages: 033-051

Over the years, various proteolytic enzymes have been employed (papain, ficin, streptokinase, streptodornase, trypsin–chymotrypsin, etc.) for the débridement of wounds. As mentioned in chapter 1, the only remaining (widely used in the US) commercially available enzymatic debrider is clostridial collagenase. One reason for this turbulent history may be related to an enzyme’s ability to degrade collagen. Howes et al. (1959) and Rao et al. [1], have demonstrated that necrotic tissue (which itself is very rich in collagen and denatured collagen) is anchored to the wound surface by strands of undenatured and partially denatured collagen fibers. Until these fibers are severed, débridement cannot take place, granulation is slowed, and thus no supportive base is available for proper epithelialization. Another aspect may be the fact that most enzymes used historically have not been highly selective in their catalytic activity. Nonselective being the inability to distinguish between healthy and necrotic tissue. Other concerns exist around the safety (i.e., anaphylactic shock in the case of papain) and/or FDA rulings/drug classifications. All of these aspects have resulted in the removal of many topically applied enzymatic debriders from clinical use. The one exception would be clostridial collagenase, which is felt to be more selective than the enzymes mentioned, previously. In addition, the FDA has sited no real safety concerns or regulatory designation concerns for bacterial collagenase.