What are matrix metalloproteinases?
The biochemistry of why chronic wounds get stuck, and why collagen, silver, and oxidized-cellulose dressings all target the same enzyme problem.
Reviewed byDavid Chahine, MDIn this guide
What MMPs actually are
Matrix metalloproteinases are a family of zinc-dependent enzymes — about 23 of them are described in humans (1) — whose job is to chew up the extracellular matrix. The "extracellular matrix" is the scaffolding between your cells: collagen, elastin, fibronectin, laminin, and a soup of other proteins.
That sounds destructive, and it is. But controlled destruction is a critical part of healthy biology. Every day, your body builds new tissue and tears down old tissue. MMPs are the demolition crew. They let new blood vessels grow into healing tissue, let immune cells migrate where they're needed, and let scar tissue remodel into something more flexible over time.
Most relevant to wound care: MMP-1, MMP-8, MMP-9, and MMP-13 are the ones that target collagen. MMP-9 (gelatinase B) is the headline name because it's the one most strongly elevated in problem wounds.
MMPs in a normally healing wound
Acute wound healing happens in four overlapping phases:
- Hemostasis (minutes): bleeding stops, a clot forms.
- Inflammation (1-4 days): neutrophils and macrophages clean up. MMPs spike to break down damaged tissue.
- Proliferation (4-21 days): new tissue forms. MMPs drop. Fibroblasts lay down new collagen.
- Remodeling (21+ days to months): scar tissue reorganizes. MMPs do controlled cycles of break-down-and-rebuild.
In an acute wound healing normally, MMPs spike in phase 2 and then back off. By phase 3, the inhibitors of MMPs (called TIMPs, tissue inhibitors of metalloproteinases) catch up, and the balance shifts toward building tissue rather than breaking it down.
What goes wrong in a chronic wound
A "chronic wound" is technically any wound that hasn't closed within 4 weeks of consistent care. In chronic wounds, the inflammation phase doesn't end. The wound gets stuck in phase 2, and MMP levels stay elevated indefinitely.
Studies comparing wound fluid from acute (healing) wounds with fluid from chronic (stalled) wounds keep finding the same shape of result. Wound fluid taken from human pressure ulcers carries elevated matrix metalloproteinase levels and elevated protease activity compared with fluid from acute surgical wounds (2), and the natural brakes on those enzymes — the TIMPs — are suppressed at the same time. How large the gap is varies widely by study, wound type, and assay, so the pattern is worth more than any single headline multiple.
The consequence is that as soon as fibroblasts lay down new collagen, excess protease activity degrades it. The wound never accumulates enough new tissue to close. Granulation tissue, when it does form, is friable — it bleeds easily and breaks apart. The wound bed becomes self-defeating.
Why MMPs are so high in DFUs and pressure injuries
Three populations of chronic wounds dominate clinical practice: diabetic foot ulcers (DFUs), pressure injuries, and venous leg ulcers (VLUs). All three end up with the same protease imbalance, for different underlying reasons.
Diabetic foot ulcers. Hyperglycemia drives several problems at once: persistent inflammation, neutrophil dysfunction (so the immune cells stay too long), formation of advanced glycation end-products (AGEs) that prolong inflammation, and chronic bacterial colonization. Arterial supply is often impaired at the same time, which is why a stalled DFU needs a circulation assessment and not just a better dressing. See our guide to collagen for diabetic foot ulcers.
Pressure injuries. Sustained ischemia (pressure cuts off blood supply) damages tissue at multiple levels. When pressure is relieved, reperfusion injury releases free radicals that drive more inflammation. The result: a wound bed where inflammatory signals never resolve.
Venous leg ulcers. Chronic venous insufficiency means pooled blood, fibrin cuffs around capillaries, and tissue hypoxia. The end state is the same — persistent inflammation, elevated MMPs, and a wound that won't close until both the wound bed and the venous insufficiency are addressed.
How collagen dressings bind MMPs
A collagen wound dressing is a sterile sheet (or powder) of purified Type I bovine collagen, the same kind of collagen your body uses to build skin scaffold. When you apply it to a wound bed with elevated MMPs, the MMPs do what they're built to do: they degrade collagen. But they degrade the dressing's collagen instead of the new collagen you are trying to grow.
This is called sacrificial substrate. The collagen dressing soaks up the enzyme load. The new tissue forming underneath gets a window of relative protection in which to organize and close the wound.
A secondary effect: the remaining collagen matrix (the part that hasn't been degraded yet) provides a physical scaffold for fibroblasts, capillaries, and granulation tissue to attach to and grow through.
As the wound heals, the collagen is gradually absorbed and replaced by your own tissue. There's no peel-off.
One safety note that applies to every collagen dressing: they are made from bovine (beef-derived) collagen. Do not use them if you are allergic to bovine products, and if the wound or the skin around it itches, burns, or breaks out in a rash after application, remove the dressing and contact your clinician.
If you want the practical step-by-step, see how to apply a collagen wound dressing.
Other MMP-modulating approaches
Collagen dressings are one approach to lowering excess MMP activity. Two others are in regular clinical use:
| Approach | How it modulates MMPs | When to use |
|---|---|---|
| Collagen dressings (e.g., Ovena, Puracol) | Sacrificial substrate — MMPs degrade dressing collagen instead of new tissue | Most stalled chronic wounds: DFUs, pressure injuries, VLUs, and surgical wounds healing open |
| Oxidized regenerated cellulose plus collagen (e.g., Promogran) | Both sacrificial substrate and chemical chelation of the metal cofactors MMPs need to function | Wounds where a clinician judges protease activity to be the limiting factor, ideally supported by a protease assay |
| Silver dressings (e.g., Acticoat, Mepilex Ag) | Indirect — silver reduces bacterial bioburden, which lowers the inflammatory signal driving MMP production | Wounds with critical bacterial colonization or active infection |
All three can be appropriate. The choice is usually driven by which problem dominates the wound: too much enzyme (collagen, or collagen plus ORC), or too much bacteria (silver). Many wounds have both, and treatment alternates.
What the clinical evidence shows
The most-cited trial of an MMP-modulating dressing is Veves et al. 2002, which randomized 276 people with diabetic foot ulcers to Promogran (a collagen/ORC combination) or moistened gauze. Complete closure at 12 weeks was 37.0% vs 28.3% — a difference that did not reach statistical significance (P = .12) — and the authors concluded that Promogran was comparable to moistened gauze (3). A marginal signal appeared only in ulcers that had been open less than six months.
The mechanism sits on firmer ground than the outcome. In an ex vivo study using wound fluid from people with diabetic foot ulcers, a collagen/ORC matrix bound and inactivated proteases, significantly reducing neutrophil elastase, plasmin, and MMP activity compared with wet gauze (4). Note what that study is and isn't: it measures enzyme activity in a dish rather than wounds closing in people, and it was run by the manufacturer of the dressing it tested.
Guidance is correspondingly measured. The WOCN Society's clinical resource guide, listing options for wounds due to diabetes or neuropathic disease, says to "[c]onsider use of collagen or hyaluronic acid dressings that might promote healing" (5) — an option to weigh, not an instruction, and one that treats collagen and hyaluronic acid as alternatives to each other. The honest summary is that collagen dressings have a well-described mechanism and a mixed clinical record. Ask your clinician whether protease load is the problem limiting your particular wound.
Ovena collagen dressings — FDA 510(k) cleared
Purified Type I bovine collagen, the same regulatory class as the hospital brands, available without a prescription. Not for use if you are allergic to bovine (beef-derived) products. Commonly FSA/HSA eligible with an itemized receipt; your plan administrator decides, and a letter of medical necessity may be required.
Shop collagen wound dressings →Frequently asked questions
What is MMP-9?
Why are MMPs elevated in diabetic foot ulcers?
How is MMP binding different from antimicrobial action?
Can MMP levels be measured?
Sources
- Nagase H, Visse R, Murphy G. Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 2006;69(3):562-573.
- Yager DR, Zhang LY, Liang HX, Diegelmann RF, Cohen IK. Wound fluids from human pressure ulcers contain elevated matrix metalloproteinase levels and activity compared to surgical wound fluids. J Invest Dermatol. 1996;107(5):743-748.
- Veves A, Sheehan P, Pham HT. A randomized, controlled trial of Promogran (a collagen/oxidized regenerated cellulose dressing) vs standard treatment in the management of diabetic foot ulcers. Arch Surg. 2002;137(7):822-827.
- Cullen B, Smith R, McCulloch E, Silcock D, Morrison L. Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers. Wound Repair Regen. 2002;10(1):16-25. Ex vivo study; the authors were employed by the manufacturer of the dressing tested.
- WOCN Society. Lower-Extremity Wounds Due to Venous Disease, Arterial Disease, or Diabetes Mellitus and/or Neuropathic Disease: Clinical Resource Guide. Revised December 2021.
