What are matrix metalloproteinases?

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:

1. Hemostasis (minutes): bleeding stops, a clot forms.
2. Inflammation (1–4 days): neutrophils and macrophages clean up. MMPs spike to break down damaged tissue.
3. Proliferation (4–21 days): new tissue forms. MMPs drop. Fibroblasts lay down new collagen.
4. 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.

The numbers are striking. Studies comparing wound fluid from acute (healing) wounds to fluid from chronic (stalled) wounds typically find:

• MMP-9 levels ~60× higher in chronic wound fluid than acute (2)
• MMP-8 levels ~10× higher in chronic wounds
• TIMP levels suppressed, meaning the brakes are off the demolition crew

The consequence is that as soon as fibroblasts lay down new collagen, the elevated MMPs degrade 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 are MMP-driven, but for different reasons.

Diabetic foot ulcers. Hyperglycemia drives multiple problems: 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. DFUs have the highest MMP burden of any common chronic wound type and are the leading cause of non-traumatic lower-limb amputation in the United States.

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. Same end state, persistent inflammation, elevated MMPs, a wound that won't close without addressing both the wound bed and the venous insufficiency.

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 your patient's new collagen.

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 the patient's own tissue. There's no peel-off.

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 also evidence-based and have a place:

All three can be appropriate. The choice is usually driven by which problem dominates the wound: too much enzyme (collagen or collagen+ORC), or too much bacteria (silver). Many wounds have both, and treatment alternates.

What the clinical evidence shows

The most-cited evidence on MMP-modulating dressings comes from a series of RCTs on Promogran (an ORC/collagen combination) in chronic DFUs. The Veves et al. 2002 trial showed significantly higher healing rates and shorter time-to-closure than standard moist wound care (3). Subsequent trials on standalone collagen dressings (Puracol, Ovena's regulatory class) have shown similar trends for DFUs, pressure injuries, and partial-thickness wounds, though most are smaller studies and meta-analyses have called for more rigorous trials.

What's accepted by major wound care societies (WOCN, AAWC, EWMA): collagen dressings are standard-of-care for stalled chronic wounds, particularly DFUs and pressure injuries stage 2 and beyond. They're a clinical mainstay, not a fringe product.

Frequently asked questions