Collagenase G & H

The underlying biochemistry

Collagenase G and H are a pair of enzymes originally discovered in a bacteria called Clostridium histolyticum — now manufactured in the lab as pure, engineered proteins. Unlike the body's own collagen-breaking enzymes, which can only make small cuts at specific spots in collagen, these bacterial enzymes break collagen down completely. PBSERUM PB220 is made with a second-generation production method: the ColG and ColH genes are built directly into the DNA of the production bacteria, which removes the need for antibiotics during manufacture. The two enzymes are then purified separately and combined in precise proportions — delivering pharmaceutical-grade purity, without the contaminants or batch-to-batch variation of older crude extracts.

Mechanism in detail

1

Two enzymes working together. ColG and ColH are two versions of collagenase, each with a slightly different shape and role. Together they use a unique two-step "chew-and-digest" mechanism 5: first an open form grabs and unwinds a collagen fiber, then a closed form wraps around it and cuts it into pieces 6. This is why they can reach and remodel the deep, cross-linked collagen that builds up in aged and scarred skin — the kind of collagen that topical retinoids, chemical peels, and laser treatments can only work around, not through.

2

Two different jobs, not the same. ColG and ColH each target different parts of the collagen network. ColH is the main workhorse — it breaks down Type I and Type III collagen, the main types found in scars, aged skin, and the fibrous bands of cellulite. ColG has a more specific role: it targets Type V collagen, a regulatory collagen that holds collagen bundles together 7. In PB220 the two enzymes work as a team — ColH clears the bulk of damaged fibers, while ColG dismantles the scaffolding that keeps disorganized bundles in place. The result is precise: amorphous, aged collagen is cleared, while healthy, properly organized collagen is left intact.

3

Reactivating your skin's collagen factories. In aged and scarred skin, the collagen network is full of broken fragments — and these broken fibers fail to give fibroblasts (the skin's collagen-making cells) the mechanical "grip" they need to do their job. When fibroblasts can't spread and anchor properly, they stop making new collagen and even start producing enzymes that break down collagen further — a self-worsening cycle. By clearing away the broken collagen, ColG and ColH restore the physical environment fibroblasts need: they re-attach, stretch out, and switch back on, producing fresh, properly organized collagen instead of disorganized scar tissue.

4

Clinical evidence. A 2025 study published in a peer-reviewed dermatology journal 1 followed 29 patients treated with PBSERUM Specific Acne Scars (ColG+ColH combined with Lyase and active ingredients, applied through microneedling). After just 4 sessions, patients showed statistically significant improvements on standard scar severity scales (ECCA, Goodman–Baron, GAIS), measurable reductions in scar size, and better skin hydration — with no adverse events reported. Separate case series have also documented PB220 successfully resolving late-onset swelling after hyaluronic acid fillers 2, stubborn cellulite fibrosis 3, and even non-surgical treatment of epidermoid cysts 4 — again, all without adverse events.

Clinical benefits

• Remodels atrophic and hypertrophic scars — statistically significant improvements in scar size, severity (ECCA, Goodman-Baron) and GAIS over 4 microneedling sessions
• Resolves late-onset periocular filler edema and fibrotic capsules when combined with hyaluronidase, avoiding post-hyaluronidase syndrome
• Reduces cellulite-associated fibrosis by targeting thick collagen septa of edematous fibrosclerotic panniculopathy
• Dissolves benign fibrotic lesions non-surgically — foreign body granulomas and epidermoid cysts with no recurrence at 4-year follow-up
• Stimulates neocollagenesis — clears fragmented collagen, restoring fibroblast mechanotransduction and driving organized Type I/III deposition
• Selective debridement — degrades amorphous, photoaged, and cross-linked collagen while sparing intact functional matrix
• Zero adverse events reported across all published PB220 clinical case series to date

Technical profile

Product code

PB220

Enzyme class

Zinc-dependent metalloprotease (M9 family / peptidase clan MA)

EC number

EC 3.4.24.3 (microbial collagenase)

Source organism

Recombinant — genes originally from Clostridium histolyticum, expressed in non-pathogenic host

Production

2nd-generation recombinant DNA; chromosomal integration (plasmid- and antibiotic-free)

ColG (Class I)

~116 kDa — cleaves Type I, III, and V collagen; unwinds microfibril scaffolding

ColH (Class II)

~110 kDa — highest collagenolytic activity; bulk degradation of Type I & III

Catalytic mechanism

Chew-and-digest two-state — open recognition, closed hydrolysis at Gly–X bonds

Cofactors

Zn²⁺ (catalytic) + Ca²⁺ (structural/stability)

pH optimum

7.0–7.5 (physiological)

Thermal stability

Tm ~54 °C with Ca²⁺; reversibly drops to ~49 °C without Ca²⁺

Specificity

Strict — Gly at P3/P1', Pro at P2/P2'; does not cleave elastin, laminin, fibronectin, or keratin

Purity

Pharmaceutical-grade; free of clostripain, neutral proteases, and endotoxin

Storage

Lyophilized, preservative-free; reconstituted before use