bFGF & microneedling. Procollagen or anti-collagen?

We get a lot of questions about individual growth factors and their role in wound healing, anti-aging, and aesthetics. A question from our friend Scott, prompted this post.

“Many post-micro needling serums contain b-FGF, and others claim to promote it eg. snail snot cream. 95% of micro needling treatments, however, are in hopes in increasing collagen, yet in every study I have seen regarding b-FGF it has been shown to directly inhibit collagen production. b-FGF has been shown to heal wounds particularly well and without scarring, so this leads me to believe that it should only be used when healthy skin is broken and the hope is to repair it back to the same condition before the immediate cause of breakage eg. after surgery to prevent a hypertrophic scar from forming at the point of incision. Is my thinking correct? And if so, would it also be beneficial following micro needling of a hypertrophic scar to reduce localized collagen and shrink the scar (similar to localized cortisone injection)? Or are collagen builders still preferred even when micro needling hypertrophic scars? Thank you for your guidance.”

Your thinking is correct, Scott. bFGF is a growth factor associated with early stage wound healing. It does increase proliferation of several cell types, and stimulates the migration of dermal fibroblasts during re-epithelialization. Sustained release of bFGF from a gelatin sheet containing bFGF promotes neoepithelialization, granulation, neovascularization and wound closure. bFGF also inhibitsTGFβ1. Now, since TGFβ1 is itself a potent collagen stimulator, you find this paradox. It both stimulates and inhibits collagen synthesis. How can that be, and what does this mean about its utility during microneedling?

Here is where we need to challenge the simple minded thinking that growth factors act in isolation. They do not. It is the net effect of an array of cytokines and growth factors that determines the role of each one. That is important in would healing, because each phase of healing has different goals. Early healing in adults in inflammatory, and the stimuli to collagen synthesis are based on an emergency response where closure to maintain a skin barrier is the main objective. bFGF can platy a role there as a collagen inducer, because its down regulating effects on TGFβ1 will be negated by other cytokines. With later stages of wound healing it is desirable to turn down collagen synthesis to prevent hypertrophic scars. bFGF may be helpful there as a scar prevention strategy. But again, it depends not on one cytokines or GF but the overall pattern. If you add bFGF to a wound where inflammation has not yet been tamed, it may relatively impotent.

You also need to appreciate that regeneration from an aesthetic viewpoint and the classical wound healing / growth factor paradigm don’t always converge. Just because something is good to heal a nasty infection prone diabetic wound (where worry about scarring is minimal) doesn’t make it a good thing for anti-ageing, where nice supple collagen remodeling rich in elastin with quality cross links is desired. In the case of bFGF, it does have a role in both, but for aesthetic regeneration we prefer to see it in combination with other complimentary growth factors, in carefully designed ratios that mimic the anti-inflammatory pattern of fetal wound healing (which is totally free of inflammation). To achieve this you either need a carefully constructed conditioned medium (e.g. from stem cell cultures tuned to the non-inflammatory agenda), or a combination of growth factors from recombinant technology in an array that mimics the non-inflammatory regenerative pattern.

If the goal is scar revision or reduction with microneedling, you need to break up the old, gnarly, rigid collagen (scar tissue) and replace it with fresh, new, supple collagen and elastin. Here the goal is to maximize remodeling (which includes stimulation of collagenases to tear down and dispose of bad collagen while building the new). You get this with microneedling, but here again you want to minimize the inflammation.

The growth factors TGFβ3 and TGFβ1 are variants of the same molecule that act in exact opposite ways. TGFβ1is potently inflammatory, whileTGFβ3 is the master at keeping inflammation at bay. Not only that, but they exist on a see saw tissues. Increasing one decreases the other, and vice versa. Further, TGFβ3 is the GF most famously associated with the fetal (inflammation free) would healing phenomenon.

Hypertrophic scars are not just too much collagen, it is disorganized collagen, cross linked under inflammation, bundles not basket weave, hard, inflexible, difficult to remodel. Its partly quantity, but also quality.

Here is our current approach to scar revision with microneedling used in our own clinic. We use the AnteAGE MD microneedling solution (which we developed) that contains bone marrow derived stem cell conditioned medium — where the stem cells have been grown under special conditions that optimizes their anti-inflammatory healing capability. To that we add additional TGFβ3 and IGF-1 (another growth factor, another topic). We have seen excellent results. The only other ingredient is hyaluronic acid (must be HMW). To avoid potential troublemakers, during the first 4-6 hours after treatment, before the fibrin plugs are stable and the barrier partly restored, we have patients self-apply the same mix. Between microneedling sessions we use a topical skin care system based on these same cytokine / GF cocktails plus additional anti-aging ingredients that have a good evidence base.

Avoid products that claim to “stimulate” growth factors. Weak science at best. Besides, microneedling itself stimulates growth factors. What we want to do as an adjunct to microneedling is push the healing response back to a more youthful one by mimicking how we do it during development. Regeneration should recapitulate generation. Human generation, not mollusc.

Hope this helps.