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MECHANISM of ACTION IN MICRONEEDLING
IMPROVEMENT OF SKIN STRUCTURE BY NEO-COLLAGENESIS AND
NEO-ANGIOGENESIS WITH THE DERMAROLLER®
Although the mechanism of action with the Dermaroller is not totally explored, nevertheless the results for the improvement
of skin structure and scars, especially acne scars, in over 100 000 cases speak a clear language. The procedure
with the Dermaroller became standard expressions in scientific literature with the terms COLLAGENINDUCTION-
THERAPY (short: CIT) and MICRONEEDLING. Our present state of knowledge is the following: A
drum shaped roller stud with 192 fine micro-needles from 0.5 to 1.5 mm in length and 0.1 mm in diameter penetrate
to dermis repeatedly for about 20 times. The skin cells react to these micro injuries and stimulation with the release
of various growth factors.
These in return stimulate the proliferation of undifferentiated cells and this reproduction results in NEOCOLLAGENESIS
and NEO-ANGIOGENESIS. New tissue structures are generated in forms of elastin- and collagen
fibers as well as new capillaries. They integrate into the existing upper dermal layer without any fibrotic traces.
New fibroblasts and capillaries will migrate through the punctured scar tissue. Both processes result in new tissue
formation to “fill” the former atrophic scar and new capillaries result in a significant better blood supply that in return
results in an improved re-pigmentation.
So far we regarded the mechanism of action of the Dermaroller for skin improvement, especially for atrophic scars,
from a more isolated aspect of the Neo-Collagenesis, and therefore the aspect of the Neo-Angiogenesis for scar repigmentation
was considered too narrowly. There is enough evidence that both disfigurements can be successfully
treated. In comparison to skin texture improvement the rectification of scars is easier to judge by the physician, patient
and subtle objective observers. According to the reports and scientific findings and clinical cases we received
from experts worldwide the rate of success for the treatment of atrophic scars is 70 to 80% after 2 to 4 procedures.
As explained further down, it is my point of view that the cell biological activities in the skin during and after Dermarolling
are far more complex as assumed till today. The wound healing mechanisms after an injury are well reName
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searched and do not require any further explanations. Although numerous needles with a diameter of 0.1 mm penetrate
the dermis and sub-dermis repeatedly the same tissue spot (about 15 to 20 times) down to a depth of maximum
1,5 mm, no wounds in the classical sense at set, and traces of fibrotic tissue could not be detected in histological examination.
(A tiny, but solid needle should not be mixed up with a hollow injection needle. Injection needles have
always an inclined cut, and will therefore act as a cutting device, that usually results in a scar).
The tiny micro-bleedings after Dermarolling originate from punctured capillaries that are “emptied” and noted as
tiny petechiae in the skin’s surface. But the needles do not cause bleeding in the classical sense. If the micro bleeding
sets free sufficient various growth factors to induce cell-proliferation is doubtful and requires more research. But
if we replace the term injury after a needle prick with the term sensation we get a totally different picture of cellbiological
sequence in the skin. But before we have a closer look at the reactions of various skin cells by signals, we
would like to shed some light on the skin improvements after Dermarolling:
Facts after one or several Dermaroller sessions:
a) Significant improvement of wrinkles and skin texture
b) The skin looks fresher and more juvenile
c) Scars and acne scars are drastically reduced
d) Pigment spots become more even or disappear in total
After a Dermaroller therapy we always observe the same reactions: NEO-COLLAGENESIS and NEOANGIOGENESIS.
Up to what extent other cell formations are stimulated for regeneration is subject to further research. But at this point
we definitely can make the statement that the Dermaroller definitely contributes to skin rejuvenation. Neo-
Angiogenesis connotes a better blood flow. The supply with more oxygen and nutrition is increased, and the evacuation
of metabolism debris is accelerated.
At this point we also would like to emphasize the fact that from our point of view no ablative procedure will stimulate
Neo-Angiogenesis, and that includes also fractional lasers. We believe it is the opposite since the “hot” laser
beam “fuses” the capillaries and other tissue, and stimuli for sprouting of new vessels will be suppressed. The laser
beam transforms protein into necrosis (>50°C) that finally transforms into fibrotic tissue. These subdermally set fibrotic
points become confluent after several treatments and result rather in an upholstering effect below wrinkles.
But it is more than unlikely that a fractional laser beam stimulates neo-angiogenesis. And additionally to this fact,
the laser beam suppresses bleeding by fusing capillaries, and this in return will stops the release of growth factors
from blood platelets. And in addition the laser beam will destroy stems cells as well as other non-differentiated cells
and obstructs their potential for proliferation.
Pic.5 Till 2005 we knew little about the mechanism of action
of the Dermaroller in respect of neo-collagenesis. But the
findings of Martin Schwarz changed the entire picture, and we
were encouraged to invest more time and financial sources to
analyze this phenomenon. The article of Min Zhao et al. in
NATURE magazine 2006 was the ignition point to invest
more time in the study of cell biology were we found many
answers.
To any injury or sensation of the epithelium the organism reacts with electrical signals, and these in return initiate a
cascade of regeneration mechanisms. Usually there is a resting potential of -80 mV between the cells and the surrounding
electrolyte, the extra cellular liquid. The internal cell is charged negative, the surrounding interstitium and
the skin surface is charged positive. Not only after an injury, but obviously already after a stimulation the skin cell
membrane becomes semi-permeable to release various chemical elements such as potassium, sodium and anionic
proteins, as well as growth factors into the interstitium. This process changes the electrolyte, the conductivity increases
and the electrical resistance decreases dramatically. At the same time the electrical charge inside the cell
drops to 0 mV or above to +30 mV. This potential difference is essential for the regenerative process. Research at
Owen Biosciences and MatTek® laboratories show, that the needles of the Dermaroller have their own electrical
potential that obviously increases the electrical potential between the intra- and extra cellular situation. These tests
were performed on laboratory skin that does not have blood vessels. But still an increase of collagen fibers and released
growth factors could be substantiated.
Based on these facts we have revised our articles and graphics about the mechanism of action during and after Dermarolling.
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Pic. 6. This change of the electrical potential was
measured on a nerve cell and takes about 1 millisecond.
Skin cells might have a slightly higher reaction time.
Pic. 7. The left graphic shows the distribution of chemical
elements in cells and the extra-cellular space before an injury
or stimulation. In this stage the membrane is (almost) not
permeable.
Pi.8. In case of epithelial stimulation nerve cells send signals
within milliseconds to the surrounding skin cells. The
membrane of the skin cells becomes permeable and releases
the chemical properties in delayed steps into the interstitium.
The electrolyte changes its conductivity (diagrammed in a
deeper blue).
Within milliseconds this process is reversed. The membrane
changes its permeability to the opposite and the previous
released chemicals return into the cells. As longs as the
nerve signal persist, this release and return from and back to
the cells continues. This continued process is called ion-pump.
We assume that cell-released growth factors, and possibly
those from punctured capillaries, stimulate stem cells and
other non-differentiated cells to proliferate. Newly produced
fibroblasts migrate towards the point of injury for repair
purposes.
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Pic. 9. But a „repair“ as in normal injuries does not take
place. Since the needles are sterile and no gaping wound exists,
the fibroblasts are possibly “fooled” by the needles. The
needles penetrate the skin only for fractions of seconds, and
the pricking channels are closed within minutes by skin’s
elasticity. (As shown in in-vitro pictures of the University of
Jena after Dermarolling).
The resting potential is restored and fibroblasts transform
into collagen fibers. Point 5 indicated the neo-angiogenesis of
capillaries (see more distinct graphics further down).
In relation to its seize the cell-membrane potential is enormous.
In average the membrane has a thickness of 70 to 100
nm. If the membrane would be up-scaled to 1 m the electrical
potential difference would be 10 million Volt. (Jaffe et a.)
Histological findings of a blinded study. Performed by Schwarz und Laaff, Freiburg/Germany, 2006. In the right biopsy
an increase of exactly 1000% of new collagen- and elastin fibers (stained purple) could be found.
Pic. 10. Not needled biopsy Pic. 11. Needles biopsy after 6 weeks.
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Pic. 12. There are a lot of discussions “how long” a needle for collagen induction should be.
The slide with the projected needle clearly indicates that new collagen formation only forms in the upper dermis and
down to an average depth of 0.5 to 0.6 mm.
There is no logic reason to use longer needles when the average skin thickness is only 1.5 mm.
As postulated by Augst et al. the new collagen formation integrates into the elastic collagen grid below the corium
but never forms a fibrotic cluster, as it is the case after wound repair by fibrosis.
Most Dermaroller treatments were performed on acne scars. The sharp needles perforate the stringent and hard scar
tissue. This supports the migrating of new capillaries and collagen fibers into the previous scar bed to form new tissue.
Pic.13. Pic.14.
Pics. 15 & 16. Patient after 2nd Dermaroller treatment (healing still in progress). Dermaroller models used: MF8 and
MS4
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Pic. 17. Neo-Angiogenesis can only be logically
explained when non-differentiated endothelial
cells proliferate and new capillary sprouts migrate
into the needled fibrotic tissue.
The previous hypo-pigmented scar tissue and its
surrounding resume a normal blood circulation
and the ivory-like scar disappears.
It sure would be a misjudgment to assume that only fibroblasts and endothelial cells would be stimulated by Dermarolling.
This would be in contrary to the phenomenon that skin-needling obviously also simulates other cells to
proliferate or to decrease over production (sebum, melanin, etc.). It was observed in many cases that pigment concentrations
associated with acne scars were evenly distributed after the treatment. The only conclusion we have at
this stage is that electrical signals stimulated by the needling process have a direct influence on all skin cells.
CONCLUSION
The body reacts to all ablative procedures with its repair mechanism – fibrosis. To Dermarolling the body reacts
with cell regeneration.
No doubt, during the development of the Dermaroller the coincidence acted like Godfather. As little is known about
needling it is was along and frustrating way for the achievement of our today’s knowledge. 1999 we started with the
development of a device for transdermal delivery with tiny and short needles (0.2 mm). Today the Dermaroller is
widely used (>95%) for skin therapies such as scars, pigmentations problems, etc. But in respect of the entire
mechanism of action we still are in need of explanation, but the facts speak a clear language. The therapeutic value
of the Dermaroller is already beyond any doubt, but we are still looking for some missing stones to form the final
mosaic. In 2007 and 2008 many physicians approached us and asked for support for further investigations and studies.
It was our pleasure to comply with their demands. We hope that most articles will be published this in 2008 to
bring us deepened insights for present and new therapies with the Dermaroller.
Therefore we would like to take the opportunity to thank all these scientists. Their commitment is our motivation.
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SIGNAL PATH FOR PROLIFERATION
ONLY stem cells in the vicinity of a distance of 1 to 2 mm
around the point and path of injury receive signals to proliferate.
Therefore we can conclude:
NOT PRESSURE stimulates the amount of new stem cells and
undifferentiated cells but the NUMBER of passes of the
Dermaroller-Needles through the skin.