Upload
decentjoe
View
232
Download
0
Embed Size (px)
Citation preview
8/9/2019 Scarless Healing Faq
1/112
Table of Contents
Summary of the thread ................................................................................................................................. 3
Summary 1 ................................................................................................................................................ 4
Scar Free Healing Thread Introduction 1.0 ................................................................................................... 6
1. Informed Education .................................................................................................................................. 7
1.1 Scarring and Regenerative Pathway ................................................................................................... 8
2 Technical Processes And Factors That Can Be Used in Scar Free Healing in Adult Tissues ..................... 16
2.1 Removal of Scar Tissue...................................................................................................................... 17
2.2 Inhibiting Fibrosis .............................................................................................................................. 18
2.2.1 ECM in Inhibiting Fibrosis ........................................................................................................... 19
2.2.2 Oligo ........................................................................................................................................... 20
2.2.3 Decorin Inhibiting Fibrosis ......................................................................................................... 21
2.3 Antibacterial Factor in Scar Free Healing Concept ........................................................................... 34
2.3.1 ECM Antibacterial Profile ........................................................................................................... 35
2.4 Inhibiting Inflammation .................................................................................................................... 36
2.4.1 Fetuin ......................................................................................................................................... 37
2.4.2 ECM in Inhibiting Inflammation ................................................................................................. 40
2.5 Growth Factors ................................................................................................................................. 41
2.6 Stem Cells .......................................................................................................................................... 42
2.6.1 ECMs & Stem Cell ...................................................................................................................... 44
2.6.2 Progenitor Cells/Stem Cells ........................................................................................................ 45
2.7 Extracellular Matrix ........................................................................................................................... 47
2.7.1 Hindsight View With Regards To A Fibrin Contaminated UBM ECM ......................................... 65
3. Various Predictions ................................................................................................................................. 93
4. Advancements (Please Read) .................................................................................................................. 95
5. Anticipation ........................................................................................................................................... 100
6. External links ......................................................................................................................................... 101
7. Linked threads ....................................................................................................................................... 102
8. FAQs ..................................................................................................................................................... 103
9. Current & previous pdfs of thread material, pre-amendments ........................................................... 104
8/9/2019 Scarless Healing Faq
2/112
9.1 Tom_Masons Original introduction: ............................................................................................... 104
10. Template Letter Headings and Bodies ................................................................................................ 105
Works Cited ............................................................................................................................................... 106
8/9/2019 Scarless Healing Faq
3/112
Summary of the thread
The summary is not yet consensus, and makes no claims to be consensus of acne.org, and no
editor claims to be an authority on this subject. There are other summaries. Spaces are always
there for other summaries for posters to write as to how they see it.
The summary here is a logically strong summary and validated by cited sources in this fact file.
(Please note: being valid does not say it is the truth. However the first summary that is cited
below, is a strong as you can get and shows it is certainly here and every angle has been
covered, the odds on it not being here must be one against a one with many zeros when you
connect. A lot of people may agree the first summary is very close to 100%. And it is other
peoples interests to come on to the board and prove it is not here if they want it gone). There is
a chance for you to write your summary as to how you see it.
Over time who knows we may have a consensus summary, as well as personal summaries,
trying to use sourced logic. Try to use cites and maybe we can reach consensus, slowly overtime.
Note this is not advice, this is cited/non cited information on scar free healing, if you need
advice seek a professional. And hope this professional is informed; there are professionals who
are more informed than the next and so on.
8/9/2019 Scarless Healing Faq
4/112
Summary 1
This thread is a discussion about the scar free healing concept. Scar free healing that for many,
will soon end disfigurement with regards to fibrosis of the fibrils.
Over the last ten year there have been claims and predictions ranging from 2007 to 2012 when
scar free healing of the fibrils will be here. (1) And over this time there have been massive
advancements...
In this thread we have seen that a lot of progress has been made, we have seen and discussed
the logic of various materials and factors, we have seen there are now applications that inhibit
inflammation and fibrosis; we have seen animals using ECM regenerate skin and hair without
strictly following a course of treatment; we have briefly hit on a component in ECM called
decorin that completely inhibits scarring, reduces wound contraction, keeps the ECM fibrils in a
normal slender woven elastin state which enables tissues to freely crawl up the ECM without
being blocked by over expression of collagen on the fibrils and we understand our tissues have
been regenerating with these slender fibrils through evolution; in 1999 scar free healing
concept was first achieved and proven when a bladder (a simple tissue like skin, Badylak, Atala
et al) regenerated (note: you can NOT have any regeneration with any fibrosis,Atala); in 2007 a
denatured 1st generation SIS ECM, denatured by a metal rim, regenerated heart tissue 95%,
bringing a further taster about the next generation ECMs (UBM-ECM) potential with our softer
tissues, considering our scarring process is the same in all our tissues. (there is a newer version
in development without the metal rim which will enable 100% resoring in the heart); We have
looked at stem cells; We have seen complete scar free healing; and in 2008 we were shown
science had announced that the genetic factors involved in perfect regeneration are
understood and can be manipulated (Heber-Katz) (note, again: you can not regenerate anytissue if you have fibrosis to paraphraseAtala law) meaning as well as having the mammal
materials to bring scar free healing we understand the micro processes of these materials In
this thread we have seen Scar free healing has been achieved and is completely understood, and
is now even understood at a micro level.
The reason for this introduction is to show new users, by cites, scar free healing, please read on
and make your own mind up.
Summary 2,
yet to be written
Summary 3,
yet to be written and so on.
Consensus summary,
yet to be written.
8/9/2019 Scarless Healing Faq
5/112
Regarding all the text outside the quote boxes, below, it is free, you are free to copy, edit and do what you want;
Permission is granted to copy, distribute and/or modify this document under the terms of the GNU Free Documentation License, Version 1.2 or
any later version published by the Free Software Foundation; with no Invariant Sections, no Front-Cover Texts, and no Back-Cover Texts. A copy
of the license is included in the section entitled"GNU Free Documentation License
The quoted boxes are quotes and links used as citations from intellectual property, they can be used without modification for cited educationalpurposes:
http://en.wikipedia.org/wiki/GNU_Free_Documentation_Licensehttp://en.wikipedia.org/wiki/GNU_Free_Documentation_Licensehttp://en.wikipedia.org/wiki/GNU_Free_Documentation_Licensehttp://commons.wikimedia.org/wiki/Commons:GNU_Free_Documentation_Licensehttp://commons.wikimedia.org/wiki/Commons:GNU_Free_Documentation_Licensehttp://commons.wikimedia.org/wiki/Commons:GNU_Free_Documentation_Licensehttp://commons.wikimedia.org/wiki/Commons:GNU_Free_Documentation_Licensehttp://en.wikipedia.org/wiki/GNU_Free_Documentation_License8/9/2019 Scarless Healing Faq
6/112
Scar Free Healing Thread Introduction 1.0
Scar Free Healing was once described as a concept were you bring the healing response to
perfect regeneration, a process once described as the Holy Grail. (2)
Fetal protein holds key
The quest for the holy grail of scarless healing had truly begun.
http://www.news.com.au/couriermail/story/0,23739,16844871-3102,00.html
Before it come about, perfect regeneration and scar free healing was once described as a
simple problem that would release the torture of disfigurement and mobility that involves
scarring of tissues.
http://www.news.com.au/couriermail/story/0,23739,16844871-3102,00.htmlhttp://www.news.com.au/couriermail/story/0,23739,16844871-3102,00.htmlhttp://www.news.com.au/couriermail/story/0,23739,16844871-3102,00.html8/9/2019 Scarless Healing Faq
7/112
1. Informed Education
There is information out there, but also misinformation. There is a need to educate about the
advancement scar free healing and how it is here. (3)
A Scarless Future: The Wound Care Update Paper 2006, pdf - P. 3
Experts remain optimistic about the future of the category, predicting a world without scars.
Research and education will be critical to the advancement of wound care practices.
Note: the above paper is now off line.
With this there is also a need to scientifically and logically think.
8/9/2019 Scarless Healing Faq
8/112
1.1 Scarring and Regenerative Pathway
In healing, without intervention an adult wound, scars. A scar is collagen over expression that
blocks off regeneration. (4) In adult tissues there is a race between scarring and regeneration to
which scarring usually wins by over expressing collagen on the fibrils, these dense fibrils thenblock the pathways for regeneration In regeneration the fibrils in our tissues should be
slender.
The scarring response amongst our softer tissues is said similar in all tissues of the body. (5) (6)
And all our tissues have the ability to regenerate in them. With the bladder and skin being
simpler tissues man has already regenerated. This gives hope for more complex tissues and
digits which will come after.
To regenerate tissue it is noted you have to eliminate the scar, (4) as in tissue engineering,
everything goes back to scar tissue formation. (4) You cant regenerate tissue if you get a
fibrotic response. Scar tissue stops the intercellular tissues regenerating. (4) (6)
(and the scar free healing concept was officially proven in 1999, (4) be it under the radar, with a
bladder (4) (a simple tissue like skin badylak et al) which was perfectly regenerated with
ECM!!!)
Take note of the Atala law: It all leads back to the scar. Eliminate the scar and you can
regenerate tissue, even digits and complex organs. You dont eliminate the scar you cannot
regenerate tissue. (4) If you remove the scar you can regenerate simple tissues and move onto
regenerating organs and limbs
Scar-free healing: from embryonic mechanisms to adult therapeutic intervention." (2004-
04-20), p. 2.
glomerulonephritis, pulmonary fibrosis, etc., which share many of the cellular and molecular
mechanisms common to scarring.
http://www.renovo.com/documents/radF37FC.pdf
Profile: Anthony Atala - Nature Biotechnology
"In tissue engineering," Atala says, "everything goes back to scar formation."
Google search, Atala goes back to scar
http://en.wikipedia.org/wiki/2004http://en.wikipedia.org/wiki/2004http://en.wikipedia.org/wiki/2004http://en.wikipedia.org/wiki/April_20http://en.wikipedia.org/wiki/April_20http://www.renovo.com/documents/radF37FC.pdfhttp://www.renovo.com/documents/radF37FC.pdfhttp://www.nature.com/nbt/journal/v24/n11/full/nbt1106-1311.htmlhttp://www.nature.com/nbt/journal/v24/n11/full/nbt1106-1311.htmlhttp://www.renovo.com/documents/radF37FC.pdfhttp://www.nature.com/nbt/journal/v24/n11/full/nbt1106-1311.htmlhttp://www.renovo.com/documents/radF37FC.pdfhttp://en.wikipedia.org/wiki/April_20http://en.wikipedia.org/wiki/20048/9/2019 Scarless Healing Faq
9/112
http://www.nature.com/nbt/journal/v24/n11/full/nbt1106-1311.html
As you can see above scar free regeneration concept was done in 1999 under the radar.
Humans can regrow fingers?It employs an entirely different process than the typical mammalian healing mechanism. Let's take the case of a
person who loses the tip of a finger. When the finger is severed, the cells die, and their contents seep into the
surrounding tissue. This alerts theimmune systemto a problem. The immune system's response to cell death is
inflammation and scar tissue. The formation of scar tissue prevents any future cellular development in the area.
That's why scars last -- cells are prevented from doing a repair job on that skin.
http://health.howstuffworks.com/extracellular-matrix.htm
As well as scar free healing in non wounded tissues, it has been cited many times scar free
healing occurs in the embryonic stage of all mammals, animals and reptiles. This stage is called
the gestation period, and this critical scar free healing period ranges from the first one third or
first half of pregnancy in mammals. It is in the first three month of pregnancy in humans. (7)
Scar-free healing: from embryonic mechanisms to adult therapeutic intervention. (2004-04-
20), p. 2.
Skin wounds on early mammalian embryos heal perfectly with no signs of scarring and
complete restitution of the normal skin architecture
http://www.renovo.com/documents/radF37FC.pdf
It has been cited that regeneration of injured tissue happens in some body parts like the liver
and mouth. And it was noted that the small tubular intestine of a dog, when transplanted to
replace a dogs heart aorta, completely reabsorbed and morphed into the host aorta tissue. (8)
A Doctor, a Pig, and a Magical Pixie Dust That Could Regrow Fingers
http://www.nature.com/nbt/journal/v24/n11/full/nbt1106-1311.htmlhttp://www.nature.com/nbt/journal/v24/n11/full/nbt1106-1311.htmlhttp://health.howstuffworks.com/immune-system.htmhttp://health.howstuffworks.com/immune-system.htmhttp://health.howstuffworks.com/immune-system.htmhttp://health.howstuffworks.com/extracellular-matrix.htmhttp://health.howstuffworks.com/extracellular-matrix.htmhttp://en.wikipedia.org/wiki/2004http://en.wikipedia.org/wiki/2004http://en.wikipedia.org/wiki/April_20http://en.wikipedia.org/wiki/April_20http://en.wikipedia.org/wiki/April_20http://en.wikipedia.org/wiki/April_20http://www.renovo.com/documents/radF37FC.pdfhttp://www.renovo.com/documents/radF37FC.pdfhttp://www.google.com/search?sourceid=navclient&ie=UTF-8&rlz=1T4ACAW_enGB316GB316&q=Atala+goes+back+to+scarhttp://www.renovo.com/documents/radF37FC.pdfhttp://en.wikipedia.org/wiki/April_20http://en.wikipedia.org/wiki/April_20http://en.wikipedia.org/wiki/2004http://health.howstuffworks.com/extracellular-matrix.htmhttp://health.howstuffworks.com/immune-system.htmhttp://www.nature.com/nbt/journal/v24/n11/full/nbt1106-1311.html8/9/2019 Scarless Healing Faq
10/112
the new part of the aorta, he discovered that the intestine had not become simply a tube to pass
blood through but had literally morphed into an aorta. And no scar tissue had formed.
http://www.esquire.com/features/esquire-100/pigfinger1007
The Axolotl Urodele amphibian came to attention, this Salamander has mastered the ability to
repair and replace most of their tissues following damage. (9) It is cited that the salamander can
regenerate wounds and limbs by forming blastemas, (10) and it was found by Ellen Heber-Katz
that the Murphy Roths Large mouse (MLR) heals without scarring on certain regions its wild
field compatriot does not. (11) It is of note that the MLR mouse has shown signs of blastema
(ECM) formation in lost limbs too. And blastemas are found extensively in the human fetus but
are less prone after birth in wounded tissue. (12)
Humans can regrow fingers?But when extracellular matrix is applied to a wound, it doesn't trigger an immune response. Instead, when it begins
to break down into surrounding tissue, it causes the cells in that tissue to start repairing the damage the way they
would in a developing fetus (or a salamander that loses a limb) -- they divide and rebuild, creating new, normal
tissue, not scar tissue.
http://health.howstuffworks.com/extracellular-matrix.htm
"Researchers Work Toward Regenerating Lost Extremities",
""You pull a tail off a salamander, and it regrows," Wolf said. "The end of the tail forms what is
called a blastema, and that blastema elongates. We think that's what happens when we put
this powder on."
http://www.infozine.com/news/stories/op/storiesView/sid/30243/
"Mouse sheds light on regeneration",
"So we did it again, and we watched them, and there it was - the holes had closed up.
http://www.esquire.com/features/esquire-100/pigfinger1007http://www.esquire.com/features/esquire-100/pigfinger1007http://health.howstuffworks.com/extracellular-matrix.htmhttp://health.howstuffworks.com/extracellular-matrix.htmhttp://www.infozine.com/news/stories/op/storiesView/sid/30243/http://www.infozine.com/news/stories/op/storiesView/sid/30243/http://www.infozine.com/news/stories/op/storiesView/sid/30243/http://www.infozine.com/news/stories/op/storiesView/sid/30243/http://news.bbc.co.uk/1/hi/sci/tech/4888080.stmhttp://news.bbc.co.uk/1/hi/sci/tech/4888080.stmhttp://www.esquire.com/features/esquire-100/pigfinger1007http://news.bbc.co.uk/1/hi/sci/tech/4888080.stmhttp://www.infozine.com/news/stories/op/storiesView/sid/30243/http://www.infozine.com/news/stories/op/storiesView/sid/30243/http://health.howstuffworks.com/extracellular-matrix.htmhttp://www.esquire.com/features/esquire-100/pigfinger10078/9/2019 Scarless Healing Faq
11/112
http://news.bbc.co.uk/1/hi/sci/tech/4888080.stm
Humans to grow replacement body partsBlastemas are found in human foetuses but disappear after birth. Regenerative medicine would
allow a genetic trigger to be applied to tissue to prompt cells to grow into the required parts.
http://www.timesonline.co.uk/tol/news/uk/science/article3867838.ece
Research has focused on the Embryonic stage, liver, mouth, the salamander, the MLR mouseand ECM with the intestinal submucosa, liver, and latterly the uninary bladder. And has
developed key insights, bringing predictions of scar free healing over the last ten year; with
experts also claiming to have seen scar free healing in 2002. (1) A case in point in 2007 using an
earlier ECM with a metal rim that was also denatured, achieved a 95% average regeneration of
our more complex tissues (13) (what happens in the heart would easily happen in simple
tissues), the only thing that was left was the metal ring and the ECM morphed into tissue, a
newer version that promises 100% healing without the metal rim is being developed; between
http://news.bbc.co.uk/1/hi/sci/tech/4888080.stmhttp://news.bbc.co.uk/1/hi/sci/tech/4888080.stmhttp://www.timesonline.co.uk/tol/news/uk/science/article3867838.ecehttp://www.timesonline.co.uk/tol/news/uk/science/article3867838.ecehttp://www.timesonline.co.uk/tol/news/uk/science/article3867838.ecehttp://news.bbc.co.uk/1/hi/sci/tech/4888080.stm8/9/2019 Scarless Healing Faq
12/112
years 2003 and 2005 complete scar free healing was shown with Alloderm; (14) and in 2008
Heber-Katz, the scientist who in 2006 announced digit regeneration would be here within five
year, announced the genetic characteristics of perfect regeneration had been achieved and
manipulated (15) meaning every angle is now covered. And in figure x you can see an example
of perfect regeneration of a melanoma patient using a denatured ECM called apligraf.
A Scarless Future: The Wound Care Update Paper 2006, P. 5, pdf
Professor Kimble believes may be a reality within the next four years.
The proper treatment of wounds and ways to minimize scarring, 2003, P. 25, pdf
I can show you scarless healing... Dr Peter Maitz, Director of Burns Unit, Concord Hospital
I think its within the foreseeable future...five to ten years. Geoff Sussman, Founder and
Director of the Wound Education & Research Group,
Monash University
Biologically itshould be feasible to have tissue heal perfectly. Professor John Harris, Head of
Department of Surgery, Sydney University
First Ever Implantation of Bioabsorbable Biostar Device at DHZB
8/9/2019 Scarless Healing Faq
13/112
The almost transparent collagen matrix consists of medically purified pig intestine, which is
broken down by the scavenger cells (macrophages) of the immune system. After about 1 year
the collagen has been almost completely (90-95%) replaced by normal body tissue: only the tiny
metal framework remains. An entirely absorbable implant is currently under development.,
DHZB NEWS, December 2007
http://www.dhzb.de/international_services/dhzb_aktuell/detail/ansicht/pressedetail/290/
The Use of Acellular Dermal Matrix for Coverage of Exposed Joint and Extensor Mechanism in
Thermally Injured Patients With Few Options
http://www.eplasty.com/article_images/eplasty08e33_fig1.gif
http://www.eplasty.com/index.php?option=com_content&task=view&id=213&Itemid=36§
=15
Humans to grow replacement body parts
http://www.dhzb.de/international_services/dhzb_aktuell/detail/ansicht/pressedetail/290/http://www.dhzb.de/international_services/dhzb_aktuell/detail/ansicht/pressedetail/290/http://www.eplasty.com/article_images/eplasty08e33_fig1.gifhttp://www.eplasty.com/article_images/eplasty08e33_fig1.gifhttp://www.eplasty.com/index.php?option=com_content&task=view&id=213&Itemid=36§=15http://www.eplasty.com/index.php?option=com_content&task=view&id=213&Itemid=36§=15http://www.eplasty.com/index.php?option=com_content&task=view&id=213&Itemid=36§=15http://www.eplasty.com/index.php?option=com_content&task=view&id=213&Itemid=36§=15http://www.eplasty.com/index.php?option=com_content&task=view&id=213&Itemid=36§=15http://www.eplasty.com/article_images/eplasty08e33_fig1.gifhttp://www.dhzb.de/international_services/dhzb_aktuell/detail/ansicht/pressedetail/290/8/9/2019 Scarless Healing Faq
14/112
her group had discovered the genetic characteristics that produce good-as-new tissue
regeneration
http://www.timesonline.co.uk/tol/news/uk/science/article3867838.ece
the key to changing the scarring response in wounded tissue, to regeneration, involves getting
the body to sense it is not injured and does not need excess collagen. Our unwounded tissues
and embryonic tissues proved to man this would lie in the course of the wound healing, early
timing, inhibition of the inflammation response, and the availability of available factors, given at
the time of wounding for the regeneration pathway instead of the scarring cascade pathway. To
reiterate the wound needs to understand it is not injured and it has to regenerate like it does
non wounded. These early insights brought forward that early intervention around the initial
time of wounding can alter the scarring response, with the early window being a criticalwindow for a scarring pathway to a regeneration pathway. (16)
The proper treatment of wounds and ways to minimize scarring, pdf - P. 6
The time taken to heal a wound is directly related to how that wound will scar the best time
to treat a scar is during the initial phases of wound healing.
There are said to be a number of processes and factors said to be involved in the non wounded
tissue and the embryonic stage and tissue engineering that brings scar free healing that can be
manipulated in wounded adult tissues to bring about scar free healing. These factors are micro
factors involved in ECM and components of ECM like decorin, hyaluronic acid etc.:
*Growth Factors for pathways
*Inhibiting fibrosis
*Inhibiting Inflammation
*Stem Cells
*Timing, immediate implantation of factors at wounding by appointment is preferred.
**Extracellular matrix, the material matrix, that is not denatured and thus has slender fibrils,
regenerates all local tissues, and controls timing of factors, brings in stem cells, if notdenatured, it resorbs, inhibits fibrosis, it inhibits inflammation. It controls morphology and cell
shape, differentiation. On the other hand, if denatured it finds it harder to resorb and attracting
collagen over expression in the fibrils which brings a fibrotic response or an encapsulation
fibrous response which blocks of intercellular signaling. The denaturing of ECM affects the
fibrosis/regeneration balance.
http://www.timesonline.co.uk/tol/news/uk/science/article3867838.ecehttp://www.timesonline.co.uk/tol/news/uk/science/article3867838.ecehttp://www.timesonline.co.uk/tol/news/uk/science/article3867838.ecehttp://www.timesonline.co.uk/tol/news/uk/science/article3867838.ece8/9/2019 Scarless Healing Faq
15/112
**Decorin a component of ECM has completely inhibited scarring in tissues keeping the fibrils
slender.
It is known our tissues are clever they have been regenerating for thousands of years, and all
our intercellular tissues need is slender fibrils in the degradable scaffold (ECM). (17)
U.S. military can regrow human limbs, organs
American military researchers say they have unlocked the secret to regrowing limbs and
recreating organs in humans who have sustained major injuries.
'Nanoscaffolding' has succesfully regrown fingertips and organs on test subjects
Friday, November 07, 2008
http://www.canada.com/topics/news/story.html?id=6864c9e0-cfcc-4cf6-b373-6d4cbabe6cd3
http://www.canada.com/topics/news/story.html?id=6864c9e0-cfcc-4cf6-b373-6d4cbabe6cd3http://www.canada.com/topics/news/story.html?id=6864c9e0-cfcc-4cf6-b373-6d4cbabe6cd3http://www.canada.com/topics/news/story.html?id=6864c9e0-cfcc-4cf6-b373-6d4cbabe6cd38/9/2019 Scarless Healing Faq
16/112
2 Technical Processes And Factors That Can Be Used in ScarFree Healing in Adult Tissues
There is an understanding, that regeneration cannot happen without scar free healing and scar
free healing involves early application of factors to a wound, inhibiting fibrosis, inhibitinginflammation, inducing stem cells anything encouraging the regenerative pathway, similar to
the early embryonic stage and salamander limb regeneration, or our unwounded adult tissue
state; hence doing all the micro processes of the non denatured ECM.
8/9/2019 Scarless Healing Faq
17/112
2.1 Removal of Scar Tissue
Removing scar tissue. Wounding by appointment. To remove a scar you have two techniques, a
scar revision or, have the scar dissolved with an enzyme, that attacks scarring to make a fresh
wound were the factors can be allowed to remodel without the fibrotic fibers (scarring/collagen
over expression etc.) blocking up the micro pores. (18)
Rebuilding the Troops
researchers have developed an enzyme that eats away scar tissue so they can dust the healthy
cells below.
http://www.popsci.com/military-aviation-space/article/2008-06/rebuilding-troops?page=
It is of note that lack of fibrinolytic enzymes brings fibrosis of tissues. (19)
Anti Fibrosis (Scar Tissue removal)
Fibrinolytic enzymes eat scar tissue and fibrosis
we make a finite amount of enzymes in a lifetime and we use up a good deal of them by the
time we reach our 40's Cystic Fibrosis patients who have virtually no enzyme production to
speak of, even as children usually don't make it past their 20's before they die of the restriction
and shrinkage in the lungs from the formation of fibrosis or scar tissue.
http://www.enzymus.com/scar_tissue_buildup
It is also of note that plasmin is a fibrinolytic enzyme our own body naturally makes. (20)
Eat Natto and Care for Your Cardiovascular System Naturally
The body naturally produces its own fibrinolytic enzyme, called plasmin.
http://www.naturalnews.com/025684.html
http://www.popsci.com/military-aviation-space/article/2008-06/rebuilding-troops?pagehttp://www.enzymus.com/scar_tissue_builduphttp://www.enzymus.com/scar_tissue_builduphttp://www.naturalnews.com/025684.htmlhttp://www.naturalnews.com/025684.htmlhttp://www.enzymus.com/scar_tissue_builduphttp://www.popsci.com/military-aviation-space/article/2008-06/rebuilding-troops?page=http://www.naturalnews.com/025684.htmlhttp://www.enzymus.com/scar_tissue_builduphttp://www.popsci.com/military-aviation-space/article/2008-06/rebuilding-troops?page8/9/2019 Scarless Healing Faq
18/112
2.2 Inhibiting Fibrosis
8/9/2019 Scarless Healing Faq
19/112
2.2.1 ECM in Inhibiting Fibrosis
Non-denatured ECM, which has decorin, hyaluronic acid, when applied to a fresh wound in the
early stages, going by it regenerates local host tissues, inhibits the fibrosis response. They key is
an early application to a fresh wound without a scar wall.
8/9/2019 Scarless Healing Faq
20/112
2.2.2 Oligo
Oligo decoys (small sugar chains) are natural therapeutics for inhibition of tissue fibrosis. (21)
TGF-beta-induced fibrosis and SMAD signaling: oligo decoys as natural therapeutics for
inhibition of tissue fibrosis and scarring,2007 Sep-Oct
http://www.ncbi.nlm.nih.gov/pubmed/17727468?ordinalpos=4&itool=EntrezSystem2.PEntrez.
Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
http://www.ncbi.nlm.nih.gov/pubmed/17727468?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov/pubmed/17727468?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov/pubmed/17727468?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov/pubmed/17727468?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov/pubmed/17727468?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum8/9/2019 Scarless Healing Faq
21/112
2.2.3 Decorin Inhibiting Fibrosis
Decorin gets its name from the fact it decorates collagen fibrils (22) (fibrils are fibres these
fibres have more fibres within the fibres).
Decorin
Asmallproteoglycan, 90-140kD, of theextracellular matrix, so called because it decorates
collagenfibres.
Thecoreproteinhas amassof approximately 42kDand is verysimilarto the core protein of
biglycanandfibromodulin. All three have highlyconserved sequencescontaining 10internal
homologousrepeats of approximately 25amino acidswithleucinerichmotifs.
Decorin has oneglycosaminoglycanchain, eitherchondroitin sulphateordermatan sulphate
and Nlinkedoligosaccharides.
This entry appears with permission from theDictionary of Cell and Molecular Biology
(11 Mar 2008)
http://www.mondofacto.com/facts/dictionary?decorin
Like ECM, and hyaluronic acid, decorin (a component of ECM) has been studied and a lot of
products are being designed on its micro mechanisms of action.
In wounds it is known there is a race between scarring and regeneration. Decorin stops scarring
by keeping the fibrils slender. Decorin plays a part in non denatured ECM healing. (Question,
would decorin salvage slightly denatured ECM?). It is the factor that tells the ECM Im not
injured, do not scar, and let the ECM be normally woven without the over expression of collagen
on the fibers. Decorin completely hinders the scarring response which enables intercellular
tissues to crawl up the ECM to win the race.
Decorin is a normal human protein, and naturally occurring extracellular matrix protein, a
proteoglycan that has a regulatory effect mechanism over TGF-, and whilst inhibiting TGF-B it
increases the expression of key MMPs that break down the ECM. (23) Evidence shows that
decorin is requiredfor the proper assembly of collagenous matrices
Extracellular matrix: review of its roles in acute and chronic wounds
Proteoglycans can also bind chemokine molecules on the surface of endothelial cells, prolonging
the inflammatory response. Although growth factors typically bind to the GAG chains of
proteoglycans, members of the transforming growth factor beta (TGF-) family bind to the core
protein of the decorin proteoglycan. TGF- directly increases scar formation by increasing the
expression of collagen, fibronectin and lysyl oxidase while reducing the expression of MMPs,
which break down the ECM. TGF- is also chemotactic for macrophages and neutrophils, which
prolongs the inflammatory response and contributes to scarring. When TGF- is bound by the
core protein of decorin it is not able to interact with its normal receptor protein on target cells,
which inhibits the activity of TGF-. Proteoglycans such as syndecan protect elastase from the
http://www.mondofacto.com/facts/dictionary?smallhttp://www.mondofacto.com/facts/dictionary?smallhttp://www.mondofacto.com/facts/dictionary?proteoglycanhttp://www.mondofacto.com/facts/dictionary?proteoglycanhttp://www.mondofacto.com/facts/dictionary?proteoglycanhttp://www.mondofacto.com/facts/dictionary?kDhttp://www.mondofacto.com/facts/dictionary?kDhttp://www.mondofacto.com/facts/dictionary?kDhttp://www.mondofacto.com/facts/dictionary?extracellular+matrixhttp://www.mondofacto.com/facts/dictionary?extracellular+matrixhttp://www.mondofacto.com/facts/dictionary?extracellular+matrixhttp://www.mondofacto.com/facts/dictionary?collagenhttp://www.mondofacto.com/facts/dictionary?fibreshttp://www.mondofacto.com/facts/dictionary?fibreshttp://www.mondofacto.com/facts/dictionary?fibreshttp://www.mondofacto.com/facts/dictionary?corehttp://www.mondofacto.com/facts/dictionary?corehttp://www.mondofacto.com/facts/dictionary?proteinhttp://www.mondofacto.com/facts/dictionary?proteinhttp://www.mondofacto.com/facts/dictionary?proteinhttp://www.mondofacto.com/facts/dictionary?masshttp://www.mondofacto.com/facts/dictionary?masshttp://www.mondofacto.com/facts/dictionary?masshttp://www.mondofacto.com/facts/dictionary?kDhttp://www.mondofacto.com/facts/dictionary?kDhttp://www.mondofacto.com/facts/dictionary?kDhttp://www.mondofacto.com/facts/dictionary?similarhttp://www.mondofacto.com/facts/dictionary?similarhttp://www.mondofacto.com/facts/dictionary?similarhttp://www.mondofacto.com/facts/dictionary?biglycanhttp://www.mondofacto.com/facts/dictionary?biglycanhttp://www.mondofacto.com/facts/dictionary?fibromodulinhttp://www.mondofacto.com/facts/dictionary?fibromodulinhttp://www.mondofacto.com/facts/dictionary?fibromodulinhttp://www.mondofacto.com/facts/dictionary?conserved+sequenceshttp://www.mondofacto.com/facts/dictionary?conserved+sequenceshttp://www.mondofacto.com/facts/dictionary?conserved+sequenceshttp://www.mondofacto.com/facts/dictionary?internalhttp://www.mondofacto.com/facts/dictionary?internalhttp://www.mondofacto.com/facts/dictionary?internalhttp://www.mondofacto.com/facts/dictionary?homologoushttp://www.mondofacto.com/facts/dictionary?homologoushttp://www.mondofacto.com/facts/dictionary?amino+acidshttp://www.mondofacto.com/facts/dictionary?amino+acidshttp://www.mondofacto.com/facts/dictionary?amino+acidshttp://www.mondofacto.com/facts/dictionary?leucinehttp://www.mondofacto.com/facts/dictionary?leucinehttp://www.mondofacto.com/facts/dictionary?richhttp://www.mondofacto.com/facts/dictionary?richhttp://www.mondofacto.com/facts/dictionary?motifshttp://www.mondofacto.com/facts/dictionary?motifshttp://www.mondofacto.com/facts/dictionary?motifshttp://www.mondofacto.com/facts/dictionary?glycosaminoglycanhttp://www.mondofacto.com/facts/dictionary?glycosaminoglycanhttp://www.mondofacto.com/facts/dictionary?chainhttp://www.mondofacto.com/facts/dictionary?chainhttp://www.mondofacto.com/facts/dictionary?chainhttp://www.mondofacto.com/facts/dictionary?chondroitin+sulphatehttp://www.mondofacto.com/facts/dictionary?chondroitin+sulphatehttp://www.mondofacto.com/facts/dictionary?chondroitin+sulphatehttp://www.mondofacto.com/facts/dictionary?dermatan+sulphatehttp://www.mondofacto.com/facts/dictionary?dermatan+sulphatehttp://www.mondofacto.com/facts/dictionary?dermatan+sulphatehttp://www.mondofacto.com/facts/dictionary?linkedhttp://www.mondofacto.com/facts/dictionary?linkedhttp://www.mondofacto.com/facts/dictionary?oligosaccharideshttp://www.mondofacto.com/facts/dictionary?oligosaccharideshttp://www.mondofacto.com/facts/dictionary?oligosaccharideshttp://www.mblab.gla.ac.uk/dictionary/http://www.mblab.gla.ac.uk/dictionary/http://www.mblab.gla.ac.uk/dictionary/http://www.mondofacto.com/facts/dictionary?decorinhttp://www.mondofacto.com/facts/dictionary?decorinhttp://www.mondofacto.com/facts/dictionary?decorinhttp://www.mblab.gla.ac.uk/dictionary/http://www.mondofacto.com/facts/dictionary?oligosaccharideshttp://www.mondofacto.com/facts/dictionary?linkedhttp://www.mondofacto.com/facts/dictionary?dermatan+sulphatehttp://www.mondofacto.com/facts/dictionary?chondroitin+sulphatehttp://www.mondofacto.com/facts/dictionary?chainhttp://www.mondofacto.com/facts/dictionary?glycosaminoglycanhttp://www.mondofacto.com/facts/dictionary?motifshttp://www.mondofacto.com/facts/dictionary?richhttp://www.mondofacto.com/facts/dictionary?leucinehttp://www.mondofacto.com/facts/dictionary?amino+acidshttp://www.mondofacto.com/facts/dictionary?homologoushttp://www.mondofacto.com/facts/dictionary?internalhttp://www.mondofacto.com/facts/dictionary?conserved+sequenceshttp://www.mondofacto.com/facts/dictionary?fibromodulinhttp://www.mondofacto.com/facts/dictionary?biglycanhttp://www.mondofacto.com/facts/dictionary?similarhttp://www.mondofacto.com/facts/dictionary?kDhttp://www.mondofacto.com/facts/dictionary?masshttp://www.mondofacto.com/facts/dictionary?proteinhttp://www.mondofacto.com/facts/dictionary?corehttp://www.mondofacto.com/facts/dictionary?fibreshttp://www.mondofacto.com/facts/dictionary?collagenhttp://www.mondofacto.com/facts/dictionary?extracellular+matrixhttp://www.mondofacto.com/facts/dictionary?kDhttp://www.mondofacto.com/facts/dictionary?proteoglycanhttp://www.mondofacto.com/facts/dictionary?small8/9/2019 Scarless Healing Faq
22/112
inhibition by alpha-1 proteinase inhibitor, suggesting that they modify the proteolytic
environment of wounds.
http://www.worldwidewounds.com/2005/august/Schultz/Extrace-Matric-Acute-Chronic-
Wounds.html
United States Patent 6509314 - Methods of preventing or reducing scarring with decorin orbiglycan
The advantage of using decorin or a functional equivalent in the methods of the present
invention is that it is a normal human protein and is believed to be involved in the natural TGF-
regulatory pathway. Thus, decorin can be used to prevent or reduce dermal scarring resulting
from burn injuries, other invasive skin injuries, and cosmetic or reconstructive surgery.
Decorin-treated wounds have been found to exhibit essentially no detectable scarring compared
to control wounds not treated with decorin.
http://www.freepatentsonline.com/6509314.html
It has been known since 1992 that decorin causes wound repair in every tissue. (24)
PROTEIN HELPS REPAIR `EVERY TISSUE,' MAY...
``This protein causes wound repair in every tissue,'' he said.THE SALT LAKE TRIBUNE SLTribune , 1992-11-26
http://nl.newsbank.com/nl-
search/we/Archives?p_product=SLTB&p_theme=sltb&p_action=search&p_maxdocs=200&p_to
pdoc=1&p_text_direct-0=10114883EC896EBC&p_field_direct-
0=document_id&p_perpage=10&p_sort=YMD_date:D&s_trackval=GooglePM
In a normal wound healing response, were extracellular matrix is not externally applied,
contraction of wounds is a factor that brings fibrosis. (25)
New mechanical insights into wound healing and scar tissue formation
When we are injured, the body launches a complex rescue operation. Specialized cells called
fibroblasts lurking just beneath the surface of the skin jump into action, enter the provisional
wound matrix (the clot) and start secreting collagen to close the wound as fast as possible. This
http://www.worldwidewounds.com/2005/august/Schultz/Extrace-Matric-Acute-Chronic-Wounds.htmlhttp://www.worldwidewounds.com/2005/august/Schultz/Extrace-Matric-Acute-Chronic-Wounds.htmlhttp://www.worldwidewounds.com/2005/august/Schultz/Extrace-Matric-Acute-Chronic-Wounds.htmlhttp://www.freepatentsonline.com/6509314.htmlhttp://www.freepatentsonline.com/6509314.htmlhttp://nl.newsbank.com/nl-search/we/Archives?p_product=SLTB&p_theme=sltb&p_action=search&p_maxdocs=200&p_topdoc=1&p_text_direct-0=10114883EC896EBC&p_field_direct-0=document_id&p_perpage=10&p_sort=YMD_date:D&s_trackval=GooglePMhttp://nl.newsbank.com/nl-search/we/Archives?p_product=SLTB&p_theme=sltb&p_action=search&p_maxdocs=200&p_topdoc=1&p_text_direct-0=10114883EC896EBC&p_field_direct-0=document_id&p_perpage=10&p_sort=YMD_date:D&s_trackval=GooglePMhttp://nl.newsbank.com/nl-search/we/Archives?p_product=SLTB&p_theme=sltb&p_action=search&p_maxdocs=200&p_topdoc=1&p_text_direct-0=10114883EC896EBC&p_field_direct-0=document_id&p_perpage=10&p_sort=YMD_date:D&s_trackval=GooglePMhttp://nl.newsbank.com/nl-search/we/Archives?p_product=SLTB&p_theme=sltb&p_action=search&p_maxdocs=200&p_topdoc=1&p_text_direct-0=10114883EC896EBC&p_field_direct-0=document_id&p_perpage=10&p_sort=YMD_date:D&s_trackval=GooglePMhttp://nl.newsbank.com/nl-search/we/Archives?p_product=SLTB&p_theme=sltb&p_action=search&p_maxdocs=200&p_topdoc=1&p_text_direct-0=10114883EC896EBC&p_field_direct-0=document_id&p_perpage=10&p_sort=YMD_date:D&s_trackval=GooglePMhttp://nl.newsbank.com/nl-search/we/Archives?p_product=SLTB&p_theme=sltb&p_action=search&p_maxdocs=200&p_topdoc=1&p_text_direct-0=10114883EC896EBC&p_field_direct-0=document_id&p_perpage=10&p_sort=YMD_date:D&s_trackval=GooglePMhttp://nl.newsbank.com/nl-search/we/Archives?p_product=SLTB&p_theme=sltb&p_action=search&p_maxdocs=200&p_topdoc=1&p_text_direct-0=10114883EC896EBC&p_field_direct-0=document_id&p_perpage=10&p_sort=YMD_date:D&s_trackval=GooglePMhttp://nl.newsbank.com/nl-search/we/Archives?p_product=SLTB&p_theme=sltb&p_action=search&p_maxdocs=200&p_topdoc=1&p_text_direct-0=10114883EC896EBC&p_field_direct-0=document_id&p_perpage=10&p_sort=YMD_date:D&s_trackval=GooglePMhttp://nl.newsbank.com/nl-search/we/Archives?p_product=SLTB&p_theme=sltb&p_action=search&p_maxdocs=200&p_topdoc=1&p_text_direct-0=10114883EC896EBC&p_field_direct-0=document_id&p_perpage=10&p_sort=YMD_date:D&s_trackval=GooglePMhttp://www.freepatentsonline.com/6509314.htmlhttp://www.worldwidewounds.com/2005/august/Schultz/Extrace-Matric-Acute-Chronic-Wounds.htmlhttp://www.worldwidewounds.com/2005/august/Schultz/Extrace-Matric-Acute-Chronic-Wounds.html8/9/2019 Scarless Healing Faq
23/112
matrix is initially soft and loaded with growth factors. The fibroblasts "crawl" around the matrix,
pulling and reorganizing the fibers. The matrix grows stiffer, and at a certain point, the
fibroblasts stop migrating and, like Popeye, change into powerful contractile cells, anchoring
themselves to the matrix and pulling the edges of the wound together.
The research reported today reveals for the first time that a mechanical mechanism is crucial for
this switch from migrating to contractile cells. To make this change, the fibroblasts need to getat their "spinach" -- the growth factor sitting in the matrix which, once liberated, stimulates the
production of smooth-muscle proteins. Previously, researchers postulated that the fibroblasts
did this by digesting the matrix. But EPFL scientist Boris Hinz, doctoral student Pierre-Jean Wipff
and their colleagues have discovered that the cells unlock the growth factor via a purely
mechanical process. With experiments using novel cell culture substrates of varying rigidity, they
found that at a certain point, the matrix is sufficiently rigid that cell-exerted force allows the
growth factor to pop out, like candy from a wrapper. Once the growth factor is available, the
fibroblast expresses the contractile proteins, sticks more firmly to the matrix and starts to
contract, pulling the matrix tightly together. In the process it liberates yet more growth factor
that in turn stimulates other fibroblasts to become contractile. The mechanical nature of the
switch ensures that the contraction only develops when the matrix is "ready."
Although this process will heal a wound quickly, if left unchecked, it can also lead to a buildup of
fibrous tissue.
http://www.eurekalert.org/pub_releases/2007-12/epfd-nmi121707.php
http://www.eurekalert.org/multimedia/pub/6269.php?from=106535
It is of note: non denatured ECMs Decorin is a solution to contraction and fibroblast
proliferation. Fibroblast proliferation that brings about more parallel collagen bundles (scar
tissue/fibrosis/cicatrices.), to attach to the woven ECM which denies the intercellular tissuesthe scaffold micro pores it needs
Decorin, that is almost absent in adult injury but present in non injured skin and embryonic
skin, that inhibits fibroblast proliferation, is also important in reducing wound contraction. (26)
Regenerative Biology and Medicine
Collagen-GAG mixtures are often used as templates, and it has been found that GAG component
is critical for the activity of the template in inhibiting contraction and promoting regeneration
(Shafritz et al., 1994). Chondroitin-6-sulfate is the commonly used GAG, but dermatan sulfate or
decorin were more effective in reducing contraction and promoting regeneration, perhaps dueto their ability to neutralize TGF-B and mitigate the inflammatory response. One of the best
results, on full-thickness porcine wounds, was obtained with a type 1 collagen/elastin mixture
(Devries et al., 1994)
http://books.google.com/books?id=3Ue5oF3INKsC&pg=PA73&dq=reducing+contraction+decori
n
http://www.eurekalert.org/pub_releases/2007-12/epfd-nmi121707.phphttp://www.eurekalert.org/pub_releases/2007-12/epfd-nmi121707.phphttp://www.eurekalert.org/multimedia/pub/6269.php?from=106535http://www.eurekalert.org/multimedia/pub/6269.php?from=106535http://books.google.com/books?id=3Ue5oF3INKsC&pg=PA73&dq=reducing+contraction+decorinhttp://books.google.com/books?id=3Ue5oF3INKsC&pg=PA73&dq=reducing+contraction+decorinhttp://books.google.com/books?id=3Ue5oF3INKsC&pg=PA73&dq=reducing+contraction+decorinhttp://books.google.com/books?id=3Ue5oF3INKsC&pg=PA73&dq=reducing+contraction+decorinhttp://books.google.com/books?id=3Ue5oF3INKsC&pg=PA73&dq=reducing+contraction+decorinhttp://www.eurekalert.org/multimedia/pub/6269.php?from=106535http://www.eurekalert.org/pub_releases/2007-12/epfd-nmi121707.php8/9/2019 Scarless Healing Faq
24/112
Decorin, which inhibits TGFB1 and regulates TGFB1 has been described as a power house in
inhibiting fibrosis. (27)
On internal tissues it would be impractical to apply many micro mechanized products based on
the micro mechanisms of decorin, so decorin has been used as a sole product for other
essential internal tissues. (27)
Using decorin, an anti-fibrosis agent, to improve muscle recovery after injuryDecorin appears to be a powerhouse
Decorin has been shown to inhibit fibrosis in the kidney, liver, and lung, so why - the Pennsylvania scientists
reasoned - would it not also stop fibers from taking over muscle tissue?
sportsinjurybulletin.com
http://www.sportsinjurybulletin.com/archive/decorin.htm
It is widely known the scarring response in all our tissues is the same. (5) (6) And decorin has
been used successfully in our tissues like skin, (28) (29)(30) the kidney, (27) liver (27) and lung,
(27) spinal cord, (31) then on to organs like muscle, (32) (33)basically every tissue in the body
that scars.
Protein Pushes Damaged Muscle Toward Repair
Researchers at the University of Pittsburgh and Childrens Hospital of Pittsburgh have found that
treating distressed muscles with a protein called decorin prevents scar tissue formation andimproves regeneration and repair.
mda.org
http://www.mda.org/research/070912musclerepair.html
Tissue Engineering and Artificial Organs
By Joseph D. Bronzino
As described above, our recent data shows that TGF-B1 plays a central role in skeletal muscle
fibrosis and that the use of antifibrotic agents (e.g., decorin, suramin, yIFN, and relaxin) to
inactivate this molecule can reduce muscle fibrosis and consequently improve muscle healing to
near-complete recovery levels. We believe that the ultimate approach to improving musclehealing after sports-related muscle injuries may involve the transplantation of muscle cells
genetically engineered to express antifibrotic agents in order to block scar tissue formation
while promoting muscle regeneration.
http://books.google.com/books?id=Seresoz8QdIC&pg=PT812&dq=decorin+antifibrotic+agents
http://www.sportsinjurybulletin.com/archive/decorin.htmhttp://www.sportsinjurybulletin.com/archive/decorin.htmhttp://www.mda.org/research/070912musclerepair.htmlhttp://www.mda.org/research/070912musclerepair.htmlhttp://books.google.co.uk/books?id=Seresoz8QdIC&pg=PT812&dq=decorin+antifibrotic+agentshttp://books.google.co.uk/books?id=Seresoz8QdIC&pg=PT812&dq=decorin+antifibrotic+agentshttp://books.google.co.uk/books?id=Seresoz8QdIC&pg=PT812&dq=decorin+antifibrotic+agentshttp://www.mda.org/research/070912musclerepair.htmlhttp://www.sportsinjurybulletin.com/archive/decorin.htm8/9/2019 Scarless Healing Faq
25/112
Internally in the spinal cord, man made recombinant grade decorin suppresses the fibrotic
response 90% and allowed the intracellular nerve fibers to crawl up the scaffold in just 4 days.
(31)
CU Doctors Reveal Spinal Cord Technology - Researchers Bring New Hope To Paralyzed
PatientsDecorin is a naturally occurring molecule in the spinal cord that suppresses scar formation. We
were able to make pharmaceutical grade Decorin and infuse it into spinal cord injury rats and
suppress the scar by up to 90 percent, which allowed the nerve fibers to cross the injury in just 4
days,"
thedenverchannel.com, 2008-05-7http://www.thedenverchannel.com/health/16164126/detail.html
It is known that fibroblast proliferation can regenerate tissue or over produce collagen in the
fibrils to form scars, hence densely populated poorly woven collagen fibers that intercellular
tissues cannot grow through. (34)
What are scars?
A scar is a mark left in the skin by the healing of a wound or surgical incision in which the
normal functional tissue (skin) is replaced by connective tissue (scar). Keloids are excessive
accumulations of scar tissue beyond what is normally seen in most people. Keloids are moreraised and thickened masses of connective tissue than scars.
What cause the scar?
After a large, deep wound has occurred to the skin, whether by accident or due to surgery, both
skin cells and connective tissue cells (fibroblasts) begin multiplying to repair the damage. The
fibroblasts form a framework upon which the skin cells can migrate and fill in the wound. It is
the balance between the rate of replication of fibroblasts versus skin cells that is important here.
If the skin cells do not replicate fast enough and the fibroblasts replicate too quickly, the result is
a dense network of fibroblasts. This dense network of fibroblasts is not easily penetrated by the
skin cells, so the skin cells have a hard time replacing the fibroblasts. What results is a dense
network of fibroblasts, in other words a scar! If the skin cells replicate quickly and keep up with
the fibroblasts, then little scar tissue is formed and the skin has a more normal appearance after
the wound has healed. This is why scars do not occur as often in younger people as in older
people because the skin cells in younger people replicate more quickly and fill in the wound with
http://www.thedenverchannel.com/health/16164126/detail.htmlhttp://www.thedenverchannel.com/health/16164126/detail.htmlhttp://www.thedenverchannel.com/health/16164126/detail.html8/9/2019 Scarless Healing Faq
26/112
normal skin tissue versus too many fibroblasts.
http://www.nomorescar.com/
It is also of note that fibroblasts in a hypoxic culture have been used to create an ECM in the
lab:
Human ECM for Devices and Therapeutics
Fibroblasts (blue DAPI stain) cultured on bead-like sphere structures produce embryonic ECM.
Creation of this material begins by using a scalable bioreactor (see Figure 2) to seed newborn
fibroblasts onto microcarriers. They are grown in suspension while being conditioned with liquid
media. Within a few days, under hypoxic culture conditions that simulate the embryonic
environment, the cells produce a dense embryonic-like extracellular matrix and secrete wnt
proteins (molecules that regulate cell-to-cell interactions in embryogenesis) and various growth
factors into the media.
http://www.devicelink.com/mddi/archive/08/05/007.html
It is of note that through many years of researching ECM a form of a hypoxic culture, involving
wnt protein, has been made into an injectable to create ECM on site.
Stem Cell Summit
Hypoxic (1-5% oxygen) and low gravity conditions stimulated cells to make embryonic matrix
http://www.histogeninc.com/downloads/stem_cell_summit.pdf
Decorin in fibroblast control: Decorin organizes ECM! It is known that in wounds fibroblast
over produce forming excess collagen, which forms a scar. (34) Decorin which to recap also
http://www.nomorescar.com/http://www.nomorescar.com/http://www.devicelink.com/mddi/archive/08/05/007.htmlhttp://www.devicelink.com/mddi/archive/08/05/007.htmlhttp://www.histogeninc.com/downloads/stem_cell_summit.pdfhttp://www.histogeninc.com/downloads/stem_cell_summit.pdfhttp://www.histogeninc.com/downloads/stem_cell_summit.pdfhttp://www.devicelink.com/mddi/archive/08/05/007.htmlhttp://www.nomorescar.com/8/9/2019 Scarless Healing Faq
27/112
reduces wound contraction, has a strong inhibitory effect on fibroblast over expression, and
clearly suppresses it in the skin except in the first 5-6 days of wounding when new non
denatured ECM scaffold material is required in a wound void. (28)
Decorin has an elegant regulatory relationship with ECM. (28)
Recovery of the Decorin-Enriched Fraction, Extract (D), From Human Skin: An Accelerated
ProtocolThis material has a strong inhibitory effect on fibroblast proliferation, and clearly suppresses it
in skin except after the first 56 days of wounding when new scaffold material is required. 2004-
09-30
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=555769
Decorin is the factor that tells the fibroblasts and non denatured ECM, There is no injury, do
not scar. (28) (29)(30)
Slam dunk one: Decorin treated wounds have been found to have no scarring and the tissue
resembled fetal wounds in the first two trimesters. (29)
Methods of preventing or reducing scarring with decorin or biglycan
Decorin-treated wounds have been found to exhibit essentially no detectable scarring compared
to control wounds not treated with decorin. The TGF--induced scarring process has been shown
to be unique to adults and third trimester human fetuses, but is essentially absent in fetuses
during the first two trimesters. The absence of scarring in fetal wounds has been correlated with
the absence of TGF in the wound bed. In contrast, the wound bed of adult tissue is heavily
deposited with TGF- and the fully healed wound is replaced by a reddened, furrowed scar
containing extensively fibrous, collagenous matrix. The decorin-treated wounds were
histologically normal and resembled fetal wounds in the first two trimesters.
http://www.freepatentsonline.com/6509314.html
It is of note hyaluronic acid is known to be a favourble carrier of the protein decorin (29)
Methods of preventing or reducing scarring with decorin or biglycan
In addition, the present invention further relates to a pharmaceutical composition containing
decorin or its functional equivalent and a pharmaceutically acceptable carrier useful in the
above methods. Pharmaceutically acceptable carriers include, for example, hyaluronic acid,http://www.freepatentsonline.com/6509314.html
Slam dunk 2: Excitingly decorin at concentrations of 100nM and 200nM has completely
controlled Keloid fibroblast proliferation (30) Enabling the ECM fibers to be and stay slender
hence woven correctly, without the over expression of collagen densing up the fibers which
denies the intercellular tissues passages to form.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=555769http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=555769http://www.freepatentsonline.com/6509314.htmlhttp://www.freepatentsonline.com/6509314.htmlhttp://www.freepatentsonline.com/6509314.htmlhttp://www.freepatentsonline.com/6509314.htmlhttp://www.freepatentsonline.com/6509314.htmlhttp://www.freepatentsonline.com/6509314.htmlhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=5557698/9/2019 Scarless Healing Faq
28/112
(Hence it has completely stopped type 1 collagen dense over expression. In fibrils it has
stopped the building up the parallel bundles of collagen fibers blocking up woven micropores in
the ECM which always leads to scarring; thus it has given a platform for normal tissues to
continue regenerating without the dense fiber scar wall on ECM which stops regeneration. It
has protected and decorated the ECM. It has completely stopped the scarring response.)
Recombinant Human Decorin Inhibits Cell Proliferation and Downregulates TGF-1
Production in Keloid Fibroblasts
VOLUME: 18 PUBLICATION DATE: Aug 01 2006
At decorin concentrations of 100 nM and 200 nM, fibroblast proliferation was completely
inhibited (P < 0.001), and the expected temporal increase in absorbance units was completely
abolished, indicating a static population (Figure 1).
http://www.woundsresearch.com/article/6067
Along with tenascin, the decorin dermal proteoglycan also directs the assembly of collagen,
This protein is a component ofconnective tissue, binds totype I collagenfibrils, (35) and an
important small proteoglycan in extracellular matrix assembly.
DCN decorin
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=16
34
Extracellular matrix proteoglycan decorin-mediated myogenic satellite cell responsiveness to
transforming growth factor-1 during cell proliferation and differentiationDecorin and
transforming growth factor-1 in satellite cellsDecorin, a small proteoglycan in the extracellular matrix
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T62-4T07XGM-
1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1
&_urlVersion=0&_userid=10&md5=d1428677762be9c48ddf810469bf771a
It has a relationship with ECM. It is of note that ECM is made predominantly of Type 1 collagen
(cite needed) which is created by fibroblast.
Type 1 collagen is a factor in scar free healing and healthy skin. (36) It is also the most abundant
collagen in the body. Fibroblasts in the adult healing scarring response over expresses Type 1collagen. (36) (Does excess collagen block up micro pores in ECM, by attaching to much of itself
to the ECM scaffold?)
On the other hand type 1 collagen when over expressed is also known to be expressed in scar
tissue. (36) Decorin, controls fibroblast proliferation keeping it at a static rate,(30) and Decorin
(that completely inhibits scar response(30)), binds to Type 1 collagen keeping regeneration
constant as needed for normal tissue.
http://www.woundsresearch.com/article/6067http://www.woundsresearch.com/article/6067http://en.wikipedia.org/wiki/Connective_tissuehttp://en.wikipedia.org/wiki/Connective_tissuehttp://en.wikipedia.org/wiki/Connective_tissuehttp://en.wikipedia.org/wiki/Type_I_collagenhttp://en.wikipedia.org/wiki/Type_I_collagenhttp://en.wikipedia.org/wiki/Fibrilhttp://en.wikipedia.org/wiki/Fibrilhttp://en.wikipedia.org/wiki/Fibrilhttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1634http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1634http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1634http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T62-4T07XGM-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=d1428677762be9c48ddf810469bf771ahttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T62-4T07XGM-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=d1428677762be9c48ddf810469bf771ahttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T62-4T07XGM-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=d1428677762be9c48ddf810469bf771ahttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T62-4T07XGM-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=d1428677762be9c48ddf810469bf771ahttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T62-4T07XGM-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=d1428677762be9c48ddf810469bf771ahttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T62-4T07XGM-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=d1428677762be9c48ddf810469bf771ahttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T62-4T07XGM-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=d1428677762be9c48ddf810469bf771ahttp://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1634http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1634http://en.wikipedia.org/wiki/Fibrilhttp://en.wikipedia.org/wiki/Type_I_collagenhttp://en.wikipedia.org/wiki/Connective_tissuehttp://www.woundsresearch.com/article/60678/9/2019 Scarless Healing Faq
29/112
Skin collagen: More than meets the eye.
The most abundant types of collagen in the skin are I and III; their fibrils form the mesh largely
responsible for the skin's mechanical properties. Other types of collagen in the skin are V, VI,
and XII. They are found in much smaller amounts and appear to have a supportive role, whose
details remain unclear.http://www.smartskincare.com/skinbiology/skinbiology_collagen.html
It is known if you have a superficial wound you will be much less likely to scar than if you have a
deep dermal wound which will usually which bring a hypertrophic scar (HTS). (37) Interestingly
in deep dermal tissue after injury there is more collagen and less decorin in the deep tissues.
(37)
Deep dermal fibroblasts contribute to hypertrophic scarring.
Fibroblasts from the deeper layers were also found to produce more collagen, but less
collagenase by mass spectrometry and collagenase assay. Interestingly, cells from the deeperlayers also produced more of the proteoglycan, versican, but less decorin. Taken together, these
data strongly demonstrate that fibroblasts from the deeper layers of the dermis resemble HTS
fibroblasts, suggesting that the deeper layer fibroblasts may be critical in the formation of HTS.
http://www.ncbi.nlm.nih.gov/pubmed/18955978?ordinalpos=4&itool=EntrezSystem2.PEntrez.
Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Decorinis known to regulate collagen fibril (fibril means slender fiber (38)) formation in the
ECM and is important in the development of the structure of the extracellular matrix.
It is of note that the expression of decorin is decreased in photo damaged skin (39)
(WO/2000/037040) SKIN CARE COMPOSITIONS CONTAINING CIS-9, TRANS-11 LINOLEIC ACID
J. Inv. Derm., (1979), 73,79-66; Griffiths et al. N. Eng. J. med. (1993) 329,530-535). In the case of
decorin, it has been shown that mRNA expression and expression of the proteoglycan is greatly
reduced in photodamaged skin in vitro (Bernstein et al. Lab. Invest. (1995) 72,662-669). The
reduction of the levels of these skin proteins is accordingly associated with a decrease in the
tensile strength of the skin causing wrinkles and laxity.
The level of decorin in skin is associated with improved condition and appearance of skin.
Increasing the level of decorin in skin is important for controlled and correct deposition of
collagen in skin which is associated with many skin benefits such as wrinkle effacement anddermal repair of photodamaged skin.
http://www.wipo.int/pctdb/en/wo.jsp?IA=EP1999009589&DISPLAY=DESC
Decorin plays a pivotal role in tissue remodeling by acting on the balance between extracellular
matrix synthesis and degradation. (40)
http://www.smartskincare.com/skinbiology/skinbiology_collagen.htmlhttp://www.smartskincare.com/skinbiology/skinbiology_collagen.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/18955978?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov/pubmed/18955978?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov/pubmed/18955978?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.wipo.int/pctdb/en/wo.jsp?IA=EP1999009589&DISPLAY=DESChttp://www.wipo.int/pctdb/en/wo.jsp?IA=EP1999009589&DISPLAY=DESChttp://www.wipo.int/pctdb/en/wo.jsp?IA=EP1999009589&DISPLAY=DESChttp://www.ncbi.nlm.nih.gov/pubmed/18955978?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.ncbi.nlm.nih.gov/pubmed/18955978?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhttp://www.smartskincare.com/skinbiology/skinbiology_collagen.html8/9/2019 Scarless Healing Faq
30/112
Effect of adenovirus-mediated overexpression of decorin on metalloproteinases, tissue
inhibitors of metalloproteinases and cytokines secretion by human gingival fibroblasts
These results suggest that decorin could modulate the expression of certain metalloproteinases
and their inhibitors, as well as the production of cytokines. Altogether, our data suggest thatdecorin might play a pivotal role in tissue remodeling by acting on the balance between
extracellular matrix synthesis and degradation.
http://cat.inist.fr/?aModele=afficheN&cpsidt=14958566
Decorin inhibits Fibrin(ogen) clotting. It is of note that Decorin promotes plasminogen/plasmin
expression. (41) Plasmin limits fibrin of which excess fibrin has been noted as the main player in
fibrosis and inflammation, plasmin has also been used for the past two decades as first-line
treatment of acute myocardial infarction to limit more fibrosis. (42) Wounds high in fibrin low
in plasmin scar, they transform the ECM along the fibrotic excess collagen pathway. Wounds
high in plasmin limit fibrin and remove fibrosis. (43) (Embryos do not have fibrin clots)
Decorin promotes plasminogen/plasmin expression within acute spinal cord injuries and by
adult microglia in vitro
http://cat.inist.fr/?aModele=afficheN&cpsidt=17743545
New Technologies for Repairing Spinal Cord Injuries:
Suppressing scar formation and bridging injury sites.
1. Controlling scar formation with Decorin:In collaboration with Integra LifeSciences, my
research team has shown that a naturally occurring suppressor of scar formation, a molecule
called Decorin, is highly effective at suppressing the formation of both misaligned scar tissue
and the levels of axon growth inhibitors at sites of spinal cord injury. More importantly we
observed the rapid growth of sensory axons across decorin treated spinal cord injuries in just 4
days. We have also shown that decorin can induce the spinal cord to make an enzyme called
Plasmin that has the ability to break down scar tissue.
http://unite2fightparalysis.org/images/uploaded/Davies.pdf
Plasmin also aids in remodeling of ECM to tissue activating latent matric metalloproteinase.
(44)
Plasmin rapidly contracts dermal fibroblasts which are populated in type 1 collagen lattices, this
contraction favors ECM remodeling. (44)
Plasmin Triggers Rapid Contraction and Degradation of Fibroblast-Populated Collagen
Lattices
Within 16 h, fibroblast-populated collagen lattices treated with plasmin rapidly contracted from
approximately 20 mm to less than 2 mm in diameter.
http://cat.inist.fr/?aModele=afficheN&cpsidt=14958566http://cat.inist.fr/?aModele=afficheN&cpsidt=14958566http://cat.inist.fr/?aModele=afficheN&cpsidt=17743545http://cat.inist.fr/?aModele=afficheN&cpsidt=17743545http://unite2fightparalysis.org/images/uploaded/Davies.pdfhttp://unite2fightparalysis.org/images/uploaded/Davies.pdfhttp://unite2fightparalysis.org/images/uploaded/Davies.pdfhttp://cat.inist.fr/?aModele=afficheN&cpsidt=17743545http://cat.inist.fr/?aModele=afficheN&cpsidt=149585668/9/2019 Scarless Healing Faq
31/112
Following lattice contraction, the fibroblasts have been shown to adopt phenotypic
characteristics which favor ECM remodeling (Unemori & Werb 1986;Nakagawa et al. 1989;Grinnell 1994
).
ECM degradation is critical to tissue remodeling. This process is essential for removing damaged
tissue and provisional matrix, facilitating cell migration and guiding angiogenesis during wound
healing and tissue repair. ECM degradation during tissue remodeling is mediated by two classesof matrix-degrading proteinases: serine proteinases and matrix metalloproteinases (for reviews
seeMatrisian 1990;1992;Krane 1994;Mignatti et al. 1996). During wound healing, the serine proteinase plasminogen
activator (PA) catalyzes the conversion of the plasma protein plasminogen to plasmin. As
plasmin, a second serine proteinase, degrades several ECM components and activates latent
matrix metalloproteinases, it is frequently implicated as a key mediator in controlling connective
tissue turnover during wound healing.
http://www.nature.com/jid/journal/v114/n4/full/5600659a.html
Retinoic Acid and Linoleic acid up-regulates Decorin, (39) as does Chromolaena Odorata (45)
(WO/2000/037040) SKIN CARE COMPOSITIONS CONTAINING CIS-9, TRANS-11 LINOLEIC ACID
The results in table 6 indicate that the c9, tll isomer enriched CLA significantly upregulates the
synthesis of decorin in human dermal fibroblasts as compared to the control and as compared
to the tlO, c12 CLA and the CLA.
Surprisingly, the data thus further indicates that the magnitude of the upregulation of decorin
synthesis in human dermal fibroblasts effected by the c9, tll isomer of conjugated linoleic acid
exceeds that of the bench-mark anti-aging dermal repair active, retinoic acid.
http://www.wipo.int/pctdb/en/wo.jsp?IA=EP1999009589&DISPLAY=DESC
SKIN TREATMENT BASED ON THE USE OF CHROMOLAENA ODORATA
The results indicate that decorin synthesis in the model is substantially up regulated by even
relatively low levels (e.g. 0.01 g/ml) of extract. Small but positive effects were also seen on
procollagen I synthesis, as compared to the control. The 1.0 g/ml sample was also
comparatively tested with the retinoic acid (1m), showing an upregulation of decorin, 138
14.0 (p = 0.035, n = 4), as determined relative to a vehicle treated control value of 100 arbitrary
units. This further indicates the magnitude of the increase of decorin synthesis in human dermal
fibroplasts effected by Chromolaena Odorata extract, compared to the effect of retinoic acid.
http://www.freepatentsonline.com/EP1367988.html
It is of note that retinoic acid receptors are expressed in the regeneration blastema. (46)
Retinoic acid and its receptors in limb regeneration
Various retinoic acid receptors are expressed in the regeneration blastema and the experiments
which have revealed functions for individual isoforms are described. These experiments reveal
http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib50#bib50http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib50#bib50http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib35#bib35http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib35#bib35http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib13#bib13http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib13#bib13http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib13#bib13http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib27http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib27http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib28http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib28http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib23http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib23http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib32http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib32http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib32http://www.nature.com/jid/journal/v114/n4/full/5600659a.htmlhttp://www.nature.com/jid/journal/v114/n4/full/5600659a.htmlhttp://www.wipo.int/pctdb/en/wo.jsp?IA=EP1999009589&DISPLAY=DESChttp://www.wipo.int/pctdb/en/wo.jsp?IA=EP1999009589&DISPLAY=DESChttp://www.freepatentsonline.com/EP1367988.htmlhttp://www.freepatentsonline.com/EP1367988.htmlhttp://www.freepatentsonline.com/EP1367988.htmlhttp://www.wipo.int/pctdb/en/wo.jsp?IA=EP1999009589&DISPLAY=DESChttp://www.nature.com/jid/journal/v114/n4/full/5600659a.htmlhttp://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib32http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib23http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib28http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib27http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib13#bib13http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib35#bib35http://www.nature.com/jid/journal/v114/n4/full/5600659a.html#bib50#bib508/9/2019 Scarless Healing Faq
32/112
that retinoids are a crucial component of the normal, regenerating limb and demonstrate the
value of the regenerating limb as an experimental system for providing functional data on
individual retinoic acid receptors.
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WX0-45K142V-
10&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=
1&_urlVersion=0&_userid=10&md5=93249ca728ea1defe693bb9ab7cb2b49
Chromolaena Odorata extract (also known as Siam weed extract), is regularly used for burns
and soft tissue treatment in Vietnam and has shown efficacy in inhibiting contraction in
hydrated collagen lattice at 50 to 200 micrograms/ml (47)
An aqueous extract of the leaves of Chromolaena odorata (formerly Eupatorium odoratum)
(Eupolin) inhibits hydrated collagen lattice contraction by normal human dermal fibroblasts.
The significant inhibition of collagen gel contraction by Eupolin extract at 50 to 200
micrograms/ml is demonstrated in various concentrations of collagen. When the extract at 50
to 150 micrograms/ml was washed out of the lattices and replaced by fresh medium withoutEupolin, the contraction of collagen by cells was resumed.
http://grande.nal.usda.gov/ibids/index.php?mode2=detail&origin=ibids_references&therow=4
6275
Crushed chromolaena odorata leaves, manufactured by the Vietnam National Institute of
Burns, make up a formulation called Eupolin ointment. (48)
Upregulation of adhesion complex proteins and fibronectin by human keratinocytes treated
with an aqueous extract from the leaves of Chromolaena odorata (Eupolin)
Eupolin ointment is a formulation of an extract from the leaves of Chromolaena odorata,
manufactured and provided by the Vietnam National Institute of Burns, Hanoi.
http://www.john-libbey-eurotext.fr/fr/revues/medecine/ejd/e-docs/00/01/89/FA/article.phtml
Eupolin ointment, which expresses decorin in wounds that have not had non-denatured ECM
added, strongly enhanced Laminin 5 and laminin 511 in the ECM,(48)
Upregulation of adhesion complex proteins and fibronectin by human keratinocytes treated
with an aqueous extract from the leaves of Chromolaena odorata (Eupolin)
We have shown that the expression and secretion of laminin 5 are strongly enhanced in cultured
keratinocytes by increasing amounts of Eupolin. Laminin 5 is crucial to the stability of epithelial
attachment, and has been called a "biological glue" as it increases adherence of epithelial
sheets to wound surfaces and the rate of assembly of a new basement membrane zone [9]. It is
the first extracellular matrix component to be expressed and deposited by migrating
keratinocytes during wound healing and is essential for the regulation of keratinocyte migration
and motility [17-20]. Laminin 5 induces the assembly of hemidesmosomes by cultured epithelial
cells and regulates cell adhesion by the alpha3beta1 integrin and the alpha6beta4 integrin, its
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WX0-45K142V-10&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=93249ca728ea1defe693bb9ab7cb2b49http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WX0-45K142V-10&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=93249ca728ea1defe693bb9ab7cb2b49http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WX0-45K142V-10&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=93249ca728ea1defe693bb9ab7cb2b49http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WX0-45K142V-10&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=93249ca728ea1defe693bb9ab7cb2b49http://grande.nal.usda.gov/ibids/index.php?mode2=detail&origin=ibids_references&therow=46275http://grande.nal.usda.gov/ibids/index.php?mode2=detail&origin=ibids_references&therow=46275http://grande.nal.usda.gov/ibids/index.php?mode2=detail&origin=ibids_references&therow=46275http://www.john-libbey-eurotext.fr/fr/revues/medecine/ejd/e-docs/00/01/89/FA/article.phtmlhttp://www.john-libbey-eurotext.fr/fr/revues/medecine/ejd/e-docs/00/01/89/FA/article.phtmlhttp://www.john-libbey-eurotext.fr/fr/revues/medecine/ejd/e-docs/00/01/89/FA/article.phtmlhttp://grande.nal.usda.gov/ibids/index.php?mode2=detail&origin=ibids_references&therow=46275http://grande.nal.usda.gov/ibids/index.php?mode2=detail&origin=ibids_references&therow=46275http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WX0-45K142V-10&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=93249ca728ea1defe693bb9ab7cb2b49http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WX0-45K142V-10&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=93249ca728ea1defe693bb9ab7cb2b49http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WX0-45K142V-10&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=93249ca728ea1defe693bb9ab7cb2b498/9/2019 Scarless Healing Faq
33/112
extracellular ligand [21]. These processes are all essential to wound healing. We believe that the
enhanced secretion of laminin 5 by Eupolin is a major finding that partly explains the clinical
effectiveness of Eupolin
http://www.john-libbey-eurotext.fr/fr/revues/medecine/ejd/e-docs/00/01/89/FA/article.phtml
concerning logic, it is of note that laminin 5 (also known as laminin 332) induces matrixassembly and cell adhesion activity of laminin-511 (also known as laminin 10). (49) ECMs
protein laminin 511 has been shown to grow hair follicles. (50)
The 3 chain short arm of laminin-332 (laminin-5) induces matrix assembly and cell adhesion
activity of laminin-511 (laminin-10)
http://cat.inist.fr/?aModele=afficheN&cpsidt=18480550
Laminin-511: Hair Growth Molecule Discovered by Stanford Researchers
http://www.hairlossfight.com/news_interviews/laminin-511.php
http://www.john-libbey-eurotext.fr/fr/revues/medecine/ejd/e-docs/00/01/89/FA/article.phtmlhttp://www.john-libbey-eurotext.fr/fr/revues/medecine/ejd/e-docs/00/01/89/FA/article.phtmlhttp://cat.inist.fr/?aModele=afficheN&cpsidt=18480550http://cat.inist.fr/?aModele=afficheN&cpsidt=18480550http://www.hairlossfight.com/news_interviews/laminin-511.phphttp://www.hairlossfight.com/news_interviews/laminin-511.phphttp://www.hairlossfight.com/news_interviews/laminin-511.phphttp://cat.inist.fr/?aModele=afficheN&cpsidt=18480550http://www.john-libbey-eurotext.fr/fr/revues/medecine/ejd/e-docs/00/01/89/FA/article.phtml8/9/2019 Scarless Healing Faq
34/112
2.3 Antibacterial Factor in Scar Free Healing Concept
It once was said our wounds need a sterile environment to have regeneration. Which lead to
treatments like drying and chemicals and treatment that completely destroy, or hinder and
denature any factors that can be used in scar free healing. (51)
A Scarless Future: The Wound Care Update Paper 2006, pdf - Page 10
The move from dry healing to moist healing is not new anymore, and is known by most medical
practitioners. However, this is not widely known amongst the public.
And this sterilization concept is equally challenged, by the Kangeroo marsupial, where the
embryo in the pouch is repeatedly contaminated by urine and faeces.
Also it is of note that adult salamanders that regenerate lost limbs with blastema, do not have
clinically sterile environments. Suggesting the blastema has antibacterial properties. And also
proving that a sterile environment is not as central to perfect regeneration.
It is also noted ECM has its own antibacterial properties, which leave the idea of sterilization of
wounds and the healing factors redundant. (52)
A-Cell Therapy Offers Renewed Hope For Horses Incurring Tendon And Ligament Injuries, p 4
http://www.acell.com/pdf/TCOTH%20ACell%20Article.pdf
http://www.acell.com/pdf/TCOTH%20ACell%20Article.pdfhttp://www.acell.com/pdf/TCOTH%20ACell%20Article.pdfhttp://www.acell.com/pdf/TCOTH%20ACell%20Article.pdf8/9/2019 Scarless Healing Faq
35/112
2.3.1 ECM Antibacterial Profile
Extracellular matrix has an impressive antibacterial profile (52)
A-Cell Therapy Offers Renewed Hope For Horses Incurring Tendon And Ligament Injuries, p 4
http://www.acell.com/pdf/TCOTH%20ACell%20Article.pdf
similar to that of the embryonic stage and as such it