Download Chronic Wounds: Collagen Might Be the Answer

Chronic Wounds:
Collagen Might Be the Answer
You are seeing a resident with a
chronic wound. This wound has eluded
your treatment plan for years. It seems
to go through a cycle during which it
improves but does not close and usually
deteriorates. Collagen could be
the answer, and here’s why.
By
Debashish
Chakravatrhy,
PhD
34
HEALTHY SKIN
TREATMENT
Harmful enzymes that
destroy collagen prevent
healing in chronic wounds.
A collagen dressing can bind
to several destructive enzymes
like a magnet to iron filings,
allowing the body’s own
collagen to heal the
chronic wound.
Improving Quality of Care Based on CMS Guidelines
35
Let’s take a look at
the normal healing process
Normal wound healing involves three specific but overlapping steps or phases – inflammatory, proliferation and maturation.
After hemostasis, the control of bleeding, the groundwork is set for the
wound to move into the first, or inflammatory, phase of healing. This typically lasts
two to three days and involves the macrophages and neutrophils cleaning the wound
debris and eliminating bacteria. These cells have a short life span and are usually able to
complete their mission in that time frame of two to three days.
The wound then progresses into the second phase, or proliferation. This phase involves
fibroblasts appearing in the wound about three days after injury. Their main function is to manufacture extracellular matrix (ECM) proteins, growth factors and angiogenic (new blood vessel) factors.
This is part of the process called granulation. The ECM consists of collagen and elastin, among
other vital proteins. Collagen is secreted by the fibroblasts and is the most abundant protein in
I
humans, accounting for nearing 70 percent of all protein. It is one of the components that largely
f you are seeing a
fill the wound in normal healing. Elastin, another protein, provides strength and elasticity to the
chronic wound in
front of you, it may
skin, though making up only about 3-4 percent of the skin’s protein. As this phase of healing
be possible that your
continues, cells migrate (epithelialization) and finally wound contraction occurs.
problem wound is stuck
in the inflammatory phase,
The final phase of wound healing, maturation, can take many more months and
where destructive enzymes
is the final strengthening phase. During maturation, collagen continues to
(examples follow) that should
reorganize in the skin, gradually replacing the original scar tissue
have long ago disappeared are
with less-scarred, normal-appearing tissue.
still present. Possibly destructive
enzymes could include:
• Elastase, which is secreted by
neutrophils and is simply not
useful at this stage in a wound’s
life. Elastase destroys elastin.
MMPs, keeping the MMPs occupied
TIMPs are described as
• Matrix metalloproteases
in the activity of breaking down the
“anti-MMPs” and must
(MMPs). The MMPs are
dressing material instead of the new
outnumber the MMPs (concepproteases that are associated
(de novo) collagen made by the
tually speaking) for the wound
with metal ions, and the worst
fibroblasts working hard in a chalto heal normally. In a chronic
of them are specific to collagen
lenging environment. The enzymes
wound, the MMP to TIMP ratio
or fragments of collagen,
are concentrated in the dressing,
is in favor of these collagenmeaning that they seek out
where collagen is plentiful, instead
destroying enzymes, MMPs.
collagen molecules and
of in the tissue, where the fibrobchemically break them down.
lasts are putting out the body’s own
How should you handle
• Elastase destroys other enzymes this problem?
collagen at low concentrations.
too – those that could be
Denatured collagen, available in
Bring fibroblasts to the wound that
useful to the wound, such as
some wound care products today,
will produce fresh collagen and fill
tissue inhibitors of matrix
is processed chemically to the
the wound bed. A very effective
metalloproteinases (TIMPs).
extent that it has lost the sophistimethod is to plant native collagen
dressings that will bind with the
36
HEALTHY SKIN
cated triple helix structure of the
collagen building block that is so
characteristic of skin collagen. It
seems that this triple helix structure
of collagen is particularly attractive
to fibroblasts.
Fibroblasts also thrive in structures
in which they can spread out threedimensionally (as they would in
real-life wound environment) and
be themselves. In other words,
they like to do the things that they
should be doing, like secreting
collagen and other important
materials of the extracellular matrix.
So, using a collagen product with
a noticeable three-dimensional
structure allows the fibroblasts to
act as normally as they possibly can.
Why native collagen-based dressings
interact with the destructive elastase
enzyme to the extent that they seem
to do is still under investigation.
Binding of a dressing material to
elastase obviously reduces the
concentration of the elastase in
the wound bed, which means that
less of the wound bed’s elastin is
destroyed. But, perhaps more
importantly, elastase is known to
play a role in creating the final
destructive form of MMPs. Taking
elastase out of play seriously
reduces the potential of MMPs
being freshly and efficiently created
in the wound bed. Elastase is also
known to destroy the beneficial
TIMP enzymes that keep the MMP
in check. A reduced elastase level
allows the TIMP concentration to
reach a level that keeps MMP
activity low in the wound bed.
There is a good chance that the
chronic but infection-free wound
that mystified you in refusing to
heal, even when you tried everything else, including addressing
all other associative factors, will
now proceed to healing.
What, then, happens to the dressing
once applied to the chronic wound?
It is taken apart (in a chemical
sense) by the MMPs to which it
was bound. The byproducts of this
binding are collagen fragments,
which are consumed by the fibroblasts. The fibroblasts will synthesize
fresh collagen (or the body’s own
de novo collagen) and secrete it out
into an environment relatively free
of MMPs, without whose removal
the newly synthesized collagen
would have been destroyed.
Improving Quality of Care Based on CMS Guidelines
37