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SECTION
ONE:
WHAT
ARE THE PROPERTIES OF NORMAL SKIN
Skin
(Biologic Properties)
Skin is a bilayer
organ whose functions are essential for survival. Although
the bilayers works as a unit, each component has specific
properties which need to be recognized if one is to
duplicate these properties with a skin substitute.
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SKIN
FUNCTIONS
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Epidermis
- protection
from desiccation
- protection
from bacterial entry
- protection
from toxins
- fluid
balance: avoiding excess evaporative loss
- neurosensory
- social-interactive
Dermis
- protection
from trauma due to elasticity, durability,
properties
- fluid
balance thru regulation of skin blood flow
- thermoregulation
thru control of skin blood flow
- growth
factors and contact direction for epidermal
replication and dermal repair
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FUNCTIONAL
COMPONENTS OF SKIN
EPIDERMIS:
The outer thinner layer known as the epidermis is composed
mainly of epithelial cells. The outermost cells contain
the protein keratin and are known as keratinocytes. The
basal or deepest epidermal cells are anchored to the
basement membrane by adhesion molecules (or glue), namely
fibronectin. These immature cells are continually dividing
and migrating toward the surface to replace lost surface
cells e.g. after an injury. The same type of regenerating
epidermal cells are found in hair follicles and other skin
appendages which are anchored in the dermis. As the cells
mature and migrate to the surface they form keratin which
becomes an effective barrier to environmental hazards such
as infection and to excess water evaporation.
Replacement of
the epidermal layer by this regenerative process takes 2-3
weeks. Cues and biologic stimuli at the wound surface are
necessary to direct proper orientation and mitotic
response of the epidermal cells. Many of the cues come
from dermal elements, especially the matrix proteins and
matrix glycosaminoglycan.
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Components
of epidermis
- outer
cells: keratinocytes
- keratin,
a tough protein on surface, preventing
bacteria or toxin entry
- inner
layer: epidermal cells which are
proliferating and migratory to surface and
will become keratinocytes
- innermost
layer: basal epidermal cells anchored to
basement membrane by adhesion molecules
- skin
appendages anchored in dermis also lined by
epidermal cells
- Langerhans’
cells, contain granules, fix antigens (felt
to be responsible for antigen-antibody and
allergy functions)
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Characteristics
of epidermis
- protection
from environmental insults
- ability
to regenerate every 2-3 weeks resulting from
biologic cues and contact direction provided
by dermis, basement membrane
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DERMIS:
The dermis
is a very dynamic layer of thick connective tissue, also
in constant turnover. The dermis is divided into a thin
superficial layer known as the papillary dermis
containing the anchoring epidermal rete pegs and the
thicker deeper portion known as the reticular dermis.
The papillary dermis is the major factory for the
proteins providing direction for epidermal replication.
The upper dermis also contains the highest blood flow. The
primary cell type is the fibroblast which produces the key
structural extra cellular matrix proteins collagen and
elastin as well as matrix or ground substance.
In
addition these cells produce the key adhesion proteins
used to attach epidermal cells to the basement membrane
and for used epidermal cell migration and replication. Fibronectin
is a key fibroblast derived signal protein for
orchestration of healing. The ground substance or matrix
is made up of complex polysaccharide - protein complex
known as glycosaminoglycan or the GAG component as well as
hyaluronic acid. The matrix provides a semi fluid which
allows for cell and connective tissue orientation
as well as nutrient diffusion to the cells and a scaffolding
for cell migration.
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Components
of dermis
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- papillary
dermis: upper dermis containing anchoring
rete pegs and also is the most biologically
active part of the dermis
- reticular
dermis: the thicker deeper portion
responsible for durability and anchoring of
skin appendages
- matrix
proteins
- collagen is the predominant protein,
mainly collagen Type 1. (besides structure;
collagen type 1 provides a contract
orientation for dividing and migrating
epithelial cells)
- fibronectin is the primary adhesive
protein playing a major role in healing
- other adhesive proteins
- ground
substance (glycosaminoglycan)
- carbohydrates protein complexes
- hyaluronic acid
- cells
- fibroblasts
- macrophages
- platelets
- endothelial cells
- blood
vessels (auto regulated flow)
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Characteristics
of dermis
- provides
durability, flexibility of skin
- factory
for all the components required for
replication and repair of epidermis and
dermis
- scaffolding
for cell migration and the conduit for
nutrient delivery
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INTERFACE:
The interface between the layers or the dermo-epidermal
junction is the basement membrane rich in the adhesive
protein fibronectin which anchors the epidermal cells from
above and dermis from below.
THICKNESS:
Average thickness of the bilayer is 1-2 mm being
considerably thinner in infants and the elderly especially
the dermis which is underdeveloped in infants and atrophic
in the elderly.
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Cell
Types
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Epidermis
-
Keratinocytes
- Epithelial cells
- Langerhan's cells
Dermis
-
Fibroblasts
- Macrophages
- Endothelial cells
- Platelets
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EPITHELIAL
CELLS: These cells make up the majority of the
epidermis. Immature cells are programmed to divide,
migrate and mature to keratin producing cells called
keratinocytes. The signals to activate this process come
from messenger proteins called growth factors as well as
through contact direction from key dermal adhesive
proteins, especially collagen.
FIBROBLASTS:
The cells of mesenchymal original are normal present in
the dermis and produce normal dermal replacement
components. After injury these cells migrate into the
wound and proliferate; in order to produce increased
quantities of these dermal proteins and matrix.
ENDOTHELIAL
CELLS: These cells make up the lining of micro
and macro vessels and also make up the lining of new
capillaries produced after injury. These cells like
fibroblasts do differentiate from local mesenchymal cells
and are also attracted into the wound by local signals.
MACROPHAGES:
These cells of mesenchymal origin are normally present in
tissue but increase in number after injury, attracted by
chemical messages released by the activation of
inflammation. The long lived cells release the protein
chemical messages, growth factors and growth stimulants
which orchestrate healing in an organized fashion.
PLATELETS:
The factor-rich particles release a host of growth factors
and adherence proteins during the initial post burn
period.
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Fibroblast
Products
- collagen
(type one in skin)
- matrix
proteins (fibronectin, tenascin, others)
- proteoglycans,
glycosaminoglycan, hyaluronic acid, other
matrix components
- cytokines
and other growth stimulants
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Macrophage
Products
- growth
factors
- growth
stimulants
- opsonins
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Characteristics
of Skin Collagen Type 1
Function
- creates
adherence to wound surface via fibrin and
fibronectin
- provides
surface orientation for epithelial cell
migration
- stimulates
dermal cell migration
Structure
- provides
dermal scaffolding and durability
- complex
surface morphology
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Characteristics
of Matrix (GAG)
Functions
- glue
or adherence properties in tissue via
cell-matrix interaction
- substrate
for migration of nutrients, cells and growth
factors
- deactivator
of toxic protease released by neutrophils
- conduit
for living fibrin, fibronectin and growth
factors in contact with the wound surface
- scaffold
for surface deposition of fibrin and
fibronectin i.e., cell guidance proteins
Structure
- the
foundation for deposition of dermal cells,
collagen, other proteins
- these
compounds also provide the scaffold for the
epidermal basement membrane
- brings
critical matrix proteins and growth factors
into contact with each other
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Dermal
Molecules Influencing Burn Wound Closure
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| Molecule |
Source |
Location |
| Collagen
type I |
Fibroblast |
Dermis
- Supports epidermal cell attachment and
migration |
| Collagen
type IV |
Epidermal
cell, fibroblast |
Lamina
densa
- Supports
epidermal cell attachment |
| Fibronectin |
Fibroblasts,
macrophage, serum |
Basement
membrane
- Dermis |
| Laminin |
Epidermal
cell |
Epidermal
cell adherence |
| Glycosaminoglycans |
Fibroblast |
Promotes
cell adherence, migration, nutrient delivery |
Fibronectin:
This adhesion protein, produced mainly by fibroblasts and
macrophages, is a large glycoprotein found in all tissues
and plasma. One of its key functions is as an attachment
protein for skin cells via collagen type I. Production is
induced with a burn. Fibronectin plays a major role in
wound healing.
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Fibronectin
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Adherence
Function
- cross
linking to fibrin (and collagen) causing
adherence of tissues to each
- key
adherence molecule attaching epithelial and
endothelial cells at cell junctions
- contact
orientation for all cells in the healing
process
Epithelialization
- cell
migration, spreading, and orientation
- cell
division
- cell
re-adherence to form a layer
Chemo
Attractant (Fibronectin Fragments)
- for
fibroblasts
- for
macrophages
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A large variety
of "polypeptide growth factors" have been
identified and named. Although each has a predominant
function on a specific cell, all growth factors have a
multitude of actions. Epidermal growth factor (EGF) is a
key component for re-epithelialization of a
partial-thickness burn, and addition of EGF to the wound
surface increases re-epithelialization. Keratinocyte
growth factor (KGF) is an important fibroblast derived
stimulant for epithelialization. Macrophages are thought
to be the main producers of growth factors; however, all
skin cells, includ9ing fibroblasts and keratinocytes, play
an important role in secreting growth factors. The initial
stimulus requires the onset of wound inflammation, and
once activated, further production continues until the
wound is healed.
Once formed the
growth factors can be rapidly deactivated by wound
proteases, e.g. collagenases, proteases, probably in an
attempt to break down surface dead tissue. Surface3
exudate is a rich source of such proteases, especially the
class of metalloproteases.
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GROWTH
FACTORS INVOLVED IN WOUND HEALING
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MOLECULE
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SOURCE
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ACTION |
| Fibroblast
Growth Factor |
Keratinocytes,
macrophages |
Stimulates
angiogenesis |
| Epidermal
Growth Factor |
Platelets |
Stimulates
epidermal cell proliferation |
| Keratinocyte
Growth Factor |
Fibroblasts |
Stimulates
epidermal cell growth |
| Interleukin
-1 |
Macrophages,
epidermal |
Stimulates
epidermal growth and motility |
| Platelet-Derived
Growth Factor |
Platelets,
macrophages |
Stimulates
epidermal growth, fibroblast proliferation |
| Transforming
Growth Factor-B |
Fibroblasts,
platelets |
Fibrosis
and increased tensile strength |
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Functions
of Skin Growth Factors
- cell
proliferation: epidermis, fibroblasts,
endothelial cells
- cell
migration: white cells, epithelial,
endothelial, fibroblast
- structure
formation: capillaries, epidermis
- cell
production of tissue proteins:
collagen, matrix proteins, keratin
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As can be seen,
skin is a very biologically active organ. Duplication of
skin properties typically requires a Bilayer structure,
the outer layer having protection properties and the
inner layer properties stimulating tissue growth.
Temporary skin
substitutes are not concerned with dermal replacement as
would be the case with a permanent skin substitute.
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Properties
of Skin Substitute
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- Bilayer
structure having properties of both an
epidermis and a dermis
- Temporary
skin substitute
- Bilayer with purpose being to protect
wound and optimize healing
- Permanent
skin substitute
-replacement for one or both layers
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