SKIN MODULE:

WOUND HEALING

FK UNIB 2013

LECTURE OVERVIEW
Important background facts
cellular

proliferation
growth factors
the extracellular matrix
The process of tissue repair
regeneration
scarring
an

illustration: skin wound healing

why do good wounds go bad?

Wound healing

Superficial regeneration

Deep repair

Factors which control healing

EGF (Epidermal Growth Factor)

TGF (Transforming Growth Factor )
Angiogenic Factors
FGF (Fibroblast Growth Factor)
PDGF (Platelet Derived Growth Factor)
IGF (Insulin Growth Factor)
IL-I (Interleukin I)
TNF (Tumor Necrosis Factor)
Erythropoiesis promoting growth factors
Erythropoietin
IL-3
IL-9
Intrinsic factors
Folikel rambut sebagai stem cell kulit

LECTURE OVERVIEW
Important background facts
cellular

proliferation

CELLULAR PROLIFERATION
Lots of cells proliferate during tissue repair:
injured tissue remnants
vascular endothelial cells
fibroblasts
You need to know a few things about:
the cell cycle
the proliferative capacities of different tissues
stem cells
growth factors
the extracellular matrix

The Cell Cycle

CELLULAR PROLIFERATION
Tissues of the body are divided into three
groups:
Continuously dividing (labile) tissues
Stable tissues
Permanent tissues

CELLULAR PROLIFERATION
Tissues of the body are divided into three
groups:
Continuously dividing (labile) tissues

cells are continuously proliferating

can easily regenerate after injury
contain a pool of stem cells
examples: bone marrow, skin, GI epithelium

Stem cells in GI epithelium

CELLULAR PROLIFERATION
Tissues of the body are divided into three
groups:
Continuously dividing (labile) tissues
Stable tissues
cells have limited ability to proliferate
limited ability to regenerate (except
liver!)
normally in G0, but can proliferate if
injured
examples: liver, kidney, pancreas

CELLULAR PROLIFERATION
Tissues of the body are divided into three
groups:
Continuously dividing (labile) tissues
Stable tissues
Permanent tissues
cells cant proliferate
cant regenerate (so injury always leads
to scar)
examples: neurons, cardiac muscle

The Cell Cycle and Different Cell

Populations

LECTURE OVERVIEW
Important background facts
cellular

proliferation
growth factors

GROWTH FACTORS
Very important in tissue repair.
Actions:
stimulate cell division and proliferation
promote cell survival

Huge list! Usually have GF in name:

EGF
TGF
PDGF

THE EXTRACELLULAR MATRIX

ECM is the network that surrounds cells
Two forms: interstitial matrix and
basement membrane
Does lots of things!
Sequesters water and minerals
Gives cells a scaffold to adhere to
Stores growth factors

The Extracellular Matrix

THE EXTRACELLULAR MATRIX

Bottom line: ECM regulates
proliferation, movement, and
differentiation of the cells living in it.
If you screw up your ECM, you cant
regenerate! Youll form a scar instead.

REGENERATION
Occurs all the time in labile tissues
Cells are constantly being lost and replaced
If demand increases, supply increases easily

Occurs in limited form in stable tissues

Remove one kidney: the other one
undergoes hypertrophy and hyperplasia
Remove half of the liver: it will grow back

Only occurs if residual tissue is intact!

SCARRING
If injury is severe, regeneration cant
happen
So, fibrosis (a scar) replaces the injured
tissue
Four components to this process:

new vessel formation (angiogenesis)

fibroblast proliferation
synthesis of collagen (scar formation)
remodeling of scar

SCARRING
By 24 hours:
Endothelial cells start
proliferating
Fibroblasts emigrate

By 3-5 days:
granulation tissue present

Weeks later:
dense fibrosis (scar)
scar is remodeled over time

SCARRING

Summary:
1. make granulation tissue
2. turn it into a chunk of
collagen

SCAR FORMATION
Processes of Scar Formation :

1. Emigration and Proliferation of

Fibroblast in the site of injury
2. Deposition of ECM
3. Tissue Remodeling

Scar Formation
Net collagen depends on increased

collagen synthesis and decreased

degradation
Scar compossed of spindle-shaped

fibroblasts, dense collagen, fragments

of elastic tissue and ECM components
Vascular regression --- pale, avascular

scar

Tissue Remodeling
Granulation tissue to Scar --- involves
transitions in the composition of The
ECM
The Balance between ECM synthesis
and degradation results in
remodeling of the connective tissue
framework

Granulation tissue

LECTURE OVERVIEW
Important background facts
cellular

proliferation
growth factors
the extracellular matrix
The process of tissue repair
regeneration
scarring
an

illustration: skin wound healing

SKIN WOUND HEALING

First intention
Second intention

first intention
healing

second intention
healing

Classification of Wounds

1) Clean Wound:

2) Clean/Contaminated Wound:

uninfected wounds in which no inflammation is

encountered but the respiratory,
gastrointestinal, genital, and/or urinary tract
have been entered.

3) Contaminated Wound:

Operative incisional wounds that follow

nonpenetrating (blunt) trauma.

open, traumatic wounds or surgical wounds

involving a major break in sterile technique that
show evidence of inflammation.

4) Infected Wound:

old, traumatic wounds containing dead tissue

and wounds with evidence of a clinical infection
(e.g., purulent drainage).

Classification of Wounds Closure

Healing by Primary Intention:

Healing by Secondary Intention:

All Layers are closed. The incision that heals by first

intention does so in a minimum amount of time, with
no separation of the wound edges, and with minimal
scar formation.
Deep layers are closed but superficial layers are left to
heal from the inside out. Healing by second is
appropriate in cases of infection, excessive trauma,
tissue loss, or imprecise approximation of tissue.

Healing by Tertiary Intention:

Also referred to as delayed primary closure.

Wound Healing

Inflammation occurs when the damaged endothelial cells

release cytokines that increase expression of integrands in
circulating lymphocytes.

Histamine, serotonin, and kinins cause vessel contraction

(thromboxane), decrease in blood loss, and act as
chemotactic factors for neutrophils, the most abundant cells
in the initial 24 hour period.

Wound Healing

Proliferative phase occurs next, after the neutrophils have

removed cellular debris and release further cytokines acting as
attracting agents for macrophages.
Fibroblasts now migrate into the wound, and secrete collagen
type III.
Angiogenesis occurs by 48 hours.
The secretion of collagen, macrophage remodeling and
secretion, and angiogenesis continues for up to 3 weeks.
The greatest increase in wound strength occurs during this
phase.

Wound Healing

Maturation phase is the final phase and starts from the 3rd
week and continues for up to 9-12 months.

This is where collagen III is converted to collagen I, and the

tensile strength continues to increase up to 80% of normal
tissue.

Surgical Wound Infection (SWI)

Incisional infections identified by purulent or
culture positive drainage is isolated from any
structure above the fascia in proximity to the initial
wound
Deep infections are characterized by purulent
drainage from subfascial drains, wound
dehiscence, or abscess formation and involve
adjacent sites manipulated during surgery.
Wound Dehiscence
Breakdown of the surgical wound

Risk Factors for SWI

Patient-related factors:
Age > 60, sex (female), weight (obesity)
Presence of remote infections
Underlying disease states
Diabetes, Congestive heart failure (CHF)
Liver disease, renal failure
Duration of preoperative stay hospitalization
> 72 hours, ICU stay
Immuno-suppression
ASA (American Society of Anesthesiologists)
physical status (3,4, or 5)

Risk Factors for SWI

Surgery-related factors:
Type of procedure, site of surgery, emergent
surgery
Duration of surgery (>60- 120 min)
Previous surgery
Timing of antibiotic administration
Placement of foreign body
Hip/knee replacement, heart valve insertion, shunt
insertion
Hypotension, hypoxia, dehydration, hypothermia

Risk Factors for SWI

Surgery related factors:
Patient preparation
Shaving the operating site
Preparation of operating site
Draping the patient
Surgeon preparation
Hand washing
Skin antiseptics
Gloving

Risk Factors for SWI

Wound-related factors:
Magnitude of tissue trauma and devitalization
Blood loss, hematoma
Wound classification
Potential bacterial contamination
Presence of drains, packs, drapes
Ischemia
Wound leakage

SKIN WOUND HEALING

Healing by First Intention
Occurs in small wounds that close easily
Epithelial regeneration predominates over
fibrosis
Healing is fast, with minimal scarring/infection
Examples:
Paper cuts
Well-approximated surgical incisions
Replaced periodontal flaps

SKIN WOUND HEALING

Healing by First Intention:
Timeline
By 24 hours
By

3-7 days

Weeks

later

SKIN WOUND HEALING

Healing by First Intention:
Timeline
By 24 hours

clot forms
neutrophils come in
epithelium begins to regenerate

SKIN WOUND HEALING

Healing by First Intention:
Timeline
By 24 hours
By

3-7 days

macrophages come in
granulation tissue is formed

new blood vessels

fibroblasts
collagen begins to bridge incision
epithelium increases in thickness

SKIN WOUND HEALING

Healing by First Intention:
Timeline
By 24 hours
By

3-7 days

Weeks

later

granulation tissue gone

collagen is remodeled
epidermis full, mature
(but without dermal appendages!)
eventually, scar forms

24 hours

6 hours

2 days

1 week

SKIN WOUND HEALING

Healing by Second
Intention
Occurs in larger wounds
that have gaps between
wound margins
Fibrosis predominates over epithelial regeneration
Healing is slower, with more inflammation and

granulation tissue formation, and more scarring

Examples:

Infarction
Large burns and ulcers
Extraction sockets
External-bevel gingivectomies

SKIN WOUND HEALING

Second intention healing has:
More inflammation
More granulation tissue
Wound contraction

Pressure ulcer of skin

Skin ulcer: large gap between edges

Skin ulcer: granulation tissue

Skin ulcer: re-epithelialization

SKIN WOUND HEALING

Wound Strength
At suture removal: 10%
Rapid increase over next 4 weeks
At third month: 70-80%

LECTURE OVERVIEW
Important background facts
cellular

proliferation
growth factors
the extracellular matrix
The process of tissue repair
regeneration
scarring
an

illustration: skin wound healing

why do good wounds go bad?

WHY DO GOOD WOUNDS GO BAD?

Extrinsic factors

Infection
Diabetes
Steroids

Type of tissue injured (labile vs. permanent)

Aberrant cell growth or ECM production

Keloid scars
Proud flesh

Keloid scar

Keloid scar

Proud flesh

Proud flesh

Proud flesh

first intention
healing

second intention
healing

LECTURE OVERVIEW
Important background facts
cellular

proliferation
growth factors
the extracellular matrix
The process of tissue repair
regeneration
scarring
an

illustration: skin wound healing

why do good wounds go bad?

TISSUE REPAIR SUMMARY

Healing Processes

Induction of an inflammatory process

Proliferation and migration of
parenchymal and connective tissue cells
Angiogenesis and granulation tissue
Synthesis of ECM proteins and collagen
deposition
Tissue remodelling
Wound contraction
Acquisition of wound strength

TISSUE REPAIR SUMMARY

Not all injuries result in permanent damage;

some are resolved almost completely

More often, there is some degree of scarring
Scar is usually good (provides a resilient patch)

but occasionally bad (can cause permanent

dysfunction)