WOUND HEALING

CELSO M. FIDEL, MD, FPS GS, FPCS

Diplomate Philippine Board of Surgery
 Key Points

1. Wound healing is a complex cellular and

biochemical cascade that leads to
restitution of integrity and function.
2. Although individual tissues may have
unique healing characteristics, all
tissues heal by similar mechanisms,
and the process undergoes phases of
inflammation, cellular migration,
proliferation, matrix deposition, and
remodeling.
 Key Points

3. Factors that impede normal healing

include local, systemic, and technical
conditions that the surgeon must take
into account.
4. Optimal outcome of acute wounds relies
on complete evaluation of the patient
and of the wound, and application of
best practices and techniques.
 Key Points

5. Clinically, excess healing can be as

significant a problem as impaired
healing; genetic, technical, and local
factors play a major role.
6. Future advances in growth factor
understanding, tissue engineering,
and dressing design are expected to
increase the armamentarium in
improving wound outcomes.
 History of Wound Healing

The earliest accounts of wound healing date back

to about 2000 B.C.,
Sumerians employed two modes of
treatment:
1. Spiritual method consisting of incantations
2. Physical method of applying poultice-like
materials to the wound.
Egyptians =Ist to differentiate infected &
diseased wounds from noninfected wounds.
 History of Wound Healing

The 1650 B.C. Edwin Smith Surgical

Papyrus, a copy of a much older document,
describes at least 48 different types of wounds.
A later document (Ebers Papyrus, 1550 B.C.)
relates the use of concoctions containing honey
(antibacterial properties), lint (absorbent
properties), and grease (barrier) for treating
wounds. These same properties are still
considered essential in contemporary daily
wound management.
 History of Wound Healing

The Greeks, equipped with the knowledge

bequeathed by the Egyptians, went even further
and classified wounds as acute or chronic in
nature.
Galen of Pergamum (120201 A.D.),
appointed as the doctor to the Roman gladiators,
had an enormous number of wounds to deal with
after gladiatorial combats. He emphasized the
importance of maintaining a moist environment
to ensure adequate healing.
 History of Wound Healing

It took almost 19 centuries for this

important concept to be proven
scientifically, when it was shown that
the epithelialization rate increases by
50% in a moist wound environment
when compared to a dry wound
environment.1
 History of Wound Healing

The next major stride in the history of wound healing

was the discovery of antiseptics and their
importance in reducing wound infections.
Ignaz Philipp Semmelweis, a Hungarian
obstetrician (18181865), noted that the incidence
of puerperal fever was much lower if medical
students, after cadaver-dissection class and before
attending childbirth, washed their hands with soap
and hypochlorite.
 History of Wound Healing

Louis Pasteur (18221895) dispelled the

theory of spontaneous generation of germs &
proved that germs were always introduced into
the wound from the environment.
Joseph Lister made one of the most significant
contributions to wound healing. On a visit to
Glasgow, Scotland, Lister noted that some areas
of the city's sewer system were less murky than
the rest. He discovered water from pipes
dumping waste containing carbolic acid (phenol)
was clear
 History of Wound Healing

In 1865, Lister began soaking his instruments in

phenol and spraying the operating rooms, reducing
the mortality rates from 50 to 15%.

This practice led to the suspension of Lister, although

subsequent confirmation of his results paved the
way for his triumphant return to Edinburgh.
 History of Wound Healing

After attending an impressive lecture by Lister

in 1876, Robert Wood Johnson left the
meeting and began 10 years of research that
would ultimately result in the production of an
antiseptic dressing in the form of cotton gauze
impregnated with iodoform. Since then,
several other materials have been used to
impregnate cotton gauze to achieve antisepsis.
 History of Wound Healing

Polymeric dressings were developed in the

1960s and 1970s. These dressings can be custom
made to specific parameters, such as permeability to
gases (occlusive vs. semiocclusive), varying degrees of
absorbency, and different physical forms.
Due to the ability to customize, the available
range of materials that aid in wound care has grown
exponentially to include an ever-expanding variety.
 History of Wound Healing

. Currently, the practice of wound healing

encompasses manipulation and/or use of, among
others,
1. Inflammatory cytokines
2. Growth factors
3. Bioengineered tissue.
It is the combination of all these modalities that
enables optimal wound healing.
 General Considerations

Most exciting & promising field in

Surgical Biology.

To reestablish physical integrity is

not the problem, but alteration of
function of a vital organ when scar
replaces Complex tissue
 Classification of Wounds

1. Clean Wounds
a. Surgical Procedure thru skin cleaned
with disinfectant
b. No entry to GIT, Respiratory Tract &
Urinary Tract
c. Infection rate less than 2%

2. Clean Contaminated Wounds

a. GIT, Respiratory T & G Urinary T are
entered
b. Infection rate less than 3%
 Classification of Wounds

3. Contaminated Wounds
a. Major CONTAMINATION
b. Infection rate-less than 5%

4. Infected Wounds
a. Established infection before
a wound is made
b. Infection rate -50% or more
 B. Mechanisms Involved in Wound Healing

1.Epithelization

a. Epidermal edges turn downward into

dermal portion of the incision. Within 24
to 48 hrs. it shows thickening .Migrating
epithelial cells move down over the
exposed portion of dermis and across the
base of the wound. By 48 hrs. epithelium
has bridged the gap.
 C. Phases of Wound Healing

Epithelialization
This process is characterized primarily by
proliferation and migration of epithelial
cells adjacent to the wound

The process begins within 1 day of injury

and is seen as thickening of the epidermis at
the wound edge.
 C. Phases of Wound Healing

Epithelialization
Marginal basal cells at edge of the wound
lose their firm attachment to underlying
dermis, enlarge, and begin to migrate across
surface of the provisional matrix.
Fixed basal cells near the cut edge undergo
a series of rapid mitotic divisions, and they
appear to migrate by moving over one
another in a leapfrog fashion until the
defect is covered.
 C. Phases of Wound Healing

Epithelialization

Once the defect is bridged, the migrating

epithelial cells lose their flattened
appearance, become more columnar in
shape, and increase their mitotic activity.
Layering of the epithelium is re-established,
and the surface layer eventually keratinizes.
 B. Mechanisms Involved in Wound Healing

1.Epithelization

Stitch Abscess
Epithelial migration also occurs in the
suture tracts. Contact with connective
tissue causes KERATINIZATION which
induces an intense localized
inflammatory reaction.
 B. Mechanisms Involved in Wound Healing

2. Contraction
a. Does not begin until the 4th day.

b. Centripetal movement of the whole

thickness of the surrounding skin
wound.
c. Also seen in the constriction of
tubular organs like the CBD and
Esophagus after injury
 B. Mechanisms Involved in Wound Healing

2. Contraction

Picture Frame Theory

New School of Thought

Specialized kind of cells the
MYOFIBROBLAST with muscle-like
contracting powers.
 B. Mechanisms Involved in Wound Healing

3. Connective Tissue Matrix Deposition

a. Fibroblast is recruited to the site
of injury and produce a new
connective tissue matrix.
b. Of major importance in primary
wound closure. The cross-linked
collagen in the connective tissue
provides strength and integrity
C. Phases of Wound Healing

1. Inflammatory or Lag Phase

a. When a tissue is injured, cellular
contents and debris are liberated
into the wound.
b. These materials initiates the clotting
cascade, w/c then deposits fibrin in
the wound to form a clot.
c. These materials allows the
inflammatory phase to continue
until white cells cleared all the debris.
C. Phases of Wound Healing

1. Inflammatory or Lag Phase

d. Initially there is vasoconstriction that
blanches a fresh wound. (5-10
minutes) due to release of
Cathecolamines. Vasodilatation
follows causing erythema of the wound
Vasoactive compounds includes:
(1.) Histamine
(2.) Serotonin
(3.) Bradykinins
C. Phases of Wound Healing

1. Inflammatory or Lag Phase

e. Increased capillary permeability allows red
cells, white cells, and platelets to leave the
vessels and enter the wound.White cells are
attracted by Chemoattractants
from the injured tissue and bacteria.

f. Wound edema is caused by the migration

of cells and fluid into the wound.
 C. Phases of Wound Healing

2. Migratory phase
a. Macrophages clear debris and
bacteria. It also releases growth
factors.
b. Fibroblast migrate to the wound to
begin the healing process.
c. Hypoxia & wound growth factors
stimulates neo-vascularization.
d. Epithelization
 C. Phases of Wound Healing

3. Proliferative phase
a. Fibroblast that have migrated to the
wound begin to form collagen &
wound strength begins to increase

b. Until the point that collagen is laid

down in the wound strength is due
to fibrin in the clot or scab
c. Wound contraction (4th-5th) day
C. Phases of Wound Healing

3. Proliferative phase
d. Tensile Strength
Strength /unit of Scar(5th) day.Refers
to load applied per unit of cross section
area in lbs/in2 or kg/cm
2

e. Burst Strength
Strength of the entire wound. Increase
in strength is rapid for 17 days & slow
for the next 10 days. Amount of pressure
necessary to rupture a viscus.
C. Phases of Wound Healing

3. Proliferative phase

f. Breaking strength -Measurement of

force required to break a wound without
regard to its dimension

g. Phenomenon of secondary healing

effect
7mm around the first wound.
C. Phases of Wound Healing

4. Remodeling Phase
a. Wound essentially healed with scar.
Haphazardly laid down collagen breaks
down and new collagen is laid down along
the line of stress.

b. Newly directed collagen as well as more cross-

links between collagen strands increase the
strength of scar.

c. Ninety(90)% original tissue strength in 6 wks.

 D. Types of Wound Closure

1. Primary Intention
a. Suture right after Surgery or after wounding.

b. Approximate wound edges

c. Clean Wound, Clean- Contaminated Wound,

Contaminated Wound if not extremely
involved and patients condition is good.

d. (+) epithelization and connective tissue

repair.
 D. Types of Wound Closure

2. Secondary Intention
No suturing
wound allowed to granulate
(+) Epithelization & Wound Contraction
Dirty Wounds
Abscess & heavily infected wounds or
Carbuncle
Miles Operation
Fistulectomy
 D. Types of Wound Closure

3. Tertiary Intention

Delayed Primary Closure

Wound left open for 3-5 days
Granulation Tissue Formation
Close wounds with sutures after 4-10
days
Wounds that are heavily contaminated
like ruptured Appendicitis, Perforated
hollow viscus
 Halsted Principles
The essentials of Halstedian Surgery; based on a
fundamental knowledge of Wound healing are known to
modern day surgeons as:
TENETS OF HALSTED
1. Gentle handling of tissues
2. The aseptic technique
3. Sharp anatomic dissection of tissues
4. Careful hemostasis, using fine, non irritating
sutures in minimal amounts
5. Obliteration of dead space in the wound
6. Avoidance of Tension
7. Importance of Rest
 E. Cytokines
Provides all the communications for cell
to cell interactions.
Role of Cytokines
1. Regulation of fibrosis
2. Healing of chronic wounds & skin
grafts
3. Vascularization
4. Enhancement of bone and tendon
strength after repair.
5. Control of malignancy
Cytokines are really wound hormones
1. Endocrine- like somatomedin or
insulin like growth factor.

2. Paracine- produced by 1 cell and

affecting an adjacent target cell
3. Autocine- secreted by a cell and then
act on receptors on the same cell

4. Intracine- produced by a cell & remain

active in the same cell
Cytokines stimulate cells to migrate to
the wound site & to produce specific
components needed for matrix repair.

These includes:

1. Proteases
2. Enzymes
3. Proteoglycans
4. Attachment glycoproteins
PDGF
Is one of several platelet-derived growth
factors and initiates many healing events.
Its functions include chemotaxis for
fibroblasts and macrophages as well as
smooth muscle cells.

TGF-B
Produced by platelets.
It increases collagen synthesis specifically by
enhancing matrix gene expression & by
inhibiting collagenase production and activity.
Excessive amount is extremely important in the
pathophysiology of fibrotic states such as keloid
and hypertrophic scar.
 F. Extracellular Matrix Metabolism

Collagen is the major component

tendon
soft tissues
bone
Ligaments

Glycosaminoglycans, Proteoglycans,
Fibronectin, Laminin, Elastin
 F. Extracellular Matrix Metabolism

Steps in Synthesis
A. Transcription- where the amount of RNA
for the specific collagen is controlled
B. Translation- where actual synthesis
occurs on ribosomes on the rough
endoplasmic reticulum
Degradation
Mammalian Collagenase coming from:
Inflammatory Cells
Fibroblast
Epithelial Cells
 F. Extracellular Matrix Metabolism
Ground Substance -Proteoglycans
composed of glycosaminoglycans sub-
units attached by covalent bonds to a
protein core. Form bottlebrush-like
structure and as macromolecules, occupy
significant space in the extracellular
matrix.
Functions
Molecular shock Absorbers
Provide for moisture storage
Sequester cytokines
 F. Components of Extracellular Matrix

COMPONENT FUNCTION

1. Collagen > Strength, support and structure of all tissues

and organs
2. Elastin > Allows tissue structures to expand/ contract
3. Fibronectin > Mediates cell matrix adhesion
4. Laminin > Binds cells to type IV collagen and heparin
sulfate
5. Proteoglycans > Moisture stores, shock absorption,
sequestration of cytokines
6 Hyaluronic > Provides fluid environment for cell movement
Acid and differentiation and binds to cytokines
 SPECIFIC WOUND HEALING
PROBLEMS
1. Gastrointestinal tract
a. Bowel anastomotic tensile strength develops
more rapidly than skin tensile strength
b. Ulcers in the stomach heals slowly
c. Major complications of intestinal anastomosis
anastomotic leakage
actual bowel wall disruption
2. Skin
a. keloids and hypertrophic scar are both
abnormal healing process that occurs after
injury from trauma and surgery
 SPECIFIC WOUND HEALING PROBLEMS
Skin
b. Keloids extend beyond the original boundaries
of the original wound usually do not regress;
it recurs after excision unless additional
therapy is given
c. Hypertrophic scar remain w/in the boundaries
of the original wound and almost always
regress over a period of time
d. Both are characterized by an over abundant
deposition of collagen
e. Intra lesional injection w/ triamcinolone is the
most promising treatment for keloids
 SPECIFIC WOUND HEALING PROBLEMS
Tendon
a. These are composed mainly of Type 1 collagen,
w/ significant amount of proteoglycan
b. The flexor tendon w/in fibrous flexor sheaths
of the digits present to the surgeon a unique
healing problem no mans land
c. Healing must occur in the sutured end of the
tendon as well as the sheath itself
 SPECIFIC WOUND HEALING PROBLEMS
Bone
After fracture, the dead material is removed
& hematoma resorbs.
Revascularization occurs & granulation tissue
bridges the defect.
Callus is formed w/c is mineralized as cartilage
and is replaced by osteod to form hard
callus, then replaced with compact bone
 SPECIFIC WOUND HEALING PROBLEMS

Chronic wounds

Fails to heal due to underlying pathology

 Suture Materials
They are fibers or strands of material used for
sewing tissues or ligating blood vessels
Used between 2500 and 3000 BC, documented
by Egyptian papyri consisting of:
1. Fibers of plant origin
2. Leather
3. Animal Tendons
4. Parchment strips
Joseph Lister in 1860 introduced Carbolic Catgut,
the 1st suture material specific for Surgery
 Suture Materials

Eventually other materials were introduced

for Surgical use:
1. Linen
2. Silk
3. Celluloid
4. Horsehair
5. Wire
In the 1930s polyvinyl-alcohol, a
synthetic material was introduced
 Types of Suture Materials
I. Absorbable Broken down or degraded by
hydrolysis or digested by enzymatic
process
1. Plain Catgut
2. Chromic Catgut
3. Polyglactin
4. Polyglycolic Acid
5. Polydioxanone
6. Polyglecaprone
 Types of Suture Materials
I Absorbable
1. Plain Catgut
a. derived from small intestine:
serosal layer of cattle
sub mucosal layer of sheep
b. Loses much of its tensile strength at the
end of one week
c. for subcutaneous tissue and ligature
purposes
 Types of Suture Materials
2. Chromic Catgut
a. same as plain catgut and treated with Chromate
compounds
b. Stronger and more slowly absorbed suture
c. Loss of tensile strength is doubled
d. Not advisable for peritoneum
3. Polyglactin
a. Synthetic braided suture whose raw material is
a copolymer of glycolide and lactide
b. Tensile strength is retained for 14 days
 Types of Suture Materials
4. Polyglycolic Acid
a. Reduced by hydrolysis to glycolic acid
b. Tensile strength completely lost by 30 days
c. Complete absorption in 90 days
5. Polydioxanone
a. Synthetic monofilament composed of polyester
of p-dioxanone
b. Tensile strength is about 70% at 14 days
c. Absorption starts close to the 90th day and is
complete in 6 months time
 Types of Suture Materials
II Non-Absorbable Sutures- those which are
not arrested by either enzymes or tissue fluid
1. Silk
2. Cotton
3. Nylon
4. Polypropylene
5. Polyester
6. Wire
7. Stainless Steel
8. Titanium
 Types of Suture Materials
II Non-Absorbable Sutures-

1. Silk
a. Most commonly used suture material
b. Protein filament produced by silkworm
c. Silk losses much of its Tensile strength when
exposed to moisture and should be used dry
 Types of Suture Materials
II Non-Absorbable Sutures-

2. Cotton
a. Stimulates an inflammatory reaction greater than
silk
b. Much cheaper than silk
 Types of Suture Materials
II Non-Absorbable Sutures-

3. Nylon
a. Comes in monofilament and a braided form
b. High tensile strength and extremely low tissue
reaction
c. The loss in Tensile strength is in the range of
15-20% per year by hydrolysis
 Types of Suture Materials
II Non-Absorbable Sutures-

4. Polypropylene
a. Synthetic monofilament suture
b. Tensile strength retention is indefinite
c. Suture encapsulated by tissue
 Types of Suture Materials
II Non-Absorbable Sutures-

5. Polyester
a. First synthetic braided suture material shown to
last indefinitely in tissues

b. Like polypropylene, they are encapsulated by

tissues and thus resist tissue degradation
 Types of Suture Materials
II Non-Absorbable Sutures-

6. Wire/Stainless steel/ Titanium

a. Very strong suture material that produces little
loss of tensile strength

b. Wire used for many years and very popular for

variety of operations( thoraco-cardiovascular,
Orthopedics, Neurosurgery)

c. Tissue reaction Minimal

 Types of Suture Materials

III Surgical Staplers

1. Modern surgical stapling devices & techniques

were first developed in the Soviet Union in
1950s by the Scientific Research Institute for
Experimental Surgical Apparatus and Instruments
in Moscow.
 Types of Suture Materials

III Surgical Staplers

2. Wide application in various fields in Surgery

a. Ligation and division
b. Resection
c. Anastomosis
d. Skin and fascial closure
 Types of Suture Materials
III Surgical Staplers
3. These Staplers significantly reduce
a. Operating Time
b. Time under Anesthesia

c. Blood loss
d. Tissue manipulation and Trauma
Facilitating postoperative healing
Edema and inflammation associated w/ manual
suturing significantly reduced
 Types of Suture Materials

III Surgical Staplers

4. They are virtually inert ,producing minimal

tissue inflammation and minimal tissue
compression
 Types of Suture Materials
IV Skin Adhesives
1. The newest suture material available in the
market today is called topical skin adhesive
e.g. DERMABOND.
a. This is a non-absorbable sterile violet-colored
liquid ( 2-octylcyanoacrylate) used primarily for
easy approximation of skin edges
2. Not recommended for use in hands and over joints
since w/ repetitive movements and washing, the
adhesive may peel off with the top layer of
epidermis
 Guidelines in Choosing a Suture
1. Select the finest suture consistent with the
tissues to be approximated
2. Suture material should have adequate tensile
strength & maintain it until purpose is served
3. It should produce the least tissue reaction
4. Select sutures with the least risk for bacterial
proliferation
5. Select sutures w/c are pliable, easy to handle
and able to maintain knot security
Guidelines in Choosing a Suture
Three principles to remember in the choice of
sutures based on their physical properties:

1. Suture should be at least as strong as normal

tissues through which they are placed.
2. Suture strength must be maintained until the
wound gains maximal strength
3. Tissue reaction to sutures should not prolong
the healing process
Variations in Healing Rate

1. Skin - 70% strength at 3-4 months

2. Fascia - 50% of original strength at 50 days

- 80 % at one year

3. Muscle - 80 % strength at 10-14 days

4. Viscera - 80 % at 14-21 days

 WOUND DRESSINGS

Films-
Mimic skin performance

Hydrocolloids-
Absorbs fluid
Debrides soft necrotic tissue
Protects wound
 WOUND DRESSINGS

Hydrogels
Creates moist environment

Foams
Debrides
High absorbancy rates
 WOUND DRESSINGS

Impregnates

Dont adhere to wound

Promotes re-epithelization
 WOUND DRESSINGS

Absorptive powders and paste

High absorbancy
Debrides necrotic and fibrous material from
wounds
Calcium alginate
High absorbent capabilities
 Factors that Inhibit Wound Healing

1. Malnutrition
2. Diabetes
3. Steroids
4. Chemotherapy
5. Vitamin C deficiency
6. Zinc deficiency