WOUND HEALING

1
Definition
• A wound is defined as a disruption in tissue integrity, leading to
division or transection of blood vessels and direct exposure of
extracelular matrix to platelets.

• Wound healing is a process that follows a predictable pattern that

can be divided into overlapping phases defined by characteristic
cellular populations and biochemical activities.
Overview
• Wound healing is a complex cellular and biochemical cascade that
leads to restitution of integrity and function.

• Although individual tissues may have unique healing characteristics,

all tissues heal by similar mechanisms and processes.

• Factors that impede normal healing include local, systemic, and

technical conditions that the surgeon must take into account.

• Optimal outcome of acute wounds relies on complete evaluation of

the patient and of the wound, and application of best practices and
techniques.
Phases of Wound Healing
• Hemostasis and Inflammation

• Proliferation

• Maturation

• Remodeling
Hemostasis and Inflammation
• Hemostasis precedes and initiates inflammation, with the ensuing
release of chemotactic factors from the wound site.

• Exposure of subendothelial collagen to platelets results in platelet

aggregation, degranulation, and activation of the coagulation
cascade leading to the formation of the fibrin clot to achieve
hemostasis.

• Increased vascular permeabilty, local prostaglandin release, and the

presence of chemotactic substances (eg. IL – 1, TNF alpha, TGF
beta, platelet factor 4, or microbial products) stimulates neutrophil
migration.
The Coagulation Cascade
• The fibrin clot also serves as a scaffolding for the migration of
inflammatory cells such as:

 Neutrophils – phagocytosis of bacteria and tissue debris.

 PMN’s – secretions of cytokines, especially TNF alpha, which
may have a significant influence on subsequent angiogenesis
and collagen synthesis.
 Macrophages
• Derived from circulating monocytes, they achieve significant numbers in the
wound by 48 – 96 hours.
• Participate in wound debridement via phagocytosis and contribute to
microbial stasis via oxygen radical synthesis and NO synthesis.
• Play a significant role in angiogenesis by recruiting and activating mediators
such as cytokines and growth factors.
 T lymphocytes
• Less numerous than macrophages, their numbers peak at about 1 week
post injury.
• Although known to be essential in the transition from the inflammatory phase
to the proliferative phase, its role in wound healing is not fully defined.
• A hypothesis suggests that lymphocytes play an active role in the
modulation of the wound environment as evidenced by decrease in wound
strength and collagen content in the depletion of T lymphocytes.
Proliferation
• Roughly spans from the 4th – 12th day and partially overlaps with the
process of inflammation.

• Fibroblasts and endothelial cells infiltrate the healing wound, marking

the onset of the proliferative phase, and the strongest chemotactic
factor for fibroblasts is platelet derived growth factor (PDGF).

• Proliferation of fibroblasts precedes its activation.

• Activation is mediated mainly by cytokines and growth factors

released by macrophages, then leading to collagen synthesis.
• Endothelial cells, which participate in angiogenesis, also proliferate
extensively during this phase.

• Their migration (from intact venules close to the wound), replication,

and new capillary tubule formation, are mediated by cytokines such
as TNF alpha, TGF beta, and VEGF (binds to receptors located on
endothelial cells).
• Matrix Synthesis

 Collagen (types I and III) plays a critical role in the successful

completion of wound healing.
• Type I Collagen – major component of the extracellular matrix.
• Type II Collagen – prominent during wound repair; attracts fibroblasts and
encourages deposition of new collagen into the wound bed.
• Collagen synthesis, as well as posttranslational modifications, is
highly dependent on systemic factors such as adequate oxygen
supply, presence of sufficient nutrients (amino acids and
carbohydrates) and cofactors (vitamins and trace metals), and the
local wound environment (vascular supply and lack of infection.
• Proteoglycan Synthesis

 Occurs after approximately 3 days from the onset of injury.

 Fibroblasts deposit ground substance (glycosaminoglycans,
which couple with proteins to form proteoglycans) into the
wound bed, and later additional collagen, which they can adhere
to for migration.
 Granulation tissue functions as rudimentary tissue, and begins
to appear in the wound already during the inflammatory phase, 2
to 5 days post wounding, and continues growing until the wound
bed is covered.
 Granulation tissue consists of:
• new blood vessels
• fibroblasts and myofibroblasts
• inflammatory cells
• endothelial cells
• provisional extracellular matrix (ECM).
• Epithelization

 The formation of granulation tissue into an open wound allows

the reepithelialization phase to take place, as epithelial cells
migrate across the new tissue to form a barrier between the
wound and the environment.
 Basal keratinocytes from the wound edges and dermal
appendages such as hair follicles, sweat glands and sebacious
glands are the main cells responsible for the epithelialization
phase of wound healing.
Scab covering a healing wound
• Healthy granulation tissue does not bleed easily.
• Dark granulation tissue can be a sign of infection, ischemia, or poor
perfusion.
• In the final phase of the proliferative stage of wound healing,
epithelial cells resurface the injury.
• It is important to remember that epithelialization happens faster when
wounds are kept moist and hydrated.
Maturation and Remodelling
• Characterized by the reorganization of previously synthesized
collagen.
• Net wound collagen content is the result of a balance between
collagenolysis (mediated by matrix metalloproteinases) and collagen
synthesis.
• Deposition of matrix at the wound site follows a characteristic
pattern:

Early matrix scaffolding constituted by fibronectin and collagen

type III

Glycosaminoglycans and proteoglycans represent the next

significant matrix components

Collagen type I constitutes the final matrix.

Hereditary Connective Tissue Diseases
• Ehler – Danlos Syndrome
 A group of connective tissue disorders, most importantly
collagen.
 Characterized by hyperelastic skin with prominent veins, easy
bruising, poor wound healing, and hyperextensible joints.
• Marfan Syndrome
 A genetic defect in fibrillin, an extracellular protein.
 Characterized by tall stature, arachnodactyly, scoliosis, pectus
excavatum, and aneurysm of the ascending aorta.
• Osteogenesis Imperfecta
 Mutation in Type I Collagen
 Characterized by brittle bones, osteopenia, scoliosis, low muscle
mass, hernias, blue sclera, and ligament and joint laxity.
Classifications of Wounds
• By cause
 Intentional – purposefully created under sterile conditions for
therapeutic reasons and closed immediately after the
intervention.
 Unintentional – accidental wounds that include traumatic
wounds, penetrating wounds, or abrasions.
 • By cleanliness
TYPE DEFINITION EXAMPLES

I – Clean An uninfected operative wound in which no inflammation

is encountered and the respiratory, alimentary, genital, or
Vascular, Neurologic, Orthopaedic
uninfected urinary tracts are not entered. Clean wounds procedures
are primarily closed and, if necessary, drained with
closed drainage

II – Clean / Contaminated Operative wounds in which the respiratory, alimentary,

genital, or uninfected urinary tracts are entered under
Operations involving the biliary tract,
controlled conditions and without unusual contamination. appendix, vagina, and oropharynx.

III – Contaminated operations with major breaks in sterile technique (for

example, open cardiac massage) or gross spillage from
Open, fresh, accidental wounds.
the gastrointestinal tract, and incisions in which acute,
non purulent inflammation is encountered

IV - Dirty Includes old traumatic wounds with retained devitalized

tissue and those taht involve existing lcinical infection of
Infected wounds, IBD abscess, wound
perforated viscera. This definition suggests that the debridement
organisms causing the postoperative infection were
present in the operative field before this operation.
• By thickness

TYPE DEFINITION

Superficial Involvement of epidermis

Partial Thickness Involvement of epidermis and dermis

Full Thickness Involvement of epidermis, dermis,

subcutaneous fat, and in some instances,
bone.
• By wound origin
TYPES DEFINITION

Superficial Break in the skin’s surface.

Incised A result of surgical intervention or sharp – edged object slicing

into the skin.
Crush A result of heavy blow or with cutting tool.

Lacerated Fragments of tissue torn away with sharp – edged object.

Stab / Puncture Made with pointed tool or weapon.

Contused Tissue injury under the skin’s surface

Secondary Caused by underlying disease; diabetic ulcers, pressure ulcers,

venous ulcers, etc.
Superficial Wound Incised Wound
Crush Wound Lacerated Wound
Puncture Wound Contusion Secondary Wound
Types of Wound Healing
• Regeneration vs. Reparation
 Regeneration (epithelialization)
• the process of returning the site of injury to its original state.
• This is seen in re-epithelialization after having minor lacerations.
 Reparation (tissue repair)
• the process of generating a scar or less functional tissue with a different
form and/or composition of the original tissue.
• Does not restore complete functionality
• Types of Reparation

TYPE DEFINITION
Primary Intention The tissue surface edges are approximated; small defect
with little risk of complications and/or infection
Secondary Intention Used when there are significant tissue losses and the
wound surface cannot be brought together (e.g.,
lacerations, burns, and ulcers); granulation tissue
(consisting of connective tissue cells and in growing young
blood vessels) is needed to close the defect → scar
formation occurs with a higher risk of infection.
Tertiary Intention Used when there is a need to delay the closure of a
wound (due to contamination risk, poor circulation, etc.)
Referrences
• Robbins and Cotrans Pathologic Basis of Disease 9 th Edition, Chapter 3 – Inflammation
and Repair

• Schwartz’s Principles of Surgery 9th Edition, Chapter 9 – Wound Healing

• https://www.learnhaem.com/courses/coagulation/lessons/normal-haemostasis/topic/the-
revised-coagulation-cascade/

• https://en.wikipedia.org/wiki/Wound_healing

• https://www.contemporaryobgyn.net/view/surgical-wound-classification

• https://www.lecturio.com/concepts/wound-healing/
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LISTENING!
“Injury alone has in all cases a tendency to produce the deposition and
the means of a cure.” – John Hunter