WOUND HEALING

“A surgeon’s role in wound management is to create

an environment in which the healing process
can proceed in an optimal fashion. “
HISTORY OF WOUND HEALING
 The earliest accounts of wound
healing date back to about 2000 B.C

 The treatment
of acute and chronic wounds is an
ancient area of specialization in
medical practice, with a long and
eventful clinical history that traces
its origins to ancient
Egypt and Greece.
HISTORY OF WOUND HEALING
 The Ebers Papyrus,
circa 1500 BC, details the
use of
1. lint (absorbent)
2. animal grease (Barrier),
and
3. honey(antibiotic )
 as topical treatments for
wounds
 HISTORY OF WOUND HEALING
 Galen of Pergamum (a Greek surgeon
who served Roman gladiators in 120–201
A.D) emphasized the importance of
maintaining a moist environment to
ensure adequate healing.
 Ambriose Paré ( French surgeon who
served in that role for french kings. He is
considered a pioneer in surgical
techniques and battlefield medicine 1510-
20 )
 He found that a simply dressed
gunshot wounds heal faster and are
less painful than when treated with
boiling oil, the previously accepted
method.
HISTORY OF WOUND HEALING
 Ignaz Philipp Semmelweis (1818-1865)
advocated need for washing hands
 Joseph Lister (1865- a British surgeon
and a pioneer of antiseptic surgery)
began soaking his instruments in
phenol and spraying the operating
rooms, reducing the mortality rates
from 50 to 15%.
 Wood Johnson(1876): – Antiseptic
dressing (cotton gauze impregnated
with iodoform).
 INTRODUCTION
 The repair of tissue damage can be broadly separated
into two processes, regeneration and healing .

 Regeneration “ is a perfect restoration of the pre-existing

tissue architecture in the absence of scar formation”

 Wound healing “is the effort of injured tissues to restore

normal function and structural integrity after injury “
PHASES OF WOUND HEALING

 • Inflammatory phase: hemo-stasis &

inflammation

 • Proliferative phase

 • Maturation and Remodelling

 – Epithelialization

 – Contraction
INFLAMMATORY PHASE:
 • “The body defenses are aimed at limiting the
amount of damage and preventing further injury”

 Hemostasis & Inflammation: hemostasis precedes

and initiates inflammation

 Local VC ; RBC & platelets adhere

 Exposed IV & V collagen leads to

platelet ,aggregation( vWF),degranulation
 Clotting cascade initiated

 “fibrin clot” : serves as scaffolding for the migration of

inflammatory cells ( PMN, Monocytes)

 ↑Vas Permeability:

 Platelet activation

 α granules ( PDGF,TGF-Beta, IGF-I, fibronectin,

fibrinogen, thrombo-spondin, vWF )

 Dense bodies ( Serotonin)

 Mast cells adhere to endothelium

 Histamine

 Serotonin
 clinical findings of inflammation,
rubor (redness), calor (heat), dolor (pain) & tumor
(swelling),
 PMN migration : peak 24-48 hrs

 Phagocytosis of bacteria & debris

 Cytokines ( TNF-alpha )

 Protease

 Macrophages: peak 48-96 hrs, “Macrophage is the one cell that is

truly central to wound healing”

 Phagocytosis

 Cytokines and GF ( TGF- Beta, VEGF,IGF-I, EGF, lactate ,)

 Regulate cell proliferation , matrix synthesis ,angiogenesis

 T – Lymphocytes: peak 1 week

 Bridge the transition from inflammatory to proliferative phase

 Not fully defined

PROLIFERATIVE PHASE:DAYS 4-12

 Fibro-genesis

 Angio-genesis
PROLIFERATIVE PHASE:
 Continuity is re-established
 PDGF recruits fibroblasts which proliferate
then gets activated ( by cytokines and GF from
macrophages )
 –matrix synthesis and remodelling
 Accumulated Lactate: regulate collagen synthesis
 Endothelial cells proliferate
 – Migrate from nearby intact venules
 – Angiogenesis of capillaries
 • Regulated by cytokines/GFs (VEGF, TNF-a, TGF-ß)
FIBROGENESIS
 The proliferative phase begins with degradation of the initial
fibrin-platelet provisional matrix.

 During fibrogenesis , fibroblasts synthesize and deposit the

matrix at the wound site

 As fibroblasts proliferate, they become predominant cell types

by 3 to 5 days in clean, non infected wounds.

 The initial fibrin matrix is replaced by a provisional matrix of

fibronectin and hyaluron, which facilitates fibroblast
migration.
 ANGIOGENESIS
 Process of new blood vessel formation
 Macrophage orchestrates angiogenesis during the inflammatory
phase.

1.Degradation of the BM of post-capillary venules

2.Migration of cells through this gap promoted by FGF, PDGF, and

TGF-β

3.Tubule or lumen formation involving cell-cell and cell-matrix

interactions.

4.Deposition of BM resulting in capillary maturation.

MATURATION AND REMODELLING
 •”The period of scar contracture with collagen cross-
linking, shrinking, and a loss of edema “

 Wound strength depends upon the quality& quantity of

deposited collagen
 It begins in the fibroblastic phase
 • Early matrix – fibronectin and collagen type III
 • Fibroplastic phase – reorganization of collagen
 – Collagenolysis by collagenase a matrix
metaloproteinase (MMPs)
 • Second matrix- GAGs &proteoglycans
 • Final matrix – collagen type I
 – Deposited over several weeks, but tensile strength
keeps on increasing over months
MATURATION AND REMODELING
 • Fibril formation & cross-linking

 Decrease collagen solubility

 – Increase strength

 – Increase resistance

 • Remodelling 6- 12 months

 The remodeling phase is resulting in a scar which is

avascular, mature, acellular ECM

“Mechanical strength never reaches uninjured levels”

EPITHELIALIZATION

 • begins within Day 1 – proliferation and

migration of epithelial cells adjacent to wound

 • Marginal basal cells lose their dermal

attachment, enlarge, flatten, and migrate across
the matrix (leapfrog) to cover the defect

 • Once covered, epithelial cells become more

columnar, increase mitotic activity and re-

establish the layered epithelium

 • In 48 hours ( approximated incised wounds )

WOUND CONTRACTION

 All wounds contract

 Myofibroblasts contain a smooth muscle actin in

thick bundles called stress fibers

 – May be responsible for contraction

 – Increases from day 7-21, fades after 4 wks

 • Movement &reorganization of the skeleton-

wound contraction
CONNECTIVE TISSUE DISORDERS

EHLER-DANLOS

 Cutis hyperelastica
defect in collagen
formation
 Thin, friable skin,
 prominent veins,
 easy bruising,
 poor wound healing,
 abnormal scar
formation,
 recurrent hernias,
 MARFAN SYNDROME
 – defect in fibrillin (assoc
with elastic fibres)
 tall stature,
 arachnodactyly,
 lax ligaments,
 hyper extensible skin,
 myopia,
 scoliosis,
 pectus excavatum,
 ascending aortic
aneurysm,
 prone to hernias
 OSTEOGENESIS IMPERFECTA –
 collagen Type I
mutation,
4subtypes
 –
Osteopenia/brittle
bones,
 low muscle mass,
hernias,
 lax ligaments,
 dermal thinning,
 increased
bruising,
 normal scarring,
 blue sclera
EPIDERMOLYSIS BULLOSA
 – epidermis &dermis lack the
protein anchors that hold
them together, resulting in
extremely fragile skin
 subtypes:
1. simplex (epidermis),
2. junctional (BM),
3. dystrophic (dermis)
 – Tissue separation and
blistering
 – Oral erosions and
oesophageal obstruction
cause poor nutrition
 ACRODEMATITIS ENTEROPATHICA
 – inability to absorb zinc via cell
surface binding and cellular
translocation, AR
 – Zinc is a cofactor for DNA
polymerase, RT
 – Impaired granulation tissue
formation,
 erythematous pustular dermatitis
 periorificial (around the natural
orifices) and acral (in the
limbs) dermatitis, alopecia (loss of
hair), and diarrhoea.
FACTORS AFFECTING WOUND HEALING
 Systemic
 Age: Dermal collagen content decreases with aging

 Nutrition:

 Arginine deficiency results in decreased wound-

breaking strength and wound collagen,

 Vitamin A increases the inflammatory response in

wound healing
 Vitamin C is required for the conversion of proline
and lysine to hydroxyproline and hydroxylysine
 Zinc deficiency leads to decreased fibroblast
proliferation
 Trauma

 Metabolic diseases :DM, uremia

 Immunosuppression: glucocorticoids reduce collagen

synthesis and wound strength.

 Connective tissue disorders

 Smoking
LOCAL
 Mechanical injury

 Infection: Inactive precursors of MMPs are activated by

bacterial proteinases

 Edema

 Ischemia/necrotic tissue

 Ionizing radiation: Causes endothelial cell injury with

endarteritis

 Low oxygen tension:profoundly deleterious effect on all

aspects of wound healing.

 Foreign bodies
EXCESS HEALING
 Hypertrophic scars

 Usually develop within 4 weeks of trauma

 Collagen bundles are wavy pattern

 Stay within the original wound, elevated less

than 4 mm

 Occur across areas of tension/flexing

 Often regress

 Tx: excision + corticosteroids

KELOIDS
 15x more common in pts with dark skin
pigmentation

 Develop 3 months –years after trauma

 Collagen fibres are larger, random & not

bundled

 Expand beyond wound edges, can

become large
KELOID
 Rarely regress

 Excision alone (45-100% recurrence)

 Excision + corticosteroid injections

 Topical silicone

 Radiation (10 to 100% recurrence when used

alone)

 Topical retinoids

 IFN-γ

 Chemotherapy (5FU,bleomycin) + external

compression
CLASSIFICATION OF SURGICAL WOUNDS
Type of wound Features
Clean 1. No hollow viscus entered
2. Primary wound closure
3. Elective procedure
Clean contaminated 1. Hollow viscus entered but controlled
2. No inflammation
3. Primary wound closure
Contaminated 1. Uncontrolled spillage from viscus
2. Inflammation apparent
3. Major break in aseptic technique
Dirty 1. Untreated, uncontrolled spillage from viscus
2.Pus in operative wound
3.Open suppurative wound, severe inflammation
CLASSIFICATION OF WOUND HEALING

 Primary intention

 Secondary intention

 Tertiary intention
PRIMARY CLOSURE
 First intention closure
 Immediately sealed wounds with simple suturing,
skin graft placement, or flap closure
 Eg. emergency laceration repair,
closure of the surgical wound
SECONDARY CLOSURE

 No active intent to seal the wound

 The wound is closed by reepithelization and

contraction with some deposition of scar tissue
DELAYED PRIMARY CLOSURE

 Tertiary intention
 Surgical intervention, such as suturing, skin graft
replacement, or flap design, after repeated
debridement and antibiotics therapy
“Treat the WHOLE patient
and not just the HOLE
in the patient”