WOUND HEALING

MEDICAL&SURGICAL PATHOLOGY 1
WOUND HEALING
Complex process, incompletely understood, through which the living organisms
attempt to restore :
• mechanical integrity
• barriers that protect against fluid loss and invading microorganisms
• fluid circulation – intravascular (blood) and interstitial (lymph)

Same basics steps in all types of wounds but with different outcomes in acute
versus chronic wounds
H E A L I N G V E R S U S R E G E N E R AT I O N
F R A N K E N S T E I N V E R S U S T E R M I N AT O R

• Aims to restore integrity and function • Flawless restoration of tissue architecture

• Speedy process • Time consuming

• Favors function over perfection • Embryonic development, bones, liver

• Outcome : scarring • Outcome : identical to the surrounding normal tissue

PHASES OF WOUND HEALING

Inflammatory Proliferative Maturational

ACTORS
PHASIC
DISTRIBUTION
OF CELL
POPULATIONS
I N F L A M M AT O RY
PHASE
I N F L A M M AT O RY P H A S E

Objectives Characteristics

1. arrest blood loss Ø increased blood flow

2. seal the wound Ø inflammatory cells migration

Ø cytokines & growth factors
3. remove alien structures (necrotic
secretion
tissue, germs, foreign bodies)
L E U KO C Y T E D I A P E D E S I S
PROLIFERATIVE
PHASE
P RO L I F E R AT I V E P H A S E

Angiogenesis Fibroplasia Epithelialization

RESULT : GRANULATION TISSUE

G R A N U L AT I O N
TISSUE
 ANGIOGENESIS
ANGIOGENESIS

EC – endothelial cells
MMP – matrix metalloproteinase
FIBROPLASIA

Macrophage & platelet-derived GF

(TGF-beta, PDGF)

Proliferation of chemoattracted and

stimulated resident fibroblasts

Collagen synthesis (starts 3-5 days

after the injury and declines after 4
weeks), followed by maturation
FIBROPLASIA
E P I T H E L I A L I Z AT I O N

Result
How Cells proliferate
and advance until
Keratinocytes firm contact is
migrate established with
When
through surrounding cells.
Starts hours interaction
after the with the Completed
injury extracellular resurfacing is
Who followed by cells
Keratinocytes matrix,
dissecting the reshaping and
from wound stratification
viable tissue
edges
from the
eschar
MATURATIONAL
PHASE
M AT U R AT I O N A L P H A S E

Wound contraction

Phenotypical Proteinases cleave Collagen fibers

change of the extracelular undergo
fibroblasts to matrix reorientation and
myofibroblasts cross linking
WOUND
HEALING
RESULT : SCAR
 FAC T O R S
T H AT
INFLUENCE
WOUND
HEALING
NUTRIENTS DEFICITS AND WOUND
HEALING
TYPES OF WOUND HEALING
• Primary (first intention) :
- immediate closure (surgical, clean wounds) : sutures/staples, skin grafting, flaps
• Secondary (spontaneous) :
- highly contaminated wounds
• Tertiary (delayed primary) :
- contaminated wounds
- partial secondary healing followed by removal of a part of the scar and surgical
closure
FAC T O R S
EXPLAINING
PRIVILEGED
WOUND
HEALING IN
ORAL
MUCOSA
ABNORMAL WOUND HEALING
Hypertrophic scars. Keloids
Chronic nonhealing wounds
HEALING TROUBLES

• A wound either heals correctly or … not.

• If not, the wound healing process either :
1. Overshoots, the results being : hypertrophic scars and keloids
2. Undershoots : atrophic scars
3. Fails, generating chronic, non-healing wounds
§ Non-healing wound may undergo neoplastic transformation
 Hypertrophic Keloid

• Frequent • Rarer than HSS but more frequent in darkly pigmented

skin
• Rich in type III collagen
• Genetic susceptibility
• Soon after injury
• Rich in type I collagen
• Usually subside with time
• Appears later than HSS
• Remain within the wound boundaries
• Rarely subsides with time
• No predominant anatomical site
• Spread out of the wound boundaries
• Pruritic but rarely painful
• Predominant on the chest, shoulders, posterior neck,
• Improve with treatment
knees, earlobes
• Low recurrence rate
• Pruritic and painful
• Poor response to treatment
• High recurrence rate
HYPERTROPHIC
SCARS
KELOID
SCARS
AT RO P H I C S C A R S
PREVENTION OF HSS AND KELOIDS
I N P R I M A RY W O U N D C L O S U R E

• Tension relief (for skin incision , follow the Langer lines)

• Wound hydration/occlusion – silicone sheets and gels to keep the wounds moist
• Use of pressure garments – wide wounds
• Avoidance of sun exposure and use of sunscreens (SPF 50+) during the first
postoperative year
 Pressure garments

Silicone sheet

Langer’s lines
T R E AT M E N T
CHRONIC WOUNDS
• Wounds that fail to heal properly over a period of 3 months
• Do not follow the described path of events
• The mechanism is poorly understood
• Dysfunctional inflammation (up-regulation of cytokine expression) and macrophage
altered behaviour are considered key elements in their evolution
• Imbalance of proteases and their inhibitors
• Altered wound pH : always alkaline in CW, inhibiting key processes during the
proliferative phase
• Bacterial contamination with biofilm formation
MAJOR
TYPES OF
CHRONIC
DIABETIC ULCER VENOUS ULCER
WOUNDS

PRESSURE ULCER
C H RO N I C W O U N D T R E AT M E N T
• Wound dressings
• Hyperbaric O2 therapy :
- addresses the most common cause of impaired wound healing – ischemia
- delivers 100% O2 at 1.9-2.5 atm
- works only if wound blood supply is adequate
• Negative pressure therapy :
- removes wound exudate
- promotes angiogenesis and cell proliferation
• Skin grafts
Hyperbaric O2 therapy Negative pressure wound therapy
EMERGING
STRATEG IES
IN
CHRONIC
WOUND
HEALING
WOUND HEALING AND CARCINOGENESIS
SIMILITUDES

• Beginning of the neoplastic process : fibroblasts are recruited, activated, and incorporated.
• Production of dysregulated matrix proteins and proteases is stimulated, forming a scaffold for tumor proliferation.
• As the tumor grows, the epithelium can be eroded away by cells expanding from below, causing ulceration at the
skin edge of the tumor.
• VEGF and other signaling molecules induce neovascularization.
• Inflammatory cells are recruited to the TME and release cytokines.
• The abnormal extracellular matrix is protumorigenic and proangiogenic.
• The tumor vasculature allows metastases to distant sites. Tumor cells are also cleared by lymphatics and can permit
lymphatic metastases.
W O U N D H E A L I N G
A N D
C A RC I N O G E N E S I S
MARJOLIN ULCER
• Aggressive squamous cancer that develops in non-
healing skin ulcers, burns and scars

• It develops on average 30 years after the skin injury