Wound Healing

Phases of Wound Healing

Phases of Wound Healing
John Hunter observed a predictable wound healing pattern dividedas 3
phases:
1. Hemostasis and inflammation
2. Proliferation
3. Maturation and Remodeling

• The sequence of these events are overlapping

• All wounds need to progress through the phases to successfully
achieve tissue integrity
A. Hemostatic/Inflammatory Phase
B. Latter inflammatory phase
C. Proliferative Phase
Phases of Wound Healing –
Hemostasis and Inflammation
• Hemostasis initiases inflammation by releasing chemotactic factors,
inciting blood vessel division and exposure of matrix to platelet
• Cellular infiltration after injury has a predetermined sequence:
Increased Vascular
Permeability
Prostaglandin Neutrophil
PMN Infiltration
Release Migration
IL-1, TNF-a, TGF-b,
platelet factor
Phases of Wound Healing
– Hemostasis and
Inflammation
• The second population that
invades the wound are
macrophages, which is
essential to successful healing
• Macrophage achieve
significant numbers in 48-96
hours
• Macrophages functions via
phagocytosis and microbial
stasis
Phases of Wound Healing -
Proliferation
• The proliferative phase spans through 4-12 days
• In this phase:
• Tissue continuity is re-established
• Fibroblast and endothelial cells infiltrate the wound
• Fibroblast activation causes matrix synthesis remodeling
• Wound fibroblast synthesize more collagen than nonwound fibroblast
• Lactate in the wound is also a collagen synthesis regulator
• Endothelial cells also proliferate extensively in this healing phase
Phases of Wound Healing –
Matrix Synthesis
Phases of Wound Healing –
Maturation and Remodeling
• This phase is characterized by reorganization of collagen
• Collagen is broken down by Matrix Metalloproteinases (MMPs)
• Wound strength and mechanical integrity are determined by quantity
and quality of collagen
• The deposition of matrix has a characteristic pattern:
• Type III Collagen for early matrix scaffolding
• Glycosaminoglycans and proteoglycans is the next matrix
• Type I collagen is the final matrix
Phases of Wound Healing –
Epithelialization
• The external barrier for the wound must be restored
• This process is done by proliferation and migration of epithelial cells
adjacent to the wound
• The process begins within 1 day of injury
• Basal cells would lose its attachment, then enlarge and migrate to the
edge of the wound
• Re-epithelialization complete in less than 48 hours
• But may take longer in larger wounds
Phases of Wound Healing
– Epithelialization
Growth Factors in Wound
healing Contraction
• Growth factors and cytokines
can stimulate cellular migration,
proliferation, and function
• The growth factors act in
autocrine, paracrine, or
endocrine manner
• Growth factor can be
chemoattractive to one type of
cell without replicating other
cell type
• All wounds undergo some
degree of contraction
• If the wound doesn’t have
surgically approximate edges,
the wound area would be
decreased
• Myofibroblasts are postulated
as responsible for the
contraction
Heritable Diseases of Connective
Tissues
Ehlers-Danlos Syndrome
• Is a defect in collagen formation
• There is genetic defect in a-chain of type V
collagen
• Classic funding includes:
• Thin, friable skin with prominent vein
• Easy brusining
• Poor wound healing
• Trophic scar formation
• Recurrent Hernia
• Hyperextensible Joints
• Gastrointestinal bleeding, hiatal hernia,
intestinal diverticulae, rectal prolapse
Osteogenesis Imperfecta
(OI)
• Patiens with OI has brittle bones,
osteopenia, low muscle mass,
hernias, and ligament and joint
laxity
• Result of type I collagen mutation
• Patients can experience:
• Dermal thinning
• Increased bruisability
• Scarring
• Skin not hyperextensible
Epydermolisis Bulosa (EB)
• Has 4 types: EB simplex, Junctional
EB, dystrophic EB, Kindler’s
Syndrome
• Manifestasion include:
• Tissue adhesion impairment
• Results in tissue separation and
blitering with minimal traua
• Blistering and ulceration
• Caused by defect in collagen type 7
COL7A1 gene
Acroderatitis
Enteropathica (AE)
• Causes inability to absorb sufficient zinc from breast ilk or food
• Zinc deficiency can impair granulation tissue formation
• Characterized by:
• Impaired wound healing
• Erytheatous pustular dermatitis
• Diagnosed by low blood zinc level
• Can be treated with oral 100-400 mg zinc sulfate
supplementation per day
Healing in Specific Tissues
Healing in Specific Tissues-
Gastrointestinal Tract
• Healing Of full-thickness injury to GI tract requires surgical or
mechanical reapposition of bowel ends
• Sutures or staples are principally used
• Failure of healing results in dehiscence, leaks, and fistulas
• Excessive healing is also troublesome, causing stricture, and
stenosis of lumen
Healing in GI tract is basically the same in cutaneous wounds with
some differences:
Healing in Specific Tissues-
Gastrointestinal Tract (Technical
Considerations)
• The ideal method of suturing two ends of bowel is still not
identified
• There is no evidence one technique has advantage than
another (example, hand suture vs stapled, continuous vs
interrupted suture, absorbable vs nonabsorbable suture)
• Anastomotic healing may be impaired by too much fluid
administration, causing accumulation of fluid in third space,
increased abdominal pressure, and tissue edema
Healing in Specific Tissues - Bone
• Most of the bone healing phase resembles in dermal healing
• The stages is as follows:
• Hematoma formation
• Liquefaction and degradation of product at fracture site
• Soft and hard callus stage
• Remodeling phase
• Bone healing is done by mesenchymal cell stimulation into chondroblasts
and osteoblasts.
• Other growth factors (PDGF, TGF-b, TNF-a, bFGF) also affects bone repair
Healing in Specific
Tissues - Cartilage
• Cartilages consisted of
chondrocytes surrounded
with extracellular matrix.
• Cartilage is very avascular
and depends on nutrient
diffusion
• Injuries to the cartilage can
cause permanent defects
due to low blood supply
Healing in Specific Tissues -
Cartilage
Healing response in cartilage depends the depth of injury
• Superficial Injury:
• Disruption of proteoglycan matrix and injury to chondrocytes
• No inflammation but increased proteoglycan synthesis
• The healing power is often inadequate, and slow causing persistent structural
defects
• Deep injuries
• Vascular channel is exposed, but can help form granulation tissue
• Fibroblasts migrate to the wound and synthesize fibrous tissue
• Structural and functional integrity restored
Healing in Specific Tissues - Tendon
• Tendons consisted of parallel collagen bundles with spindle
cells
• Bone and muscles are very mobile, so the damaged ends are
usually separate
• Tendon and ligaments healing are similar to other areas of
body (Hematoma, organization, reparative tissue, scar)
• Structural integrity in damaged tendon is never same to
undamaged tendon
Healing in Specific Tissues - Nerve
• There are 3 types of nerve injury (Neurapraxia, axonotmesis,
neurotmesis)
• Every nerve healing progress through these steps:
Regeneration of axons Migration and
Survival of axonal
that reach the distal connection of
bodies
stump nerve ends

• There is several factors in nerve healing, such as growth factors, cell

adhesion molecules, and nonneuronal cells and receptor
Healing in Specific
Tissues - Nerve
• The phagocyte removes
degenerating axons and
myelin
• Regenerating axonal sprouts
appear from proximal stump
and probe the distal stump
Healing in Specific Tissues – Fetal
Wound Healing
• The main difference between fetal vs adult wounds are scar
formation (no scar formation in fetal wounds)
• There is a phase of transition between fetal to adult healing,
beginning at 3rd trimester
• The other differences between fetal and adult wound are:
• Wound environment: Fetus is in sterile fluid environment
• Inflammation: Fetal inflammation is reduced
• Growth factor: No TGF-b in fetal wounds
• Wound matrix: High hyaluronic acid production
CLASSIFICATION OF WOUND
Classification of Wounds
• Wounds are classified as acute or chronic
• Acute wounds has predictable manner and time frame, often
well-healed
• Surgical wounds can heal in several ways:
• First Intention
• Secondary Intention
• Tertiary intention
Clinical
approaches to
would closure
Wound
mechanical
Classification of
Wounds
• Normal healing is affected
by systemic and local
factors.
• Complications in wounds
can lead to failure of
healing or development of
chronic non healing wound
FACTORS AFFECTING WOUND
HEALING
Factors affecting wound healing
Advanced Age
• Aging has intrinsic physiologic changes resulting in delayed or
impaired healing
• Studies has found a correlation between older age and poor
healing outcomes
• But there may be other factors such as cardiovascular disease,
metabolic diseases, cancer, and drug usage in elderly
• In animal studies, noncollagenous protein may accumulate in
wounded sites
Factors affecting wound healing
Hypoxemia, Anemia, Hypoperfusion
• Low oxygen tension has deleterious effect in wound healing
• Fibroplasia is impaired by hypoxic environment
• Optimal collagen synthesis also requires oxygen
• Major factor affecting oxygen delivery are hypoperfusion for
systemic reasons or due to local causes
• Mild to moderate normovolemic anemia does not appear to
affect wound oxygen tension and collagen synthesis
Factors affecting wound healing
Steroid and Chemotherapeutic Drug
• Large doses or chronic glucocorticoid usage can reduce collagen
synthesis and wound strength
• The stronger the anti inflammatory effect of steroid, effect on
wound healing is worse
• Steroid also inhibit epithelialization and contraction, also
increases wound infection
• All chemotherapeutic antimetabolic drug can inhibit early cell
proliferation and DNA and protein synthesis
Factors affecting wound healing
Metabolic Disorders
• Diabetes Mellitus can increase wound infection and failure
• Uncontrolled diabetes can reduce inflammation,
angiogenesis, and collagen synthesis
• Obesity, insulin resistance, hyperglycemia, uremia, and
diabetic renal failure can impair wound healing
Factors affecting wound healing
Nutrition
• Poor nutritional intake or lack of individual nutrients can alter wound
healing
• Arginine deficiency can result in decreased wound breaking strength
• Vitamin C deficiency can impair collagen synthesis and cross-linking
• Vitamin A supplements can benefit wound healing y increased
lysosomal membrane lability, macrophage influx, and collagen synthesis
• Zinc deficiency can decrease fibroblast proliferation, and impair overall
ound strength
Effect of Malnutrition on collagen
deposition
Factors affecting wound healing
Infections
• Many operations fail because development of wound
infections
• Infection is also a major problems in implants
• Infection can cause dehiscence or recurrence of hernia in
abdominal closures
• Antibiotic prophylaxis are effective to reduce wound
infection rate, and tailored to the type of surgery
Infections - Prophylactics
Chronic Wounds
Chronic Wounds
• Chronic wounds are defined as wound that failed to preceed
trhough process that produces satisfactory anatomic and
functional integrity
• The majority of wound that not healed in 3 months are
considered chronic
• Skin ulcers are a major component of chronic wounds
• Many factors can cause chronic wounds, such as repeated
trauma, poor perfusion or oxygenation, and/or excessive
inflammation
Chronic Wounds – Ischemic
Arterial Ulcers
• These wounds occurs due to lack of blood supply
• Painful at presentation
• Usually associated with other symptoms of peripheral vascular
disease
• Commonly occurs in distal portions of extremities
• Usually has shallow with smooth margins
• Prevention is extremely important, such as removing restrictive
stockings, repositioning in bed patients, and surveillance
Chronic Wounds – Venous Static
Ulcers
• Caused by venous stasis and hydrostatic back pressure
• Venous stasis is caused by incompetence of superficial or
deep venous systems
• There is alteration and distention of dermal capillaries 
Leakage of dibrinogen  Perivascular cuffing  Impaired
oxygen exchange  Ulceration
• Capillary damage also leads to extravasation of hemoglobin
• There is also irritating products to the skin
Chronic Wounds – Diabetic
Wounds
• Up to 25% diabetic patients has risk of ulcers
• The major contributor of diabetic ulcers are neuropathy, foot
deformity, and ischemia.
• Loss of sensory function can cause unrecognized injury
• Once ulceration occurs, chances of healing are poor
• It is important to maintain adequate blood sugar level
• Wide debridement is also the cornerstone of treatment
Chronic Wounds – Decubitus or
Pressure Ulcers
• Tissue necrosis develops soft
tissue is compressed between
bony prominence and external
surface
• Excessive pressure causes
capillary collapse and impairs
nutrient delivery
• Pressure ulcer formation also
accelerated when there is
friction, hear forces, and moisture
Excess Healing
Treatment of Wounds
Treatment of Wounds – Local Care
• Wound must be examined for depth, configuration, extend of
nonviable tissue, foreign bodies, and other contaminants
• Examination of wound may require irrigation and
debridement of edges, supported by local anesthesia
• Wound should be anestesized for patient comfort
• Irrigation is best achieved with normal saline
• After that, wound should be cleaned, inspected, and clip the
surrounding hair
Treatment of Wounds – Local Care
• In open wounds, principally the smallest suture is required
• Nonabsorbable or slowly absorbing sutures are best used for
deep fascial layers
• Subcutaneous tissues should be closed with absorbable sutures
• In areas of significant tissue loss, musculocutaneous flaps may
be required for closure
• After closing deep tissues, skin edges must be reapproximated
for cosmesis and to aid in rapid healing
Treatmen
t of
Wounds –
Local
Care
Treatment of Wounds – Antibiotics
• Antibiotics should be used when there is an obvious wound
infection
• The signs of infections is erythema, cellulitis, swelling, and
purulent discharge
• Indiscriminate antibiotic usage must be avoided
• Antibiotics of acute wound must be based on organisms
suspected to be found on the wound
Treatment of Wounds – Dressings
• The purpose of dressing is to provide ideal environment for
wound healing
• Covering the wound with a dressing mimics the barrier role
of epithelium
• Compression also provides hemostasis and limits edema
• Hydration and oxygen tension also can be controlled
• Exposed wounds are more inflamed and develops more
necrosis
Types of Dressings

Absorbent Nonadherent Occlusive

Dressing Dressing Dressing
Types of Dressings

Hydrophilic Hydrocolloid Medicated

Dressing Dressing Dressing
Treatment of Wounds – Skin
Replacements
• Skin replacements can prevent evaporative losses and
infection, providing optimal healing environment
• The options available are skin grafts, skin substitutes
• Skin grafts have different thickess (parsial, full) and have
many types (autografts, allogeneic grafts, xenogeneic grafts)
• Skin substitutes are manufactured by tissue engineering,
and has (theoretical) advantages of not requiring painful
gravest, and applied wfreely
Skin Grafts
Treatment of Wounds – Gene or
Cell Therapy
• Using genes such as genes expressing interleukin-8, PDGF,
IGF-1, keratinocyte growth factor, and laminin-5
• Still difficult and challenging because of the signals needed
to express the genes used
• Mesenchymal stem cells can be used for delivery vectors of
many genes
• The cells used can expresss VEGF, PDGF, bFGF, and MMP-9
Thank You