ProcrastiNotes: Surgery

Wound Healing

Phases Of Wound Healing

Normal wound healing follows a predictable pattern; divided

into overlapping phases

Defined by characteristic cellular populations and biochemical

activities
Hemostasis and Inflammation
Proliferation
Maturation and Remodeling

All wounds need to progress through this series to successfully

re-establish integrity
Hemostasis and Inflammation(Day 0 Day 5)

First phase of wound healing

Hemostasis

Precedes and initiates Inflammation with ensuing release of

chemotactic factors from the wound site
WOUNDING (disruption of tissue integrity) DIVISION/splitting of
blood vessels EXPOSURE of subendothelial collagen PLATELET:
Aggregation, Degranulation, Activation alpha-granules release
wound active substances: PDGF, TGF-beta, PAF, fibronectin, 5-HT

Fibrin Clot:
Fluid plasma containing Fibrinogen
Fibrinogen Fibrin Strands forming the clot
Achieves hemostasis
Serves as scaffolding for inflammatory cell migration

Inflammation

Normal acute reaction of the tissues after injury

Immediate response: constriction followed by vasodilation

allowing extravasation of fluid

Cellular infiltration follows a characteristic sequence

Neutrophils (Polymorpho Nuclei; PMN)

First infiltrating cells

Peak at 24-48 hours

Stimulants/attractants to PMN migration

increased vascular permeability

local prostaglandin release

presence of chemotactic substances

Complement factors, IL-1, TNF-alpha, TGFbeta, Platelet fector 4, bacterial products

Primar y Role: Phagocytosis of bacteria and tissue

debris

Wound Debridement

Limiting Infection

Other Functions:

Major source of early inflammatory cytokines

Secrete TNF-a
influences angiogenesis and collagen
synthesis

Secrete Collagenase
participates in remodeling

Do not appear to play a role in collagen deposition or

acuisition of wound strength
Macrophages

Second population of inflammatory cells

derived from circulating monocytes

Peak at 48-96 hours

remain present until wound healing is complete

essential to successful healing

Primar y Role: Phagocytosis of bacteria and tissue

debridement

Other functions

Synthesis of ROS and Nitric oxide

contributes to microbial stasis

Recruitment of other cells (Most pivotal

7
function) via
Mediators: cytokines and growth factors
direct cell-cell interaction

Regulate cell proliferation, matrix synthesis and

angiogenesis
releasing of mediators: TGF-b, VEGF, IGF,
EGF and lactate
Significant role in regulating angiogensis,
matrix deposition, remodeling
T-Lyphocytes

Less numerous than macrophages

Peak at about 1 week post-injury

Primar y Role: Exact role is not fully defined;

although is still essential to wound healing

Marks the transition from inflammatory to

proliferative phase

Suggested Role: modulation of wound environment

Other Functions:

downregulating effect on fibroblast collagen

synthesis via cell-associated interferon-gamma,
TNF-a, and IL-1

Proliferation(Day 3 Day 14)

Second phase of wound healing

Establishment of tissue continuity

Fibroblasts and Endothelial cells: last cell populations to

infiltrate the healing wound

PDGF: strongest fibroblast chemotactic factor

Fibroblasts
proliferate and activated once they enter the wound
environment
Primar y Role: matrix synthesis remodeling

fibroplasia: fibroblast proliferation and synthesis

Activation mediated by cytokines and growth factors
secreted by macrophages
Fibroblasts isolated from wounds (vs non-wound
fibroblasts)

synthesize more collagen

proliferate less

actively carry out matrix contraction

Endothelial Cells
proliferates extensively
Primar y Role: participate in angiogenesis (forming new
capillaries)

revascularization of the wound proceeds in parallel

with fibroplasia

essential to wound healing: provides the blood supply

to active reparative cells
Migrate from intact venules close to the wound
Mediators

TNF-a

TGF-b

VEGF

macrophages are a major source

VEGF receptors are specifically located on

endothelial cells
Matrix Synthesis

Collagen
most abundant protein in the body
critical role in adult wound healing completion

Deposition, Maturation and Remodeling are essential

to wound integrity
Type I:

major component of extracellular matrix (ECM) in the

skin

ProcrastiNotes: Surgery

Type III:

normally present in the skin

becomes more prominent during the repair process

Structure and Synthesis

Every 3rd Amino Acid: Glycine (Gly)

Every 2nd position: either Proline (Pro) or Lysine (Lys)

Protocollagen:

first translational product released into the ER

Prolyl Hydroxylase

Proline-Lysyl (Pro-Lys) Hydroxylase

Hydroxylates Proline and Lysine residues

Configuration that enables to them to cross link

Requirements for Proylyl Hydroxylase activity

Oxygen and Iron as cofactors

a-ketoglutarate as cosubstrate

Ascorbic acid (Vit. C) as electron donor

Following these hydroxylation and glycosylation (with

glucose and galactose at hydroxylysine) the
protocollagen assumes an a-hellical structure

Procollagen:

Three a-hellical chains formed at a right-handed

superhelix

Cross linking of covalent lysine residues

strengthens the procollagen molecule

Procollagen (procollagen peptidase) further

polymerization and cross-linking COLLAGEN
monomer further cross linking and polymerization
via intra-and inter- molecular covalent bonds
Synthesis and Modifications depend on systemic factors

Adequate oxygen supply

Sufficient nutrients

Amino acids

Carbohydrates

Cofactors

Vitamins (A and C)

Trace minerals (Zinc)

Local wound environment

Vascular supply

Lack of infection
Proteoglycan
Glycosaminoglycans (GAGs) coupled with proteins
Comprise a large portion of the ground substance (matrix)
of the granulation tissue
Major GAGs present in wounds; synthesized by fibroblasts
greatly during the first 3 weeks

dermatan

chondroitin sulfate
Sulfated Proteoglycans

provides the lattice for assembly of collagen into

fibrils and fibers

extent of sulfation is critical indetermining the

configuration of collagen
Scar Collagen

Deposition occurs with incorporation of

proteoglycans
Proteiglycan content diminish with scar maturation and
collagen remodeling

Wound Healing

Maturation and Remodeling (6 to 12 months)

Fibroplastic Phase

marks the start of the Maturation and Remodeling

Primar y Role: reorganization of previously synthesized

collagen

Net wound collagen content

balance between Collagenolysis (by action of matrix
metalloproteinases) and Collagen Synthesis (by action of
the fibroblasts)

Remodeling improves the Quantity and Quality of newly

deposited collagen
determines strength and mechanical integrity in the fresh
wound

Characteristic pattern of wound site matrix deposition

Early Matrix: Scaffolding

Fibronectin

Collagen Type III

Next Significant Matrix Components

GAGs

Proteoglycans
FInal Matrix

Collagen Type I

Maximal Collagen Deposition

Collagen in the wound reaches a plateau (equal synthesis
and lysis)

however strength still continues to increase for

several more months
Arbitrarily set at one month post injury
Can already engage in strenuous activities

Fibril formation and cross-linking result in

decreased collagen solubility
increased strength
increased resistance to enzymatic degradation of the
collagen matrix

Scar remodeling continues for 6 to 12 months postinjury

resulting in a mature, avascular, acellular scar
mechanical strength of a scar NEVER achieves that of the
uninjured tissue

Turnover of Collagen in Extracellular Matrix

occurs both in the healing wound and in normal tissue
homeostasis
Collagenolysis

by action of the enzyme Collagenase

a class of matrix metalloproteinases

require activation
Lysis and Synthesis are strictly controlled by cytokines and
growth factors

ex. TGF-b:

increase collagen transcription

stimulates metalloproteinase inhibitors

decreases collagen breakdown
Balance of deposition and degradation is the ultimate
determinant of wound strength and integrity
Epithelialization (complete in 48 hours)

Primar y Role: restores the external barrier

Characterized by proliferation and migration of epithelial
cells adjacent to the wound

Process
Begins within 1 day of injury

thickening of the epidermis at the wound edge

Marginal basal cells at the edge of the wound

lose their firm attachment to the dermis enlarge

begin to migrate across the surface of the provisional
matrix
Fixed basal cells in the zone near the cut edge

undergo rapid mitotic divisions

ProcrastiNotes: Surgery

Wound Healing

migrate by moving over one another in a Leapfrog

fashion

Bridges the defect

Lose their flattened appearance become columnar

in shape with increased mitotic activity

Layering is re-established and surface keratinizes

Re-epithelialization is complete in 48 hours

may take substantially longer in large wounds

(significant epidermal/dermal defect)
If only the epithelium and superficial dermis are damaged

ex. split thickness skin graft or superficial seconddegree burns

repair consists primarily of re-epithelialization with

very little or absent fibroplasia and granulation
formation
Mediators

loss of contact inhibition

exposure to fibronectin (constituent of the ECM)

cytokines produced by immune mononuclear cells

EGF

TGF-b

fibroblast growth factor

PDGF

insulin-like growth factor I

Wound Contraction (Day 5 to Day 12-15)

inward movement of the wound edge

initiated immediately after injury

Myofibroblast
major cell responsible for contraction
Posesses a Cytoskeletal structure (differs from normal
fibroblasts)
Stress Fibers

a-smooth muscle actin in thick bundles

provides contractile capability

Detectable on Day 6 to Day 21

Undergoes apoptosis after 4 weeks

Myofibroblast detection does not correspond directly to

initiation of wound contraction

Contraction: Movement of cells with concomitant

reorganization of cytoskeleton

Regulation: remains poorly defined

TGF-b: promote contractions even in the asbence of serum
PDGF: may increase contraction or have no effect
FGF and EGF: moderate enhancement or have no effect
Types of Wound Closure

Primary Intention
Wounds that are immediately sealed

Simple suturing, skin graft placement, flap closure

Close the wound at the time of initial presentation
Used mostly for CLEAN wounds

Secondary Intention
No active intent/intervention to seal the wound
Allow the wound to heal on its own

Closes primarily by re-epithelialization and contraction

Used for CONTAMINATED and CLEAN-CONTAMINATED
wounds and for large wounds with significant tissue loss

Tertiary Intention
Delayed Primary Closure
Close the wound after a period of secondary healing
Place sutures allow to stay open for a few days
subsequent closure of the wound
Used for DIRTY wounds (after debridement); although
antibiotics today have rendered this irrelevant
Now ONLY used for bite wounds (i.e. dog, cat, human bites)

Role of Growth Factors in Normal Healing

Growth Factor Wound Cell Origin Cellular and Biologic
Effects
Platelet Derived
Growth Factor
(PDGF)

> Platelets,
macrophages,
monocytes, smooth
muscle cells,
endothelial cells
> a-granules of
platelets

Fibroblast
Growth Factor
(FGF)

> Fibroblasts,
endothelial cells,
smooth muscle cells,
chondrocytes

> Activate TGF -b

> Stimulate neutrophils
and macrophages
> Stimulate chemotaxis
> Stimulate fibroblast
and smooth muscle
proliferation
> Stimulate collagen
synthesis
> Stimulate collagenase
activity
> Stimulate angiogenesis
> Angiogenesis:
Endothelial cell
proliferation and
migration
> Collagen synthesis
> Wound contraction
> Matrix synthesis
> Epithelialization
> Produce KGF

Epithelial Growth > Platelets

Factor (EGF)
(degranulation),
macrophages,
monocytes

> Re-epithelialization:
proliferation and
migration of ALL
epithelial cell types
> Angiogenesis
> Collagenase

Keratinocyte
Growth Factor
(KGF)

> Keratinocytes,
fibroblasts

> Homologous with FGF

> Keratinocyte
stimulation

Transforming
Growth Factorbeta (TGF-b)

> Platelets, T-cells,

macrophages,
monocytes,
neutrophils

> Reverse inhibition of

healing by
glucocorticoids
> Monocyte secretion of:
FGF, PDGF, TNF-a and IL1
> fibroblast chemotaxis
and proliferation
> Collagen synthesis
> Less dermal scarring

TGF-a

> Ketatinocytes,
platelets
macrophages

> Homologous to EGF

> Mesencymal, epithelial
and endothelial growth
> Endothelial chemotaxis

Insulin-like
Growth Factors
(IGF I and II)

> Platelets (IGF-I in

liver; IGF-II in fetuses)

> Protein ECM synthesis

> Increase glucose
transport

Vascular
Endothelial
Growth Factor
( VEGF)

> Macrophages,
Fibroblasts,
Keratinocytes

> Homologous to PDGF

> Endothelial cell
proliferation
> Angiogenesis

Granulocytemacrophage
Colonystimulating
factor (GM-C SF)

> Macrophage,
monocytes,
endothelial cells,
fibroblasts

> Macrophage
differentiation/
proliferation

Interleukin-1 (IL1)

> inflammatory cells

> Lymphocyte
proliferation
> Collagenase activity

ProcrastiNotes: Surgery

Wound Healing

Factors Affecting Wound Healing

Healing does not always occur in a straightforward undisturbed

fashion

Various factors can interfere with healing

Local Factors

Infection

Foreign bodies

Ischemia/Necrotic tissue

Venous insufficiency

Local toxins

Hypoxia/ Low oxygen tension

Collagen synthesis requires oxygen as a cofactor in
hydoxylating the Pro and Lys side chains

Irradiation
non-selective treatment
kills both pathogenic cells and cells that may contribute to
wound healing

Mechanical trauma
Impedes the re-epithelialization and contraction of the
wound and creates a fresh wound

Explore

Injury in underlying tissues

Cleanse

Irrigation using saline only

Effective in debrididement of foreign material

Iodine, H2O2, antiseptics may impair wound healing

if directly applied due to injury to neutrophils and
macropahges
Hemostasis
Debride nonviable tissue
Betadine surrounding skin (not directly on the wound)
Antibiotics
Tetanus
Approximation
Deep layers

Fascial layers only

Absorbable suture
Superficial Layers

Meticulous alignment

Nonabsorable sutures in skin

Staples

Monofilament

Dermal Glues
Follow-up
Cellulitis? Drainage?
Suture Removal (Dependent on the strength of the wound;
which depends on collagen synthesis)

4-5 days for face

Faster healing rates

7-10 days for other areas of the skin

Systemic Factors

Cancer

Alcoholism

Jaundice

Malnutrition
Vitamins A and C and Zinc contribute to Collagen synthesis

Diabetes Mellitus (Metabolic Disorders)

Reduction in inflammation, angiogenesis and collagen
synthesis
Large and small vessel disease contributes to local hypoxia Is the wound tetanus prone?

Uremia (Metabolic Disorder)

Tetanus Prone
Non-tetanus Prone
decreased wound collagen synthesis and decreased
breaking strength
Wound Age
> 6 hours
< 6 hours

Old Age
Configuration
Stellate wound,
Linear wound
Impaired noncollagen protein accumulation at wound site
avulsion, abrasion
impairs the mechanical properties of scarring

Corticosteroids and Chemotherapeutic agents

Depth
> 1 cm
< 1 cm
Inhibition of inflammatory phase of wound healing and less
Mechanism
of
Missile,
crush,
burn,
Sharp
surface
release of lysosomal enzymes
Injury
frostbite
Affects angiogenesis, neutrophil and macrophage
migration and fibroblast proliferation
Signs of Infection

Cigarette smoking
Devitalized Tissue
Causes peripheral vasoconstriction, which decreases the
Present
Absent
supply to the regenerative cells acting upon the wound
Contaminants
(dirt, feces, soil,
Treatment of Wounds
saliva)

Prioritize a COMPLETE history and a THOROUGH physical exam

Immunization schedule and What to give
Most cutaneous wounds are obvious and easily diagnosed
and non-life threatening
Patient Status
TD
TIG
TD
TIG
Wounded patient may have less apparent problems:
Unknown
Dose
or
Yes
Yes
Yes
No
Potentially lethal and demand immediate attention
<3

Takes priority over wound management

Antirabies should be given to patients who have been
3 or more doses
No**
No
No**
No
bitten by animals
Assess the patient's tetanus immunization status (See
TD Tetanus and diptheria toxoids (for adult use)
tables on Tetanus Prone wounds and Immunization

For children < 7 years old Diptheria, Tetanus and Pertusis

schedules)
vaccine adsorbed is preferable (compared to tetanus toxoid

Examination of the wound should assess

alone)
Depth and configuration of the wound

TD preferable for people 7 years and above (compared to

Extent of nonviable tissue
toxoid alone)
Presence of contaminants

** Give to patients with 3 or more doses if

Preparation
Tetanus Prone and last dose was 5 years ago
Anesthetesize: Lidocaine W/ epinephrine
Non-tetanus prone and last dose was 10 years ago

W/o Epinephrine: on fingers, toes, ears, nose or penis TIG Tetanus immune Globulin (human)
due to risk of necrosis secondary to terminal arteriole

Only give it to tetanus prone patients

vasospasm

ProcrastiNotes: Surgery

Wound Healing

Antibiotic Prophylaxis

Not indicated for most wounds

Should only be used when there is an obvious wound infection

Indiscriminate use of antibiotics may cause emergence of
multidrug-resistant bacteria

Presence of a host response constitutes an infection. Signs of

Infection:
Erythemia
Cellulitis
Swelling
Purulent discharge

Treatment is based on (Indications)

Suspected organisms found in the infected wound

Single organism = Single antibiotic

Multiple organisms (i.e. enteric contamination)

= broad-spectrum antibiotic
Patient's overall immune status

Impaired by diabetes, chronic disease or medications

= broad-spectrum antibiotic
Location of the wound

Extensive injuries to the central area of the face

(Danger zone)

Lymphedematous extremities
Quality of tissue perfusion to that region

Patients with valvular disease

Introduction of Foreign Bodies into the wound (i.e.
prostheses, implants, mesh)
Stool-contaminated and Bite wounds
Wounds with extensive amounts of devitalized tissue (farm
injuries)

May be part of irrigations or dressings

Contaminated (Class III)

Infection Rate: 15.2-16.3 (10-15% accdg to the ppt)

Description
Shows signs of infection or inflammation but ABSENT
purulent or fecal material
Extensive introduction of bacterial into a normally sterile
area

major breaks in the sterile technique

gross spillage of viscus contents

incision through inflamed (non-purulent) tissue

Entry into infected tissue, bone, urine or bile
Emergency surgeries without proper preparation
Give antibiotic prophylaxis

Examples
Emergency cholecystectomy for acute cholecystitis
Emergency surgery for small bowel perforation due to
trauma
Open accidental wounds encountered early after injury
Open cardiac massage

Dirty (Class IV)

Infection Rate: 28-40% (30% accdg to the ppt)

Description
Presence of fecal or purulent material in the wound
Traumatic wounds in which a significant delay in treatment
has occurred

necrotic tissue is present

Wounds created in the presence of purulent material
Wounds created to access a perforated viscus (GIT/GUT/RT)
accompanied by a high degree of contamination
Give antibiotic prophylaxis

Examples
Classifications of Operative Wounds
Emergency surgery for generalized peritonitis
Clean (Class I)
Surgery for ruptured appendicitis

Infection Rate: 1.5-5.1 % (1-3% (accdg. to the ppt)

Diverticulitis

Description
Perforated peptic ulcer
no infection/inflammation is present

Presence of E.coli in the peritoneal cavity

only skin microflora potentially contaminate the wound
Trauma surgery with colon perforation
no hollow viscus (GIT/GUT/RT organs) that contain microbes
Drainage of abscess
is entered
Debridement of soft tissue infection
no opening of GIT/GUT/RT
atraumatic
Surgical Site Infections
generally no need to give antibiotic prophylaxis

infections of the tissues, organs or spaces exposed by surgeons

Examples
during an invasive procedure
Elective Surgery

most common post operative infection

Thyroidectomy
Method of Wound Closure
Breast Surgery (excision, lumpectomy, MRM)

Direct Approximation

Introduction of a foreign body

Sutures, staples, tapes, tissue adhesives
Prosthetic device (Mesh, valve), Implants
Skin Graft
Still classified as a clean wound, but would elicit the use of
Autograft
an antibiotic prophylactic
Classified as class ID
Use only if dermis and epidermis is gone (compromised)

Local Flap
Clean-Contaminated (Class II)
Random or axial

Infection Rate: 2.1-9.5% (3-5% accdg. to the ppt)

Distant Flap

Description
Requires microvascular anastomoses
entails opening of the GIT/GUT/RT (has indigenous bacterial
flora)
Dressings

under controlled circumstances without significant

Purpose
spillage of contents
Provide the ideal environment ofr wound healing
Minor breaks in sterile technique
Facilitate the major changes taking place during healing

Give antibiotic prophylaxis

Mimics the barrier role of the epithelium and prevents further

Examples
damage
Elective surgery

Compression: hemostasis and limits edema

Cholecystectomy

Consider the desired environment and the injured tissue before

Gastrectomy
application
Colon resection

ProcrastiNotes: Surgery

Wound Healing

Warm, Moist environment

Biologic Dressings

allograft, amnion, xenograft

Synthetic Biologic Dressings

Biobrane

Hydrogel Dressings

Semipermeable or Nonpermeable membranes

Op-site, Duoderm
Wounds containing necrotic tissue, foreign bodies or other
debris

Wet-to-dry dressings

Wet-to-wet

Enzymatic Dressings

Travase, Santyl, Accuzyme

To lower the bacterial count in infected wounds

Silver sulfadiazine
To prevent bacterial contamination

Xeroflo

Fine meshed gauze impregnated with a

hydrophilic substance

N-terface

synthetic, finemeshed gauze

Classifications Presented in the Book
Primary Dressing

Placed directly on the wound

may provide absorption of fluids and prevent

desiccation, infection and adhesion of a secondary
dressing
Secondary Dressing

Placed on the primary dressing

for further protection, absorption, compression and

occlusion
Absorbent dressings

Prevents accumulation of wound fluid

Prevents maceration of the wound and bacterial

overgrowth

Absorb water without getting soaked

Nonadherent Dressings

Impregenated with paraffin, petroleum jelly or watersoluble jelly

Secondary dressing must be palced on top to seal the

edges and prevent desiccation and infection
Occlusive and Semiocclusive

good environment for a clean, minimally exudative

wounds

Waterproof and impervious to microbes but

permeable to water vapor and oxygen
Composite (has Hydrophilic and Hydrophobic portions)

Hydrophilic aids in absorption

Hydrophobic waterproof; prevents absorption

Hydrocolloid and Hydrogel

attempts to combine the benefits of occlusion and

absorbency

complex structures with water fluid absorption

occurs with particle swelling

aids in atraumatic removal of the dressing

leaves a yellowish-brown gelatinous mass after

dressing removal

allow a high rate of evaporation without

compromising wound hydration

useful in BURN TREATMENT

Alginates

derived from brown algae

polymers gel, swell and absorb a great deal of fluid

Used in

skin loss wounds

open surgical wounds with medium exudation

full-thickness chronic wounds

Absorbable Materials

used as hemostats

Collagen, gelatin, oxidise cellulose and oxidized

regenerated cellulose
Medicated dressings

drug-delivery system

shown to increase epithelialization by 28%

Healing in Specific Tissues

Gastrointestinal Tract

Serosal and Mucosal healting MAY occur without scarring

The early integrity of anastomosis is dependent on

Formation of a Fibrin Seal

Forms on the serosal side

particular care is noted in organs without serosa

(esophagus, rectum)

Achieves water tightness

Suture holding capacity of the intestinal wall

Dependent on mucosal and sub-mucosal layers

Determines the strength of anastomosis contributed

by surgeons

No evidence that different suturing techniques influence better

wound healing (all have the same results)
Bone: Undergoes phases of healing
Soft Callus Stage (3-4 days after injury)

Formation of soft tissue bridges between fractured bone

segments

Deposited where neovascularization has taken place

Internal Splint

Prevents damage to newly laid blood vessels

Achieves fibrocartilaginous union

Characterized by the end of pain and inflammatory signs

Hard Callus Stage (2-3 months)

Mineralizationo f soft callus converstion to bone

Leads to complete bony union

Considered strong enough

Allows weight bearing

Appear healed on radiographs

Remodeling Phase

excessive callus is reabsorbed

recanalization of the marry cavity

allows for correct transmission of forces

restores bone contour

Cartilage

Very avascular
Dependent on diffusion for transmittal of nutrients across
the matrix
Hypervascular perichondrium: substantially contributes to
nutrition

Injuries may be associated with permanent defects due to

meager and tenuous blood supply leads to low amount of
angiogenesis and less supply for wound healing cells

Superficial Injuries
disruption of proteoglycan matrix and injury to the
chondrocytes
no inflammatory response (low blood supply)
increased synthesis of proteoglycan and collagen are
entirely dependent on the chondrocyte
End Result

Overally regeneration is incomplete

Slow to heal

Often result in persistent structural defects

Deep Injuries
Involve the underlying bone and soft tissue

ProcrastiNotes: Surgery

Wound Healing

Exposure of vascular channels of surrounding damaged

tissue

may help in granulation formation

Hemorrhage

initiates the inflammatory response subsequent

activation of cellular function for repair granulation
tissue development migration of fibroblasts to the
wound fibrous tissue undergoes chondirification
hyaline cartilage
End Result

Restores the structural and functional integrity of the

injured site

Tendon and Ligaments

Tendon: muscle to bone

Ligament: bone to bone

Healing depends on vasculature

Hypovascular: heal with less motion and more scar
formation

Tenocytes
Specialized cells
metabolically very active
retain a large regenerative potential even in the absence of
vascularity

restoration of mechanical integrity may never be equal to

undamaged tendon
Nerves

Three types of injuries

Neurapraxia

focal demyelination
Axonotmesis

interruption of axonal continuity but preservation of

Schwann cell basal lamina
Neurotmesis

complete nerve transection

Predictable pattern of changes involves three crucial steps

Survival of axonal cell bodies
Regeneration of axons that grow across the transected
nerve to reach the distal stump
Migration and connection of the regenerating nerve ends
to the appropriate nerve ends or organ targets

Wallerian Degeneration
phagocytic removal of degenerating axons and myelin
sheath from the distal stump
cleans the area to accommodate the axonal sprouts from
the proximal stump
Fetal Wound Healing

Main difference from adult: Apparent LACK of SCAR formation

and resembles tissue regeneration

Transition Wound
Phase during gestational life where a more adult-like
healing pattern emerges
occurs at the beginning of the third trmister
loss of ability to regenerate skin appendages
leads to a classic adult-patterned healing with scar
formation

although overall still continues faster than in adults

Environment
Bathed in fluuid

Sterile

Temperature stable

Inflammation
Immature fetal immune system Reduced fetal
inflammation less robust inflammatory response
decreased scar formation
Neutropenic, low PMNs and macrophages

Growth Factors
Absent TGF-b

has a significant role in scarring

balance of TGFb isoforms has a significant role in

scarring

blocking TGFb1 and TGFb2 reduces scar

formation

exogenous TGFb3 downregulates 1 and 2 but

results in scarring
Wound Matrix
Excessive and extended hyaluronic acid production

Hyaluronic acid high molecular weight GAG

produced by fibroblasts

also produced in adult wounds

synthesis is sustained in fetal wounds

Synthesis can be stimulated by components of

amniotic fluid (fetal urine)
Fetal fibroblasts produce more collagen
More hylauronic acid + more collagen more orderly
organization of collagen
Hyaluronic acid is used to inhibit postoperative adhesion
formation