Dr. Sunita Pathak presented on wound healing and bone healing. Wound healing involves coagulation, inflammation, new tissue growth, remodeling, and scar formation. It can occur through primary intention, secondary intention, or tertiary intention. Bone healing follows injury and involves hematoma formation, inflammation, new tissue and bone growth to fill the fracture site, and remodeling of the bone over time. Key processes include formation of a soft and hard callus to join the broken bone fragments.

1. Presented by:
Dr Sunita Pathak

2. CONTENTS
• Introduction
• Definition
• Healing of skin wounds
• Healing in bone
• Healing of nervous tissue
• Factors influencing healing
• Complications of wound healing
• Conclusion
• References

3. Wound healing
Essential and primitive process common to all
multicellular organisms.
Cells assume embryonic features,
Migration,
Divides,
Differentiates to produce extracellular matrix.

4. Healing is summation of a number of processes which
follow injury
Coagulation,
Inflammation,
Matrix synthesis and deposition,
Angiogenesis,
Fibroplasia,
Epithelialisation,
Contraction,
Remodelling and scar maturation.
Process by which tissues are restored to an
anatomic and physiologic arrangement.

5. Definition
Wound
• Any breach in the surface of the body or any tissue
disruption deep to skin produced by the application of
energy is a wound.
Healing
• Body response to injury in an attempt to restore normal
structure and function.

6. HEALING OF WOUNDS CONSISTS OF
TWO PROCESSES:
Regeneration
&
Repair

7. Proliferation of parenchymal cells .
Results in complete restoration of original tissues.
Replacement of lost cell by their own kind takes place.

8. LABILE CELLS: multiply throughout the life under
normal physiologic conditions.
Remain in cell cycle from one mitosis to another.
STABLE CELLS : Decrease or loose their ability to
proliferate but retain capacity to multiply in response to
stimuli throughout life.
Resting phase (G0) but can be stimulated to enter the
cell cycle.
PERMANENT CELLS :Highly specialized cells that do
not undergo mitotic division in postnatal life even after
injury.
Depending on their regenerating capacity
cells can be divided into 3 types:

9. Relationship of Parenchymal cells with
cell cycle

10. EXAMPLES
• Continuously dividing (labile) cells:
– Surface epithelium and excretory ducts of glands (skin,
gi/gu mucosa, biliary tract, pancreas)
– Marrow hematopoietic cells
– Stem cells in multiple organs (immature, undifferentiated
cells)
• Quiescent (stable) cells in G0:
– Organ parenchymal cells (liver, kidneys)
– Mesenchymal cells (fibroblasts, smooth muscle,
endothelium, chondrocytes, osteocytes)
• Nondividing permanent cells (can’t re-enter cell
cycle)
– Neurons, skeletal & cardiac myocytes

11. Repair is derived from Latin word reparare means
“to prepare again.”
It is the replacement of tissue defect by fibrous
tissue.

12. Growth Factors in Repair
• EGF: enhances the proliferation of fibroblasts and
endothelial cells.
• PDGF: produced by platelets, macrophages
endothelial cells, and smooth muscle cells.
• It enhances the proliferation of fibroblasts and
smooth muscle cells.
• FGF: enhances the proliferation and recruitment of
macrophages and fibroblasts.

13. Growth Factors in Repair
• TGF-beta: produced by platelets, endothelial cells, T-
cells, and macrophages.
o In low concentration, it induces PDGF and proliferation of
fibroblasts and smooth muscle.
o In high concentration, it inhibit growth and enhances ECM
and collagen synthesis (Fibrosis).
• VEGF: enhances angiogenesis.
• Cytokines: IL-1, TNF induce fibroblast proliferation.

14. Time after injury
Hemostasis
Inflammation
Proliferation
Resolution/ Remodeling
PMNs, Macrophages, Lymphocytes
Reepithelialization, Angiogenesis, Fibrogenesis,
Vessel regression, Collagen remodeling
Fibrin clot, platelet
deposition
1D 3D 1wk 6wk 8wk

15. 1.CLOT FORMATION
Blood Clot fills the wound.
Fibrinonectin is cross linked to fibrin, collagen, and other
ECM products by transglutaminase giving clot provisional
strenght.
Clot on reaching surface becomes dry to form crust or
scab.
Prevents oozing of blood from wound.
Provides mechanical barrier to bacteria.

16. 2. INFLAMMATORY PHASE
 PMN, macrophages, lymphocytes
& mast cells are major cells
involved in wound healing.
 Derived from three sources:
 Cells normally present in tissues.
 Cells extravasated when blood
vessels damaged .
 Cells carried in intact blood
vessels adjacent to wound that exit
by means of diapedesis.

17. Platelet derived cytokines recruit leukocytes to the site of
damage by process of chemotaxis.
PMN are the Ist to invade wound and appear in response to
phagocytic stimuli or binding of chemotactic stimuli .
Neutrophil cell surface receptors react with IgM & IgG ; with
C5a & C5b; & with arachidonic acid metabolites.
Neutrophils contain various enzymes & reactive oxygen
metabolites (oxygen free radicals) that kill engulfed bacteria &
destroys damaged tissue.
Macrophages phagocytose RBC , fibrin & cellular debris.

18. Phagocytosis

19. INFLAMMATORY PHASE

20. 3. FORMATION OF GRANULATION TISSUE
NEOVASCULARISATION/
ANGIOGENESIS:
 Endothelial cells at the margins
of severed blood vessels
proliferate.
 New blood vessels are of single
layer endothelium which permit
red cells & plasma to leak freely.
Granulation tissue has
edematous appearance.

21. • Wound healing requires rich blood supply to sustain
newly formed tissue.
• It is evident in erythema (redness) of the new scar.
• Capillary density decreases as the need reduces and
scar matures.
Macrophages release- angiogenic factor in response
to low tissue oxygen tension.
• Work as chemoattractant.
• Basic FGF and VEGF .

22. FIBROBLASTS PROLIFERATION:
 Fibroblasts proliferate & invade clot at the same time
as endothelial cells.
 Derived from fibrocytes & fibroblasts .
Cytokines involved FGF, PDGF, TGF-beta, IL-1

23. PROLIFERATIVE PHASE

24. 4. ORGANIZATION:
Gradual replacement of clot
by newly formed blood
vessels & fibrobalsts called
granulation tissue.
Pink granular appearance
which is due to blood vessels,
fibroblasts & leukocytes.

25. Highly vascular thus bleeds easily, lacks nerves thus
insensitive and resistant to infection due to presence of
macrophages.
As collagen deposition continues granulation issue
becomes less vascular & cellular progressively.
This conversion of granulation tissue to fibrous scar is
called cicatrization/ contracture.

26. GRANULATION TISSUE

27. 5. REEPITHELIALIZATION
Epithelial cells
(keratinocytes) migrate
across the wound bed
from the wound edge.
The keratinocytes divide
and form layers or strata.

28. Once the stratified layer is complete, the keratinocytes
undergo a morphological change to become the
epidermis, the normal barrier layer of the skin.
The new tissue continues to be remodelled.
 Numbers of fibroblasts fall and capillary bundles
become organised.

29. 6. WOUND CONTRACTION:
Begins by 2-3 days &
completes by 14th day.
Wound is reduced by app.
80% of its original size.
Results in rapid healing.

30. 6. WOUND CONTRACTION
• Theories for contraction
• Dehydration of wound due to removal of fluid.
• Contraction of collagen.
• Presence of myofibroblasts in granulation tissue.

31. • Fibroblast-to-myofibroblast differentiation represents a key
event during wound healing and tissue repair.
• The high contractile force generated by myofibroblasts is
beneficial for physiological tissue remodeling.
• Detrimental for tissue function when it becomes excessive
such as in hypertrophic scars, in virtually all fibrotic diseases
and during stroma reaction to tumors.

32. EPITHELIALIZATION AND
CONTRACTION

33. Continues for months or up to 2 years.
Collagen fibres are reorganised to increase tensile
strength.
The type of collagen produce changes ( type III to
type I).
7. REMODELING:
The scar initially has about 5% of the tissue’s pre-injury
strength. The scar may mature to 80% of its original
strength.

34. • Collagen remodeling – depends on balance between
new collagen formation and collagen destruction.
• Collagenase and Matrix metalloproteinase.
• Collagen becomes increasingly organized.
• Fibronectin gradually disappears.
• Hyaluronic acid and glycosaminoglycans are replaced
by proteoglycans.
• Water is resorbed.
• These events allow collagen fibers to lie closer
together, facilitating collagen crosslinking.

35. MATURATION PHASE

37. HEALING BY PRIMARY INTENTION
HEALING BY SECONDARY INTENTION
HEALING BY TERTIARY INTENTION

38. •Wounds which are :
-clean & uninfected
-surgically incised
-without much loss of cells & tissue
-edges of wound are approximated by
surgical sutures

39. 1. Initial Haemorrhage:
Wound is filled with blood which clots, &
seals wound against dehydration &
infection.
2. Acute Inflammatory response:
-Occurs within 24hrs.
-Polymorphs appear from margins of
incision.
-By 3rd day polymorphs are replaced by
macropphages .

40. 3.Epithelial changes:
• Basal cells from both cut margins
begin proliferating & migrating
towards incisional space in form of
epithelial spurs .
• Separate underlying viable dermis
from the overlying necrotic material &
clot, forming a scab which is cast off.
• By 5th day multilayered new
epidermis is formed which is
differentiated into superficial & deep
layers.

41. 4. Organisation:
• By 3rd day fibroblasts also invade
the wound area.
• By 5th day new collagen fibrils
start to form which dominate till
healing is complete.
• In 4 weeks, scar tissue with
vascular & cellular elements &
epithelialised surface is formed.

42. 4. Suture tracks:
• Each suture track is a separate
wound .
• When sutures are removed on 7th
day much of epithelialised suture
track is avulsed & remaining
epithelial tissue is absorbed.
• Sometimes suture track may get
infected (stitch abscess) or
epithelial cells may persist in track
(implantation cyst)

43. •Occurs in wounds having following
characteristics:
-open with large tissue defects.
-having extensive loss of cells &
tissue.
-open wound not approximated by
surgical sutures.

44. •Healing takes place from
base upwards as well as
margin inwards.
•Often results in large scar
formation.

45. 1. Initial Haemorrhage:
Blood fills in the wound after
injury & forms clot.
2. Inflammatory Phase:
Macrophages clear off debris
as in primary union.
clot
Neutrophils
Capillaries
Epithelial cells

46. Fibroblasts
Granulation
tissue
Macrophages
3. Epithelial changes
• Epithelial spurs proliferate & re-
epithelialise the gap but does not
cover the surface completely.
• Granulation tissue from base
starts filling the gap.
• Scab is formed which is cast off .

47. 4. Granulation tissue:
• Proliferartion & neovascularisation
from adjoining viable tissue results
in granulation tissue formation .
• Main bulk of healing occurs by
granulation tissue.
• Granulation tissue is deep red,
granular & very fragile.
• Scar on maturation becomes pale & white due to
increase in collagen & decrease in vascularity.

48. Fibrous union
5. Wound contraction
• Wound contracts to 1/3rd to
1/4th of its original size due to
presence of myofibroblasts in
granulation tissue.
• Not seen in primary wound
healing.
• Occurs at time when active
granulation tissue is being
formed.

49. 6. Presence of infection:
• Bacterial contamination of an open wound delays
the healing process due to release of toxins that
provoke necrosis, suppuration & thrombosis .
• Debridement helps preventing bacterial infection.

50. SECONDARY HEALING

51. •Gross loss of tissue at the wound site.
•These wounds occur following injury or
an operation where tissue is excised
and foreign material or infection is
present.

52. • Necrotic tissue must be debrided.
• Often revision surgery to remove
dead tissue is necessary.
• The wound is kept open to allow
exudate to drain, preventing the
spread of deep infection and aiding
granulation.

53. •The wound base is treated to
encourage granulation tissue growth.
•The edges of the wound will begin to
contract aiding closure.

54. •When foreign material has been
removed,
•Necrotic tissue debrided
•Infection is no longer present,
•Wound edges are brought together
to achieve closure (delayed primary
closure).

55. COMPONENTS OF EXTRACELLULAR
MATRIX AND FUNCTION
Component Function
1. Collagen -strength, support, structure
2. Elastin - allows tissue to expand and contract
3. Fibronectin - mediates cell matrix adhesion
4. Laminin - binds cells to type iv
collagen and heparin sulfate
5. Proteoglycans -stores moisture , shock absorption,
6. Hyaluronic acid - a fluid environment for cell movement
and differentiation; binds to cytokines

56. STRENGTH OF REPAIRED WOUND
• Tensile strength- load capacity per unit area.
• Maximum achieved in 90 days.
• Usually it is 80% of original strength.
• Bursting strength- force required to break a
wound regardless of its dimension.

57. CLINICAL WOUND HEALING
• Epithelial migration – 1mm/day
• Requires intervention if larger than 5 cm

59. •Simple
•Compound
•Greenstick
•Transverse
•Oblique
•Spiral
•Comminuted
•Impacted
Comminuted
Spiral
Compound
Oblique

60. Bone Healing
Fracture results in
well defined
progression of
tissue response
To remove
tissue debris
To reestablish
vascular supply
To produce a
new skeletal
matrix

61. Time after injury
Hematoma
Inflammation
Soft callus
Callus
PMNs, Macrophages, Lymphocytes
Granulation, matrix
Ossification, woven bone
Fibrin mesh
Inflammation
Remodeling
Absorbtion/deposition, strength, lamellate
0-3 WK 3-6 WK 6-12 WK 6-12 M 1-12 YR

62. 1. Haematoma formation:
Bleeding from torn blood
vessels fills the area surrounding
fracture.
Loose meshwork is formed by
blood & fibrin clot which acts as
framework for subsequent
granulation tissue formation.

63. 2. Local inflammatory
response:
Occurs at site of injury with
exudation of fibrin, RBC,
inflammatory exudate &
debris.
Necrosed bones are
scavanged by macrophages
& osteoclasts.

64. 3. Ingrowth of granulation
tissue:
Originates from soft tissue
of bone (marrow, endosteum
periosteum) & from soft
tissue around bone.

65. Neovascularisation &
proliferation of
mesenchymal cells from
periosteum & endosteum.
Soft tissue callus is thus
formed which joins ends of
fractured bones.

66. 4. Provisional/ Pro callus
formation:
Callus is derived from Latin word
for “hard”.
Cells of periosteum lay down
collagen as well as osteoid
matrix in granulation tissue.
Osteoid undergoes ossification &
is called woven bony callus.

67. Bony callus predominates
wherever fracture fragment are
properly aligned.
Greater amount of cartilage is
formed where movement of
fracture fragment is more.
Seen mainly in superficial part of
callus, thickest part of external
callus.

68. Procallus is composed of woven
bone & catillage with its
characteristic fusiform appearance
& having 3 components:

69. External callus:
The subperiostal part mainly formed
from osteoproginator cells in
deeper layer of periosteum.
Intemediate callus:
Portion that lies in line with cortex
of bone.
Internal callus:
Formed from endosteal cells, is the
portion that fills the original marrow
cavity.

70. Procallous acts as scaffolding
on which osseous components
of lamellar bone is formed.
Woven bone is cleared away
by osteoclasts & the cartilage
disintegrates .

71. Neovascularisation takes place.
Osteoblasts lay down osteoid
which is calcified .

72. During lamellar bone
formation osteoblastic
& osteoclastic activity
remodels the united
ends.

73. External callus is cleared
away.
Compact bone is formed in
place of in intermediate
callus.
Bone marrow cavity develops
in place of internal callus.

74. Overview of bone Healing

75. EARLY COMPLICATIONS
Local
• Vascular injury.
• Visceral injury causing damage to structures such as the brain,
lung or bladder.
• Damage to surrounding tissue, nerves or skin.
• Wound Infection - more common for open fractures.
• Fracture blisters.
Systemic
• Fat embolism.
• Shock.
• Thromboembolism (pulmonary or venous).

76. DELAYED COMPLICATIONS
Local
• Delayed union (fracture takes longer than normal to heal).
• Malunion (fracture does not heal in normal alignment).
• Non-union (fracture does not heal).
• Joint stiffness.
• Vascular necrosis.
• Osteomyelitis
• Growth disturbance or deformity.
Systemic
• Gangrene, Tetanus, Septicaemia
• Fear of mobilising.

77. NERVE HEALING

79. Peripheral nerve injury classification
• In 1943, Seddon
– Neurapraxia (Class I)
– Axonotmesis (Class II)
– Neurotmesis (Class III)

80. Central Nervous system
• Nerve cells of brain, spinal cord and ganglia are not
replaced.
• Axons of CNS show no significant regeneration.
• Neuroglial cells may show proliferation of astrocytes
called gliosis.

81. Peripheral Nervous System
• Have regenerative capacity.
• Degeneration may cause peripheral neuropathy or
traumatic neuroma.
• 3 main types of degenerative processes.
Wallerian degeneration.
Axonal degeneration.
Segmental demyelination.

82. Wallerian Degeneration
• Transection of axon.
• Accumulation of organelles in proximal and distal
ends of trasection sites.
• Axon and myelin sheath disintegrate upto next node
of Ranvier followed by phagocytosis.
• Regeneration by sprouting of axons and proliferation
of Schwann cells from the proximal ends.

83. Axonal Degeneration
• Begins at the peripheral terminal and proceeds
backwards towards nerve cell body.
• Cell body undergoes chromatolysis.
• Schwann cell regeneration.
• Regenerative reaction is limited or absent.

84. Segmental Demyelination
• Between two nodes of Ranvier leaving denuded axon
segment.
• Axon segment remains intact.
• Schwann cell proliferation leads to remyelination.
• Repeated demyelination and remyelination lead to
concentric proliferation of Schwann cells-Onion bulbs
found in hypertrophic neuropathy.

85. Traumatic Neuroma
• Process of regeneration hampered due to hematoma
or fibrous scar.
• Axonal sprouts with Schwann cells and fibroblasts
form peripheral mass.
• Traumatic or stump neuroma.

86. PERIPHERAL NERVE
REGENERATION

89. FACTORS AFFECTING HEALING
Local Factors
• Infection
• Poor blood supply
• Foreign bodies
• Movement
• Ionising radiation
• Ultraviolet light
• Type, size and location
Systemic Factors
• Age
• Nutrition
• Systemic infection
• Glucocorticoids
• Uncontrolled diabetes
• Haematological
abnormalities

90. LOCAL FACTORS
Necrotic tissue
 Acts as barrier to ingrowth of reparative tissue
 Niche and nutrient source
Blood supply
 Richly vascularised-faster healing
 Decrease vascularity-decrease in oxygen tension-
delayed union, fibrous union
Foreign material-
 Bacterial proliferation
 Acts as heaven for bacteria
 Antigenic –stimulates chronic inflammatory
reaction

91. Movement
 Damages the newly growing granulation tissue
Radiation
 Slows healing process
Ultraviolet light
 Facilitates healing process
Type size and location
 Healing by resolution or organisation

92. AGE:
Fast in young age but normal
in old age unless associated
with disease, dietery
deficiency or ischemia.
oDecrease in collagen formation
oDecrease in epithelialization
oDecrease in level of growth factors

93.  Vitamin C Deficiency: Results in capillary fragility and
formation of unstable collagen which is quickly
degraded by collagenolysis.
 Vitamin E Deficiency: Vitamin E functions as membrane
stabilizer & is also required for lyzozyme function
.Deficiency inhibits wound healing.
 Vitamin A Deficiency: Decreases collagen synthesis &
stability.
NUTRITION

94. • Vitamin K Deficiency: Vital in the normal clotting
cascade.
• Deficiencies in vitamin K will affect the synthesis of
prothrombin and factors II, VII, IX, and X.

95. ZINC DEFICIENCY:
Enzymes like DNA & RNA
polymerase are zinc dependent.
Excess zinc also inhibits wound
healing by decreasing chemotaxis &
bacterial phagocytosis.

96. MEDICAMENTS
Corticosteroids:
 Suppression of inflammation.
 Steroids inhibits availability of leukocytes.
 Phagocytosis is reduced.
 Inhibits connective tissue formation.
 Impairs granulation tissue formation.
 Decreases collagen formation .

97.  Other medications:
 Warfarin & Heparin decreases fibrin matrix
formation.
 Cyclosporin A inhibits T helper cells but not T-
suppressor cells & has deleterious effect on
wound healing.
MEDICAMENTS

98. DIABETES:
Increased infection susceptibility because of
decreased phagocytic capacity of cells & neutrophil
chemotaxis.
Hyperglycemia results in decreased activity of
phagocytes & production of abnormal collagen by
fibroblasts.
Insulin is also required for collagen formation.

99. SYSTEMIC PERFUSION DEFECT- SHOCK:
 Heamorrhagic & cardiogenic shock decreases
blood volume & cardiac output.
 There is peripheral vasoconstriction causing
impaired wound oxygenation resulting in
fibroblasts damage at injury site.

100. GENETIC DEFECTS:
Collagen synthesis abnormality is seen in Ehlers
Danlos syndrome.
Patients have fragile skin & decreased wound strength.
Connective tissue abnormalities
due to defects:
Inherent strength
Elasticity
Integrity
Healing properties

101. Ehlers-Danlos Syndrome
– is an inherited connective tissue disorder
– Four major clinical features
• Skin hyper-extensibility
• Joint hyper-mobility
• Tissue fragility
• Poor wound healing

102. Ehlers-Danlos Syndrome
hypermobile joints
skin hyperelasticity

103. COAGULATION DISORDERS:
 Poor fibrin network & abnormal
platelet adhesion is seen in
Haemophilia & von-Willebrand’s
disease resulting in delayed wound
healing.

104. SMOKING:
Impairs wound perfusion and
oxygenation.
CO binds preferentially to Hb to form
CarboxyHb which reduces oxygen release
to healing tissue.
Nicotine also stimulates catecholamine
release which increases heart rate &
oxygen demand which shunts blood away
from healing wound.

105. ALCOHOL CONSUMPTION:
• Decreases host resistance- increases chance of
infection.
• Reduction in wound angiogenesis.

106. COMPLICATIONS
• Due to entry of bacteria
• Delays healing
Infection
• Persistence of epithelial cells
Implantation
cyst
• Coloured particulate material
left in wound
Pigmentation

107. COMPLICATIONS
• Dehiscence or incisional hernia
• Ulceration
Deficient scar
formation
• Hypertophic scar
• Keloid formation
Excessive
formation of
repair component
• Contractures or Cicatrisation
• Palm,sole,anterior aspect of thorax
Excessive
contraction

108. HYPERTROPHIC SCAR
• Imbalance in collagen
production and degradation.
• Either over production OR
Low degradation.
• Usually along tension lines.
• Contracture occurs more in
areas with laxity.
• Red, elevated scars.

109. KELOID
• African>Asians>
Caucasians.
• Tumour like projection of
connective tissue(Claw
like).
• Extends beyond wound
margins.

110. Hypertrophic scar Keloid
Never get worse after 6 months
Itching is usually not present
Non-tender
Non vascular
Does not spread to normal tissue
Continues to get worse even after 1 year
& upto few year
Severe itching is present
Margin is tender
Vascular, red, erythematous
Spread to normal tissue ,has a claw like
process
Precipitating factors
Young persons
Scar crossing the normal skin creases
Over sternum & joints
Negro race
Tuberculous patients
Women
Hereditary & familial
Over sternum
vaccination site
Complications
Do not occur Ulceration, infection

111. Non Healing Wound
• Wound that fails to progress
through an orderly
sequence of repair in a
timely fashion.
• Arbitrary time point: 3-
4weeks.

112. Although wound healing is divided into various
steps , it is actually a continuous process with many
events occurring concurrently.
Though the oral mucosa has many similarities
to skin and uses the same principle of repair, wound
of mucosa especially the gingiva , often heal without
formation of scar tissue.
Thus surgery within the mouth can be
undertaken without fear of producing scar tissue.
Without capacity to heal, we could not survive.

113. References
• John L. Burns, John S. Mancoll, Linda G. Phillips. Impairments to wound healing.
Clin Plastic Surg 30 (2003) 47–51
• Boris Hinz, Sem H. Phan,Victor J. Thannickal, Andrea Galli, Marie-Luce Bochaton-
Piallat, and Giulio Gabbiani.The MyofibroblastOne Function, Multiple Origins. Am J
Pathol. Jun 2007; 170(6): 1807–1816.
• Boris Hinz .Formation and Function of the Myofibroblast during Tissue
Repair.Journal of Investigative Dermatology (2007) 127, 526–537.
• S. Guo and L.A. DiPietro*Factors Affecting Wound Healing J Dent Res. Mar 2010;
89(3): 219–229.
• Basic pathology Robbins – 7th edition
• Textbook Of Pathology- Harsh Mohan 4th edition
• Textbook of oral pathology by Shafer Hine Levy ,(4th edition and 7th edition)
• Minor oral surgery by Geoffrey L Howe (3rd edition)
• Medscape.com
• Wikipedia.org