WOUND HEALING.ppt

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

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. Woundhealing
Essentialandprimitiveprocesscommontoall
multicellularorganisms.
Cellsassumeembryonicfeatures,
Migration,
Divides,
Differentiatestoproduceextracellularmatrix.

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 Latinword repararemeans
“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.
oIn low concentration, it induces PDGF and proliferation of
fibroblasts and smooth muscle.
oIn 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
BloodClotfillsthewound.
Fibrinonectiniscrosslinkedtofibrin,collagen,andother
ECMproductsbytransglutaminasegivingclotprovisional
strenght.
Clotonreachingsurfacebecomesdrytoformcrustor
scab.
Preventsoozingofbloodfromwound.
Providesmechanicalbarriertobacteria.

16. 2. INFLAMMATORY PHASE
PMN,macrophages,lymphocytes
&mastcellsaremajorcells
involvedinwoundhealing.
Derivedfromthreesources:
Cellsnormallypresentintissues.
Cellsextravasatedwhenblood
vesselsdamaged.
Cellscarriedinintactblood
vesselsadjacenttowoundthatexit
bymeansofdiapedesis.

17. Plateletderivedcytokinesrecruitleukocytestothesiteof
damagebyprocessofchemotaxis.
PMNaretheIsttoinvadewoundandappearinresponseto
phagocyticstimuliorbindingofchemotacticstimuli.
NeutrophilcellsurfacereceptorsreactwithIgM&IgG;with
C5a&C5b;&witharachidonicacidmetabolites.
Neutrophilscontainvariousenzymes&reactiveoxygen
metabolites(oxygenfreeradicals)thatkillengulfedbacteria&
destroysdamagedtissue.
MacrophagesphagocytoseRBC,fibrin&cellulardebris.

18. Phagocytosis

19. INFLAMMATORY PHASE

20. 3. FORMATION OF GRANULATION TISSUE
NEOVASCULARISATION/
ANGIOGENESIS :
Endothelialcellsatthemargins
ofseveredbloodvessels
proliferate.
Newbloodvesselsareofsingle
layerendotheliumwhichpermit
redcells&plasmatoleakfreely.
Granulation tissue has
edematousappearance.

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 :
Fibroblastsproliferate&invadeclotatthesametime
asendothelialcells.
Derivedfromfibrocytes&fibroblasts.
CytokinesinvolvedFGF,PDGF,TGF-beta,IL-1

23. PROLIFERATIVE PHASE

24. 4. ORGANIZATION:
Gradualreplacementofclot
bynewly formedblood
vessels&fibrobalstscalled
granulationtissue.
Pinkgranularappearance
whichisduetobloodvessels,
fibroblasts&leukocytes.

25. Highly vascular thus bleeds easily, lacks nerves thus
insensitiveand 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. Oncethestratifiedlayeriscomplete,thekeratinocytes
undergoamorphologicalchangetobecomethe
epidermis,thenormalbarrierlayeroftheskin.
Thenewtissuecontinuestoberemodelled.
Numbersoffibroblastsfallandcapillarybundles
becomeorganised.

29. 6. WOUND CONTRACTION :
Beginsby2-3days&
completesby14
th
day.
Woundisreducedbyapp.
80%ofitsoriginalsize.
Resultsinrapidhealing.

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.InitialHaemorrhage:
Woundisfilledwithbloodwhichclots,&
sealswoundagainstdehydration&
infection.
2.AcuteInflammatoryresponse:
-Occurswithin24hrs.
-Polymorphsappearfrommarginsof
incision.
-By3
rd
daypolymorphsarereplacedby
macropphages.

40. 3.Epithelialchanges:
•Basalcellsfrombothcutmargins
beginproliferating&migrating
towardsincisionalspaceinformof
epithelialspurs.
•Separateunderlyingviabledermis
fromtheoverlyingnecroticmaterial&
clot,formingascabwhichiscastoff.
•By5
th
daymultilayerednew
epidermisisformedwhichis
differentiatedintosuperficial&deep
layers.

41. 4.Organisation:
•By3
rd
dayfibroblastsalsoinvade
thewoundarea.
•By5
th
daynewcollagenfibrils
starttoformwhichdominatetill
healingiscomplete.
•In4weeks,scartissuewith
vascular&cellularelements&
epithelialisedsurfaceisformed.

42. 4.Suturetracks:
•Eachsuturetrackisaseparate
wound.
•Whensuturesareremovedon7
th
daymuchofepithelialisedsuture
trackisavulsed&remaining
epithelialtissueisabsorbed.
•Sometimessuturetrackmayget
infected(stitchabscess)or
epithelialcellsmaypersistintrack
(implantationcyst)

43. •Occursinwoundshavingfollowing
characteristics:
-openwithlargetissuedefects.
-havingextensivelossofcells&
tissue.
-openwoundnotapproximatedby
surgicalsutures.

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.Epithelialchanges
•Epithelialspursproliferate&re-
epithelialisethegapbutdoesnot
coverthesurfacecompletely.
•Granulationtissuefrombase
startsfillingthegap.
•Scabisformedwhichiscastoff.

47. 4.Granulationtissue:
•Proliferartion&neovascularisation
fromadjoiningviabletissueresults
ingranulationtissueformation.
•Mainbulkofhealingoccursby
granulationtissue.
•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.Woundcontraction
•Woundcontractsto1/3
rd
to
1/4
th
ofitsoriginalsizedueto
presenceofmyofibroblastsin
granulationtissue.
•Notseeninprimarywound
healing.
•Occursattimewhenactive
granulationtissueisbeing
formed.

49. 6.Presence of infection:
•Bacterialcontaminationofanopenwounddelays
thehealingprocessduetoreleaseoftoxinsthat
provokenecrosis,suppuration&thrombosis.
•Debridementhelpspreventingbacterialinfection.

50. SECONDARY HEALING

51. •Grosslossoftissueatthewoundsite.
•Thesewoundsoccurfollowinginjuryor
anoperationwheretissueisexcised
andforeignmaterialorinfectionis
present.

52. •Necrotictissuemustbedebrided.
•Oftenrevisionsurgerytoremove
deadtissueisnecessary.
•Thewoundiskeptopentoallow
exudatetodrain,preventingthe
spreadofdeepinfectionandaiding
granulation.

53. •Thewoundbaseistreatedto
encouragegranulationtissuegrowth.
•Theedgesofthewoundwillbeginto
contractaidingclosure.

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
Fractureresults 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.Haematomaformation:
Bleedingfromtornblood
vesselsfillstheareasurrounding
fracture.
Loosemeshworkisformedby
blood&fibrinclotwhichactsas
framework forsubsequent
granulationtissueformation.

63. 2. Localinflammatory
response:
Occursatsiteofinjurywith
exudationoffibrin,RBC,
inflammatoryexudate&
debris.
Necrosed bones are
scavangedbymacrophages
&osteoclasts.

64. 3.Ingrowthofgranulation
tissue:
Originatesfromsofttissue
ofbone(marrow,endosteum
periosteum)&fromsoft
tissuearoundbone.

65. Neovascularisation &
proliferation of
mesenchymal cellsfrom
periosteum&endosteum.
Softtissuecallusisthus
formedwhichjoinsendsof
fracturedbones.

66. 4.Provisional/Procallus
formation:
CallusisderivedfromLatinword
for“hard”.
Cellsofperiosteumlaydown
collagenaswellasosteoid
matrixingranulationtissue.
Osteoidundergoesossification&
iscalledwovenbonycallus.

67. Bony callus predominates
whereverfracturefragmentare
properlyaligned.
Greateramountofcartilageis
formedwheremovement of
fracturefragmentismore.
Seenmainlyinsuperficialpartof
callus,thickestpartofexternal
callus.

68. Procallus is composed of woven
bone & catillagewith 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. Procallousactsasscaffolding
onwhichosseouscomponents
oflamellarboneisformed.
Wovenboneisclearedaway
byosteoclasts&thecartilage
disintegrates.

71. Neovascularisationtakesplace.
Osteoblastslaydownosteoid
whichiscalcified.

72. Duringlamellarbone
formationosteoblastic
&osteoclasticactivity
remodelstheunited
ends.

73. Externalcallusiscleared
away.
Compactboneisformedin
placeofinintermediate
callus.
Bonemarrowcavitydevelops
inplaceofinternalcallus.

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 Ranvierfollowed 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
backwardstowards nerve cell body.
•Cell body undergoes chromatolysis.
•Schwann cell regeneration.
•Regenerative reaction is limited or absent.

84. Segmental Demyelination
•Between two nodes of Ranvierleaving 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
•Ionisingradiation
•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 ingrowthof 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:
Increasedinfectionsusceptibilitybecauseof
decreasedphagocyticcapacityofcells&neutrophil
chemotaxis.
Hyperglycemiaresultsindecreasedactivityof
phagocytes&productionofabnormalcollagenby
fibroblasts.
Insulinisalsorequiredforcollagenformation.

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 jointsskin 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:
Impairswoundperfusionand
oxygenation.
CObindspreferentiallytoHbtoform
CarboxyHbwhichreducesoxygenrelease
tohealingtissue.
Nicotinealsostimulatescatecholamine
releasewhichincreasesheartrate&
oxygendemandwhichshuntsbloodaway
fromhealingwound.

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
•Colouredparticulate material
left in wound
Pigmentation

107. COMPLICATIONS
•Dehiscence or incisionalhernia
•Ulceration
Deficient scar
formation
•Hypertophicscar
•Keloidformation
Excessive
formation of
repair component
•Contractures or Cicatrisation
•Palm,sole,anterioraspect of thorax
Excessive
contraction

108. HYPERTROPHIC SCAR
•Imbalanceincollagen
productionanddegradation.
•EitheroverproductionOR
Lowdegradation.
•Usuallyalongtensionlines.
•Contractureoccursmorein
areaswithlaxity.
•Red,elevatedscars.

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

110. Hypertrophicscar Keloid
Never get worse after 6 months
Itchingis usually not present
Non-tender
Non vascular
Does not spread to normal tissue
Continues to get worse even after 1year
& uptofew year
Severeitching 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
Tuberculouspatients
Women
Hereditary & familial
Over sternum
vaccination site
Complications
Do not occur Ulceration, infection

111. Non Healing Wound
•Woundthatfailstoprogress
through an orderly
sequenceofrepairina
timelyfashion.
•Arbitrarytimepoint:3-
4weeks.

112. Althoughwoundhealingisdividedintovarious
steps,itisactuallyacontinuousprocesswithmany
eventsoccurringconcurrently.
Thoughtheoralmucosahasmanysimilarities
toskinandusesthesameprincipleofrepair,wound
ofmucosaespeciallythegingiva,oftenhealwithout
formationofscartissue.
Thussurgerywithinthemouthcanbe
undertakenwithoutfearofproducingscartissue.
Withoutcapacitytoheal,wecouldnotsurvive.

113. References
•John L. Burns, John S. Mancoll, Linda G. Phillips. Impairments to wound healing.
ClinPlastic Surg30 (2003) 47–51
•Boris Hinz,SemH. Phan,VictorJ. Thannickal,Andrea Galli,Marie-Luce Bochaton-
Piallat,andGiulioGabbiani.TheMyofibroblastOneFunction, Multiple Origins. Am J
Pathol. Jun 2007; 170(6): 1807–1816.
•BorisHinz
.
Formation and Function of the Myofibroblastduring Tissue
Repair.Journalof Investigative Dermatology(2007)127,526–537.
•S. GuoandL.A. DiPietro
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