Incorporation of Contracture Formation during Dermal Wound

Incorporation of Contracture
Formation during Dermal Wound
Healing: a Mathematical Model
W.M. Boon
Dr. ir. J. F. Vermolen
Prof. dr. ir. C. Vuik
Dr. ir. J. H. Dubbeldam
D. Koppenol, MSc
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Opzet
• Onderzoeksdoel
• Biologisch proces
• Wiskundig model
• Componenten
• Contractie
• Resultaten
• Conclusies & aanbevelingen
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Onderzoeksdoel
• Wondgenezing
• Vorming van nieuw weefsel
• Sterkte afhankelijk van de mate van isotropie
• Samentrekking van het weefsel (contractie)
• Contractuur vorming
• Modelleren van het volledige proces
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Gebied
• Doorsnede huid
• Wondgebied
• 3 weken
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Biologisch proces
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Biologisch Proces
tPA
PDGF
Fibrine
Leukocyten
• Fibrine klont gevormd
• Afbraak door tPA
• PDGF verspreidt via diffusie
• Leukocyten arriveren
• TGF-β wordt uitgescheden
TGF-β
• Chemoattractant
• Fibroblasten arriveren
• Myofibroblasten
• Celdeling
Fibroblasten en
Myofibroblasten
• Collageen productie
• Contractie
Collageen
Contractie
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Wiskundig model
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Componenten: Cellen
• Discrete schijven
• Receptoren
• Leukocyten
• Bloedsomloop
• Fibroblasten en myofibroblasten
• Omliggend gebied
• Celdeling
• Beweging
• Celdood
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Componenten: Cytokines
• Diffusievergelijkingen
• tPA: Afbraak fibrine
• PDGF: Aantrekking leukocyten
• TGF-β: Aantrekking (myo)fibroblasten
• Grid
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Componenten: Vezels
• Fibrine
• Collageen
• Dichtheid en oriëntatie
• Tensor
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Contractie
• Samentrekking van het weefsel
• Tijdelijke krachten
• Fibroblasten en myofibroblasten
• Permanente krachten
• Myofibroblasten
• Vorming van contractuur
• Invloed op alle componenten
• Discreet
• Continu
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Tijdelijke krachten
• Puntkracht
• Kromme rond cel
• Opsplitsen in lijnstukken
• Meerdere puntkrachten
• Formulering
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Permanente krachten
• Contractuur vorming
• Elementsgewijs
• Timer per element
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Resultaten
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Celpopulaties
Aantal cellen
150
Leukocyten
Fibroblasten
100
50
0
0
100
200
300
Tijd (uren)
400
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500
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Resultaten cellen
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Resultaten cytokines
Gemiddelde concentratie
0.4
PDGF
TGF-
0.3
0.2
0.1
0
0
100
200
300
Tijd (uren)
400
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500
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Resultaten cytokines
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Resultaten vezels
Gemiddelde dichtheid
1
0.8
0.6
Collageen
Fibrine
0.4
0.2
0
0
100
200
300
Tijd (uren)
400
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500
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Resultaten vezels
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Resultaten: Vezels
Collageen anisotropie
0.4
0.3
0.2
95e percentiel
Gemiddelde
0.1
5e percentiel
0
0
100
200
300
Time (hours)
400
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500
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Contractie
Relatieve oppervlakte
1.05
95e percentiel
Gemiddelde
1
5e percentiel
0.95
0.9
0.85
0
100
200
300
Tijd (uren)
400
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500
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Toename in tijdelijke krachten
Relatieve oppervlakte
1.05
1
0.95
0.9
0.85
0
100
200
300
Tijd (uren)
400
Challenge the future
500
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Conclusies en aanbevelingen
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Conclusies
• Hybride model: Discrete cellen en continue concentraties
• Verschillende stappen van wondgenezing
• Toevoeging van contractie
• Bewegend grid
• Invloed op alle componenten
• Vorming contractuur
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Aanbevelingen
• Groter oppervlak
• Tensor representatie verder benutten
• Differentiatie tot myofibroblast
• Model als basis
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model
Vragen
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Incorporation of Contracture Formation during Dermal Wound Healing: a Mathematical Model