Skin Grafting Chris Agam OReilly€¦ · Skin y Largest organ y Protects from dehydration,...

Skin GraftingChris Agam

Jason OReilly

Skin

Largest organ Protects from dehydration, chemicals, temperature controlThree basic layers

Epidermis, made of keratinocytesDermis, made of fibroblast, vasculature and collagenHypodermis, made adipose and macrophages [1]

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Model of Skin

4

8 axis of stress were appliedin vivo

Tested expansion andcontraction

800 data point were usedto find stress and strain on 4 subjects [2]

Model Of Skin

From Fung’s equation of Langer line

Giving partial derivatives

5

[2]

Model of Skin

6[2]

Wound Healing

Stages1) Inflammation2) Granulation , scar tissue3) Epithelial layer start to form4) Collagen/Fibrin matrix forms [3]

Skin can’t grow on direct bone, nerves or cartilage without appropriate natural covers[4]

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When Are Skin Grafts Used?

In cases where large portions of skin are lost beyond the ability of unassisted repairCommonly used in burn victims and for cosmetic reasons

Skin grafts are important for structural features:Sweat glands to regulate temperatureProtection of innardsNerves for feeling of sensation, pain, heat, and cold[1]

8

Historically

1785 – Giuseppe Baronio’s

research resulted in first successful skin grafts in animals[5]

10

1823 ‐

Christian Bünger

performed the first clinical skin graft on the nose

1869 ‐

Jacques‐Louis Reverdin

Pinch graft

1870‐

Paul Bert investigated the biocompatibility of skin grafts

1870 –

George Lawson first full‐thickness graft [5]

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1823 ‐

Christian Bünger


1869 ‐


Pinch graft

1870‐


1870 –


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1823 ‐

Christian Bünger


1869 ‐


Pinch graft

1870‐


1870 –


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1823 ‐

Christian Bünger


1869 ‐


Pinch graft

1870‐


1870 –


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1823 ‐

Christian Bünger


1869 ‐


Pinch graft

1870‐


1870 –


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1874 –

Thiersch

began usage of thin skin grafts[5]

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At the same time, Wolfe was making advancements in full thickness grafts, which became known as “Wolfe” grafts[5]

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1929 – Blair split skin graftBlair and Barret‐Brown invented the electric

dermatome making skin removal less error prone[5]

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1960 –

Medawar won the Nobel Prize and was eventually knighted for his work on skin graft

rejection[5]

Medawar studied the immunological response of skin grafts using homozygote twins and chimeras

He studied what made grafts tolerable

Found that mice can become tolerant to a specific donor

If the mouse is injected with lymphoid from another non‐tolerated donor, the graft will be rejected[6,12]

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1960 –


rejection[5]





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1960 –


rejection[5]





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1960 –


rejection[5]





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1960 –


rejection[5]





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•Classic skin graft•Artificial skin graft

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Skin Grafts: The Basics

For a skin graft to survive, three conditions must be met:

1.

Potential for survival after removal

2.

Recipient site must have vascular supply

3.

The local environment must be favorable so the attachment will occur[9]

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Where Does One Cuts the Dermis?

Varying thickness of the dermis yield differing results due to the different material aspects of the dermis at different levels[9].

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Split Thickness Graft

Consists of epidermis and portion of the dermisThe portion of the dermis taken depends on the specific case[10]

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Thin Skin Grafts

The upper portion of the dermis gives rise to the following properties of thin grafts:

1. Dermal blood vesicles arborize

as they rise in the

dermis2.

Finer capillary network

3.

Less volume to vascularize[10]

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Thin Skin Grafts

The upper portion of the dermis gives rise to the following properties of thin grafts:

1. Dermal blood vesicles arborize

as they rise in the

dermis2.

Finer capillary network

3.

Less volume to vascularize[10]

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Skin is often glossy

Skin is pale and contrasts markedly with skin

Coarseness of damaged area will be evident through the skin[9,10]

Thin Skin GraftsPros Cons

Can heal quickly

Does not damage donor site as much

Donor site heals faster allowing for more transplants

Can cover larger area and greater chance of survival

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Skin is often glossy

Skin is pale and contrasts markedly with skin

Coarseness of damaged area will be evident through the skin[9,10]

Thin Skin GraftsPros Cons

Can heal quickly

Does not damage donor site as much

Donor site heals faster allowing for more transplants

Can cover larger area and greater chance of survival

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Thick Skin Grafts

The biomaterials of the lower dermis causes the following benefits for thick grafts:

1.

Less susceptible to traumatic injury

2.

Better cosmetic result[10]

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Thick Skin GraftsPros Cons

Less susceptible to traumatic injury, acts as a cushion

Increase in elasticity

Better cosmetic result, more natural complexion

Takes longer to heal

Difficult to find large suitable donor sites

Donor site takes longer to heal[9,10]

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Thick Skin GraftsPros Cons

Less susceptible to traumatic injury, acts as a cushion

Increase in elasticity

Better cosmetic result, more natural complexion

Takes longer to heal

Difficult to find large suitable donor sites

Donor site takes longer to heal[9,10]

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Donor Site Location

The donor site for the skin graft must have very similar biomaterial properties to the grafting location

For instance, for a facial graft the donor site is often the upper shoulders due to similarities to facial skin

The graft will retain the properties of the donor site[10]

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The most important factor for graft survival is the preparation of the recipient site

The site must meet physiologic conditions to be accepted and nourished

Skin grafts cannot be done directly on bone, cartilage, tendon, or nerve without the respective coverings[14]

Graft Survival

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Graft Survival

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Graft Survival

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Graft Survival

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Operation Techniques

Each type of skin graft has their own specific operating techniquesAll grafts general begin with the following treatment of the donor site:

1.

Anesthesia2.

Epinephrine for vasoconstriction(optional)

3.

Anti‐bacteria agents[9]

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Full Thickness Operation

The skin is marked, treated and removed using a scalpel to incise the markings, and a skin hook to remove the skin itself

Adipose tissue is removed from the bottom of the dermis since it has poor vascularization [9]

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Split thickness may be harvested several ways

The most commonly used instrument is the blade dermatome using an rapidly oscillating blade

Some surgeons use manual equipment, knifes or scalpel to remove skin for irregular patterns[11]

Split‐thickness Operation

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Split thickness may be harvested several ways

The most commonly used instrument is the blade dermatome using an rapidly oscillating blade

Some surgeons use manual equipment, knifes or scalpel to remove skin for irregular patterns[11]

Split‐thickness Operation

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Meshing

A split‐thickness skin graft may be meshed by running it through a mechanical meshing unitThis allows for expansion of the surface area as needed for patients where only small donation sites are available[9]

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Inserting the Graft

Recipient site must be inspected for hemostatis

The graft should fit perfectly into place to maximize peripheral contact and surface contact with no folds for more vascularization

Suturing or stapling of the graft reinforce contact[9]

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Post‐graft

Adherence to wound bed via thin fibrin network

Period of time between grafting and revascularization

Full circulation after just 7 days[9]

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Wound Contraction

During healing, contraction may cause serious functional or cosmetic problems as a result of differing properties of donor and recipient areas

Over joints, contraction can cause decease in range of motion[10]

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Regeneration

Hair will rarely grow from thin graftsSweat glands and sebaceous glands may regenerate depending on thickness of graft and depends on the recipient siteNerve fibers will regenerate in thin grafts fasterSkin will be dry and scaly until sweat glands regain function[4]

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Reinnervation

Occurs initially on periphery of graft and proceeds inwardsThis process may take several yearsFull thickness grafts reinnervated more completely

PigmentationFull‐thickness grafts are likely to retain complexion of donor siteThinner grafts may remain pale or possibly hyperpigmentation may occur[15]

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Reinnervation

Occurs initially on periphery of graft and proceeds inwardsThis process may take several yearsFull thickness grafts reinnervated more completely

PigmentationFull‐thickness grafts are likely to retain complexion of donor siteThinner grafts may remain pale or possibly hyperpigmentation may occur[15]

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Graft Failure

Most common source of failure is poor adhesion to recipient siteShearing forces or movement of the graftPoor vascularization of recipient siteContamination and immune responses leading to inflammation and deterioration of fibrin[10]

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Skin Culture: History

1975 – Rheinwald and Green culture the first skin transplant (multiple layers of keratinocytes)

1981 – O’Connor completes the firsthuman transplant with at cultured epithelial autograph (CEA)[1]

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Skin Banks

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By 2016 half of the orthopaedic surgery will need banked tissue

Typically 34,000‐62,000 grafts per year in Canada

Projected increase of 10,000 per year (2006)

Tissue supply is not where the demand is

Building CEA

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Grown on scaffolds that are natural to the human body or biodegradable

Scaffold material like collagen and fibrin are ideal

keratinocytes are “seeded” on to the scaffold with a culture medium in a bioreactor

Typically take 3 week to enough skin to perform a graft

Building CEA

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A fibrin matrix , is biocompatible is the glue of the healing process

Fibrin helps reduce the riskof rejection

The matrix allows for thicker CEA with more layers

Building CEA

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CEAPros Cons

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Great temporal patch to assist in wound healing

Bio dressing

Thin skin graft alternative

Grafts beyond the epidermis

Very fragile, weak against shear stress

Open to infection, due to the protection of multiple layer

Biocompatibility, lack of integrin

Expensive and labour intensive[1]

Extra Cellular Material

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Full thickness grafts

Multiple cell types

3‐D scaffolding

Improve vasculature

Better integration with the body[1]

ECM

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Multiple cell layersEpitheal cellDermal cellBasement cells

More complex ECMstructure

Better cell development

ECM

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Multiple cell layersEpitheal cellDermal cellBasement cells

More complex ECMstructure

Better cell development

Composite Skin Stress vs. Strain

Artificial skin grafts attempt to have properties as close to human skin as possibleIn experiments using mice, they analyzed these properties with various composite skinsThey used a xenogeneic acellular dermal matrix Dermal papilla cells were placed on this matrixIn the control group, DPCs were not used

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[13]



63

[13]



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[13]



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[13]

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Case Study: ICX‐SKN

3‐D Fibrin network

Seeded with fibroblast

Full thickness

Full integration with remolding of patient’s real skin

28 day cycle [8]

Problems With All Grafts

Lack of Sensitivity

Wrong pigmentation

Hair growth/ sweat glands

Scarring

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Future

The replacement should not be a “replacement”

We need to better understand the skin

More complex tissue engineering

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References

1. Hansjor

Hauser, Martin Fussenegger, Artifical

Skin,

Tissue Engineering, Humana Press, 2007, pg 167‐1822.

Y. A. Kvistedal, P. M. F. Nielsen, Estimating

material parameters of human skin in vivo, Biomechanics and Modeling in Mechanobiology,

Springer, 20073.

Viktor Nedovic, Ronnie Willaert, Bioartificial

Skin ,

Application of Cell Immobilisation

Biotechnology, Springer, 2005, pg 55‐68

69

References

4.

Ioannis

Yannas, Regeneration of Skin, Tissue and Organ Regeneration in Adults, Springer, 2001, pg 93‐

1375.

Paolo Santoni‐Rugiu, Philip J.Sykes, A History of

Plastic Surgery, Springer , 2007 pg 121‐1396.

http://nobelprize.org/nobel_prizes/medicine/laurea

tes/1960/medawar‐lecture.html

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References

7.

Masahiro Kino‐oka

, Masahito Taya, Development of Culture Techniques of Keratinocytes

for Skin

Graft Production, Advances in Biochemical Engineering/Biotechnology, Springer, vol

91, 2007,

pg 135‐1698.

Melody Boyd, Marzena

Flasza, Penny A Johnson,

John St Clair Roberts, Paul Kemp, Integration and persistence of an investigational human living skin equivalent (ICX‐SKN) in human surgical wounds,

Regenerative Medicine, vol

2, iss

4, pg 363‐370

71

References

9.

John W. Skouge, Skin Grafting, The John Hopkins Medical Institutions, Churchhill

Livingstone, 1991

10.

Rudolph, Fisher, Ninnemann, Skin Grafting, Little, Brown and Company, 1979

11.

Roberto Rudge

Ramos, An easy and safe method of split‐thickness skin graft fixation, BurnsVolume

33,

Issue 8, , December 2007, Pages 1074‐1075.http://www.sciencedirect.com/science/article/B6T2

‐4PMJB5W‐2/2/d2d0809f129e19b2e213b55a1df89c4c)

72

References

12.

Betul

Gozel

Ulusal, Ali Engin

Ulusal, Fu Chan Wei, Chun‐Yen Lin, Allograft Mass as a Possible

Contributing Factor to the Skin Transplant Outcome, Journal of Surgical ResearchIn

Press,

Uncorrected Proof, , Available online 13 June 2008.(http://www.sciencedirect.com/science/article/B6W

M6‐4SRM58V‐ 1/2/2c3ff7f28afab5db3edb7115786da2a9)

73

References

14.

Shao‐Hai

Qi, Po Liu, Ju‐Lin Xie, Bin Shu, Ying‐Bin Xu, Chang‐Neng

Ke, Xu‐Sheng

Liu, Tian‐Zeng

Li,

Experimental study on repairing of nude mice skin defects with composite skin consisting of

xenogeneic

dermis and epidermal stem cells and hair follicle dermal papilla cells, BurnsVolume

34,

Issue 3, , May 2008, Pages 385‐392.(http://www.sciencedirect.com/science/article/B6T

52‐4PMT5WY‐ 1/2/cca37780421bcaab1bce883f3cc210c7)

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References

15.

British Journal of Dermatology, Volume 156, Issue 1 (p 165‐167)

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Skin Grafting Chris Agam OReilly€¦ · Skin y Largest organ y Protects from dehydration,...

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