8550048-artificial-skin

8/7/2019 8550048-Artificial-Skin

1/53

Artificial Skin


2/53

Anatomy and function of skin History

Preparation of Artificial Skin

Design Parameters Commercially available Artificial Skin

Artificial Skin A Necessity

Recent Advances in Artificial Skin The Future


3/53

Skin


4/53

Skin is the external covering of living tissue of

an animal. It is the largest organ

Functions

Anatomical barrier Temperature/Moisture Regulation

Sensation

Vitamin D synthesis

Excretion

Aesthetics and communication - Blushing


5/53

Layers Epidermis

Stratum corneum

Stratum lucidum

Stratum granulosum

Stratum spinosum Stratum basale

Dermis

Papillary Reticular

Hypodermis

Optical Coherence Tomography

of fingertip


6/53

Allograft From cadavers, but limited

Autograft From the same patient but a

different site. Also, the site for this minimal

Xenograft - From other animals, but problem

of graft rejection remains and it cannot be

rectified by immunosuppressants


7/53

Artificial Skin :

The term artificial skin has been used to

describe a cell-free membrane comprising a

highly porous graft copolymer of type I

collagen and chondroitin 6-sulfate whichdegrades at a specific rate in the wound and

regenerates the dermis in dermis-free

wounds in animal models and patients


8/53

History of Artificial Skin

The first synthetic skin was invented by

John F. Burke, V. Yannas, at the Massachusetts

Institute of Technology (MIT)

In 1979 Burke and Yannas used their artificial skin

on their first patient, a woman whose burns covered

over half her body

Integra is the first FDA approved tissue engineered

product for burn and reconstructive surgery. It was

Patented on August 14, 1990


9/53

Preparing Artificial Skin


10/53

Cultured skin cells , polyglycolic fabric ,

collage gels and glycosaminoglycans are

incorporated

Rapid Keratinocyte cultures are obtained bygrowing the same on a feeder layer of

irradiated fibroblasts.

Also , neonatal fibroblasts are being used(Paed Medical Center , Munster Germany )


11/53

The graft is a bilayer membrane.

In this approach, the top layer , a Silicone Layer

incorporates the features of moisture control.

While the bottom layer delivers the performance ofsealing the skin breach and preventing scarring.

The top layer is removed after a period of about 10

15 days.

Following removal of the top layer, the epidermal

cover is provided by covering with a thin epidermal

graft.


12/53


13/53

Design Parameters :

The ratio of the time constant of biodegradation to

the time constant for normal healing of a skin

incision ideally must be unity

Adequate Moisture Flux Dermis Regeneration Template - porous matrix

seeded with cells, induces synthesis of a new

dermis, simultaneously synthesis of a new

epidermis occurs by migration of epithelial cell. The depth of tissue loss must be known as epithelial

cells cannot migrate if loss of tissue is high.


14/53

Limitation

3-4 weeks are required for the cell expansion

in the graft

Certain limitations while implanting the graft Air pocketing between graft and underlying skin

Shear stresses can cause buckling of the skin while

grafting

Excess or low Moisture flux may cause lifting of the skin

or edema underneath

No appendages of skin

Take rates are less.


15/53

Advantages

Less Scarring

Reduction in the nutritional requirements may

be observed while using skin substitutes Can be used even in extensive burns

Does not initiate an inflammatory or foreign body

response


16/53


17/53

Biological skin substitutes

The epidermis injuries are healed byregeneration of the epidermis

The migration of keratinocytes from theperiphery of the wound and the proliferationwould lead to the total healing without scars

However if dermis is injured recovery isharder since the dermis cannot regenerate


18/53

In order to shorten the healing process or

abolish the side effects, skin substitutes

should be used temporarily or permanently.


19/53

Desired properties for skinsubstitutes Adhere to the substrate Be durable and sufficiently elastic to tolerate

some deformation

Allow evaporative water loss at the ratetypical of the external layer

Have optimal water permeability to prevent

either desiccation of the wound or fluidaccumulation under the covering


20/53

Categories of skin substitutes

Skin substitutes for wound closure

Skin substitutes for wound cover

Wound closure requires a material to restore theepidermal barrier function and become incorporatedinto the healing wound

Wound cover necessitates a material which relies inthe in growth of granulation for adhesion.

They are used in superficial burns


21/53

Skin substitutes for woundcover Biobrane

Transcyte

Cultured allogenic keratinocytes

Apligraf(graft skin)

Dermagraft


22/53

Biobrane

It is a bilaminate membraneof nylon mesh bonded to athin layer of slicone which issemipermeable

The nylon mesh is coatedwith peptides to aidadherence

Used temporarily for freshlyexcised full thicknesswounds


23/53

Transcyte

The difference betweentrancyte and biobrane is theseeding the neonatalfibroblast on to the collagencoated nylon membrane

Since nylon is notbiodegradable, it cannot beused as a dermal substitute

The removal process ismore successful because ofless bleeding


24/53


25/53

Cultured allogenickeratinocytes The survival period of allogenic cells is one

week

The healing with allogenic cells can be

enhanced with cytokines and growth factorsby the cells

They are used as dressing for chronic

wounds


26/53

Apligraf(graft skin)

Composed of two layers.

Inner layer- gel type 1 bovine collagen with

living neonatal fibroblast

Outer layer neonatal allogenic

keratinocytes

Used to treat chronic ulcers


27/53

Dermagraft

Cyropreserved human

fibroblast derived dermal

substitute on polyglactin-

910 mesh scaffold

Enhances healing bystimulating the ingrowth of

firbovascular tissue from the

wound bed

Used in chronic lesions


28/53

Skin substitutes for woundclosure Alloderm

Integra

Cultured autologous keratinocytes

Composite epidermal skin substitutes


29/53

Alloderm

Derived from humancadaveric skin in which theepidermis is removed andcellular components of thedermis are extracted and

preserved to avoid specificimmune response

After application, the woundbed is repopulated,revascularised and

incorporated into the tissue


30/53


31/53


32/53

Integra

Produced by Burke andYannas, producer ofGAG(gylcosamine)sponges.

Widely accepted skinsubstitute

Integration of the GAGsponge with a silicone layer

Pore size-70-200micrometer,to allow themigration of patients ownendothelial cells andfibroblasts


33/53

Pore size small- delay or the prevention of

biointegration is observed

Pore size large- insufficient attachment are

for invading host cells Advantage-improved elasticity

Disadvantage- cost

C lt d t l


34/53

Cultured autologouskeratinocytes

Grown in vitro conditions as confluent sheets

Since they are fragile, they require separation

from tissue culture substrate by using

proteolytic enzyme before they are applied tothe wound bed

C lt d t l d li


35/53

Cultured autologous deliverysystems

Fibrin-glue suspension

Fibrin glue sheets

Upside down membrane delivery systems

Sprayed cell suspension

C it id l d l


36/53

Composite epidermal-dermalskin substitute Healing quality can be enhanced by

combining the cultured keratinocytes with adermal matrix

Keratinocytes should be maintained on abiomaterial Epidermis binds-to the biomaterial and

receives adequate nutrition, the epidermal

barrier is replaced.


37/53

COST

Approximately 700 for 125 cm 2

(Journal of Pediatric Orthopaedics 14(5):381-384,September 2005)


38/53

Need for Artificial SkinA Clinical Scenario

The necessity or importance of any

substance, (ARTIFICIAL SKIN, in our case)cant be quoted any better than a comparison

between its existence and its absence


39/53

Study I

Indian Journal Of Plastic Surgery Jan 08

Dr R Shunmugakrishnan , Dr V Narayanan ,

Dr P Thirumalai

Madurai Medical College , Madurai.

Of 150 patients , 86 died. None with >55%

BSA survived.

No mention of Artificial Skin Grafting.


40/53

Study II

Welsh Regional Burns Unit, MorristonHospital, Swansea NHS Trust, Swansea, UK

31 August 1999

An 11 year old boy had 60% BSA burns excisedand artificial skin (Integra) applied. None of the

burn wound was grafted. At 3 weeks post burn

his serum biochemistry was normal, except for a

low serum albumin. This was the first report toshow that a reduction in nutritional requirements

may be observed using skin substitutes.


41/53

DID THE PEOPLE AT THE GOVT HOSPITALDECEASE , DUE TO THE ABSENCE OFARTIFICIAL SKIN ?

We cannot blindly jump into conclusions thatArtificial Skin, saved the boy.

But , it is a Golden rule that Dehydration becorrected first in a burns patient , and only then

compromising the breach in his/her skin isadvisable. As donor skin is limited, we seek something Artificial


42/53

Recent Advances
http://www.sciencedaily.com/images/2008/01/080104140344-large.jpg


43/53

Artificial Skin From Hair

Roots Fraunhofer - Gesellschaft (2008, January 4). Growing Artificial

Skin From Hair Roots

Euroderm and the Fraunhofer Institute for Cell Therapy andImmunology in Leipzig have been granted approval to produceartificial skin from patients own cells.

Few hairs off the back of the patients head are pulled

Adult stem cells from the roots are extracted,

Proliferated in a cell culture for about two weeks.


44/53

ICX-SKN - Mimicking nature

Paul Kemp and colleagues at British biotech

company Intercytex

Fully and consistently integrates into the

human body

No need for further grafting


45/53


46/53

FILM Skin For robots, ArtificialLimbs Flexible, Integrated, Lightweight, Multifunctional skin

Oak Ridge National Laboratory's Nanomaterials

Synthesis and Properties Group

Carbon Nanotubes are being used

The material can be designed to behave as both a

temperature and pressure sensor, as a flexible

electrical conductor, or as part of a polymer materialwith mechanical and thermal properties similar to

those of human skin.


47/53

Skin cells genetically engineeredto be resistant to bacteria Scientists at the Cincinnati Shriners Hospital for

Children have engineered bacteria resistant skin

cells.

Due to delay in angiogenesis, the skin is vulnerableto bacteria as there are no circulating macrophages.

Hence incorporating anti-bacterial

factors like Human Beta Defensin 4,

will help void bacteria

at an initial stage


48/53

In the Near Future


49/53

Self Healing Artificial Skin

http://www.mvac.uiuc.edu

Microvascular Autonomic Composites

Initiative (VAC) is creating materials with a

microvascular network, capable of pumpingself-healing polymers to repair sites of skin

breech

Skin capable of healing, even though only toa certain degree, could prove incredibly

useful for the robotics industry.


50/53

The surface layer acts as a catalystfor the healing agent, causing it to

polymerize upon contact

Microvascular network embedded in the

substrate layer carrying the healing agent

Residue healing agent repairing cracks

on the surface of the VAC material.


51/53

Microvascular Autonomic Composites

Initiative (VAC) is for Robotic Skin..

Imagine the same with our Artificial Skin

Skin that regenerates when breeched

accidentally or intentionally


52/53

References

Biomedical Engineering Handbook - J.D.Bronzino

Journal of US-China Medical Science , Jul. 2007,

Volume 4, No.7 (Serial No.32)

Successful Use of a Physiologically AcceptableArtificial Skin in the Treatment of Extensive Burn

Injury John F Burke , MD

Tissue Engineering Concepts and Strategies ,

Amulya K Saxena Internet


53/53

8550048-artificial-skin

Documents