ARTIFICIAL SKIN AND ARTIFICIAL CARTILAGE

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ARTIFICIAL SKIN
PRESENTED BY
PWADUBASAHIYI COSTON PWAVODI 20143883 MSC. FELIX
CHIBUZO OBI 20144610 MSC. MICHAEL OLABOYE AMUSAN
20103181 ARTIFICIAL ORGANS DEPARTMENT OF
BIOMEDICAL ENGINEERING..
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INTRODUCTION

• The term artificial skin is used to describe any
  material used to replace (permanently or
  temporarily) or to mimic the dermal and epidermal
  layers of the skin.
• The primary current application of artificial
  skin is for the treatment of skin loss or damage
  on burn patients.
• Alternatively however, artificial skin is now
  being used in some places to treat patients with
  skin diseases, such as diabetic foot ulcers, and
  severe .1

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ANATOMICAL OVERVIEW OF THE SKIN

• Human skin is comprised of two primary layers,
  the dermis and the epidermis. A diagram of a
  typical section of human skin is shown here. The
  epidermis is comprised of keratinocytes of
  varying levels of differentiation.
• As can be seen in the figure, the epidermis
  contains no blood vessels meaning transport of
  nutrients to the epidermis occurs from the dermis
  below 2.

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BRIEF HISTORY OF THE ARTIFICIAL SKIN

• 3000-2500BC, India Skin is allegedly
  transplanted by Hindus from the buttocks to
  repair mutilated ears and noses.
• 1442, Italy An allogenous skin graft was
  performed by Branca de Branca who used a mans
  arm skin to transplant the nose of the mans
  slave onto himself.
• 1871, England Pollock proposes skin grafts for
  burn treatment.
• 1998, United States First tissue engineered skin
  (Apligraf) is approved by the FDA.
• 2001, United States Dermagraft, Orcel, Composite
  Cultured Skin are FDA approved 4.
• 2002, United States Integra is FDA approved for
  treatment of severe burns 4.

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PROCESSES INVOLVED IN THE MANUFACTURE OF THE
ARTIFICIAL SKIN

• Skin is usually donated by other donors.
• Fibroblasts are removed from the donated skin and
  are frozen until they are needed.
• The fibroblasts are placed on a polymeric mesh
  scaffolding, gather oxygen, and grow new cells.
• The cells are then transferred to a culture
  system.After 4 weeks the polymer mesh dissolves
  and leaves behind a new layer of dermal skin.
• When the growth cycle is completed, they add more
  nutrients. Keratinocytes are added to the
  collagen and are exposed to air to form
  epidermal layers.
• The skin is now completed and is stored in
  sterile contains until ready to use.

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• Skin Grafts
• Skin grafts are required for patients with skin
  damage that is too significant for self-repair.
  As stated before, one of the primary requirements
  for artificial skin is for the treatment of
  severe burn victims. 2
• Skin grafts are also often done on patients with
  ulcers, skin loss from cancer removal, and
  plastic surgery 1
• The skin required for a skin graft can be
  obtained from three sources the patient
  themselves (autograft), another human
  (allograft), or from animals such as pigs or cows
  (xenografts)2. Allografts and xenografts can
  only be used as temporary wound coverings as they
  are typically rejected within 7 to 10 days or 3
  to 5 days respectively 2.

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• Artificial Skin Treatments
• Since 2001, a total of 4 skin repair devices have
  been FDA approved. These include Dermagraf,
  Orcel, Integra, and Composite Cultured Skin 4.
  Composite Cultured Skin is specifically for
  children with recessive dystrophic epidermolysis
  bullosa and also contain living cells.

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AREAS OF APPLICATION

• Artificial Skins are primarily used for the
  Treatment of Skin loss or damage on burn
  Patients. Alternative Areas of Application of
  Artificial Skins includes
• -Treatment of patients with skin diseases, such
  as diabetic foot ulcers, and severe scarring.
• - Plastics and Cosmetic Surgery.

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ADVANTAGES AND DISADVANTAGES

• ADVANTAGES
• -Chances of survival for burn patients.
• -Artificial skin seals the wound preventing fluid
  loss and bacteria from entering through the
  wound.
• - The fear of Stigmatization of the Patient is
  eliminated
• DISADVANTAGES
• -Risks of Infection and Rejection by the Patients
• -Lack of vascularization to the implanted skin or
  skin cells can lead to cell death which provides
  a breeding ground for bacteria.
• -Loss of Sensitivity
• -Cut of Blood Supply.
• -Complication could arise due to Skin Adhesion
  and/or fluid buildup between the wounded site and
  the transplanted skin.
• - Artificial Skins are very expensive.

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RECENT DEVELOPMENTS OF THE ARTIFICIAL
SKIN/ONGOING RESEARCH

• Though artificial skin has aided significantly in
  skin regeneration, there remain several areas for
  improvement. Ongoing Research attempt to produce
  bacteria-resistant skin cell cultures that can be
  used in artificial skin. Ideally, this would
  allow in vitro replication of a patients own
  genetically modified skin cells. These cells
  could then be put into the artificial matrix for
  bacteria-free growth.
• Another current trend in Artificial is the
  creation of Electronic Skin. Scientist are
  working towards the Incorporation of flexible
  pressure transducers and Bioreceptors to the
  Artificial Skin, these will give a sense of Touch
  to the Patients.
• Outside of artificial biological skin, synthetic
  skin is being developed in hopes of enabling the
  sensation of touch to non-living structures.
  Flexible pressure transducers may eventually
  allow us to create an electronic skin with
  signals to mimic the sense of touch. This has
  applications in robotics including advanced
  prosthetic limbs 8.

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RECENT DEVELOPMENTS OF THE ARTIFICIAL
SKIN/ONGOING RESEARCH

• Other advances have been made in the application
  of cells to the matrices. Dr. Fiona Woods has
  produced a spray on skin called Cellspray. This
  method takes healthy cells from the patient and
  creates a suspension culture of the cells. The
  cells are then distributed by spraying them
  evenly across the matrix. It is believed that
  this method will be beneficial because the
  suspension cell culture can be produced much
  faster (5 days) than traditional methods which
  require formation of a sheet of cells (21 days).
  Though this procedure has not been through
  clinical trials, it was controversially used on
  burn victims in conjunction with traditional
  methods in the Bali bombings in 2004. Further
  testing is required before this treatment can
  officially be deemed successful.

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CONCLUSION

• The ultimate goals of current artificial skin
  technologies are to provide protection from
  infection, dehydration, and protein loss after
  severe skin loss or damage.

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REFERENCES

• 1 Dantzer, E., Queruel, P., Salinier, L.,
  Palmier, B., Quinot, J. F. (2001). Integra, a
  new surgical alternative for the treatment of
  massive burns. Clinical evaluation of acute and
  reconstructive surgery 39 case. Annales De
  Chirurgie Plastique Esthétique, 46(3), 173-189.
  http//www.ncbi.nlm.nih.gov/pubmed/11447623
• 2 Roos, D. (2012). Skin grafts. Retrieved
  02/29, 2012, from http//health.howstuffworks.com/
  skin-care/information/anatomy/skin-graft.htm
• 3 Heman, A. R. (2002). The history of skin
  grafts. Retrieved 02/29, 2012, from
  http//findarticles.com/p/articles/mi_m0PDG/is_3_1
  /ai_110220336/

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ARTIFICIAL CARTILAGE
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INTRODUCTION

• Articular cartilage is a highly organized
  avascular tissue composed of chondrocytes
  embedded within an extracellular matrix of
  collagens, proteoglycans and noncollagenous
  proteins. Its primary function is to enable the
  smooth articulation of joint surfaces, and to
  cushion compressive, tensile and shearing forces.
  Hyaline cartilage has one of the lowest
  coefficients of friction known for any surface to
  surface contact. 
• Cartilage is unique as it is an avascular,
  aneural tissue, in which cells survive for a
  lifetime, without intercellular connections.Owing
  to its sophisticated composition, its high water
  content and its ability to withstand hydrostatic
  pressurization, cartilage is capable of
  transferring enormous forces relatively evenly
  from one subchondral bone plate to the other.

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OVERVIEW OF THE ANATOMY OF THE CARTILAGE

• Cartilage is a flexible connective tissue found
  in many areas in the bodies of humans and other
  animals, including the joints between bones, the
  rib cage, the ear, the nose, the bronchial tubes
  and the intervertebral discs. It is not as hard
  and rigid as bone but is stiffer and less
  flexible than muscle.
• ARTICULAR CARTILAGE?
• Hyaline articular cartilage is a complex
  structure, developed and progressively refined
  over hundreds of millions of years. Articular
  cartilage provides smooth articulation under
  variable loads and impaction for very long
  periods of time. It serves as the load-bearing
  material of joints, which has excellent friction,
  lubrication and wear characteristics. The
  cartilage thickness varies significantly across
  articular surfaces of the same joint. Normal
  hyaline cartilage has a glossy, bluish white,
  homogenous appearance, firm consistency and some
  elasticity. .

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• Cells called chondrocytes
• Abundant extracellular matrix
• Fibers collagen elastin
• Jellylike ground substance of complex sugar
  molecules
• 60-80 water (responsible for the resilience)
• No nerves or vessels

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BRIEF HISTORY OF THE ARTIFICIAL CARTILAGE

• The history up to 1900 is told chronologically,
  divided into (1) recognition of the tissue, (2)
  structure, and (3) chemistry. The twentieth
  century is sketched with a timeline of
  discoveries that at the time were important and a
  bibliography of journal review articles.
• By 1900 the avascular, aneural state and
  fibrillar composition have been accepted. The
  nutrition of articular cartilage remained in
  dispute. The composition of the binding substance
  and its relation to collagen remained unknown.
  Research in the first half of the twentieth
  century continued to be impeded by lack of
  technology. The advent of electron microscopy,
  isotopic tracer technics and enzymology rapidly
  accelerated the understanding of hyaline
  cartilage beginning in the 1950s.

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MANUFACTURING PROCESSES

• Unique building block of articular cartilage
  matrix is Type II collagen
• Middle architectural zone called the netting is
  made of aggregates of proteoglycans called
  glycosamino- glycans (GAGs) This netting holds
  water i.e. gives this zone its hydrophilic
  character that yields the low friction, fluid
  wave enabling smooth joint motion

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• Restore smooth articular cartilage surface
• Relieve patient symptoms and improve function
• Match biomechanical/biochemical properties of
  normal hyaline cartilage
• Prevent or slow progression of focal chondral
  injury to end- stage arthritis
• Scaffolds to enhance Micr0-fx marrow cell
  stimulation
• 2nd Generation Cell Techniques
• Minced Cartilage ( One stage techniques)
• 3rd Generation cell techniques
• Concurrent Use of Growth factors/ BMPs
• Enhanced Stem cell derived

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Scaffolds

• Region-specific
• Conductive several substrates
• Including chitosan/ fibrinogen
• Bio-replaced
• Cost-effective
• May act as Micro-fx adjunct
• ie Scaffold guided regeneration

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2nd Generation Cell Therapies

• Autogenous cells
• Seeded scaffold or liquid gel
• Minimizes periosteal related complications
• Allows arthroscopic implant

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3rd Generation Cell Based

• Autogenous
• Allogeneic
• 3-D Cartilage graft
• Technical ease might allow
• arthroscopic insertion with
• bioadhesive

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Other 3rd Generation Potential Enhancements

• Expanded Juvenile chondrocytes
• Scaffold independent cx
• Clinical Phase I completed
• FDA Phase II/III IND/BLA pending

Sheep Allograft 8 Weeks
Juvenile Cartilage
Adult Cartilage
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CURRENT TRENDS/RESENT DEVELOPMENT OF THE
ARTIFICIAL CARTILAGE

• A resent development of the Artificial Cartilage
  is it use in the treatment of knee Injury.
  Studies have shown that almost half of all
  running injuries are knee injuries, tears could
  sometimes occur. For instance, Meniscus (the
  cartilage pad between the thigh and shin bones)
  tears can occur when a runner takes a misstep or
  twists, pivots or compresses the knee joint in
  the wrong way.
• Biomedical Engineers are now able to implant
  Artificial Cartilage into patients knee that
  could restore much of the function to the damaged
  meniscus.
• Another recent Application of the Artificial
  Cartilage is in Allograft Osteochongraph
  Transplantation (AOT). This is the process
  whereby the Cartilage is obtained from a recently
  deceased donor. It is then tested in the
  Laboratory to make sure it is free from Infection
  before been transplanted to the Patient.
•  

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ONGOING RESEARCH IN THE ARTIFICIAL CARTILAGES

• A number of ongoing research projects are
  currently investigating more efficient and
  effective ways of repairing cartilage.
• Examples of current research projects include
• investigating ways of using different sources of
  stem cells to generate new cartilage (for
  example, bone marrow or fat)
• using donor stem cells to regenerate cartilage
• combining cartilage and stem cells to improve
  repair
• Although these projects are still in the early
  stages, researchers are optimistic they will lead
  to new kinds of treatment.

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AREAS OF APPLICATIONS OF THE ARTIFICIAL CARTILAGE

• The Treatment of knee Injury
• Articular Cartilage the smooth, white tissue
  that covers the ends of bones where they come
  together to form joints
• Nose, Ear etc

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ADVANTAGES OF THE ARTIFICIAL CARTILAGE.

• It can protect runners from arthritis and total
  knee replacement
• It can be use to correct birth defects
• It brings hope and confidence to Patients
•  
• DISADVANTAGES OF THE ARTIFICIAL CARTILAGE
• The Risk of complication and Infection
• It could be rejected the patients body
• Its expensive

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