Asma Yahyouche

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Biomaterials Science at Oxford
Tissue Engineering a new healthcare technology

• Asma Yahyouche
•  Biomaterials Group
• Department of Materials, University of Oxford
• Parks Road, Oxford, OX1 3PH, UK
•  

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Biomaterials

• Biomaterials science may be the most
  multidisciplinary of all the sciences which
  encompasses aspects of medicine, biology,
  chemistry, engineering and materials science.
• Biomaterials are Non-viable materials used in
  a medical devices intended to interact with
  biological systems D.F. Williams, 1987

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Biomaterials Examples

• Joint replacements
• Bone plates
• Bone cement
• Hip Joint
• Artificial ligaments and tendons
• Dental implants for tooth fixation
• Blood vessel prostheses
• Heart valves
• Skin repair devices
• Cochlear replacements
• Contact lenses

Hip joint
Heart valve
Knee joint
Skin
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Biomaterials at Oxford
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Human Tissue Damage

• Disease (e.g cancer, infection).
• Trauma (e.g accidental, surgery).
• Congenital abnormalities (e.g birth defects).
• Current clinical treatment based on

Grafts and Transplants
Artificial Biomaterials
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Organ transplant

• High cost 400B in USA each year
• US 1July 2001- 30 June 2002

Organ transplant No. patients on waiting list No. patients received treatment No. Patients died waiting Cost per operation in 1987
Lung 3 757 1 071 463 -
Heart 4 097 2 155 589 110 000
Kidney 50 240 14 385 3 052 30 000
Liver 17 379 5 261 1 861 238 000
Pancreas 1 151 541 28 40 000
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Example Bone Fractures in UK

• Bone is second transplanted tissue after blood.
• Healthcare in the United Kingdom alone set to
  cost over 900 million each year.
• Each year in the UK 150,000 fractures due to
  osteoporosis
• Hip fracture is associated with high morbidity
  and mortality.
• 30-50 of these hip operations with require
  subsequent revision surgery.

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Total Hip Joint Replacement

• 50,000 hip replacements (arthroplasties) in
  Britain each year.
• Hydroxyapatite porous coatings in orthopaedic
  prostheses Bioactivity, Osteoconductivity.
• Problem Infections in orthopedic surgery (10 of
  cases)

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Biomaterials

• Prostheses have significantly improved the
  quality of life for many ( Joint replacement,
  Cartilage meniscal repair, Large diameter blood
  vessels, dental)
• However, incompatibility due to elastic mismatch
  leads to biomaterials failure.

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Conclusion

• Tissue loss as a result of injury or disease, in
  an increasing ageing population, provide reduced
  quality of life for many at significant
  socioeconomic cost.
• Thus a shift is needed from tissue replacement to
  tissue regeneration by stimulation the bodys
  natural regenerative mechanisms.

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Tissue Engineering

• National Science Foundation first defined tissue
  engineering in 1987 as an interdisciplinary
  field that applies the principles of engineering
  and the life sciences towards the development of
  biological substitutes that restore, maintain or
  improve tissue function

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Tissue engineering

• Potential advantages
• unlimited supply
• no rejection issues
• cost-effective

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Scaffolds

• A 3D substrate that is key component of tissue
  engineering
• It needs to fulfil a number of requirement
• - Controllably Porous structure
• - Interconnecting porosity
• - Appropriate surface chemistry
• - Appropriate mechanical
  
• properties
• - Biodegradable material
• - Tailorable

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Scaffolds Materials

• Synthetic polymers
• Aliphatic polyesters such as
  polyglycolic acid (PGA), polylactic acid ( PLLA),
  copolymers ( PLGA) and polycaprolactone ( PCL)
  are commonly used in tissue engineering.
• Natural polymers
• Most popular natural polymer used in
  tissue engineering is collagen.

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Synthetic polymers

• More controllable from a compositional and
  materials processing viewpoint.
• Scaffold architecture are widely recognized as
  important parameters when designing a scaffold
• They may not be recognized by cells due to the
  absence of biological signals.

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Natural polymers

• Natural materials are readily recognized by
  cells.
• Interactions between cells and biological ECM are
  catalysts to many critical functions in tissues
• These materials have poor mechanical properties.

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Cells
Chen and Mooney Pharmaceutical Research, Vol. 20,
No. 8, August 2003.
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Cells
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Growth factors
3H thymidine uptake of chondrocytes
encapsulated in collagen/chitosan/GAG scaffolds
with and without TGF-ß1 microspheres (S, S-TGF).
Cumulative TGF-ß1 release from chitosan
microspheres.
J.E. Lee et al. / Biomaterials 25 (2004) 41634173
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Oxford Biomaterials group

• Collagen
• Rapid prototyping
• 3D wax printer

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Why collagen?

• It is the ideal scaffold material
• is an important ECM molecule and is the major
  structural component in the body.
• posses ideal surface for cell attachment in the
  body.
• biocompatible and degrades into harmless
  products that are metabolized or excreted.
• a very poor antigen , non-toxic.

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Collagen processing

• This technique allow the control over pore size
  and porosity.
• Achieved through variation of freezing
  temperature and collagen dispersion concentration

Dry collagen scaffold
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Indirect Solid Freeform fabrication
(ISFF)
Computer Aided Design
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AutoCAD design
Collagen scaffold fabrication
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3-D printing
From Dr. Chaozong Liu
Printing video
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Tissue engineering scaffold controlled
architecture

• Featured with
• Pre-defined channels with highly porous
  structured matrix
• With suitable chemistry for tissue growth
  Collagen or HA
• No toxic solvent involved, it offers a strong
  potential to integrate cells/growth factors with
  the scaffold fabrication process.

From Dr. Terry Socholas
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Advantages of ISFF

• Control of the external structure

Technology CT/MRI CAD
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Heart valve tissue engineering
Collagen scaffold of heart valve
Valve cells
Heart valve post- implantation
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Scaffolds with microchannels
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Aclian Blue staining revealed that extensive
chondrogenesis were produced along the channels.
Sirius Red staining revealed collagens production
( osteogenesis) in the periphery.
hMSCs seeded channelled collagen scaffold
stained with Sirius Red and Alcian Blue
SEM images of scaffolds with channels and open
porosity.
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Take home message

• Biomaterials are materials interact with
  biological tissue
• Its a multi-disciplinary subject
• Important application include
• efficient drug delivery in the body
• Development of artificial tissue replacement
  similar to the original for clinical use
• By tracking elemental fluctuation archaeology
  information can be revealed