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					    Tissue Engineering:
a new healthcare technology
              Asma Yahyouche
             Biomaterials Group
 Department of Materials, University of Oxford
     Parks Road, Oxford, OX1 3PH, UK

• 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]
        Biomaterials: Examples
•   Joint replacements
•   Bone plates
•   Bone cement
•   Hip Joint
•   Artificial ligaments and
•   Dental implants for tooth   Heart valve   Hip joint
•   Blood vessel prostheses
•   Heart valves
•   Skin repair devices
•   Cochlear replacements
•   Contact lenses
                                Knee joint       Skin
        Biomaterials at Oxford

               Biomaterials Group
                 Materials Dept.

Drug Delivery Systems          characterization
                                   of Teeth

                             In vitro Testing
   Tissue Engineering           Cell culture
                              Tissue expander
      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
                              Organ transplant
• High cost : $400B in USA each year
US: 1July 2001- 30 June 2002

      Organ               No. patients on          No. patients         No. Patients died          Cost per
                           waiting list              received                waiting           operation in 1987
    transplant                                      treatment

 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
[Cooper .T (1987): Human Organ Transplantation: Societal, medical-legal, regulatory, and Reimbursement
    Issues ed. Cowen D.H et al, Health Administration Press Ann Arbor, MI, pp. 19-26]
 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
• Hip fracture is associated with high morbidity and
• 30-50% of these hip operations with require
  subsequent revision surgery.
           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)
• 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.
• 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 body’s natural regenerative
            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”
          Tissue engineering
• Potential advantages:
   – unlimited supply
   – no rejection issues
   – cost-effective

 Human Cell                               Nutrients,
 Suspension          Scaffold              Growth
              electrical       chemical
                      Bioreactorstimuli    H
                       system           Implantation
                      mechanical         operation
     • A 3D substrate that is key
       component of tissue engineering
     • It needs to fulfil a number of
           - Controllably Porous structure
           - Interconnecting porosity
           - Appropriate surface chemistry
           - Appropriate mechanical
           - Biodegradable material
           - Tailorable
            Scaffolds Materials
• Synthetic polymers:

       Aliphatic polyesters such as polyglycolic acid (PGA),
  polylactic acid ( PLLA), copolymers ( PLGA) and
  polycaprolactone ( PCL) are commonly used in tissue

• Natural polymers:

      Most popular natural polymer used in tissue
  engineering is collagen.
           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.
             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.

Chen and Mooney Pharmaceutical Research, Vol. 20, No. 8, August 2003.
                                      Growth factors

                                                     [3H] thymidine uptake of chondrocytes
             Cumulative TGF-β1 release from          encapsulated in collagen/chitosan/GAG
              chitosan microspheres.                 scaffolds with and without TGF-β1
                                                      (S, S-TGF).
J.E. Lee et al. / Biomaterials 25 (2004) 4163–4173
   Oxford Biomaterials group

• Collagen

• Rapid prototyping:
3D wax printer
               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.
            Collagen processing
                        • This technique allow
                          the control over pore
                          size and porosity.

                        • Achieved through
                          variation of freezing
                          temperature and
                          collagen dispersion
Dry collagen scaffold     concentration
Indirect Solid Freeform fabrication

         Computer Aided Design
                        1    2 Jet Head                         Dissolve away         Negative
                                                                 biosupport            mould


  AutoCAD design            Negative mould fabrication process

                                                                          Freezing   Collagen/HA
Scaffold   Critical Point Drying          Removal of BioBuild
                                                                          at -30°C     casting

                                    Collagen scaffold fabrication
                        3-D printing

From Dr. Chaozong Liu              Printing video
       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

  From Dr. Terry Socholas
            Advantages of ISFF
• Control of the external structure:

     Heart valve tissue engineering

Valve cells     Collagen scaffold   Heart valve post-
                of heart valve      implantation
Scaffolds with microchannels

                               Aclian Blue staining revealed that
                               extensive chondrogenesis were produced
                               along the channels. Sirius Red staining
                               revealed       collagens        production
                               ( osteogenesis) in the periphery.

SEM images of scaffolds with    hMSCs seeded channelled collagen scaffold
channels and open porosity.     stained with Sirius Red and Alcian Blue
           Take home message
• Biomaterials are materials interact with biological
• It’s 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

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