Tissue Engineering:
a new healthcare technology
Asma Yahyouche
Biomaterials Group
Department of Materials, University of Oxford
Parks Road, Oxford, OX1 3PH, UK
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]
Biomaterials: Examples
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•
•
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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
Heart valve
Knee joint
Hip joint
Skin
Biomaterials at Oxford
Biomaterials Group
Materials Dept.
Drug Delivery Systems
Nano-SIMS
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
No. patients on
waiting list
No. patients
received
treatment
No. Patients died
waiting
Cost per
operation in 1987
Lung
Heart
3 757
1 071
463
-
4 097
2 155
589
$ 110 000
Kidney
Liver
Pancreas
50 240
14 385
3 052
$ 30 000
17 379
5 261
1 861
$ 238 000
1 151
541
28
$ 40 000
Organ
transplant
[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
osteoporosis
• Hip fracture is associated with high morbidity and
mortality.
• 30-50% of these hip operations with require
subsequent revision surgery.
Total Hip Joint Replacement
•
•
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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)
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.
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 body’s natural regenerative
mechanisms.
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
Biopsy
Human Cell
Suspension
Scaffold
Nutrients,
Growth
Factors
electrical
chemical
stimuli
Bioreactorstimuli
Implantation
system
operation
mechanical
stimuli
H
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
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.
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.
Cells
Chen and Mooney Pharmaceutical Research, Vol. 20, No. 8, August 2003.
Cells
Growth factors
Cumulative TGF-β1 release from
chitosan microspheres.
J.E. Lee et al. / Biomaterials 25 (2004) 4163–4173
[3H] thymidine uptake of chondrocytes
encapsulated in collagen/chitosan/GAG
scaffolds with and without TGF-β1
microspheres
(S, S-TGF).
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.
Dry collagen scaffold
• Achieved through
variation of freezing
temperature and
collagen dispersion
concentration
Indirect Solid Freeform fabrication
(ISFF)
Computer Aided Design
1
2 Jet Head
Mill
Dissolve away
biosupport
Negative
mould
Elevator
AutoCAD design
Scaffold
Negative mould fabrication process
Critical Point Drying
Removal of BioBuild
Freezing
Collagen/HA
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
process.
From Dr. Terry Socholas
Advantages of ISFF
• Control of the external structure:
Technology:
CT/MRI
CAD
Heart valve tissue engineering
Valve cells
Collagen scaffold
of heart valve
Heart valve postimplantation
Scaffolds with microchannels
Design
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
channels and open porosity.
hMSCs seeded channelled collagen scaffold
stained with Sirius Red and Alcian Blue
Take home message
• Biomaterials are materials interact with biological
tissue
• 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