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Asma Yahyouche Biomaterials Group Department of Materials, University of Oxford Parks Road,...
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Tissue Engineering: a new healthcare technology
Asma Yahyouche Biomaterials Group
Department of Materials, University of OxfordParks 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• Joint replacements • Bone plates • Bone cement • Hip Joint• Artificial ligaments and tendon
s • Dental implants for tooth fixati
on • Blood vessel prostheses • Heart valves • Skin repair devices • Cochlear replacements • Contact lenses
Hip jointHeart valve
Knee joint Skin
Biomaterials at Oxford
Nano-SIMS characterization
of TeethDrug Delivery Systems
Biomaterials Group Materials Dept.
In vitro TestingCell culture
Tissue expanderTissue Engineering
• Disease (e.g cancer, infection).• Trauma (e.g accidental, surgery).• Congenital abnormalities (e.g birth
defects).
• Current clinical treatment based on:
Human Tissue Damage
Grafts and Transplants
Artificial Biomaterials
Organ transplant
• High cost : $400B in USA each yearUS: 1July 2001- 30 June 2002
[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]
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
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.
• 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)
Total Hip Joint Replacement
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.
• 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
Tissue engineering
• Potential advantages: – unlimited supply – no rejection issues– cost-effective
Bioreactorsystem
Scaffold
Biopsy
mechanical stimuli
electrical stimuli
chemical stimuli
Human Cell Suspension
Nutrients, Growth Factors
Implantationoperation
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.
Growth factors
[3H] thymidine uptake of chondrocytes encapsulated in collagen/chitosan/GAG scaffolds with and without TGF-β1 microspheres (S, S-TGF).
Cumulative TGF-β1 release from
chitosan microspheres.
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 concentrationDry collagen scaffold
Indirect Solid Freeform fabrication (ISFF)
Computer Aided Design
AutoCAD design
Scaffold
Jet Head
Mill
Elevator
21 Dissolve away biosupport
Collagen/HA
casting
Negative mould
Freezing
at -30°CRemoval of BioBuildCritical Point Drying
Negative mould fabrication process
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 post- implantation
Scaffolds with microchannels
Design
SEM images of scaffolds with channels and open porosity.
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
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