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

1. 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

2. 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]

3. 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

4. Biomaterials Group Materials Dept. Drug Delivery Systems Nano-SIMS characterization of Teeth Tissue Engineering In vitro Testing Cell culture Tissue expander Biomaterials at Oxford

5. 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 ArtificialBiomaterials

6. Organ transplant • High cost : $400B in USA each year US: 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]

7. 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.

8. 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)

9. 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.

10. 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.

11. TissueEngineering • 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”

12. Tissue engineering • Potential advantages: • unlimited supply • no rejection issues • cost-effective

13. Biopsy Nutrients, Growth Factors Human Cell Suspension Scaffold electrical stimuli chemical stimuli H Bioreactor system Implantation operation mechanical stimuli

14. 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

15. 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.

16. 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.

17. 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.

18. Cells Chen and Mooney Pharmaceutical Research, Vol. 20, No. 8, August 2003.

19. Cells

20. 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

21. Oxford Biomaterials group • Collagen • Rapid prototyping: 3D wax printer

22. 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.

23. 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

24. Indirect Solid Freeform fabrication (ISFF) Computer Aided Design

25. 1 2 Jet Head Mill Negative mould Dissolve away biosupport Elevator Negative mould fabrication process Collagen/HA casting Freezing at -30°C Scaffold Critical Point Drying Removal of BioBuild AutoCAD design Collagen scaffold fabrication

26. 3-D printing From Dr. Chaozong Liu Printing video

27. 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

28. Advantages of ISFF • Control of the external structure: Technology: CT/MRI CAD

29. Heart valve tissue engineering Collagen scaffold of heart valve Valve cells Heart valve post- implantation

30. Design Scaffolds with microchannels

31. 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.

32. 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